file which includes the original illustrations4 ,see #deifb-;h4htm or #deifb-;h4zip3 7https3_/_/www4gutenberg4org_/cache_/epu b_/#deifb_/pg#deifb-;images4html7 or 7https3_/_/www4gutenberg4org_/files_/#de ifb_/deifb-;h4zip7 ,images of the original pages are available through ,internet ,archive_/,american ,libraries4 ,see https3_/_/archive4org_/details_/organism aswholef#jjloeb ,transcriber's note3 ,text enclosed by underscores is in italics 7italics74 ,text enclosed by equal signs is in bold face 7bold74 ,subscripted characters are enclosed by curly brackets1 for example1 ,c,h 7indicating 'concentration of hydrogen'74 ,a few superscripts1 indicated by the carat character 77 occur in the advertising material at the end of the book where #ho and #hvo are used as alternative abbreviations for 'octavo' 7paper size74 ,,the ,,organism ,,as ,a ,,whole ,from a ,physicochemical ,viewpoint by ,,jacques ,,loeb1 ,m4,d41 ,ph4,d41 ,sc4,d4 ,member of the ,rockefeller ,institute for ,medical ,research ,with #ea ,illustrations ,g4 ,p4 ,putnam's ,sons ,new ,york and ,london ,the ,knickerbocker ,press ,copyright1 #aiaf by ,jacques ,loeb ,the ,knickerbocker ,press1 ,new ,york ,to ,,the ,,memory ,,of ,,denis ,,diderot ,of the ,encyclopdie and the ,systme de la nature 8,he was one of those simple1 disinterested1 and intellectually sterling workers to whom their own personality is as nothing in the presence of the vast subjects that engage the thoughts of their lives40 ,,john ,,morley4 7,article ,diderot1 ,encyclopdia ,britannica47 ,,preface ,it is generally admitted that the individual physiological processes1 such as digestion1 metabolism1 the production of heat or of electricity1 are of a purely physicochemical character2 and it is also conceded that the functions of individual organs1 such as the eye or the ear1 are to be analysed from the viewpoint of the physicist4 ,when1 however1 the biologist is confronted with the fact that in the organism the parts are so adapted to each other as to give rise to a harmonious whole2 and that the organisms are endowed with structures and instincts calculated to prolong their life and perpetuate their race1 doubts as to the adequacy of a purely physicochemical viewpoint in biology may arise4 ,the difficulties besetting the biologist in this problem have been rather increased than diminished by the discovery of ,mendelian heredity1 according to which each character is transmitted independently of any other character4 ,since the number of ,mendelian characters in each organism is large1 the possibility must be faced that the organism is merely a mosaic of independent hereditary characters4 ,if this be the case the question arises3 ,what moulds these independent characters into a harmonious whole8 ,the vitalist settles this question by assuming the existence of a pre-established design for each organism and of a guiding 8force0 or 8principle0 which directs the working out of this design4 ,such assumptions remove the problem of accounting for the harmonious character of the organism from the field of physics or chemistry4 ,the theory of natural selection invokes neither design nor purpose1 but it is incomplete since it disregards the physicochemical constitution of living matter about which little was known until recently4 ,in this book an attempt is made to show that the unity of the organism is due to the fact that the egg 7or rather its cytoplasm7 is the future embryo upon which the ,mendelian factors in the chromosomes can impress only individual characteristics1 probably by giving rise to special hormones and enzymes4 ,we can cause an egg to develop into an organism without a spermatozon1 but apparently we cannot make a spermatozon develop into an organism without the cytoplasm of an egg1 although sperm and egg nucleus transmit equally the ,mendelian characters4 ,the conception that the cytoplasm of the egg is already the embryo in the rough may be of importance also for the problem of evolution since it suggests the possibility that the genus- and species-heredity are determined by the cytoplasm of the egg1 while the ,mendelian hereditary characters cannot contribute at all or only to a limited extent to the formation of new species4 ,such an idea is supported by the work on immunity1 which shows that genus- and probably species-specificity are due to specific proteins1 while the ,mendelian characters may be determined by hormones which need neither be proteins nor specific or by enzymes which also need not be specific for the species or genus4 ,such a conception would remove the difficulties which the work on ,mendelian heredity has seemingly created not only for the problem of evolution but also for the problem of the harmonious character of the organism as a whole4 ,since the book is intended as a companion volume to the writer's former treatise on ,the ,comparative ,physiology of the ,brain a discussion of the functions of the central nervous system is omitted4 ,completeness in regard to quotation of literature was out of the question1 but the writer notices with regret1 that he has failed to refer in the text to so important a contribution to the subject as ,sir ,e4 ,a4 ,schfer's masterly presidential address on 8,life0 or the addresses of ,correns and ,goldschmidt on the determination of sex4 ,credit should also have been given to ,professor ,raymond ,pearl for the discrimination between species and individual inheritance4 ,the writer wishes to acknowledge his indebtedness to his friends ,professor ,e4 ,g4 ,conklin of ,princeton1 ,professor ,richard ,goldschmidt of the ,kaiser ,wilhelm ,institut of ,berlin1 ,dr4 ,p4 ,a4 ,levene of the ,rockefeller ,institute1 ,professor ,t4 ,h4 ,morgan of ,columbia ,university1 and ,professor ,hardolph ,wasteneys of the ,university of ,california who kindly read one or more chapters of the book and offered valuable suggestions2 and he wishes especially to thank his wife for suggesting many corrections in the manuscript and the proof4 ,the book is dedicated to that group of freethinkers1 including d',alembert1 ,diderot1 ,holbach1 and ,voltaire1 who first dared to follow the consequences of a mechanistic science--incomplete as it then was--to the rules of human conduct and who thereby laid the foundation of that spirit of tolerance1 justice1 and gentleness which was the hope of our civilization until it was buried under the wave of homicidal emotion which has swept through the world4 ,diderot was singled out1 since to him the words of ,lord ,morley are devoted1 which1 however1 are more or less characteristic of the whole group4 ,j4 ,l4 ,the ,rockefeller ,institute for ,medical ,research1 ,august1 #aiaf ,,contents ,,page ,,chapter ,i ,introductory ,remarks #a ,,chapter ,,ii ,the ,specific ,difference between ,living and ,dead ,matter and the ,question of the ,origin of ,life #ad ,,chapter ,,iii ,the ,chemical ,basis of ,genus and ,species3 #dj ,i4--,the ,incompatibility of ,species not ,closely ,related #dd ,,ii4--,the ,chemical ,basis of ,genus and ,species and of ,species ,specificity #ec ,,chapter ,,iv ,specificity in ,fertilization #ga ,,chapter ,v ,artificial ,parthenogenesis #ie ,,chapter ,,vi ,determinism in the ,formation of an ,organism from an ,egg #abh ,,chapter ,,vii ,regeneration #aec ,,chapter ,,viii ,determination of ,sex1 ,secondary ,sexual ,characters1 and ,sexual ,instincts3 ,i4--,the ,cytological ,basis of ,sex ,determination #aih ,,ii4--,the ,physiological ,basis of ,sex ,determination #bad ,,chapter ,,ix ,mendelian ,heredity and its ,mechanism #bbi ,,chapter ,x ,animal ,instincts and ,tropisms #bec ,,chapter ,,xi ,the ,influence of ,environment #bhf ,,chapter ,,xii ,adaptation to ,environment #cah ,,chapter ,,xiii ,evolution #cdf ,,chapter ,,xiv ,death and ,dissolution of the ,organism #cdi ,index #cga ,the ,organism as a ,whole ,,chapter ,i ,,introductory ,,remarks #a4 ,the physical researches of the last ten years have put the atomistic theory of matter and electricity on a definite and in all probability permanent basis4 ,we know the exact number of molecules in a given mass of any substance whose molecular weight is known to us1 and we know the exact charge of a single electron4 ,this permits us to state as the ultimate aim of the physical sciences the visualization of all phenomena in terms of groupings and displacements of ultimate particles1 and since there is no discontinuity between the matter constituting the living and non-living world the goal of biology can be expressed in the same way4 ,this idea has more or less consciously prevailed for some time in the explanation of the single processes occurring in the animal body or in the explanation of the functions of the individual organs4 ,nobody1 not even a scientific vitalist1 would think of treating the process of digestion1 metabolism1 production of heat1 and electricity or even secretion or muscular contraction in any other than a purely chemical or physicochemical way2 nor would anybody think of explaining the functions of the eye or the ear from any other standpoint than that of physics4 ,when the actions of the organism as a whole are concerned1 we find a totally different situation4 ,the same physiologists who in the explanation of the individual processes would follow the strictly physicochemical viewpoint and method would consider the reactions of the organism as a whole as the expression of non-physical agencies4 ,thus ,claude ,bernard1#a who in the investigation of the individual life processes was a strict mechanist1 declares that the making of a harmonious organism from the egg cannot be explained on a mechanistic basis but only on the assumption of a 8directive force40 ,bernard assumes1 as ,bichat and others had done before him1 that there are two opposite processes going on in the living organism3 7#a7 the phenomena of vital creation or organizing synthesis2 7#b7 the phenomena of death or organic destruction4 ,it is only the destructive processes which give rise to the physical manifestations by which we judge life1 such as respiration and circulation or the activity of glands1 and so on4 ,the work of creation takes place unseen by us in the egg when the embryo or organism is formed4 ,this vital creation occurs always according to a definite plan1 and in the opinion of ,bernard it is impossible to account for this plan on a purely physicochemical basis4 #a ,bernard ,c41 ,leons sur les ,phnomnes de la ,vie4 ,paris1 #ahhe1 i41 #bb-fd4 ,there is so to speak a pre-established design of each being and of each organ of such a kind that each phenomenon by itself depends upon the general forces of nature1 but when taken in connection with the others it seems directed by some invisible guide on the road it follows and led to the place it occupies4444 ,we admit that the life phenomena are attached to physicochemical manifestations1 but it is true that the essential is not explained thereby2 for no fortuitous coming together of physicochemical phenomena constructs each organism after a plan and a fixed design 7which are foreseen in advance7 and arouses the admirable subordination and harmonious agreement of the acts of life4444 ,we can only know the material conditions and not the intimate nature of life phenomena4 ,we have therefore only to deal with matter and not with the first causes or the vital force derived therefrom4 ,these causes are inaccessible to us1 and if we believe anything else we commit an error and become the dupes of metaphors and take figurative language as real4444 ,determinism can never be but physicochemical determinism4 ,the vital force and life belong to the metaphysical world4 ,in other words1 ,bernard thinks it his task to account for individual life phenomena on a purely physicochemical basis--but the harmonious character of the organism as a whole is in his opinion not produced by the same forces and he considers it impossible and hopeless to investigate the 8design40 ,this attitude of ,bernard would be incomprehensible were it not for the fact that1 when he made these statements1 the phenomena of specificity1 the physiology of development and regeneration1 the ,mendelian laws of heredity1 the animal tropisms and their bearing on the theory of adaptation were unknown4 ,this explanation of ,bernard's attitude is apparently contradicted by the fact that ,driesch#b and v4 ,uexkll1#c both brilliant biologists1 occupy today a standpoint not very different from that of ,claude ,bernard4 ,driesch assumes that there is an ,aristotelian 8entelechy0 acting as directing guide in each organism2 and v4 ,uexkll suggests a kind of ,platonic 8idea0 as a peculiar characteristic of life which accounts for the purposeful character of the organism4 v4 ,uexkll supposes as did ,claude ,bernard and as does ,driesch that in an organism or an egg the ultimate processes are purely physicochemical4 ,in an egg these processes are guided into definite parts of the future embryo by the ,mendelian factors of heredity--the so-called genes4 ,these genes he compares to the foremen for the different types of work to be done in a building4 ,but there must be something that makes of the work of the single genes a harmonious whole1 and for this purpose he assumes the existence of 8supergenes40#d v4 ,uexkll's ideas concerning the nature of a ,mendelian factor and of the 8supergenes0 are expressed in metaphorical terms and the assumption of the 8supergenes0 begs the question4 ,the writer is under the impression that this author was led to his views by the belief that the egg is entirely undifferentiated4 ,but the unfertilized egg is not homogeneous1 on the contrary1 it has a simple but definite physicochemical structure which suffices to determine the first steps in the differentiation of the organism4 ,of course1 if we suppose as do v4 ,uexkll and ,driesch that the egg has no structure1 the development of structure becomes a difficult problem--but this is not the real situation4 #b ,driesch1 ,h41 ,the ,science and ,philosophy of the ,organism4 #b vols4 ,the ,gifford ,lectures1 #aijg and #aijh4 #c v4 ,uexkll1 ,j41 ,bausteine zu einer biologischen ,weltanschauung4 ,mnchen1 #aiac4 #d v4 ,uexkll1 ,j41 ,bausteine zu einer biologischen ,weltanschauung4 ,mnchen1 #aiac1 p4 #baf4 #b4 ,claude ,bernard does not mention the possibility of explaining the harmony or apparent design in the organism on the basis of the theory of evolution1 he simply considers the problem as outside of biology4 ,it was probably clear to him as it must be to everyone with an adequate training in physics that natural selection does not explain the origin of variation4 ,driesch and v4 ,uexkll consider the ,darwinian theory a failure4 ,we may admit that the theory of a formation of new species by the cumulative effect of aimless fluctuating variations is not tenable because fluctuating variation is not hereditary2 but this would only demand a slight change in the theory2 namely a replacement of the influence of fluctuating variation by that of equally aimless mutations4 ,with this slight modification which is proposed by de ,vries1#e ,darwin's theory still serves the purpose of explaining how without any pre-established plan only purposeful and harmonious organisms should have survived4 ,it must be said1 however1 that any theory of life phenomena must be based on our knowledge of the physicochemical constitution of living matter1 and neither ,darwin nor ,lamarck was concerned with this4 ,moreover1 we cannot consider any theory of evolution as proved unless it permits us to transform at desire one species into another1 and this has not yet been accomplished4 #e de ,vries1 ,h41 ,die ,mutationstheorie4 ,leipzig1 #aija4 ,it may be of some interest to point out that we do not need to make any definite assumption concerning the mechanism of evolution and that we may yet be able to account for the fact that the surviving organisms are to all appearances harmonious4 ,the writer pointed out that of all the #ajj1jjj1jjj conceivable crosses of teleost fish 7many of which are possible7 not many more than #aj1jjj1 i4 e41 about one-hundredth of one per cent41 are able to live and propagate4 ,those that live and develop are free from the grosser type of disharmonies1 the rest are doomed on account of a gross lack of harmony of the parts4 ,these latter we never see and this gives us the erroneous conception that harmony or 8design0 is a general character of living matter4 ,if anybody wishes to call the non-viability of #ii-ii_/ajj per cent4 of possible teleosts a process of weeding out by 8natural selection0 we shall raise no objection1 but only wish to point out that our way of explaining the lack of design in living nature would be valid even if there were no theory of evolution or if there had never been any evolution4 #c4 v4 ,uexkll is perfectly right in connecting the problem of design in an organism with ,mendelian heredity4 ,the work on ,mendelian heredity has shown that an extremely large number of independently transmissible ,mendelian factors help to shape the individual4 ,it is not yet proven that the organism is nothing but a mosaic of ,mendelian factors1 but no writer can be blamed for considering such a possibility4 ,if we assume that the organism is nothing but a mosaic of ,mendelian characters it is difficult indeed to understand how they can force each other into a harmonious whole#f2 even if we make ample allowance for the law of chance and the corresponding wastefulness in the world of the living4 ,but it is doubtful whether this idea of the rle of ,mendelian factors is correct4 ,the facts of experimental embryology strongly indicate the possibility that the cytoplasm of the egg is the future embryo 7in the rough7 and that the ,mendelian factors only impress the individual 7and variety7 characters upon this rough block4 ,this idea is supported by the fact that the first development--in the sea urchin to the gastrula stage inclusive--is independent of the nucleus1 which is the bearer of the ,mendelian factors4 ,not before the skeleton or mesenchyme is formed in the sea urchin egg is the influence of the nucleus noticeable4 ,this has been shown in the experiments of ,boveri in which an enucleated fragment of an egg was fertilized with a spermatozon of a foreign species4 ,if this is generally true1 it is conceivable that the generic and possibly also the species characters of organisms are determined by the cytoplasm of the egg and not by the ,mendelian factors4 #f ,this difficulty is also felt by mechanistic writers like ,child1 who on page #ab of his recent book on ,senescence and ,rejuvenescence 7,chicago1 #aiae7 makes the following remarks3 8,these theories of ,weismann do not account satisfactorily for the peculiarly constant course and character of development and morphogenesis4 ,if we follow them to their logical conclusion1 which their authors have not done1 we find ourselves forced to assume the existence of some sort of controlling and co-ordinating principle outside the units themselves and superior to them4 ,if the units constitute the physicochemical basis of life1 as their authors maintain1 then this controlling principle1 since it is an essential feature of life1 must of necessity be something which is not physicochemical in nature4 ,in short these theories lead us in the final analysis to the same conclusion as that reached by the neovitalists4 ,if we are not content to accept this conclusion we must reject the theories40 ,these last sentences do not exhaust all the possibilities1 since the writer is trying to show in this book that the widest acceptance of the chromosome theory of heredity is compatible with a consistent physicochemical conception of the organism as a whole4 ,in any case1 we can state today that the cytoplasm contains the rough preformation of the future embryo4 ,this would show then that the idea of the organism being a mosaic of ,mendelian characters which have to be put into place by 8supergenes0 is unnecessary4 ,if the egg is already the embryo in the rough we can imagine the ,mendelian factors as giving rise to specific substances which go into the circulation and start or accelerate different chemical reactions in different parts of the embryo1 and thereby call forth the finer details characteristic of the variety and the individual4 ,the idea that the egg is the future embryo is supported by the fact that we can call forth a normal organism from an unfertilized egg by artificial means2 while it is apparently impossible to cause the spermatozon to develop into an organism outside the egg4 #d4 ,the influence of the whole on the parts is nowhere shown more strikingly than in the field of regeneration4 ,it is known that pieces cut from the plant or animal may give rise to new growth which in many cases will restore somewhat the original organism4 ,instead of asking what is the cause of this so-called regeneration we may ask1 why the same pieces do not regenerate as long as they are parts of the whole4 ,in this form the mysterious influence of the whole over its parts is put into the foreground4 ,we shall see that growth takes place in certain cells when certain substances in the circulation can collect there4 ,the mysterious influence of the whole on these parts consists often merely of the fact that the circulating specific or non-specific substances--we cannot yet decide which--will in the whole be attracted by certain spots and that this will prevent them from acting on other parts of the organism4 ,if such parts are isolated the substances can no longer flow away from these parts and the parts will begin to grow4 ,it thus becomes utterly unnecessary to endow such organisms with a 8directing force0 which has to elaborate the isolated parts into a whole4 #e4 ,the same difficulty which we have discussed in regard to morphogenesis exists also in connection with those instincts which preserve the life of the organism and of the race4 ,the reader need only be reminded of all the complicated instincts of mating by which sperm and eggs are brought together2 or those by which the young are prevented from starvation to realize the apparently desperate problems in store for a mechanist1 to whom the assumption of design is meaningless4 ,and yet we are better off in regard to our knowledge of the instincts than we are in regard to morphogenesis1 as in the former we can show that the apparent instincts in some cases obey simple physicochemical laws with almost mathematical accuracy4 ,since the validity of the law of gravitation has been proved for the solar system the idea of design in the motion of the planets has lost its usefulness1 and this fact must serve us as a guide wherever we attempt to put science beyond the possibility of mysticism4 ,as soon as we can show that a life phenomenon obeys a simple physical law there is no longer any need for assuming the action of non-physical agencies4 ,we shall see that this has been accomplished for one group of animal instincts2 namely those which determine the relation of animals to light1 since these are being gradually reduced to the law of ,bunsen and ,roscoe4 ,this law states that the chemical effect of light equals the product of intensity into duration of illumination4 ,some authors object to the tendency toward reducing everything in biology to mathematical laws or figures2 but where would the theory of heredity be without figures8 ,figures have been responsible for showing that the laws of chance and not of design rule in heredity4 ,biology will be scientific only to the extent that it succeeds in reducing life phenomena to quantitative laws4 ,those familiar with the theories of evolution know the extensive rle ascribed to the adaptations of organisms4 ,the writer in #ahhi called attention to the fact that reactions to light--e4 g41 positive heliotropism--are found in organisms that never by any chance make use of them2 and later that a great many organisms show definite instinctive reactions towards a galvanic current--galvanotropism--although no organism has ever had or ever will have a chance to be exposed to such a current except in laboratory experiments4 ,this throws a different light upon the seemingly purposeful character of animal reactions4 ,heliotropism depends primarily upon the presence of photosensitive substances in the eye or the epidermis of the organism1 and these substances are inherited regardless of whether they are useful or not4 ,it is only a metaphor to call reactions resulting from the presence of photosensitive substances 8adaptation40 ,in this book other examples are given which show that authors have too often spoken of adaptation to environment where the environment was not responsible for the phenomena4 ,the blindness of cave animals and the resistance of certain marine animals to higher concentrations of sea water are such cases4 ,cunot speaks of 8preadaptation0 to express this relation4 ,the fact is that the 8adaptations0 often existed before the animal was exposed to surroundings where they were of use4 ,this relieves us also of the necessity of postulating the existence of the inheritance of acquired characters1 although it is quite possible that the future may furnish proof that such a mode of inheritance exists4 #f4 ,we have mentioned that according to ,claude ,bernard two groups of phenomena occur in the living organism3 7#a7 the phenomena of vital creation or organizing synthesis 7especially in the egg and during development72 7#b7 the phenomena of death or organic destruction4 ,these two processes are briefly discussed in the first and last chapters4 ,these introductory remarks may perhaps make it easier for the reader to retain the thread of the main ideas in the details of experiments and tables given in this book4 ,,chapter ,,ii ,,the ,,specific ,,difference ,,between ,,living ,,and ,,dead ,,matter ,,and ,,the ,,question ,,of ,,the ,,origin ,,of ,,life #a4 ,each organism is characterized by a definite form and we shall see in the next chapter that this form is determined by definite chemical substances4 ,the same is true for crystals1 where substance and form are definitely connected and there are further analogies between organisms and crystals4 ,crystals can grow in a proper solution1 and can regenerate their form in such a solution when broken or injured2 it is even possible to prevent or retard the formation of crystals in a supersaturated solution by preventing 8germs0 in the air from getting into the solution1 an observation which was later utilized by ,schroeder and ,pasteur in their experiments on spontaneous generation4 ,however1 the analogies between a living organism and a crystal are merely superficial and it is by pointing out the fundamental differences between the behaviour of crystals and that of living organisms that we can best understand the specific difference between non-living and living matter4 ,it is true that a crystal can grow1 but it will do so only in a supersaturated solution of its own substance4 ,just the reverse is true for living organisms4 ,in order to make bacteria or the cells of our body grow1 solutions of the split products of the substances composing them and not the substances themselves must be available to the cells2 second1 these solutions must not be supersaturated1 on the contrary1 they must be dilute2 and third1 growth leads in living organisms to cell division as soon as the mass of the cell reaches a certain limit4 ,this process of cell division cannot be claimed even metaphorically to exist in a crystal4 ,a correct appreciation of these facts will give us an insight into the specific difference between non-living and living matter4 ,the formation of living matter consists in the synthesis of the proteins1 nucleins1 fats1 and carbohydrates of the cells1 from the split products4 ,to give an historical example1 ,pasteur showed that yeast cells and other fungi could be raised on the following sterilized solution3 water1 #ajj gm41 crystallized sugar1 #aj gm41 ammonium tartrate1 #j4b gm4 to #j4e gm41 and fused ash from yeast1 #j4a gm4#g ,he undertook this experiment to disprove the idea that protein or organic matter in a state of decomposition was needed for the origin of new organisms as the defenders of the idea of spontaneous generation had maintained4 #g ,pasteur1 ,l41 ,annal4 d4 ,chim4 et d4 ,physique1 #ahfb1 #c sr41 lxiv41 #a4 #b4 ,that such a solution can serve for the synthesis of all the compounds of living yeast cells is due to the fact that it contains the sugars4 ,from the sugars organic acids can be formed and these with ammonia 7which was offered in the form of ammonium tartrate7 may give rise to the formation of amino acids1 the 8building stones0 of the proteins4 ,it is thus obvious that the synthesis of living matter centres around the sugar molecule4 ,the phosphates are required for the formation of the nucleins1 and the work of ,harden and ,young suggests that they play also a rle in the alcoholic fermentation of sugar4 ,chlorophyll1 under the influence of the red rays of light1 manufactures the sugars from the ,,co of the air4 ,this makes it appear as though life on our planet should have been preceded by the existence of chlorophyll1 a fact difficult to understand since it seems more natural to conceive of chlorophyll as a part or a product of living organisms rather than the reverse4 ,where then should the sugar come from1 which is a constituent of the majority of culture media and which seems a prerequisite for the synthesis of proteins in living organisms8 ,the investigations of ,winogradsky on nitrifying1#h sulphur and perhaps also on iron bacteria have to all appearances pointed a way out of this difficulty4 ,it seemed probable that there were specific micro-organisms which oxidized the ammonia formed in sewage or in the putrefaction of living matter1 but the attempts to prove this assumption by raising such a nitrifying micro-organism on one of the usual culture media1 all of which contained organic compounds1 failed4 ,led by the results of his observations on sulphur bacteria it occurred to ,winogradsky that the presence of organic compounds stood in the way of raising these bacteria1 and this idea proved correct4 ,the bacteria oxidizing ammonia to nitrites were grown on the following medium2 #a gm4 ammonium sulphate1 #a gm4 potassium phosphate1 #a gm4 magnesium carbonate1 to #a litre of water4 ,from this medium1 which is free from sugar and contains only constituents which could exist on the planet before the appearance of life1 the nitrifying bacteria were able to form sugars1 fatty acids1 proteins1 and the other specific constituents of living matter4 ,winogradsky proved1 by quantitative determination1 that with the nitrification an increase in the amount of carbon compounds takes place4 8,since this bound carbon in the cultures can have no other source than the ,,co and since the process itself can have no other cause than the activity of the nitrifying organism1 no other alternative was left but to ascribe to it the power of assimilating ,,co40#i 8,since the oxidation of ,,nh is the only source of chemical energy which the nitrifying organism can use it was clear a priori that the yield in assimilation must correspond to the quantity of oxidized nitrogen4 ,it turned out that an approximately constant ratio exists between the values of assimilated carbon and those of oxidized nitrogen40 ,this is illustrated by the results of various experiments as shown in ,table ,i4 #h ,winogradsky1 ,s41 8,die ,nitrification10 ,handb4 d4 tech4 ,mykol41 #aijd-jf1 iii41 #acb4 #i ,winogradsky1 loc4 cit41 p4 #afc and ff4 ,,table ,i ---------------------------------------- ---------- ,no4 #e ,no4 #f ,no4 #g ,no4 #h ------------------------------------ mg4 mg4 mg4 mg4 ,oxidized ,n #gbb4j #ejf4a #ibh4c #hae4d ,assimilated ,c #ai4g #ae4b #bf4d #bb4d ---------------------------------------- ---------- ,ratio ,n3,c #cf4f #cc4c #ce4b #cf4d ---------------------------------------- ---------- ,it is obvious that #a part of assimilated carbon corresponds to about #ce4d parts oxidized nitrogen or #if parts of nitrous acid4 ,these results of ,winogradsky were confirmed in very careful experiments by ,e4 ,godlewski1 ,sr4#aj #aj ,godlewski1 ,e41 ,anz4 d4 ,akad4 d4 ,wissensch4 in ,krakau1 #ahib1 #djh2 #ahie1 #agh4 ,the nitrites are further oxidized by another kind of micro-organisms into nitrates and they also can be raised without organic material4 ,winogradsky had already previously discovered that the hydrogen sulphide which is formed as a reduction product from ,ca,s,o or in putrefaction by the activity of certain bacteria can be oxidized by certain groups of bacteria1 the sulphur bacteria4 ,such bacteria1 e4 g41 ,beggiatoa1 are also commonly found at the outlet of sulphur springs4 ,they utilize the hydrogen sulphide which they oxidize to sulphur and afterwards to sulphates1 according to the scheme3 7#a7 #b;,h,s ,o #b;,h,o ,s 7#b7 ,s #c,o #b;,h,o #b;,h,,so ,the sulphuric acid is at once neutralized by carbonates4 ,winogradsky assumes that the oxidation of ,h,s by the sulphur bacteria is the source of energy which plays the same rle as the oxidation of ,,nh plays in the nitrifying bacteria1 or the oxidation of carbon compounds--sugar and others--in the case of the other lower and higher organisms4 ,winogradsky has made it very probable that sulphur bacteria do not need any organic compounds and that their nutrition may be accomplished with a purely mineral culture medium1 like that of the nitrite bacteria4 ,on the basis of this assumption they should also be able to form sugars from the ,,co of the air4 ,nathanson#aa discovered in the sea water the existence of bacteria which oxidize thiosulphate to sulphuric acid4 ,they will develop if some ,na,s,o1 is added to sea water4 ,these bacteria can only develop if ,,co from the air is admitted or when carbonates are present4 ,for these organisms the ,,co cannot be replaced by glucose1 urea1 or other organic substances4 ,such bacteria must therefore possess the power of producing sugar and starch from ,,co without the aid of chlorophyll4 ,similar observations were made by ,beijerinck on a species of fresh-water bacteria4#ab #aa ,nathanson1 ,mitteil4 d4 zool4 ,station1 ,neapel1 #aijb4 #ab ,beijerinck1 ,m41 ,folia ,microbiologica1 #aiad1 iii41 #ia4 ,finally the case of iron bacteria may briefly be mentioned though ,winogradsky's views are not accepted by ,molisch4 ,we may1 therefore1 consider it an established fact that there are a number of organisms which could have lived on this planet at a time when only mineral constituents1 such as phosphates1 ,k1 ,mg1 ,,so1 ,,co1 and ,o besides ,,nh1 or ,,sh1 existed4 ,this would lead us to consider it possible that the first organisms on this planet may have belonged to that world of micro-organisms which was discovered by ,winogradsky4 ,if we can conceive of this group of organisms as producing sugar1 which in fact they do1 they could have served as a basis for the development of other forms which require organic material for their development4 ,in #ahhc the small island of ,krakatau was destroyed by the most violent volcanic eruption on record4 ,a visit to the islands two months after the eruption showed that 8the three islands were covered with pumice and layers of ash reaching on an average a thickness of thirty metres and frequently sixty metres40#ac ,of course all life on the islands was extinct4 ,when ,treub in #ahhf first visited the island1 he found that blue-green alg were the first colonists on the pumice and on the exposed blocks of rock in the ravines on the mountain slopes4 ,investigations made during subsequent expeditions demonstrated the association of diatoms and bacteria4 ,all of these were probably carried by the wind4 ,the alg referred to were according to ,euler of the nostoc type4 ,nostoc does not require sugar1 since it can produce that compound from the ,,co of the air by the activity of its chlorophyll4 ,this organism possesses also the power of assimilating the free nitrogen of the air4 ,from these observations and because the ,nostocace generally appear as the first settlers on sand the conclusion has been drawn that they or the group of ,schizophyce to which they belong formed the first settlers of our planet4#ad ,this conclusion is not quite safe since in the settlement of ,krakatau as well as in the first colonizing of sand areas the nature of the first settler is determined chiefly by the carrying power of wind 7or waves and birds74 #ac ,ernst1 ,a41 ,the ,new ,flora of the ,volcanic ,island of ,krakatau1 ,cambridge1 #aijh4 #ad ,euler1 ,h41 ,pflanzenchemie1 #aiji1 ii4 and iii41 #adj4 ,we may now return from this digression to the real object of our discussion1 namely that the nutritive solutions of organisms must be very dilute and consist of the split products of the complicated compounds of which the organisms consist4 ,the examples given sufficiently illustrate this statement4 ,the nutritive medium of our body cells is the blood1 and while we take up as food the complicated compounds of plants or animals1 these substances undergo a digestion1 i4 e41 a splitting up into small constituents before they can diffuse from the intestine into the blood4 ,thus the proteins are digested down to the amino acids and these diffuse into the blood as demonstrated by ,folin and by ,van ,slyke4 ,from here the cells take them up4 ,the different proteins differ in regard to the different types of amino acids which they contain4 ,while the bacteria and fungi and apparently the higher plants can build up all their different amino acids from ammonia1 this power is no longer found in the mammals which can form only certain amino acids in their body and must receive the others through their food4 ,as a consequence it is usually necessary to feed young animals on more than one protein in order to make them grow1 since one protein1 as a rule1 does not contain all the amino acids needed for the manufacture of all the proteins required for the formation of the material of a growing animal4#ae #ae ,this fact was thoroughly established by ,mendel and ,osborne4 ,a summary of their work is given in ,underhill1 ,f4 ,p41 ,physiology of the ,amino ,acids1 #aiaf4 #c4 ,the essential difference between living and non-living matter consists then in this3 the living cell synthetizes its own complicated specific material from indifferent or non-specific simple compounds of the surrounding medium1 while the crystal simply adds the molecules found in its supersaturated solution4 ,this synthetic power of transforming small 8building stones0 into the complicated compounds specific for each organism is the 8secret of life0 or rather one of the secrets of life4 ,what clew have we in regard to the nature of this synthetic power8 ,we know that the comparatively great velocity of chemical reactions in a living organism is due to the presence of enzymes 7ferments7 or to catalytic agencies in general4 ,some of these catalytic agencies are specific in the sense that a given catalyzer can accelerate the reaction of only one step in a complicated chemical reaction4 ,while these enzymes are formed by the action of the body they can be separated from the body without losing their catalytic efficiency4 ,it was a long time before scientists succeeded in isolating the enzyme of the yeast cell which causes the alcoholic fermentation of sugar2 and this gave rise to the premature statement that it was not possible to isolate this enzyme since it was bound up with the life of the yeast cell4 ,such a statement was even made by a man like ,pasteur1 who was usually a model of restraint in his utterances1 and yet the work of ,buchner proved him to be wrong4 ,the general mechanism of the action of the hydrolyzing enzymes is known4 ,the old idea of de la ,rive1 that a molecule of enzyme combines transitorily with a molecule of substrate2 the further idea1 which may possibly go back to ,engler1 that the molecule of substrate is disrupted in the 8strain0 of the new combination and that the broken fragments fall off or are easily knocked off by collision from the ferment molecule which is now ready to repeat the process1 seems to be correct4 ,on the assumption that the velocity of enzyme reaction is proportional to the mass of the enzyme and that de la ,rive's idea was correct1 ,van ,slyke and ,cullen were able to calculate the coefficients of the velocity of enzyme reactions for the fermentation of urea and other substances1 and the agreement between calculated and observed values was remarkable4#af #af ,van ,slyke1 ,d4 ,d41 and ,cullen1 ,g4 ,e41 ,jour4 ,biol4 ,chem41 #aiad1 xix41 #ada4 ,while the hydrolytic action of enzymes is thus clear the synthesis in the cell is still a riddle4 ,an interesting suggestion was made by van't ,hoff1 who in #ahih expressed the idea that the hydrolytic enzymes should also act in the opposite direction1 namely synthetically4 ,thus it should not only be possible to digest proteins with pepsin but also to synthetize them from the products of digestion with the aid of the same enzyme4 ,this expectation was based on the idea that the enzyme did not alter the equilibrium between the hydrolyzed and non-hydrolyzed part of the substrate but only accelerated the rate with which the equilibrium was reached4 ,van't ,hoff's idea omitted1 however1 the possibility that in the transitory combination between enzyme molecule and substrate a change in the molecular configuration of the substrate or in the distribution of intramolecular strain may take place4 ,the first apparently complete confirmation of van't ,hoff's suggestion appeared in the form of the synthesis of maltose from grape sugar by the enzyme maltase1 which decomposes maltose into grape sugar4 ,by adding the enzyme maltase from yeast to a forty per cent4 solution of glucose ,croft ,hill#ag obtained a good yield of maltose4 ,it turned out1 however1 that what he took for maltose was not this compound but an isomer1 namely isomaltose1 which has a different molecular configuration and cannot be hydrolyzed by the enzyme maltase4 #ag ,hill1 ,c41 ,jour4 ,chem4 ,soc41 #ahih1 lxxiii41 #fcd4 ,lactose is hydrolyzed from kephyr by an enzyme lactase into galactose and glucose2 by adding this enzyme to galactose and glucose a synthesis was obtained not of lactose but of isolactose2 the latter1 however1 is not decomposed by the enzyme lactase4 ,e4 ,f4 ,armstrong has worked out a theory which tries to account for this striking phenomenon by assuming 8that the enzyme has a specific influence in promoting the formation of the biose which it cannot hydrolyze40#ah ,the theory is very ingenious and seems supported by fact4 ,this then would lead to the result that certain hydrolytic enzymes may have a synthetic action but not in the manner suggested by van't ,hoff4 #ah ,armstrong1 ,e4 ,f41 ,proc4 ,royal ,soc41 #aije1 ,b4 lxxvi41 #eib4 ,the principle enunciated by ,armstrong1 that in the synthetic action of hydrolytic enzymes not the original compound but an isomer is formed which can not be hydrolyzed by the enzyme1 may possibly be of great importance in the understanding of life phenomena4 ,it shows us how the cell can grow in the presence of hydrolytic enzymes and why in hunger the disintegration of the cell material is so slow4 ,it was at first thought that the formation of isomers contradicted the idea of the reversible action of enzymes1 but this is not the case2 on the contrary1 it supports it but makes an addition which may solve the riddle of what ,claude ,bernard called the creative action of living matter4 ,we shall come back to this problem in the last chapter4 ,kastle and ,loevenhart demonstrated the synthesis of a trace of ethylbutyrate by lipase if the latter enzyme was added to the products of the hydrolysis of ethylbutyrate1 ethyl alcohol1 and butyric acid by the same enzyme4#ai ,taylor#bj obtained the synthesis of a slight amount of triolein by the addition of the dried fat-free residue of the castor bean to a mixture of oleinic acid and glycerine4444 ,no synthesis occurred with acetic1 butyric1 palmitic1 and stearic acids with glycerine1 mannite1 and dulcite1 and the experiments with the last two alcohols and oleinic acid likewise yielded no synthesis4 #ai ,kastle1 ,j4 ,h41 and ,loevenhart1 ,a4 ,s41 ,am4 ,chem4 ,jour41 #aijj1 xxiv41 #dia4 #bj ,taylor1 ,a4 ,e41 ,univ4 ,cal4 ,pub41 #aijd1 ,pathology1 i41 #cc2 ,jour4 ,biol4 ,chem41 #aijf1 ii41 #hg4 ,this suggests possibly a specific action of the enzyme4 ,if this slight reversible action had any biological significance 7which might be possible1 since in the organism secondary favourable conditions might be at work which are lacking in vitro7 there should be a parallelism between masses of lipase in different kinds of tissues and fat synthesis4 ,loevenhart indicated that this might be a fact1 but a more extensive investigation by ,h4 ,c4 ,bradley has made this very dubious4#ba #ba ,bradley1 ,h4 ,c41 ,jour4 ,biol4 ,chem41 #aiac1 xiii41 #djg4 ,very little is known concerning the reversible action of the hydrolytic protein enzymes4 ,a4 ,e4 ,taylor digested protamine sulphate with trypsin and found that after adding trypsin to the products of digestion a precipitate was formed after long standing2 and we may also refer to experiments of ,robertson with pepsin on the products of caseinogen to which we shall return in the next chapter4 ,it therefore looks at present as if van't ,hoff's idea of reversible enzyme action might hold in the modification offered by ,armstrong4 ,it remains doubtful1 however1 whether this reversibility can explain all the synthetic processes in the cell4 ,no objection can be offered at present if any one makes the assumption that each cell has specific synthetic enzymes or some other synthetic mechanisms which are still unknown4 ,the mechanisms for the synthesis of proteins must have one other peculiarity3 they must be specific in their action4 ,we shall see in the next chapter that each species seems to possess one or more proteins not found in any other but closely related species4 ,each organism develops from a tiny microscopic germ and grows by synthetizing the non-specific building stones 7amino acids7 into the specific proteins of the species4 ,this must be the work of the yet unknown synthetic enzymes or mechanisms4 ,the elucidation of their character would seem one of the main problems of biology4 ,needless to say crystallography is not confronted with problems of such a nature4 ,the fact that the living cell grows after taking up food has given rise to curious misunderstandings4 ,traube has shown that drops of a liquid surrounded with a semipermeable membrane may increase in volume when put into a solution of lower osmotic pressure4 ,this has led and is possibly still leading to the statement that the process of growth by a living cell has been imitated artificially4 ,only one feature has been imitated1 the increase in volume2 but the essential feature of the process in the living cell1 i4 e41 the formation of the specific constituents of the living cell from non-specific products1 has of course not been imitated4 #d4 ,the constant synthesis then of specific material from simple compounds of a non-specific character is the chief feature by which living matter differs from non-living matter4 ,with this character is correlated another one2 namely1 when the mass of a cell reaches a certain limit the cell divides4 ,this is perhaps most obvious in bacteria which on the proper nutritive medium take up food1 grow1 and divide into two bacteria1 each of which takes up food1 divides1 and grows ad infinitum1 as long as the food lasts1 provided the harmful products of metabolism are removed4 ,if it be true that specific synthetic ferments exist in each cell it follows that the cell must synthetize these also1#bb as otherwise the synthesis of specific proteins would have to come to a standstill4 #bb ,this would lead to the idea that the enzymes in the cell also synthetize molecules of their own kind1 or that1 in other words1 the synthetic processes in the cell are of the nature of autocatalysis4 ,loeb1 ,der chemische ,character des ,befruchtungsvorgangs1 ,leipzig1 #aijh4 ,robertson1 ,t4 ,b41 ,arch4 f4 ,entwicklngsmech41 #aijh1 xxv41 #eha2 xxvi41 #ajh2 #aiac1 xxxvii41 #dig2 ,am4 ,jour4 ,physiol41 #aiae1 xxxvii41 #a2 ,robertson and ,wasteneys1 ,h41 ,arch4 f4 ,entwicklngsmech41 #aiac1 xxxvii41 #dhe4 ,ostwald1 ,wo41 ber die zeitlichen ,eigenschaften der ,entwicklungsvorgnge1 ,leipzig1 #aijh4 ,this problem of synthesis leads to the assumption of immortality of the living cell1 since there is no a priori reason why this synthesis should ever come to a standstill of its own accord as long as enough food is available and the proper outside physical conditions are guaranteed4 ,it is well known that ,weismann has claimed immortality for all unicellular organisms and for the sex cells of metazoa1 while he claimed the necessity of death for the body cells of the latter4 ,leo ,loeb was led by his investigations on the transplantation of cancer to assume immortality not only for the cancer cell but also for the body cell of the organism4 ,he had found in transplanting a malignant tumor from one individual to another that the tumor grew2 that it was not the cells of the host but the transplanted tumor cells of the graft which grew and multiplied1 and that this process could be repeated apparently indefinitely so that it was obvious that the transplanted tumor cells outlived the original animal4 ,such experiments have since been carried on so long that we may now say that an individual cancer cell taken from an animal and transplanted from time to time on a new host lives apparently indefinitely4 ,leo ,loeb had found that these tumor cells are simply modified somatic cells4 ,he therefore suggested that the somatic cells might be considered immortal with the same right as we speak of the immortality of the germ cells of such animals4#bc #bc ,loeb1 ,leo1 ,jour4 ,med4 ,res41 #aija1 vi41 #bh2 ,arch4 f4 ,entwicklngsmech41 #aijg1 xxiv41 #fee4 ,this view receives its support first from the fact that certain trees like the ,sequoia live several thousand years and may therefore be considered immortal and second1 from the method of tissue culture4 ,the method of cultivating tissue cells in a test tube1 in the same way as is done for bacteria1 was first proposed and carried out by ,leo ,loeb1 in #ahig1bd but his test-tube method did not permit the observation of the transplanted cell under the microscope4 ,this was made possible by a modification of the method by ,harrison1 who established the fact that the axis cylinder grows out from the ganglionic cell4 ,harrison and ,burrows then perfected the method for the cultivation of the cells of warm-blooded1 animals1 and with the aid of these methods ,carrel succeeded in keeping connective-tissue cells of the heart of an early chick embryo alive more than four years1 and these cells are still growing and dividing4#be ,only very tiny masses of cells can be kept alive in this way since all the cells in the centre of a piece die on account of lack of oxygen2 and every two days a few cells from the margin of the piece have to be transferred to a new culture medium4 #bd ,loeb1 ,leo1 ber die ,entstehung von ,bindegewebe1 ,leucocyten und rothen ,blutkrperchen aus ,epithel und ber eine ,methode isolierte ,gewebsteile zu zchten4 ,chicago1 #ahig4 #be ,while this has been demonstrated thus far only for connective-tissue cells it may be true also for other cells4 ,this effect of lack of oxygen explains also why the immortality of the somatic cells is not obvious4 ,death in a human being consists in the stopping of heart beat and respiration1 which also terminates the action of the brain or at least of consciousness4 ,immediately after the cessation of heart beat and respiration the cells of muscle and of the skin and probably many or most other organs are still alive and might continue to live if transferred to another body with circulation and respiration4 ,as a consequence of the lack of oxygen supply in the dead body they will1 however1 die comparatively rapidly4 ,it may be stated that hearts taken out of the body after a number of hours can still beat again when put into the proper solutions and upon receiving an adequate oxygen supply4 ,the idea that the body cells are naturally immortal and die only if exposed to extreme injuries such as prolonged lack of oxygen or too high a temperature helps to make one problem more intelligible4 ,the medical student1 who for the first time realizes that life depends upon that one organ1 the heart1 doing its duty incessantly for the seventy years or so allotted to man1 is amazed at the precariousness of our existence4 ,it seems indeed uncanny that so delicate a mechanism should function so regularly for so many years4 ,the mysticism connected with this and other phenomena of adaptation would disappear if we could be certain that all cells are really immortal and that the fact which demands an explanation is not the continued activity but the cessation of activity in death4 ,thus we see that the idea of the immortality of the body cell if it can be generalized may be destined to become one of the main supports for a complete physicochemical analysis of life phenomena since it makes the durability of organisms intelligible4 #e4 ,this generalized idea of the immortality of some or possibly most or all somatic cells has a bearing upon the problem of the origin of life on our planet4 ,the experiments of ,spallanzani1 ,schwann1 ,schroeder1 ,pasteur1 ,tyndall1 and all those who have worked with pure cultures of micro-organisms1 have proved that no spontaneous generation of living from non-living matter can be demonstrated2 and the statements to the contrary were due to experimental errors inasmuch as the new organisms formed were the offspring of others which had entered into the culture medium by mistake4 ,in the last chapter of that most fascinating book ,worlds in the ,making1#bf ,arrhenius discusses the possibility of life being eternal and of living germs of very small dimensions--e4 g41 the spores of micro-organisms--being carried through space from one planet to another or even from one solar system to another4 ,if it be true that there is no spontaneous generation2 if it be true that all cells are potentially immortal1 we may indeed seriously raise the question3 ,may not life after all be eternal8 ,such ideas were advocated by ,richter in a rather phantastic way and more definitely by ,helmholtz as well as ,kelvin4 ,the latter authors assumed that in the collision of planets or worlds on which there is life1 fragments containing living organisms will be torn off and these fragments will move as seed-bearing stones through space4 8,if at the present instant no life existed upon this earth1 one such stone falling upon it might 444 lead to its becoming covered with vegetation40 ,arrhenius points out the difficulties which oppose such a view1 as1 e4 g41 the fact 8that the meteorite in its fall towards the earth becomes incandescent all over its surface and any seeds on it would therefore be deprived of their germinating power40 #bf ,arrhenius1 ,s41 ,worlds in the ,making1 ,london and ,new ,york1 #aijh1 p4 #bab4 ,arrhenius suggests another and much more ingenious idea based on the fact that for particles below a certain size the mechanical pressure produced by light waves--the radiation pressure--can overcome the attractive force of gravitation4 ,bodies which according to ,schwarzschild would undergo the strongest influence of solar radiation must have a diameter of #j4jjjaf mm4 supposing them to be spherical4 ,the first question is therefore3 ,are there any living seeds of such extraordinary minuteness8 ,the reply of the botanist is that spores of many bacteria have a size of #j4jjjc or #j4jjjb mm41 and there are no doubt much smaller germs which our microscopes fail to disclose4 ,this assumption is undoubtedly correct4 ,we will1 in the first instance1 make a rough calculation of what would happen if such an organism were detached from the earth and pushed out into space by the radiation pressure of our sun4 ,the organism would first of all have to cross the orbit of ,mars2 then the orbits of the smaller and of the outer planets4444 ,the organisms would cross the orbit of ,mars after twenty days1 the ,jupiter orbit after eighty days1 and the orbit of ,neptune after fourteen months4 ,our nearest solar system would be reached in nine thousand years4 ,for the assumption of eternity of life only the transference of germs from one solar system to another would have to be considered and the question arises whether or not germs can keep their vitality so many thousands of years4 ,arrhenius thinks that this is possible on account of the low temperature 7which must be below -#bbj ,c47 at which no chemical reaction and hence no decomposition and deterioration are possible in the spores2 and on account of the absence of water vapour4 ,the question then arises3 ,have we any facts to warrant the assumption that spores may remain alive for thousands of years under such conditions and retain their power of germination8 ,we know that seeds have a very limited vitality1 and the statement that grain found in the ,egyptian tombs was still able to germinate has long been recognized as a myth4 ,miss ,white#bg found that in wheat grains1 there appeared a well-marked drop in their germinating power after about the fourth year1 reaching zero in eleven to seventeen years4 ,in a drier climate they last longer than in a moist climate4 ,it is of importance that the hydrolyzing enzymes in the seeds1 such as diastase1 erepsin1 remained unimpaired even after the germinating power of the seeds had disappeared4 ,the seeds were able to resist for two days the temperature of liquid air1 though the subsequent germination was delayed by this treatment4 ,macfadyen#bh exposed non-sporing bacteria1 viz41 ,b4 typhosus1 ,b4 coli communis1 ,staphylococcus pyogenes aureus1 and a ,saccharomyces to liquid air4 ,the experiments showed that a prolonged exposure of six months to a temperature of about -#aij has no appreciable effect on the vitality of micro-organisms4 ,to judge by the results there appeared no reason to doubt that the experiment might have been successfully prolonged for a still longer period4 #bg ,white1 ,j41 ,proc4 ,roy4 ,soc41 #aiji1 ,b1 lxxxi41 #dag4 #bh ,macfadyen1 ,a41 ,proc4 ,roy4 ,soc41 #aijc1 lxxi41 #gf4 ,paul ,becquerel#bi found that seeds which possess a very thick integument may live longer than the grain in ,miss ,white's experiments4 ,the thickness of the integument prevents the exchange of gases between air and seed4 ,thus seeds of leguminoses 7,cassia bicapsularis1 ,cytisus biflorus1 ,leucna leucocephala1 and ,trifolium arvense7 had retained their power of germination for eighty-seven years4 ,becquerel has shown that the dryness of the membrane is very essential for such a duration of life1 since when dry it is impermeable for gases and the slow chemical reactions inside the grain become impossible4 #bi ,becquerel1 ,p41 ,revue gnrale des ,sciences1 #aiad1 xxv41 #eei4 ,in the cosmic space there is no water vapour1 no atmosphere1 and a low temperature1 and there is hence no reason why spores should lose appreciably more of their germinating power in ten thousand years than in six months4 ,we must therefore admit the possibility that spores may move for an almost infinite length of time through cosmic space and yet be ready for germination when they fall upon a planet in which all the conditions for germination and development exist1 e4 g41 water1 proper temperature1 and the right nutritive substances dissolved in the water 7inclusive of free oxygen74 ,while thus everything is favourable to ,arrhenius's hypothesis1 ,becquerel raises the objection that the spores going through space would yet be destroyed by ultraviolet light4 ,this danger would probably exist only as long as the germ is not too far from a sun4 ,the difficulty is a real one since the ultraviolet rays have a destructive effect even in the absence of oxygen4 ,it is possible1 however1 that there are spores which can resist this effect of ultraviolet light4 ,arrhenius's theory can not of course be disproved and we must agree with him that it is consistent not only with the theories of cosmogony but also with the seeming potential immortality of certain or of all cells4 ,the alternative to ,arrhenius's theory is that living matter did originate and still originates from non-living matter4 ,if this idea is correct it should one day be possible to discover synthetic enzymes which are capable of forming molecules of their own kind from a simple nutritive solution4 ,with such synthetic enzymes as a starting point the task might be undertaken of creating cells capable of growth and cell division1 at least in the apparently simple form in which these phenomena occur in bacteria2 viz41 that after the mass has reached a certain 7still microscopic7 size it divides into two cells and so on4 ,if ,arrhenius is right that living matter has had no more beginning than matter in general1 this hope of making living matter artificially appears at present as futile as the hope of making molecules out of electrons4 ,the problem of making living matter artificially has been compared to that of constructing a perpetuum mobile2 this comparison is1 however1 not correct4 ,the idea of a perpetuum mobile contradicts the first law of thermodynamics1 while the making of living matter may be impossible though contradicting no natural law4 ,pasteur's proof that spontaneous generation does not occur in the solutions used by him does not prove that a synthesis of living from dead matter is impossible under any conditions4 ,it is at least not inconceivable that in an earlier period of the earth's history radio-activity1 electrical discharges1 and possibly also the action of volcanoes might have furnished the combination of circumstances under which living matter might have been formed4 ,the staggering difficulties in imagining such a possibility are not merely on the chemical side--e4 g41 the production of proteins from ,,co1 and ,n--but also on the physical side if the necessity of a definite cell structure is considered4 ,we shall see in the sixth chapter that without a structure in the egg to begin with1 no formation of a complicated organism is imaginable2 and while a bacterium may have a simple structure1 such a structure as it possesses is as necessary for its existence as are its enzymes4 ,attempts have repeatedly been made to imitate the structures in the cell and of living organisms by colloidal precipitates4 ,it is needless to point out that such precipitates are of importance only for the study of the origin of structures in the living1 but that they are not otherwise an imitation of the living since they are lacking the characteristic synthetic chemical processes4 ,,chapter ,,iii ,,the ,,chemical ,,basis ,,of ,,genus ,,and ,,species #a4 ,it is a truism that from an egg of a species an organism of this species only and of no other will arise4 ,it is also a truism that the so-called protoplasm of an egg does not differ much from that of eggs of other species when looked at through a microscope4 ,the question arises3 ,what determines the species of the future organism8 ,is it a structure or a specific chemical or groups of chemicals8 ,in a later chapter we shall show that the egg has a simple though definite structure1 but in this chapter we shall see that the egg must contain specific substances and that these substances which determine the 8species0 and specificity in general are in all probability proteins4 ,since solutions of different proteins look alike under a microscope we need not wonder that it is impossible to discriminate microscopically between the protoplasm of different eggs4 ,the idea of definiteness and constancy of species1 a matter of daily observation in the case of man and higher animals in general1 was not so readily accepted in the case of the micro-organisms1 which on account of their minuteness and simplicity of structure are not so easy to differentiate4 ,there existed for a long time serious doubt whether or not the simplest organisms1 the bacteria1 possessed a definite 8specificity0 like the higher organisms1 or whether they were not endowed1 as ,warming put it1 with an 8unlimited plasticity10 which forbade classifying them according to their form into definite species as ,cohn had done4 ,an interesting episode in this discussion1 which was settled about twenty-five years ago arose concerning the sulphur bacteria1 which often develop in large masses on parts of decaying plants or animals along the shore4 ,sir ,e4 ,ray ,lankester found collections of red bacteria covering putrefying animal matter in a vessel and forming a continuous membrane along its wall4 ,these red bacteria were of very different shape1 size1 and grouping1 but they seemed to be connected by transition forms4 ,they had a common character1 however1 namely1 their peach-coloured appearance4 ,this common character1 together with their association in the same habitat1 led ,lankester to the then justifiable belief that they all belonged to one species which was protean in character and that the different forms were only to be considered as phases of growth of this one species4 ,the presence of the same red pigment 8,bacterio-purpurin0 seemed justly to indicate the existence of common chemical processes4 ,cohn1 on the contrary1 considered the different forms among these red bacteria 7they are today called sulphur bacteria since they oxidize the hydrogen sulphide produced by bacteria of putrefaction to sulphur and sulphates7 as definite and distinct species1 in spite of their common colour and their association4 ,later observations showed that ,cohn was right4 ,winogradsky#cj succeeded in proving by pure culture experiments that each of these different forms of sulphur bacteria was specific and did not give rise to any of the other forms of the same colour found in the same conditions4 #cj ,winogradsky1 ,s41 ,beitrge zur ,morphologie und ,physiologie der ,bacterien4 ,leipzig1 #ahhh4 ,the method of pure line breeding inaugurated by ,johannsen#ca has shown that the degree of definiteness goes so far that apparently identical forms with only slight differences in size may breed true to this size2 but for reasons which will become clear later on we may doubt whether they are to be considered as definite species4 #ca ,johannsen1 ,w41 ,elemente der exacten ,erblichkeitslehre4 #b;d ed41 #aiac4 ,the fact of specificity is supported by the fact of constancy of forms4 de ,vries has pointed out that regardless of the possible origin of new species by mutation the old species may persevere4 ,walcott has found fossils of annelids1 snails1 crustaceans1 and alg in a precambrian formation in ,british ,columbia whose age 7estimated on the rate of formation of radium from uranium7 may be about two hundred million years and estimated on the basis of sedimentation sixty million years4 ,and yet these invertebrates are so closely related to the forms existing today that the systematists have no difficulty in finding the genus among the modern forms into which each of these organisms belongs4 ,w4 ,m4 ,wheeler1 in his investigations of the ants enclosed in amber1 was able to identify some of them with forms living today1 though the ants observed in the amber must have been two million years old4 ,the constancy of species1 i4 e41 the permanence of specificity may therefore be considered as established as far back as two or possibly two hundred millions of years4 ,the definiteness and constancy of each species must be determined by something equally definite and constant in the egg1 since in the latter the species is already fixed irrevocably4 ,we shall show first that species if sufficiently separated are generally incompatible with each other and that any attempt at fusing or mixing them by grafting or cross-fertilizing is futile4 ,in the second part of the chapter we shall take up the facts which seem destined to give a direct answer to the question as to the cause of specificity4 ,it is needless to say that this latter question is of paramount importance for the problem of evolution1 as well as for that of the constitution of living matter4 ,i4 ,the ,incompatibility of ,species not closely ,related #b4 ,it is practically impossible to transplant organs or tissues from one species of higher animals to another1 unless the two species are very closely related2 and even then the transplantation is uncertain and the graft may either fall off again or be destroyed4 ,this specificity of tissues goes so far that surgeons prefer1 when a transplantation of skin in the human is intended1 to use skin of the patient or of close blood relations4 ,the reason why the tissues of a foreign species in warm-blooded animals cannot grow well on a given host has been explained by the remarkable experiments of ,james ,b4 ,murphy of the ,rockefeller ,institute4#cb ,murphy discovered that it is possible to transplant successfully any kind of foreign tissue upon the early embryo of the chick4 ,even human tissue transplanted upon the chick embryo will grow rapidly4 ,this shows that at this early stage the chick embryo does not yet react against foreign tissue4 ,this lack of reaction lasts until about the twenty-first day in the life of the embryo2 then the growth of the graft not only ceases but the graft itself falls off or is destroyed4 ,murphy noticed that this critical period coincides with the development of the spleen and of lymphatic tissue in the chick and that a certain type of migrating cells1 the so-called lymphocytes1 which develop in the lymphatic tissue1 gather at the edge of the graft in great numbers1 and he suggested that these lymphocytes 7by a secretion of some substance87 rid the host of the graft4 ,he applied two tests both of which confirmed this idea4 ,first he showed that when small fragments of the spleen of an adult chicken are transplanted into the embryo the latter loses its tolerance for foreign grafts4 ,the second proof is still more interesting4 ,it was known that by treatment with ,roentgen rays the lymphocytes in an animal could be destroyed4 ,it was to be expected that an animal so treated would have lost its specific resistance to foreign tissues4 ,murphy found that this was actually the case4 ,on fully grown rats in which the lymphocytes had been destroyed by ,x-rays 7as ascertained by blood counts7 tissues of foreign species grew perfectly well4 ,these experiments have assumed a great practical importance since they can also be applied to the immunization of an animal against transplanted cancer of its own species4 ,murphy found that by increasing the number of lymphocytes in an animal 7which can be accomplished by a mild treatment with ,x-rays7 the immunity against foreign grafts as well as against cancer from the same species can be increased4 ,it is quite possible that the apparent immunity to a transplantation of cancer produced by ,jensen1 ,leo ,loeb1 and ,ehrlich and ,apolant through the previous transplantation of tissue in such an animal was due to the fact that this previous tissue transplantation led to an increase in the number of lymphocytes in the animal4 ,the medical side1 however1 lies outside of our discussion1 and we must satisfy ourselves with only a passing notice4 ,the facts show that each warm-blooded animal seems to possess a specificity whereby its lymphocytes destroy transplanted tissue taken from a foreign species4 #cb ,murphy1 ,j4 ,b41 ,jour4 ,exper4 ,med41 #aiac1 xvii41 #dhb2 #aiad1 xix41 #aha2 xix41 #eac2 ,murphy and ,morton1 ,j4 ,j41 ,jour4 ,exper4 ,med41 #aiae1 xxii41 #bjd4 ,a lesser though still marked degree of incompatibility exists also in lower animals for grafts from a different species4#cc ,the graft may apparently take hold1 but only for a few days1 if the species are not closely related4 ,joest apparently succeeded in making a permanent union between the anterior and posterior ends of two species of earthworms1 ,lumbricus rubellus and ,allolobophora terrestris4 ,born and later ,harrison healed pieces of tadpoles of different species together4 ,an individual made up of two species ,rana virescens and ,rana palustris lived a considerable time and went through metamorphosis4 ,each half regained the characteristic features of the species to which it belonged4 ,it seems1 however1 that if species of tadpoles of two more distant species are grafted upon each other no lasting graft can be obtained1 e4 g41 ,rana esculenta and ,bombinator igneus4 ,these experiments were made at a time when the nature and bearing of the problem of specificity was not yet fully recognized4 ,the rle of lymphocytes in these cases has never been investigated4 ,the grafted piece always retained the characteristics of the species from which it was taken4 #cc ,the reader is referred to ,morgan's book on ,regeneration 7,new ,york1 #aija71 for the literature on this subject4 ,plants possess no leucocytes and we therefore see that they tolerate a graft of foreign tissues better than is the case in animals4 ,as a matter of fact heteroplastic grafting is a common practice in horticulture1 although even here it is known that indiscriminate heteroplastic grafting is not feasible and that therefore the specificity is not without influence4 ,the host is supposed to furnish only nutritive sap to the graft and in this respect does not behave very differently from an artificial nutritive solution for the raising of a plant4 ,the law of specificity1 however1 remains true also for the grafted tissues3 neither in animals nor in plants does the graft lose its specificity1 and it never assumes the specific characters of the host1 or vice versa4 ,the apparent exceptions which ,winkler believed he had found in the case of grafts of nightshade on tomatoes turned out to be a further proof of the law of specificity4 ,winkler1 after the graft had taken1 cut through the place of grafting1 after which operation a callus formation occurred on the wound4 ,in most cases either a pure nightshade or a pure tomato grew out from this callus4 ,in some cases he obtained shoots from the place where graft and host had united1 which on one side were tomato1 on the other side nightshade4 ,what really happened was that the shoots had a growing point whose cells on the one side consisted of cells of nightshade1 on the other side of tomato4#cd ,we know of no case in which the cell of a graft has lost its specificity and undergone a transformation into the cell of the host4 #cd ,baur1 ,e41 ,einfhrung in die experimentelle ,vererbungslehre4 ,berlin1 #aiaa1 p4 #bcb4 #c4 ,another manifestation of the incompatibility of distant species is found in the domain of fertilization4 ,the eggs of the majority of animals cannot develop unless a spermatozon enters4 ,the entrance of a spermatozon into an egg seems also to fall under the law of specificity1 inasmuch as in general only the sperm of the same or a closely related species is able to enter the egg4 ,the writer#ce has found1 however1 that it is possible to overcome the limitation of specificity in certain cases by physicochemical means1 and by the knowledge of these means we may perhaps one day be able to more closely define the mechanism of specificity in this case4 ,he found that the eggs of a certain ,californian sea urchin1 which cannot be fertilized by the sperm of starfish in normal sea water1 will lose their specificity towards this type of foreign sperm if the sea water is rendered a little more alkaline1 or if a little more ,ca is added to the sea water1 or if both these variations are effected4 ,godlewski has confirmed the efficiency of this method for the fertilization of sea-urchin eggs with the sperm of crinoids4 #ce ,literature on this subject in ,chapter ,,iv4 ,illustration3 ,,fig4 #a4 ,five-days-old larv from a sea urchin 7,strongylocentrotus purpuratus7 and a starfish 7,asterias7 4 7,front view47 ,illustration3 ,,fig4 #b4 ,five-days-old larv of ,strongylocentrotus purpuratus produced by artificial parthenogenesis4 7,side view47 ,the larv in ,figs4 #a and #b are identical in appearance1 proving that heterogeneous hybridization leads to a larva with purely maternal characters4 ,if such heterogeneous hybridizations are carried out1 two striking results are obtained4 ,the one is that the resulting larva has only maternal characteristics 7,figs4 #a and #b71 as if the sperm had contributed no hereditary material to the developing embryo4 ,this result could not have been predicted1 for if we fertilize the egg of the same ,californian sea urchin1 ,strongylocentrotus purpuratus1 with the sperm of a very closely related sea urchin1 ,s4 franciscanus1 the hereditary effect of the spermatozon is seen very distinctly in the primitive skeleton formed by the larva4#cf 7,fig4 #c47 ,in the case of the heterogeneous hybridization the spermatozon acts practically only as an activating agency upon the egg and not as a transmitter of paternal qualities4 #cf ,loeb1 ,j41 ,king1 ,w4 ,o4 ,r41 and ,moore1 ,a4 ,r41 ,arch4 f4 ,entwicklngsmech41 #aiaj1 xxix41 #ced4 ,illustration3 ,,fig4 #c4 ,five-days-old larv of two closely related forms of sea urchins 7,s4 purpuratus and ,s4 franciscanus 74 ,in this case the larva has also paternal characters as shown by the skeleton4 ,the second striking fact is that while the sea-urchin eggs fertilized with starfish sperm develop at first perfectly normally they begin to die in large numbers on the second and third day of their development1 and only a very small number live long enough to form a skeleton2 and these are usually sickly and form the skeleton considerably later than the pure breed4 ,it is not quite certain whether the sickliness of these heterogeneous hybrids begins or assumes a severe character with the development of a certain type of wandering cells1 the mesenchyme cells2 it would perhaps be worth while to investigate this possibility4 ,the writer was under the impression that this sickliness might have been brought about by a poison gradually formed in the heterogeneous larv4 ,he investigated the effects of heterogeneous hybridization also in fishes1 which are a much more favourable object4 ,the egg of the marine fish ,fundulus heteroclitus can be fertilized with the sperm of almost any other teleost fish1 as ,moenkhaus#cg first observed4 ,this author did not succeed in keeping the hybrids alive more than a day1 but the writer has kept many heterogeneous hybrids alive for a month or longer1#ch and found the same two striking facts which he had already observed in the heterogeneous cross between sea urchin and starfish3 first1 practically no transmission of paternal characters1 and second1 a sickly condition of the embryo which begins early and which increases with further development4 ,the heterogeneous fish hybrids between1 e4 g41 ,fundulus heteroclitus and ,menidia have usually no circulation of blood1 although the heart is formed and beats and blood-vessels and blood cells are formed2 the eyes are often incomplete or abnormal though they may be normal at first2 the growth of the embryo is mostly retarded4 ,in exceptional cases circulation may be established and in these a normal embryo may result1 but such an embryo is chiefly maternal4 #cg ,moenkhaus1 ,w4 ,j41 ,am4 ,jour4 ,anat41 #aijd1 iii41 #bi4 #ch ,loeb1 ,j41 ,jour4 ,morphol41 #aiab1 xxiii41 #a4 ,this incompatibility of two gametes from different species does not show itself in the case of heterogeneous hybridization only1 but also though less often in the case of crossing between two more closely related forms4 ,the cross between the two related forms ,s4 purpuratus and ,s4 franciscanus is very sturdy and shows no abnormal mortality as far as the writer's observations go4 ,if1 however1 the reciprocal crossing is carried out1 namely that of ,s4 franciscanus and ,s4 purpuratus 1 the development is at first normal1 but beginning with the time of mesenchyme formation the majority of larv become sickly and die2 and again the question may be raised whether or not the beginning of sickliness coincides with the development of mesenchyme cells4 ,if we assume that the sickliness and death are due to the formation of a poison1 we must assume that the poison is formed by the protoplasm of the egg1 since otherwise we could not understand why the reciprocal cross should be healthy4 ,all of these data agree in this one point1 that the fusion by grafting or fertilization of two distant species is impossible1 although the mechanism of the incompatibility is not yet understood4 ,it is quite possible that this mechanism is not the same in all the cases mentioned here1 and that it may be different when two different species are mixed and when incompatibility exists between varieties1 as is the case in the graft on mammals4 ,,ii4 ,the ,chemical ,basis of ,genus and ,species and of ,species ,specificity #d4 ,fifty or sixty years ago surgeons did not hesitate to transfuse the blood of animals into human beings4 ,the practice was a failure1 and ,landois#ci showed by experiment that if blood of a foreign species was introduced into an animal the blood corpuscles of the transfused blood were rapidly dissolved and the animal into which the transfusion was made was rendered ill and often died4 ,the result was different when the animals whose blood was used for the purpose of transfusion belonged to the same species or a species closely related to the animal into which the blood was transfused4 ,thus when blood was exchanged between horse and donkey or between wolf and dog or between hare and rabbit no hemoglobin appeared in the urine and the animal into which the blood was transfused remained well4#dj ,this was the beginning of the investigations in the field of serum specificity which were destined to play such a prominent rle in the development of medicine4 ,friedenthal was able to show later that if to #aj c4c4 of serum of a mammal three drops of defibrinated blood of a foreign species are added and the whole is exposed in a test tube to a temperature of #ch;,c4 for fifteen minutes the blood cells contained in the added blood are all cytolyzed2 that this1 however1 does not occur so rapidly when the blood of a related species is used4 ,he could thus show that human blood serum dissolves the erythrocytes of the eel1 the frog1 pigeon1 hen1 horse1 cat1 and even that of the lower monkeys but not that of the anthropoid apes4 ,the blood of the chimpanzee and of the human are no longer incompatible1 and this discovery was justly considered by ,friedenthal as a confirmation of the idea of the evolutionists that the anthropoid apes and the human are blood relations4#da #ci ,landois1 ,l41 ,zur ,lehre von der ,bluttransfusion4 ,leipzig1 #ahge4 #dj ,this is probably true only within the limits of exactness used in these experiments4 #da ,friedenthal1 ,h41 8,experimenteller ,nachweis der ,blutverwandtschaft40 ,arch4 f4 ,physiol41 #aijj1 #did4 ,this line of investigation had in the meanwhile entered upon a new stage when ,kraus1 ,tchistowitch1 and ,bordet discovered and developed the precipitin reaction1 which consists in the fact that if a foreign serum 7or a foreign protein7 is introduced into an animal the blood serum of the latter acquired after some time the power of causing a precipitate when mixed with the antigen1 i4 e41 with the foreign substance originally introduced into the animal for the purpose of causing the production of antibodies in the latter2 while1 of course1 no such precipitation occurs if the serum of a non-treated rabbit is mixed with the serum of the blood of the foreign species4 ,in #ahig ,kraus discovered that if the filtrates from cultures of bacteria 7e4 g41 typhoid bacillus7 are mixed with the serum of an animal immunized with the same serum 7e4 g41 typhoid serum7 it causes a precipitate2 and that this precipitin reaction is specific4 ,this fact was confirmed and has been extended by the work of many authors4 ,tchistowitch in #ahii observed that the serum of rabbits which had received injections of horse or eel serum caused a precipitate when mixed with the serum of these latter animals4 ,bordet found in #ahii that if milk is injected into a rabbit the serum of such a rabbit acquires the power of precipitating casein1 and ,fish found that this reaction is specific inasmuch as the lactoserum from cow's milk can precipitate only the casein of cow's milk but not that of human or goat milk4 ,wassermann and ,schtze reached the same result independently of each other4 ,myers and later ,uhlenhuth showed that if white of egg from a hen's egg is injected into a rabbit1 precipitins for white of egg are found in the serum of the latter1 and ,uhlenhuth#db found1 by trying the white of egg of different species of birds1 that the precipitin reaction called forth by the blood of the immunized animal is specific1 inasmuch as the proteins from a hen's egg will call forth the formation of precipitins in the blood of the rabbit which will precipitate only the white of egg of the hen or of closely related birds4 #db ,uhlenhuth1 ,p41 and ,steffenhagen1 ,k41 ,kolle-,wassermann1 ,handb4 d4 pathol4 ,mikroorg41 #bnd ,ed41 #aiac1 iii41 #beg4 ,to ,nuttall#dc belongs the credit of having worked out a quantitative method for measuring the amount of precipitate formed1 and in this way he made it possible to draw more valid conclusions concerning the degree of specificity of the precipitin reaction4 ,he found by this method that when the immune serum is mixed with the serum or the protein solution used for the immunization a maximum precipitate is formed1 but if it is mixed with the serum of related forms a quantitatively smaller precipitate is produced4 ,in this way the degree of blood relationship could be ascertained4 ,he thus was able to show that when the blood of one species1 e4 g41 the human1 was injected into the blood of a rabbit1 after some time the serum of the rabbit was able to cause a precipitate not only with the serum of man1 or chimpanzee1 but also of some lower monkeys2 with this difference1 however1 that the precipitate was much heavier when the immune serum was added to the serum of man4 ,the method thus shows the existence of not an absolute but of a strong quantitative specificity of blood serum4 ,this statement may be illustrated by the following table from ,nuttall4 ,the antiserum used for the precipitin reaction was obtained by treating a rabbit with human blood serum4 ,the forty-five bloods tested had been preserved for various lengths of time in the refrigerator with the addition of a small amount of chloroform4 #dc ,nuttall1 ,george ,h4 ,f41 ,blood ,immunity and ,blood ,relationship1 ,cambridge ,univ4 ,press1 #aijd4 ,,table ,,ii ,,quantitative ,,tests ,,with ,,anti-,,primate ,,sera ,tests with ,antihuman ,serum ---------------------------------------- -------------------------- ,blood of ,precipitum ,percentage ,amount ---------------------------------------- -------------------------- ,primates ,man 4#jca #ajj ,chimpanzee 4#jd #acj 7loose precipitum7 ,gorilla 4#jba #fd ,ourang 4#jac #db ,cynocephalus mormon 4#jac #db ,cynocephalus sphinx 4#jji #bi ,ateles geoffroyi 4#jji #bi ,insectivora ,centetes ecaudatus 4#j #j ,carnivora ,canis aureus 4#jjc #aj 7loose precipitum7 ,canis familiaris 4#jja #c ,lutra vulgaris 4#jjc #aj 7concentrated serum7 ,ursus tibetanus 4#jjbe #h ,genetta tigrina 4#jja #c ,felis domesticus 4#jja #c ,felis caracal 4#jjjh #c ,felis tigris 4#jjje #b ,ungulata ,ox 4#jjc #aj ,sheep 4#jjc #aj ,cobus unctuosus 4#jjb #g ,cervus porcinus 4#jjb #g ,rangifer tarandus 4#jjb #g ,capra megaceros 4#jjje #b ,equus caballus 4#jjje #b ,sus scrofa 4#j #j ,rodentia ,dasyprocta cristata 4#jjb #g 7concentrated serum clots7 ,guinea-pig 4#j #j ,rabbit 4#j #j ,marsupialia ,petrogale xanthopus ,petrogale penicillata ,onychogale frenata ,onychogale unguifera 4#j #j ,onychogale unguifera ,macropus bennetti ,thylacinus cynocephalus ---------------------------------------- -------------------------- ,among the ,primate bloods that of the ,chimpanzee gave too high a figure1 owing to the precipitum being flocculent and not settling well1 for some reason which could not be determined4 ,the figure given by the ,ourang is somewhat too low1 and the difference between ,cynocephalus sphinx and ,ateles is not as marked as might have been expected in view of the qualitative tests and the series following4 ,the possibilities of error must be taken into account in judging of these figures2 repeated tests should be made to obtain something like a constant4 ,other bloods than those of ,primates give small reactions or no reactions at all4 ,the high figures 7#aj7 obtained with two ,carnivore bloods can be explained by the fact that one gave a loose precipitum1 and the other was a somewhat concentrated serum4#dd #dd ,nuttall1 ,blood ,immunity and ,blood ,relationship1 pp4 #cai and #cbj4 ,we have mentioned that even the proteins of the egg are specific according to ,uhlenhuth4 ,graham ,smith1 one of ,nuttall's collaborators1 applied the latter's quantitative method to this problem and confirmed the results of ,nuttall4 ,a few examples may serve as an illustration4 ,,table ,,iii ,,tests ,,with ,,anti-,,duck',s-,,egg ,,serum ---------------------------------------- -------------------- ,material tested ,amount of ,percentage precipitum ---------------------------------------- -------------------- ,duck's egg-albumin 4#jchd #ajj ,pheasant's 4#jcbh #he ,fowl's 4#jbcd #fa ,silver ,pheasant's 4#jadj #cf ,blackbird's 4#jjfe #ae ,crane's 4#jjea #ad ,moorhen's 4#jjdf #ab ,thrush's 4#jjdf #ab ,emu's 4#jjah #e ,hedge-,sparrow's trace 8 ,chaffinch's 4 #j ,tortoise serum trace 8 ,turtle serum 8 ,alligator serum 4 #j ---------------------------------------- -------------------- ,frog1 ,amphiuma1 and ,dogfish sera1 as well as ,tortoise and ,dogfish egg-albumins1 were also tested1 with negative results4 ,,table ,,iv ,,tests ,,with ,,anti-,,fowl',s-,,egg ,,serum ---------------------------------------- -------------------- ,material tested ,amount of ,percentage precipitum ---------------------------------------- -------------------- ,fowl's egg-albumin 7old7 4#jaei #ajj ,fowl's 7fresh7 4#jadj #hh ,silver ,pheasant's 4#jjge #dg ,pheasant's 4#jjge #dg ,crane's 4#jjdf #bi ,blackbird's 4#jjdf #bi ,duck's 4#jjcg #bc ,moorhen's 4#jjbh #ah ---------------------------------------- -------------------- ,thrush1 ,emu1 ,greenfinch1 and ,hedge-sparrow egg-albumins were tested and gave traces of precipita1 as also did ,tortoise and ,turtle sera4 ,the egg-albumins of the ,tortoise1 ,frog1 ,skate1 and two species of ,dogfish did not react4 ,alligator1 ,frog1 ,amphiuma1 and ,dogfish sera also yielded no results4#de #de ,nuttall1 pp4 #cde and #cdf4 ,by improving the quantitative method in various ways1 ,welsh and ,chapman#df were able to explain why the precipitin reaction with egg-white was not strictly specific but gave also1 though quantitatively weaker1 results with the egg-white of related birds4 ,they found that by a new method devised by them 8it is possible to indicate in an avian egg-white antiserum the presence of a general avian antisubstance 7precipitin7 together with the specific antisubstance40 #df ,welsh1 ,d4 ,a41 and ,chapman1 ,h4 ,g41 ,jour4 ,hygiene1 #aiaj1 x41 #agg4 ,the ,bordet reaction was not only useful in indicating the specificity and blood relationship for animals but also among plants4 ,thus ,magnus and ,friedenthal#dg were able to demonstrate with ,bordet's method the relationship between yeast 7,saccharomyces cerevisi7 and truffle 7,tuber brumale74 #dg ,magnus1 ,w41 and ,friedenthal1 ,h41 ,ber4 d4 deutsch4 bot4 ,gesellsch41 #aijf1 xxiv41 #fja4 #e4 ,we must not forget1 while under the spell of the problem of immunity1 that we are interested at the moment in the question of the nature of the specificity of living organisms4 ,it is only logical to conclude that the fossil forms of invertebrate animals and of alg and bacteria1 which ,walcott found in the ,cambrian and which may be two hundred million years old1 must have had the same specificity at that time as they or their close relatives have today2 and this raises the question3 ,what is the nature of the substances which are responsible for and transmit this specificity8 ,it is obvious that a definite answer to this question brings us also to the very problem of evolution as well as that of the constitution of living matter4 ,there can be no doubt that on the basis of our present knowledge proteins are in most or practically all cases the bearers of this specificity4 ,this has been found out not only with the aid of the precipitin reaction but also with the anaphylaxis reaction1 by which1 as the reader may know1 is meant that when a small dose of a foreign substance is introduced into an animal a hypersensitiveness develops after a number of days or weeks1 so that a new injection of the same substance produces serious and in some cases fatal effects4 ,this hypersensitiveness1 which was first analysed by ,richet1#dh is specific for the substance which has been injected4 ,now all these specific reactions1 the precipitin reaction as well as the anaphylactic reaction1 can be called forth by proteins4 ,thus ,richet1 in his earliest experiments1 showed that only the protein-containing part of the extract of actinians1 by which he called forth anaphylaxis1 was able to produce this phenomenon1 and later he showed that it was generally impossible to produce anything resembling anaphylaxis by non-protein substances1 e4 g41 cocain or apomorphin4#di ,wells isolated from egg-white four different proteins 7three coagulable proteins and one non-coagulable7 which can be distinguished from each other by the anaphylaxis reaction1 although all come from the same biological object4#ej ,michaelis as well as ,wells found that the split products of the protein molecule are no longer able to call forth the anaphylaxis reaction4 ,since peptic digestion has the effect of annihilating the power of proteins to call forth anaphylaxis1 we are forced to the conclusion that the first cleavage products of proteins have already lost the power of calling forth immunity reactions4 #dh ,richet1 ,c41 ,l'anaphylaxie4 ,paris1 #aiab4 #di ,quoted from ,wells1 ,h4 ,g41 ,jour4 ,infect4 ,diseases1 #aijh1 v41 #ddi4 #ej ,ibid41 #aiaa1 ix41 #adg4 ,a pretty experiment by ,gay and ,robertson#ea should be mentioned in this connection4 ,robertson had shown that a substance closely resembling paranucleins both in its properties and its ,c1 ,h1 and ,n content can be formed from the filtered products of the complete peptic hydrolysis of an approximately four per cent4 neutral solution of potassium caseinate by the action of pure pepsin at #cf;,c4 #ea ,gay1 ,f4 ,p41 and ,robertson1 ,t4 ,b41 ,jour4 ,biol4 ,chem41 #aiab1 xii41 #bcc4 ,he considered this a case of a real synthesis of proteins from the products of its hydrolytic cleavage4 ,this interpretation was not generally accepted and received a different interpretation by ,bayliss and other workers4 ,gay and ,robertson were able to show that paranuclein when injected into an animal will sensitize guinea-pigs for anaphylactic intoxication for either paranuclein or casein and apparently indiscriminately4 ,the products of complete peptic digestion of casein had no such effect1 but the synthetic product of this digestion obtained by ,robertson's method has the same specific antigenic properties as paranuclein1 thus making it appear that ,robertson had indeed succeeded in causing a synthesis of paranuclein with the aid of pepsin from the products of digestion of casein by pepsin4 ,there are a few statements in the literature to the effect that the specificity of organisms might be due to other substances than proteins4 ,thus ,bang and ,forssmann claimed that the substances 7antigens7 responsible for the production of hemolysis were of a lipoid nature1 but their statements have not been confirmed1 and ,fitzgerald and ,leathes#eb reached the conclusion that lipoids are non-antigenic4 ,ford claims to have obtained proof that a glucoside contained in the poisonous mushroom ,amanita phalloides can act as an antigen4 ,but aside from this one fact we know that proteins and only proteins can act as antigens and are therefore the bearers of the specificity of living organisms4 #eb ,fitzgerald1 ,j4 ,g41 and ,leathes1 ,j4 ,b41 ,univ4 ,cal4 ,pub41 #aiab1 8,pathology10 ii41 #ci4 ,bradley and ,sansum#ec found that guinea-pigs sensitized to beef or dog hemoglobin fail to react or react but slightly to hemoglobin of other origin4 ,the hemoglobins tried were dog1 beef1 cat1 rabbit1 rat1 turtle1 pig1 horse1 calf1 goat1 sheep1 pigeon1 chicken1 and man4 #ec ,bradley1 ,h4 ,c41 and ,sansum1 ,w4 ,d41 ,jour4 ,biol4 ,chem41 #aiad1 xviii41 #dig4 #f4 ,it would be of the greatest importance to show directly that the homologous proteins of different species are different4 ,this has been done for hemoglobins of the blood by ,reichert and ,brown1#ed who have shown by crystallographic measurements that the hemoglobins of any species are definite substances for that species4 ,the crystals obtained from different species of a genus are characteristic of that species1 but differ from those of other species of the genus in angles or axial ratio1 in optical characters1 and especially in those characters comprised under the general term of crystal habit1 so that one species can usually be distinguished from another by its hemoglobin crystals4 ,but these differences are not such as to preclude the crystals from all species of a genus being placed in an isomorphous series 7p4 #cbg74 #ed ,reichert1 ,e4 ,t41 and ,brown1 ,a4 ,p41 8,the ,differentiation and ,specificity of ,corresponding ,proteins and other ,vital ,substances in ,relation to ,biological ,classification and ,organic ,evolution40 ,carnegie ,institution ,publication ,no4 #aaf1 ,washington1 #aiji4 ,as far as the genus is concerned it was found that the hemoglobin crystals of any genus are isomorphous4 ,in some cases this isomorphism may be extended to include several genera1 but this is not usually the case1 unless as in the case of dogs and foxes1 for example1 the genera are very closely related4 ,the most important question for us is the following3 ,are the differences between the corresponding hemoglobin crystals of different species of the same genus such as to warrant the statement that they indicate chemical differences8 ,if this were the case we might say that blood reactions as well as hemoglobin crystals indicate that differences in the constitution of proteins determine the species specificity and1 perhaps1 also species heredity4 ,the following sentences by ,reichert and ,brown seem to indicate that this may be true for the crystals of hemoglobin4 ,the hemoglobins of any species are definite substances for that species4 ,but upon comparing the corresponding substances 7hemoglobins7 in different species of a genus it is generally found that they differ the one from the other to a greater or less degree2 the differences being such that when complete crystallographic data are available the different species can be distinguished by these differences in their hemoglobins4 ,as the hemoglobins crystallize in isomorphous series the differences between the angles of the crystals of the species of a genus are not1 as a rule1 great2 but they are as great as is usually found to be the case with minerals or chemical salts that belong to an isomorphous group 7p4 #cbf74 ,as ,professor ,brown writes me1 the difficulty in answering the question definitely1 whether or not the hemoglobins of different species are chemically different1 lies in the fact that there is as yet no criterion which allows us to discriminate between a species and a ,mendelian mutation except the morphological differences4 ,it is not impossible that while species differ by the constitution of some or most of their proteins1 ,mendelian heredity has a different chemical basis4 ,it is regrettable that work like that of ,reichert and ,brown cannot be extended to other proteins1 but it seems from anaphylaxis reactions that we might expect results similar to those in the case of the hemoglobins4 ,the proteins of the lens are an exception inasmuch as1 according to ,uhlenhuth1 the proteins of the lens of mammals1 birds1 and amphibians cannot be discriminated from each other by the precipitin reaction4#ee #ee ,uhlenhuth1 ,das biologische ,verfahren zur ,erkennung und ,unterscheidung von ,menschen und ,tierblut1 ,jena1 #aije1 p4 #ajb4 #g4 ,the serum of certain humans may cause the destruction or agglutination of blood corpuscles of certain other humans4 ,this fact of the existence of 8isoagglutinins0 seems to have been established for man1 but ,hektoen states that he has not been able to find any isoagglutinins in the serum of rabbits1 guinea-pigs1 dogs1 horses1 and cattle4 ,landsteiner found the remarkable fact that the sera of certain individuals of humans could hemolyze the corpuscles of certain other individuals1 but not those of all individuals4 ,a systematic investigation of this variability led him to the discovery of three distinct groups of individuals1 the sera of each group acting in a definite way towards the corpuscles of the representatives of each other group4 ,later observers1 for example ,jansky and ,moss1 established four groups4 ,these groups are1 according to ,moss1#ef as follows3 ,group #a4 ,sera agglutinate no corpuscles4 ,corpuscles agglutinated by sera of ,groups #b1 #c1 #d4 ,group #b4 ,sera agglutinate corpuscles of ,groups #a1 #c4 ,corpuscles agglutinated by sera of ,groups #c1 #d4 ,group #c4 ,sera agglutinate corpuscles of ,groups #a1 #b4 ,corpuscles agglutinated by sera of ,groups #b1 #d4 ,group #d4 ,sera agglutinate corpuscles of ,groups #a1 #b1 #c4 ,corpuscles agglutinated by no serum4 #ef ,moss1 ,w4 ,l41 ,johns ,hopkins ,hospital ,bulletin1 #aiaj1 xxi41 #fb4 ,the relative frequency of the four groups follows from the following figures4 ,of one hundred bloods tested by ,moss in series of twenty there were found3 #aj belonging to ,group #a4 #dj belonging to ,group #b4 #g belonging to ,group #c4 #dc belonging to ,group #d4 ,groups #b and #d are in the majority and in overwhelming numbers1 which indicates that1 as a rule1 the sera agglutinate the blood corpuscles of individuals of the other groups1 but not those of individuals belonging to the same group4 ,the phenomenon that a serum agglutinates no corpuscles 7,group #a71 or that the corpuscles are agglutinated by no serum 7,group #d71 are the exceptions4 ,it is obvious that1 as far as our problem is concerned1 only ,groups #b and #c are to be considered4 ,there is no ,mendelian character which refers only to one half of the individuals except sex4 ,since nothing is said about a relation of ,groups #b and #c to sex such a relation probably does not exist4 #h4 ,the facts thus far reported imply the suggestion that the heredity of the genus is determined by proteins of a definite constitution differing from the proteins of other genera4 ,this constitution of the proteins would therefore be responsible for the genus heredity4 ,the different species of a genus have all the same genus proteins1 but the proteins of each species of the same genus are apparently different again in chemical constitution and hence may give rise to the specific biological or immunity reactions4 ,we may consider it as established by the work of ,mc,clung1 ,sutton1 ,e4 ,b4 ,wilson1 ,miss ,stevens1 ,morgan1 and many others1 that the chromosomes are the carriers of the ,mendelian characters4 ,these chromosomes occur in the nucleus of the egg and in the head of the sperm4 ,now the latter consists1 in certain fish1 of lipoids and a combination of nucleinic acid and protamine or histone1 the latter a non-coagulable protein1 more resembling a split product of one of the larger coagulable proteins4 ,a4 ,e4 ,taylor#eg found that if the spermatozoa of the salmon are injected into a rabbit1 the blood of the animal acquires the power of causing cytolysis of salmon spermatozoa4 ,when1 however1 the isolated protamines or nucleinic acid or the lipoids prepared from the same sperm were injected into a rabbit no results of this kind were observed4 ,h4 ,g4 ,wells more recently tested the relative efficiency of the constituents of the testes of the cod 7which in addition to the constituents of the sperm contained the proteins of the testicle74 ,from the testicle he prepared a histone 7the protein body of the sperm nucleus71 a sodium nucleinate1 and from the sperm-free aqueous extract of the testicles a protein resembling albumin was separated by precipitation4#eh ,the albumin behaved like ordinary serum albumin or egg albumin1 producing typical and fatal anaphylactic reactions and being specific when tried against mammalian sera4 ,the nucleinate did not produce any reactions when guinea-pigs were given small sensitizing and larger intoxicating doses 7#j4a gm47 in a three weeks' interval2 a result to be expected1 since no protein is present in the preparation4 ,the histone was so toxic that its anaphylactic properties could not be studied4 #eg ,taylor1 ,a4 ,e41 ,jour4 ,biol4 ,chem41 #aijh1 v41 #caa4 #eh ,wells1 ,h4 ,g41 ,jour4 ,infect4 ,diseases1 #aiaa1 ix41 #aff4 ,it is not impossible that protamines and histones might be found to act as specific antigens if they were not so toxic4 ,the positive results which ,taylor observed after injection of the sperm might have been due to the proteins contained in the tail of the spermatozoa1 which in certain animals at least does not enter the egg and hence can have no influence on heredity4 ,it is thus doubtful whether or not any of the constituents of the nucleus contribute to the determination of the species4 ,this in its ultimate consequences might lead to the idea that the ,mendelian characters which are equally transmitted by egg and spermatozon1 determine the individual or variety heredity1 but not the genus or species heredity4 ,it is1 in our present state of knowledge1 impossible to cause a spermatozon to develop into an embryo1#ei while we can induce the egg to develop into an embryo without a spermatozon4 ,this may mean that the protoplasm of the egg is the future embryo1 while the chromosomes of both egg and sperm nuclei furnish only the individual characters4 #ei ,loeb1 ,j41 and ,bancroft1 ,f4 ,w41 ,jour4 ,exper4 ,zol41 #aiab1 xii41 #cha4 ,,chapter ,,iv ,,specificity ,,in ,,fertilization #a4 ,we have become acquainted with two characteristics of living matter3 the specificity due to the specific proteins characteristic for each genus and possibly species and the synthesis of living matter from the split products of their main constituents instead of from a supersaturated solution of their own substance1 as is the case in crystals4 ,we are about to discuss in this and the next chapter a third characteristic1 namely1 the phenomenon of fertilization4 ,while this is not found in all organisms it is found in an overwhelming majority and especially the higher organisms1 and of all the mysteries of animated nature that of fertilization and sex seems to be the most captivating1 to judge from the space it occupies in folklore1 theology1 and 8literature40 ,bacteria1 when furnished the proper nutritive medium1 will synthetize the specific material of their own body1 will grow and divide1 and this process will be repeated indefinitely as long as the food lasts and the temperature and other outside conditions are normal4 ,it is purely due to limitation of food that bacteria or certain species of them do not cover the whole planet4 ,but1 as every layman knows1 the majority of organisms grow only to a certain size1 then die1 and the propagation takes place through sex cells or gametes3 a female cell--the egg--containing a large bulk of protoplasm 7the future embryo7 and reserve material2 and the male cell which in the case of the spermatozon contains only nuclear material and no cytoplasmic material except that contained in the tail which in some and possibly many species does not enter the egg4 ,the male element--the spermatozon--enters the female gamete--the egg--and this starts the development4 ,in the case of most animals the egg cannot develop unless the spermatozon enters4 ,the question arises3 ,how does the spermatozon activate the egg8 ,and also how does it happen that the spermatozon enters the egg8 ,we will first consider the latter question4 ,these problems can be answered best from experiments on forms in which the egg and the sperm are fertilized in sea water4 ,many marine animals1 from fishes down to lower forms1 shed their eggs and sperm into the sea water where the fertilization of the egg takes place1 outside the body of the female4 ,the first phenomenon which strikes us in this connection is again a phenomenon of specificity4 ,the spermatozon can1 as a rule1 only enter an egg of the same or a closely related species1 but not that of one more distantly related4 ,what is the character of this specificity8 ,the writer was under the impression that a clue might be obtained if artificial means could be found by which the egg of one species might be fertilized with a distant species for which this egg is naturally immune4 ,such an experiment would mean that the lack of specificity had been compensated by the artificial means4 ,it is well known that the egg of the sea urchin cannot as a rule be fertilized with the sperm of a starfish in normal sea water4 ,the writer tried whether this hybridization could not be accomplished provided the constitution of the sea water were changed4 ,he succeeded in causing the fertilization of a large percentage of the eggs of the ,californian sea urchin1 ,strongylocentrotus purpuratus1 with the sperm of various starfish 7e4 g41 ,asterias ochracea7 and ,holothurians by slightly raising the alkalinity of the sea water1 through the addition of some base 7,na,o,h or tetraethylammoniumhydroxide or various amines71 the optimum being reached when #j4f c4c4 ,n_/#aj ,na,o,h is added to #ej c4c4 of sea water4 ,it is a peculiar fact that this solution is efficient only if both egg and sperm are together in the hyperalkaline sea water4 ,if the eggs and sperm are treated separately with the hyperalkaline sea water and are then brought together in normal sea water no fertilization takes place as a rule1 while with the same sperm and eggs the fertilization is successful again if both are mixed in the hyperalkaline solution4 ,from this the writer concluded that the fertilizing power depends on a rapidly reversible action of the alkali on the surface of the two gametes4 ,it was found that an increase of the concentration of calcium in the sea water also favoured the entrance of the ,asterias sperm into the egg of purpuratus2 and that if ,c,ca was increased it was not necessary to add as much ,na,o,h4 ,the spermatozon enters the egg through the so-called fertilization cone1 i4 e41 a protoplasmic process comparable to the pseudopodium of an amboid cell4 ,the analogy of the process of phagocytosis--i4 e41 the taking up of particles by an amboid cell--and that of the engulfing of the spermatozon by the egg presents itself4 ,we do not know definitely the nature of the forces which act in the case of phagocytosis--although surface tension forces and agglutination have been suggested2 both are surface phenomena and are rapidly reversible4 ,we should then say that the specificity in the process of fertilization consists in a peculiarity of the surface of the egg and spermatozon which in the case of ,s4 purpuratus and ,asterias can be supplied by a slight increase in the ,c,,oh or ,c,ca4 ,by this method fifty per cent4 or more of the eggs of purpuratus could be fertilized with the sperm of the starfish ,asterias ochracea1 capitata1 ,ophiurians1 and ,holothurians1 while with the sperm of another starfish1 ,pycnopodia spuria1 only five per cent41 and with the sperm of ,asterina only one per cent4 could be fertilized4#fj ,godlewski succeeded by the same method in fertilizing the eggs of a ,naples starfish with the sperm of a crinoid4#fa ,the writer did not succeed in bringing about the fertilization of the egg of another sea urchin in ,california1 ,strongylocentrotus franciscanus1 with the sperm of a starfish4 ,although these eggs formed a membrane in contact with the sperm1 the latter did not enter the egg2 nor has the writer as yet succeeded in causing the sperm of ,asterias to enter the egg of ,arbacia4 #fj ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijc1 xcix41 #cbc2 #aijd1 civ41 #cbe2 ,arch4 f4 ,entwcklngsmech41 #aiaj1 xxx41 ,,ii41 #dd2 #aiad1 xl41 #caj2 ,science1 #aiad1 xl41 #caf4 #fa ,godlewski1 ,e41 ,arch4 f4 ,entwcklngsmech41 #aijf1 xx41 #egi4 ,kupelwieser#fb observed that the spermatozon of molluscs may occasionally enter into the egg of ,s4 purpuratus in normal sea water and later1 at ,naples1 he observed the same for the sperm of annelids4 ,in these cases no development took place4 ,in teleost fishes the spermatozon can enter the eggs of widely different species but with rare exceptions all the embryos will die in an early stage of development4#fc #fb ,kupelwieser1 ,h41 ,arch4 f4 ,entwcklngsmech41 #aiji1 xxvii41 #dcd2 ,arch4 f4 ,zellforsch41 #aiab1 viii41 #ceb4 #fc ,see ,chapter ,,ii4 #b4 ,the fact that an increase in the alkalinity or in the concentration of calcium allowed foreign sperm to enter the egg of the sea urchin1 suggested the idea that a diminution of alkalinity or calcium in the sea water might block the entrance of the sperm of sea urchin into eggs of their own species4 ,this was found to be correct2 when we put eggs and sperm of the same species of sea urchin into solutions whose concentration of ,ca or of ,,oh is too small1 the sperm1 although it may be intensely active1 cannot enter the egg4 ,for the purpose of these experiments the ovaries and testes of the sea urchins were not put into sea water1 but instead into pure m_/#b ,na,cl and after several washings in this solution were kept in it 7they remain alive for several days in pure m_/#b ,na,cl74 ,several drops of such sperm and one drop of eggs were in one series of experiments put into #b4e c4c4 of a neutral mixture of m_/#b ,na,cl and #c_/h m ,mg,cl in the proportion in which these two salts exist in the sea water4 ,in such a neutral solution eggs of ,arbacia or purpuratus are not fertilized no matter how long they remain in it1 although the spermatozoa swim around the eggs very actively4 ,that no spermatozon enters the eggs can be shown by the fact that the eggs do not divide 7although they can segment in such a solution if previously fertilized in sea water or some other efficient solution74 ,when1 however1 eggs and sperm are put into #b4e c4c4 of the same solution of ,na,cl,mg,cl1 containing in addition one drop of a ,n_/#ajj solution of ,na,o,h 7or ,,nh or benzylamine or butylamine7 or eight drops of m_/#ajj ,na,h,c,o1 most1 and often practically all of the eggs at once form fertilization membranes and segment at the proper time1 indicating that fertilization has been accomplished4 ,the same result can be obtained if the eggs are transferred into a neutral mixture of ,na,cl,mg,cl,ca,cl 7in the proportion in which these salts exist in the sea water7 or into a neutral mixture of ,na,cl,mg,cl,k,cl,ca,cl4 ,in such neutral mixtures the eggs form fertilization membranes and begin to segment4 ,the eggs are not fertilized in a neutral solution of ,na,cl or of ,na,cl,k,cl4#fd #fd ,loeb1 ,j41 ,science1 #aiad1 xl41 #caf2 ,am4 ,naturalist1 #aiae1 xlix41 #beg4 ,it is1 therefore1 obvious that if we diminish the alkalinity of the solution surrounding the egg and deprive this solution of ,ca,cl we establish the same block to the entrance of the spermatozon of ,arbacia into the egg of the same species as exists in normal sea water for the entrance of the sperm of the starfish into the egg of purpuratus4 ,the 8block0 created in this way1 to the entrance of the sperm of ,arbacia into the egg of the same species is also rapidly reversible4 ,we reach the conclusion1 therefore1 that the specificity which allows the sperm to enter an egg is a surface effect which can be increased or diminished by an increase or diminution in the concentration of ,,oh as well as of ,ca4 ,the writer has shown that an increase in the concentration of both substances may cause an agglutination of the spermatozoa of starfish to the jelly which surrounds the egg of purpuratus4#fe ,it is thus not impossible that the specificity which favours the entrance of a spermatozon into an egg of its own species may consist in an agglutination between spermatozon and egg protoplasm 7or its fertilization cone72 and that this agglutination is favoured if the ,c,,oh or ,c,ca or both are increased within certain limits4 #fe ,loeb1 ,arch4 f4 ,entwcklngsmech41 #aiad1 xl41 #caj4 ,godlewski discovered a very interesting form of block to the entrance of the spermatozon into the egg which takes place if two different types of sperm are mixed4 ,he had found that the sperm of the annelid ,chtopterus is able to enter the egg of the sea urchin and that in so doing it causes membrane formation4 ,the egg1 however1 does not develop but dies rapidly1 as is the case when we induce artificial membrane formation1 as we shall see in the next chapter4 ,godlewski found that if the sperm of ,chtopterus and the sperm of sea urchins are mixed the mixture is not able to induce development or membrane formation1 since now neither spermatozon can enter2 blood has the same inhibiting effect as the foreign sperm4 ,the mixture does not interfere with the development of the eggs if they are previously fertilized4#ff #ff ,godlewski1 ,e41 ,arch4 f4 ,entwcklngsmech41 #aiaa1 xxxiii41 #aif4 ,the phenomenon was further investigated by ,herlant#fg who found that if the sperm of a sea urchin is mixed with the sperm of certain annelids 7,chtopterus7 or molluscs1 and if after some time the eggs of the sea urchin are added to the mixture of the two kinds of sperm no egg is fertilized4 ,if1 however1 the solution is subsequently diluted with sea water or if the egg that was in this mixture is washed in sea water1 the same sperm mixture in which the egg previously remained unfertilized will now fertilize the egg4 ,from these and similar observations ,herlant draws the conclusion that the block existed at the surface of the egg1 inasmuch as a reaction product of the two types of sperm is formed after some time which alters the surface of the egg and thereby prevents the sperm from entering4 ,this view is supported not only by all the experiments but also by the observation of the writer that foreign sperm or blood is able to cause a real agglutination after some time if mixed with the sperm of a sea urchin or a starfish4#fh ,we can imagine that the precipitate forms a film around the egg and acts as a block for the agglutination between egg and spermatozon4 ,the block can be removed mechanically by washing4 #fg ,herlant1 ,m41 ,anat4 ,anzeiger1 #aiab1 xlii41 #efc4 #fh ,loeb1 ,j41 ,jour4 ,exper4 ,zol41 #aiad1 xvii41 #abc4 #c4 ,the fact has been mentioned that the most motile sperm will not be able to enter into the egg if certain other conditions 7specificity or ,c,,oh or ,c,ca7 are not fulfilled4 ,on the other hand1 living but immobile sperm cannot enter the egg under any conditions4 ,if we add a trace of ,,kcn to the sperm of ,arbacia so that the spermatozon becomes immobile no egg is fertilized even if the eggs and the sperm are thoroughly shaken together2 while the same spermatozoa will fertilize these eggs as soon as the ,,hcn has evaporated and they again become motile4 ,it was formerly thought that the spermatozon had to bore itself into the egg1 being propelled by the movements of the flagellum4 ,it is1 however1 more probable that only a certain energy of vibration is needed on the part of the spermatozon to make the latter stick to the surface of the egg and agglutinate and that later forces of a different character bring the spermatozon into the egg4 ,the fact that under normal conditions a very slight degree of motility on the part of the spermatozon allows it to enter the egg of its own species seems to favour such a view4 ,it is a common experience that spermatozoa become very active when they reach the neighbourhood of an egg4 v4 ,dungern assumed that only foreign sperm became thus active1 but ,f4 ,r4 ,lillie#fi has pointed out that this may be a specific effect4 ,the writer tested this idea on the sperm and eggs of two species of starfish and of sea urchins4 ,it should be mentioned that the eggs of the starfish used in this experiment were completely immature and could not be fertilized1 while the eggs of the sea urchins were mature4 ,the testicles and ovaries had been kept in ,na,cl and all the sperm was immotile4 ,eggs and sperm were mixed together in a pure m_/#b ,na,cl solution where the sperm was only rendered motile by the proximity of eggs4 ,the following table gives the result4#gj #fi ,lillie1 ,f4 ,r41 ,jour4 ,exper4 ,zol41 #aiad1 xvi41 #ebc4 #gj ,loeb1 ,j41 ,am4 ,naturalist1 #aiae1 xlix41 #beg4 ,,table ,v ,,specificity ,,of ,,activation ,,of ,,sperm ,,by ,,eggs ---------------------------------------- --------------------------- ,asterias ,asterina ,franciscanus,purpuratus ---------------------------------------- --------------------------- ,asterias ,immediately,no ,moderately ,slight effect 7immature7 very activation4 active4 in immediate motile4 contact with egg4 ,asterina ,not motile4,violent ,violent ,slight effect 7immature7 activity4 activity4 only near the egg4 ,franciscanus,slightly ,no motility4 ,immediately ,immediately 7mature7 motile4 active4 active4 ,purpuratus ,slightly ,slight effect,immediately ,immediately 7mature7 motile in immediate active4 active4 after some contact time4 with eggs4 ---------------------------------------- --------------------------- ,the spermatozoa of starfish show a marked specificity inasmuch as they are strongly activated only by the eggs of their own species1 although in this experiment these were immature1 and to a slight degree only by the eggs of the sea urchin purpuratus4 ,but it is also obvious that the specificity is far from exclusive since the immature eggs of ,asterina activate the sperm of the sea urchin franciscanus as powerfully as is done by the mature eggs of the sea urchin purpuratus and franciscanus4 ,in studying these results the reader must keep in mind first that all these experiments were made in a ,na,cl solution and second that it requires a stronger influence to activate the spermatozoa of the starfish1 which are not motile at first even in sea water1 than the sea urchin spermatozoa which are from the first very active in such sea water1 and which may therefore be considered as being at the threshold of activity in pure ,na,cl solution4 ,wasteneys and the writer 7in experiments not yet published7 did not succeed in demonstrating an activating effect of the eggs of various marine teleosts upon sperm of the same species4 #d4 ,f4 ,r4 ,lillie#ga has studied the very striking phenomenon of transitory sperm agglutination which takes place when the sperm of a sea urchin or of certain annelids is put into the supernatant sea water of eggs of the same species4 ,if we put one or more drops of a very thick sperm suspension of the ,californian sea urchin ,s4 purpuratus carefully into the centre of a dish containing #c c4c4 of ordinary sea water and let the drop stand for one-half to one minute and then by gentle agitation mix the sperm with the sea water the mass of thick sperm which is at first rather viscous is distributed equally in sea water in a few seconds and the result is a homogeneous sperm suspension4 ,when1 however1 the same experiment is made with the sea water which has been standing for a short time over a large mass of eggs of the same species1 the thick drop of sperm seems to be less miscible and instead of a homogeneous suspension we get1 as a result1 the formation of a large number of distinct clusters which are visible to the naked eye and which may possess a diameter of #a or #b mm4 ,the rest of the sea water is almost free from sperm4 ,these clusters of spermatozoa may last for from two to ten minutes and then dissolve by the gradual detachment of the spermatozoa from the periphery of the cluster4 #ga ,lillie1 ,f4 ,r41 ,science1 #aiac1 xxxviii41 #ebd2 ,jour4 ,exper4 ,zol41 #aiad1 xvi41 #ebc2 ,biol4 ,bull41 #aiae1 xxviii41 #ah4 ,this phenomenon seems to occur in sea urchins and annelids4 ,the writer has vainly looked for it in different forms of the ,californian starfish or molluscs and in fish at ,woods ,hole4 ,lillie failed to find it in the starfish at ,woods ,hole4 ,the writer found that the sperm of the ,californian sea urchin ,strongylocentrotus purpuratus will form clusters with the egg sea water of purpuratus but not with that of franciscanus2 while the sperm of franciscanus will agglutinate with the egg sea water of both species1 but the clusters last a little longer with the eggs of its own species4 ,he also found that the clusters are more durable in a neutral than in a slightly alkaline solution and that the agglutination disappears the more rapidly the more alkaline the solution4 ,the presence of bivalent cations1 especially ,ca1 also favours the agglutination4 ,it was also found that this agglutination occurs only when the spermatozoa are very motile2 thus if a trace of ,,kcn is added to a mass of thick sea-urchin sperm so that the spermatozoa become immotile a drop of this sperm will not agglutinate when put in egg sea water of the same species2 while later1 after the ,,hcn has evaporated1 the same sperm will agglutinate when put into such sea water4 ,the writer suggests the following explanation of the phenomenon4 ,the egg sea water contains a substance which forms a precipitate with a substance on the surface of the spermatozon whereby the latter becomes slightly sticky4 ,this precipitate is slowly soluble in sea water and the more rapidly the more alkaline 7within certain limits74 ,only when the spermatozoa run against each other with a certain impact will they stick together1 as ,lillie suggested4 ,lillie assumes that this agglutinating substance contained in egg sea water is required to bring about fertilization and he therefore calls it 8fertilizin40#gb ,but this assumption seems to go beyond the facts inasmuch as the existence of such an agglutinating substance can only be proved in a few species of animals 7sea urchins and annelids72 and as1 moreover1 sea-urchin sperm can fertilize eggs which will not cause the sperm to agglutinate1 e4 g41 the egg of franciscanus can be fertilized by sperm of purpuratus1 although the egg sea water of franciscanus causes no agglutination of the sperm of purpuratus4 ,when the jelly surrounding the egg of the ,californian sea urchin ,s4 purpuratus is dissolved with acid and the eggs are washed1 the eggs will not cause any more sperm agglutination2 and yet one hundred per cent4 of such eggs can be fertilized by sperm4#gc #gb ,lillie1 ,f4 ,r41 loc4 cit4 #gc ,loeb1 ,j41 ,jour4 ,exper4 ,zol41 #aiad1 xvii41 #abc2 ,am4 ,naturalist1 #aiae1 xlix41 #beg4 #e4 ,it is well known that if an egg is once fertilized it becomes impermeable for other spermatozoa4 ,this cannot well be due to the fact that the egg develops2 for the writer found some time ago that eggs of ,strongylocentrotus purpuratus which are induced to develop by means of artificial parthenogenesis can be fertilized by sperm4 ,the following observation leaves no doubts in this respect4 ,when the unfertilized eggs of purpuratus are put for two hours into hypertonic sea water 7#ej c4c4 of sea water#h c4c4 #b-a_/b m ,na,cl7 and then transferred into sea water it occasionally happens that a certain percentage of the eggs will begin to divide into #b1 #d1 #h or more cells1 without developing any further4 ,when to such eggs after they have remained in the resting stage for a number of hours or a day1 sperm is added1 some or all of the blastomeres form a fertilization membrane and now begin to develop into larv2 and if the spermatozon gets into a blastomere of the #b- or #d-;cell stage normal plutei will result4 ,when the sperm is added while the eggs are in active parthenogenetic cell division the individual blastomeres into which a spermatozon enters will also form a fertilization membrane1 but such blastomeres perish very rapidly4 ,it is not yet possible to state why it should make such a difference for the possibility of development whether the spermatozon enters into a blastomere when at rest or when it is in active nuclear division1 although the idea presents itself that in the latter case an abnormal mix-up and separation of chromosomes and other constituents may be responsible for the fatal result4 ,whatever may be the explanation of this phenomenon it proves to us that it is not the process of development in itself which acts as a block to the entrance of a spermatozon into an egg which is already fertilized4#gd #gd ,loeb1 ,j41 ,arch4 f4 ,entwcklngsmech41 #aijg1 xxii41 #dgi2 ,artificial ,parthenogenesis and ,fertilization1 ,chicago1 #aiac1 p4 #bdj4 ,when the spermatozon enters the egg of the sea urchin it calls forth the formation of a membrane--the fertilization membrane4 ,it might be considered possible that this membrane formation or the alteration underlying or accompanying it is responsible for the fact that an egg once fertilized becomes immune against a spermatozon4 ,we shall see in the next chapter that it is possible to call forth the membrane in an unfertilized sea-urchin egg by treating it with butyric acid4 ,this membrane is so tough in the egg of ,strongylocentrotus that no spermatozon can get through it2 in the egg of ,arbacia the membrane is occasionally replaced by a soft gelatinous film4 ,if no second treatment is given to such eggs they will disintegrate in a comparatively short time1 but when sperm is added some or most of the eggs will develop in the way characteristic of fertilized eggs4#ge ,when the membrane is too tough to allow the spermatozon to enter the egg it can be shown that if the membrane is torn mechanically the egg can still be fertilized by sperm4 #ge ,loeb1 ,j41 ,science1 #aiac1 xxxviii41 #gdi2 ,arch4 f4 ,entwcklngsmech41 #aiad1 xxxviii41 #bgg2 ,wasteneys1 ,h41 ,jour4 ,biol4 ,chem41 #aiaf1 xxiv41 #bha4 ,should it be possible that the spermatozon can no longer agglutinate with the fertilized egg or that those phagocytotic reactions which we suppose to play a rle in the entrance of the spermatozon into the egg are no longer possible after a spermatozon has entered8 ,the mere fact of development is apparently not the cause which bars a spermatozon from entering an egg already fertilized by sperm4 ,lillie assumes that the egg loses its 8fertilizin0 in the process of membrane formation since the sea water containing such eggs no longer gives the agglutinin reaction with sperm1 and he believes that the lack of 8fertilizin0 in the fertilized egg or in the egg after membrane formation is the cause of the block in the fertilized egg4 ,but we have seen that the artificial membrane formation does not create such a block although it puts an end to the 8fertilizin0 reaction4 ,in the egg of purpuratus the 8fertilizin0 reaction ceases when the jelly surrounding the egg is dissolved by an acid and the eggs are repeatedly washed2 yet such eggs can easily be fertilized by sperm4 ,lillie does not assume that the 8fertilizin0 causes an agglutination between egg and spermatozon--we should assent to such an assumption--but that the 8fertilizin0 acts like an 8amboceptor0 between egg and spermatozon1 the latter being the complement1 the former the antigen4 ,the pathologist would probably object to this interpretation since no 8amboceptor0 is needed for agglutination4 ,the writer has had some doubts concerning the value of ,ehrlich's side-chain theory which1 besides1 can only be applied in a metaphorical sense to the mechanism of the entrance of the spermatozon into the egg4#gf #gf ,loeb1 ,j41 ,am4 ,naturalist1 #aiae1 xlix41 #beg4 ,the writer may be permitted to illustrate by a special case his reason for declining to accept ,ehrlich's side-chain theory4 ,ehrlich and ,sachs found that if to a given mass of toxin small quantities of antitoxin are added successively the first fraction added neutralized more than the later fractions2 and on the basis of this reasoning ,ehrlich concluded that ten different toxins were contained in the diphtheria toxin4 ,arrhenius showed that the same phenomenon can be obtained when a weak base like ,,nh,,oh is neutralized by a weak acid 7e4 g41 boric acid72 hence we should assume that ,,nh,,oh consists of ten different forms of ammonia4 ,both cases1 the saturation of toxin with antitoxin and ammonia with boric acid are equilibrium phenomena4 7,arrhenius1 ,s41 ,quantitative ,laws in ,biological ,chemistry1 ,london1 #aiae47 #f4 ,the reason that an egg once fertilized with sperm cannot be fertilized again may be found in a group of facts which we will now discuss1 namely1 the self-sterility of many hermaphrodites4 ,the fact that hermaphrodites are often self-sterile1 while their eggs can be fertilized with sperm from a different individual of the same species has played a great rle in the theories of evolution4 ,we are here only concerned with the mechanism which determines the block to the entrance of a spermatozon into an egg of the same hermaphroditic individual4 ,castle#gg observed and studied the phenomenon of self-sterility in an ,ascidian1 ,ciona intestinalis1 which is hermaphroditic4 ,animals which were kept isolated discharged both eggs and sperm into the surrounding sea water4 ,often no egg was fertilized1 but in some cases five1 ten1 or as many as fifty per cent4 of the eggs could be successfully fertilized with sperm from the same individual2 while if several individuals were put into the same dish as a rule one hundred per cent4 of the eggs which were discharged segmented4 ,morgan#gh found that the eggs of various females differ in their power of being fertilized by sperm of the same individual while one hundred per cent4 could usually be fertilized with sperm of a different individual4 ,he found in addition that if the eggs of ,ciona are put for about ten minutes into a two per cent4 ether solution in sea water in a number of cases the percentage of eggs fertilized by sperm of the same individual shows a slight increase4 ,fuchs#gi has reported results similar to those of ,castle and ,morgan4 #gg ,castle1 ,w4 ,e41 ,bull4 ,mus4 ,comp4 ,zol41 ,harvard1 #ahif1 xxvii41 #bjc4 #gh ,morgan1 ,t4 ,h41 ,jour4 ,exper4 ,zol41 #aijd1 i41 #ace2 ,arch4 f4 ,entwcklngsmech41 #aiaj1 xxx41 #bjf4 #gi ,fuchs1 ,h4 ,m41 ,jour4 ,genet41 #aiae1 iv41 #bae4 ,a new point of attack has been introduced into the work of self-sterility in plants by the consideration of heredity4 ,darwin found that in ,reseda which is moncious 7or hermaphroditic7 certain individuals are either completely self-sterile or completely self-fertile2 and ,compton showed that apparently self-fertility is a ,mendelian dominant to self-sterility4#hj #hj ,quoted from ,fuchs4 ,according to ,jost this self-sterility in hermaphroditic plants is due to the fact that if pollen of the same plant is used the normal growth of the pollen tube is inhibited1 while this inhibition does not exist for pollen from a different individual4 ,correns calls these substances which prevent the adequate growth of pollen1 8inhibitory0 substances1 and finds that they can apparently be transmitted to the offspring4 ,he made experiments on ,cardamine pratensis which is self-sterile4#ha ,he fertilized two individuals of ,cardamine crosswise and raised sixty plants of the first generation4 ,he compared the fertility of these ,f plants toward 7a7 their parents1 and 7b7 foreign plants4 ,all the fertilizations with the foreign plants were successful1 but the fertilizations with the parents were only partly successful4 ,according to their reaction they could be divided into four groups3 7,a7 fertile with both parents4 ,type bg 7,b7 fertile with one 7,b71 sterile with the other parent 7,g74 7a7 fertile with ,b1 sterile with ,g4 ,type b,g 7b7 fertile with ,g1 sterile with ,b4 ,type ,bg 7,c7 sterile with both parents4 ,type ,,bg #ha ,correns1 ,c41 ,biol4 ,centralbl41 #aiac1 xxxiii41 #chi4 ,it was found that approximately fifteen of the sixty children belonged to each of the four groups4 ,this should be expected if the inhibitory substance to each parent is transmitted to the children independently4 ,half of the children will thus inherit the inhibitory substance of one parent and the other half will inherit the inhibitory substance of the other parent4 ,this agrees with the assumption that there are definite determiners for the inhibitory substances in the children which will be transmitted to half of the children4 ,rather complicated assumptions are needed to explain all the facts observed by ,correns on this basis and since the subject is still under investigation we need not go further into the details4 ,to us the assumption and experimental support of the idea that self-sterility is caused by the presence of a substance inhibitory to the entrance of a spermatozon is important4 ,should it be possible that the block created by the entrance of a spermatozon into the egg is also due to an inhibitory substance carried by a spermatozon into the egg2 and furthermore that the effect of the inhibitory substance should be the prevention of further agglutination of the spermatozon with the egg or of the growth of the pollen tube in plants8 ,on such an assumption self-sterility would be due to a lack of agglutination between the egg of a hermaphrodite and a spermatozon of the same individual4 ,the experiments on the agglutinins have shown that while isoagglutinins 7i4 e41 agglutinins for other individuals of the same species7 are common auto-agglutinins 7i4 e41 agglutinins for cells of the same individual7 rarely if ever occur4 #g4 ,a positive chemotropism of the spermatozoa toward an egg of the same species has been demonstrated in a few cases1 but it seems that this phenomenon is not determined by that type of substances which give rise to species specificity4 ,the famous experiment of ,pfeffer on the spermatozoa of ferns inaugurates this line of investigation4 ,he found that such spermatozoa when moving in a straight line through the water will be deviated in their course if they come near an archegonium2 they will then turn toward it1 enter it1 and enter the egg4 ,pfeffer showed that #j4ja per cent4 malic acid if put into a capillary tube will attract the spermatozoa of ferns4 ,when the liquid in the tube contains only #j4ja per cent4 malic acid the spermatozoa of ferns very soon move toward the opening of the capillary tube and within from five to ten minutes many hundreds of spermatozoa may accumulate in the tube4 ,the malic acid acts as well in the form of a free acid as in the form of salts4#hb #hb ,pfeffer1 ,untersuchungen aus dem botanischen ,institut zu ,tbingen1 #ahha-ahhe1 i41 #cfc4 ,these experiments were continued and amplified by ,shibata4 ,bruchmann#hc found that the spermatozoa of ,lycopodium are positively chemotactic to citric acid and salts of this acid1 although no citric acid could be shown in the contents of the archegonia4 ,they are also positively chemotactic to the watery extract from archegonia4 #hc ,bruchmann1 ,h41 ,flora1 #aiji1 ic41 #aic4 ,dewitz1 ,buller1 and the writer have vainly tried to prove the existence of a positive chemotropism of spermatozoa to eggs of the same species4 ,lillie claims to have proved a positive chemotropism of the sperm of sea urchins to 8fertilizin10 but such a conclusion is only justified if a method similar to that of ,pfeffer's with capillary tubes1 gives positive results2 such a method was not used in ,lillie's experiments4 ,it seems that the fertilization of the egg by sperm is rendered possible by two facts2 first that where fertilization takes place outside the body egg and sperm are shed simultaneously by the two sexes4 ,this can be easily observed in the case of fish4 ,but it is also the case in invertebrates4 ,thus the writer has observed that the sea urchins ,strongylocentrotus purpuratus at the shore of ,pacific ,grove all spawn simultaneously4 ,the examination extended over several miles of shore4 ,at such spawning seasons the sea water becomes a suspension of sperm4 ,the second fact guaranteeing the fertilization of the eggs is the overwhelming excess of spermatozoa over eggs4 ,the enormous waste in animated nature is in agreement with the idea of a lack of purpose2 since in this case the laws of chance must play a great rle2 and the origin of durable organisms by laws of chance is only comprehensible on the basis of an enormous wastefulness1 for which evidence is not lacking4 ,,chapter ,v ,,artificial ,,parthenogenesis #a4 ,the majority of eggs cannot develop unless they are fertilized1 that is to say1 unless a spermatozon enters into the egg4 ,the question arises3 ,how does the spermatozon cause the egg to develop into a new organism8 ,the spermatozon is a living organism with a complicated structure and it is impossible to explain the causation of the development of the egg from the structure of the spermatozon4 ,no progress was possible in this field until ways were found to replace the action of the living spermatozon by well-known physicochemical agencies4#hd ,various observers such as ,tichomiroff1 ,r4 ,hertwig1 and ,t4 ,h4 ,morgan had found that unfertilized eggs may begin to segment under certain conditions1 but such eggs always disintegrated in their experiments without giving rise to larv4 ,in #ahii the writer succeeded in causing the unfertilized eggs of the sea urchin ,arbacia to develop into swimming larv1 blastul1 gastrul1 and plutei1 by treating them with hypertonic sea water of a definite osmotic pressure for about two hours4 ,when such eggs were then put back into normal sea water many segmented and a certain percentage developed into perfectly normal larv1 blastul1 gastrul1 and plutei4#he ,soon afterward this was accomplished by other methods for the unfertilized eggs of a large number of marine animals1 such as starfish1 molluscs1 and annelids4 ,none of these eggs can develop under normal conditions unless a spermatozon enters4 ,these experiments furnished proof that the activating effect of the spermatozon upon the egg can be replaced by a purely physicochemical agency4#hf #hd ,the substitution of well-known physicochemical agencies for the mysterious action of the spermatozon was the task the writer set himself in this work and not the explanation of natural parthenogenesis1 as the author of a recent text-book seems to assume4 #he ,loeb1 ,j41 ,am4 ,jour4 ,physiol41 #ahii1 iii41 #ace2 #aijj1 iii41 #dcd4 #hf ,loeb1 ,j41 ,artificial ,parthenogenesis and ,fertilization1 ,chicago1 #aiac4 ,the reader is referred to this book for the literature on the subject4 ,the first method used in the production of larv from the unfertilized eggs did not lend itself to an analysis of the activating effect of the spermatozon upon the egg1 since nothing was known about the action of a hypertonic solution1 except that it withdraws water from the egg2 and there was no indication that the entrance of the spermatozon causes the egg to lose water4 ,no further progress was possible until another method of artificial parthenogenesis was found4 ,when a spermatozon enters the egg of a sea urchin or starfish or certain annelids1 the surface of the egg undergoes a change which is called membrane formation2 and which consists in the appearance of a fine membrane around the egg1 separated from the latter by a liquid 7,figs4 #d and #e74 ,o4 and ,r4 ,hertwig and ,herbst had observed that such a membrane could be produced in an unfertilized egg if the latter was put into chloroform or xylol1 but such eggs perished at once4 ,it was generally assumed1 moreover1 that the process of membrane formation was of no significance in the phenomenon of fertilization1 except perhaps that the fertilization membrane guarded the fertilized egg against a further invasion by sperm4 ,however1 since the fertilized egg is protected against this possibility by other means the membrane is hardly needed for such a purpose4 ,illustration3 ,,fig4 #d4 ,unfertilized egg surrounded by spermatozoa 7whose flagellum is omitted in the drawing74 ,,fig4 #e4 ,the same egg after a spermatozon has entered4 ,the fertilization membrane is separated from the egg by a clear space4 ,in #aije the writer found that membrane formation1 or rather the change of the surface of the egg underlying the membrane formation1 is the essential feature in the activation of the egg by a spermatozon4 ,he observed that when unfertilized eggs of the ,californian sea urchin ,strongylocentrotus purpuratus are put for from one and a half to three minutes into a mixture of #ej c4c4 of sea water#b4f c4c4 ,n_/#aj acetic or propionic or butyric or valerianic acid and are then put into normal sea water all or the majority of the eggs form membranes2 and that such eggs when the temperature is very low will segment once or repeatedly and may even--if the temperature is as low as #d;,c4 or less--develop into swimming blastul#hg2 but they will then disintegrate4 ,on the other hand1 if they are kept at room temperature they will develop only as far as the aster formation and nuclear division and then begin to disintegrate4 ,it should be mentioned that the time which elapses between artificial membrane formation and nuclear division is greater than that between the entrance of a spermatozon and nuclear division4 #hg ,the reader will find a description of the development of this egg in the next chapter4 ,it was obvious1 therefore1 that artificial membrane formation induced by butyric acid initiates the processes underlying development of the egg but that for some reason the egg is sickly and perishes rapidly4 ,when1 however1 such eggs were given a short treatment with hypertonic sea water or with lack of oxygen or with ,,kcn they developed into normal larv4 ,this new or improved method of artificial parthenogenesis is as follows3 ,the eggs are put for from two to four minutes into #ej c4c4 sea water containing a certain amount of ,n_/#aj butyric acid 7#b4f c4c4 in the case of ,s4 purpuratus in ,california and #b4j c4c4 in the case of ,arbacia in ,woods ,hole74 ,ten or fifteen minutes later the eggs are put into hypertonic sea water 7#ej c4c4 sea water#h c4c4 #b-a_/b m ,na,cl or ,ringer solution or cane sugar7 in which they remain1 at #ae ,c4 from thirty-five to sixty minutes in the case of purpuratus1 and from #ag-a_/b minutes to #bb-a_/b minutes at #bc in the case of ,arbacia at ,woods ,hole4 ,if the eggs are then transferred to normal sea water they will develop4 ,in making these experiments1 which have been repeated and confirmed by numerous investigators1 it should be remembered that this effect of the hypertonic solution has a high temperature coefficient 7about two for #aj ,c47 and that a slight overexposure to the hypertonic sea water injures the eggs so that development is abnormal4 ,by this method it is possible to imitate the activating effect of the living spermatozon upon the egg in every detail and eggs treated in this way will develop in large numbers into perfectly normal larv4 ,we shall see later that they can also be raised to the adult state4 #b4 ,the next task was to find out the nature of the action of the two agencies upon the development of the egg4 ,it soon became obvious that the membrane formation 7or the alteration underlying membrane formation7 was the more important of the two1 since in the eggs of starfish and annelids this was sufficient for the production of larv1 and that the second treatment had only the corrective effect1 of overcoming the sickly condition in which mere membrane formation had left the eggs4 ,it was1 therefore1 of great interest to ascertain what substances or agencies caused membrane formation in the egg1 since it now became clear that the spermatozon could only cause membrane formation by carrying one such substance into the egg4 ,these investigations led the writer to the result that all those substances and agencies which are known to cause cytolysis or hemolysis 7see ,chapter ,,iii7 will also induce membrane formation1 and that the essential feature in the causation of development is a cytolysis of the superficial or cortical layer of the egg4 ,as soon as this layer is destroyed the development of the egg can begin4 ,the substances and agencies which cause cytolysis and hence1 if their action is restricted to the surface of the egg1 will induce development are1 besides the fatty acids3 7#a7 saponin or solanin or bile salts2 7#b7 the solvents of lipoids1 benzol1 toluol1 amylene1 chloroform1 aldehyde1 ether1 alcohols1 etc42 7#c7 bases2 7#d7 hypertonic or hypotonic solutions2 7#e7 rise in temperature1 and 7#f7 certain salts1 e4 g41 ,ba,cl and ,sr,cl in the case of the egg of purpuratus1 and according to ,r4 ,lillie1 ,na,i or ,na,c,n,s in the egg of ,arbacia4 ,whenever we submit an unfertilized sea-urchin egg to any of these agencies and restrict the cytolysis to the superficial or cortical layer of the egg 7i4 e41 if we transfer the egg to normal sea water before the cytolytic agent has had time to diffuse into the main egg7 the egg will form a membrane and behave as if the membrane formation had been called forth by a fatty acid1 with this difference only1 that the various agencies are not all equally harmless for the egg4#hh #hh ,the reader is referred for details to the writer's book on the subject4 ,if the idea was correct that the change underlying membrane formation was essentially a cytolysis of the cortical layer of the egg1 it was to be expected 7from the data contained in ,chapter ,,iii7 that the blood serum or the cell extracts of foreign species would also cause membrane formation and thus induce the development of the unfertilized egg1 while serum of animals of the same species or genus would have no such effects4 ,this was found to be correct4 ,in #aijg the writer showed that the blood serum of a ,gephyrean worm1 ,dendrostoma1 was able to cause membrane formation in the egg of the sea urchin4 ,when added in a dilution of #a c4c4 of serum to #ejj or #ajjj c4c4 of sea water to eggs of purpuratus a certain number formed fertilization membranes4 ,it was found later that the serum and tissue extracts of a large number of animals1 especially of mammals 7rabbit1 pig1 ox1 etc471 had the same effect1 though it was necessary to use higher concentrations1 one-half sea water and one-half isotonic blood serum4 ,the eggs of every female sea urchin1 however1 did not give the reaction and not all the eggs even of sensitive females formed membranes4 ,the writer found1 however1 that it was possible to increase the susceptibility of the eggs against foreign blood serum by putting them into a #c_/h m solution of ,sr,cl for from five to ten minutes 7or possibly a little longer7 before exposing them to the foreign blood serum4 ,ba,cl acts similarly4 ,the fact that ,sr,cl alone can cause membrane formation in unfertilized eggs if they are left long enough in the solution suggests that the sensitizing effect of the substance consists in a modification of the cortical layer similar to that underlying membrane formation2 and that the subliminal effect of a short treatment with ,sr,cl and the subliminal effect of the foreign serum when combined suffice to bring about the membrane formation4 ,not only the watery extract of foreign cells but also that of foreign sperm1 induces membrane formation in the sea-urchin egg4 ,the watery extract of sperm of starfish is especially active1 but the degree of activity varies considerably with the species of starfish from which the sperm is taken4 ,the eggs of different species of sea urchins also show a different degree of susceptibility for the sperm of foreign species4 ,thus the eggs of ,strongylocentrotus purpuratus require a higher concentration of sperm extract than the eggs of ,s4 franciscanus4 ,for the latter the amount of foreign cell constituents which suffices to call forth membrane formation is so small that contact with almost any foreign living spermatozon produces this effect2 and as a rule no previous sensitizing action of ,sr,cl is required4 ,when we bring the unfertilized eggs of ,s4 franciscanus into contact with the living sperm of starfish or shark or even of fowl1 the eggs form a fertilization membrane without previous sensitization4 ,a specific substance from the foreign spermatozon causes membrane formation before the spermatozon has time to enter the egg4 ,the effect is the same as if artificial membrane formation had been called forth with butyric acid1 i4 e41 they begin to develop and then disintegrate unless they receive a second short treatment4 ,when1 however1 we treat the eggs with the watery extracts from the cells of their own or closely related species we find that these extracts are utterly inactive1 even if used in comparatively strong concentrations4 ,this agrees with the results given in ,chapter ,,iii4 ,these phenomena lead to a very paradoxical result2 namely that while in the case of foreign sperm we can cause membrane formation by both the living and the dead spermatozon1 only the living spermatozon of the same species can induce membrane formation4 ,this might find its explanation on the assumption that the active substance contained in the foreign sperm or serum is water-soluble and a protein1 while the activating or membrane-forming substance in the spermatozon is insoluble in water but soluble in the egg 7or in lipoids74 ,if this assumption is correct the two substances are essentially different4 ,robertson#hi has succeeded in extracting a substance from the sperm of the sea urchin which causes membrane formation of the sea-urchin egg after the latter has been sensitized by a treatment with ,sr,cl4 ,it seems to the writer that if the substance extracted by ,robertson were the real fertilizing agent contained in the spermatozon it should fertilize the egg without a previous sensitization of the egg with ,sr,cl being required4 #hi ,robertson1 ,t4 ,b41 ,arch4 f4 ,entwcklngsmech41 #aiab1 xxxv41 #fd4 #c4 ,the action of acids in the mechanism of artificial parthenogenesis provides some interesting physiological problems4 ,when unfertilized sea-urchin eggs are left in sea water containing any of the lower fatty acids up to capronic1 the eggs will form no membranes1 while in such sea water1 and they will show no outer signs of cytolysis 7swelling74 ,when1 however1 the eggs are left in sea water containing any of the fatty acids from heptylic upward the eggs will form membranes while in the acid sea water and soon afterward will cytolyze completely and swell enormously4 ,in solutions of the mineral acids no membranes are formed and none are formed as a rule when the eggs are transferred back to sea water4 ,when both a mineral and a lower fatty acid1 e4 g41 butyric1 are added to sea water the mineral acid acts as if it were not present1 i4 e41 the eggs form membranes when transferred back to sea water if the concentration of the butyric acid is high enough4 ,all these data are comprehensible if we assume that only that part of the acid causes membrane formation which is lipoid soluble1 while the water soluble part is not involved in the process of membrane formation2 and that the cytolysis or swelling of the whole egg can only take place in the higher fatty acids 7heptylic or above7 which are little soluble in water and very soluble in lipoids1 while the lower fatty acids1 whose water solubility is comparatively high1 can only bring about a cytolysis and swelling in the cortical layer but not in the rest of the egg4 ,this makes it appear as though the part undergoing an alteration in membrane formation was a lipoid2 and this would harmonize with the assumption that the specific membrane-inducing substance in the spermatozon is not soluble in water1 but soluble in fat4 #d4 ,these and other observations led the writer to the view that the essential process which causes development might be an alteration of the surface of the egg1 in all probability an alteration of the superficial layer probably of the nature of a superficial cytolysis4 ,the question remains3 ,what could be the physicochemical nature of this cytolysis8 ,the writer had suggested in former papers that in the cytolysis underlying membrane formation lipoids were dissolved1 and he supposed that the substance to be dissolved might be a calcium-lipoid compound which might form a continuous layer under the surface of the egg4#ij v4 ,knaffl1 working on the cytolysis of eggs in the writer's laboratory1 gave the following idea of the process3 ,protoplasm is rich in lipoids2 probably it is mainly an emulsion of these and proteins4 ,any physical or chemical stimulus which can liquefy the lipoids causes cytolysis of the egg4 ,the protein of the egg can really only swell or be dissolved if the condition of aggregation of the lipoid is altered by chemical or physical agencies4 ,the mechanism of cytolysis consists in the liquefaction of the lipoids and thereupon the lipoid-free protein swells or is dissolved by taking up water4444 ,hence this supports ,loeb's view that membrane formation is induced by the liquefaction of lipoids4#ia #ij ,loeb1 ,j41 ber den chemischen ,charakter des ,befruchtungsvorgangs1 etc41 ,leipzig1 #aijh4 #ia v4 ,knaffl1 ,e41 ,arch4 f4 d4 ges4 ,physiol41 #aijh1 cxxiii41 #bgi4 ,the writer suggested that the destruction of an emulsion in the cortical layer might possibly be the essential feature of the alteration leading to membrane formation and development4 ,it had been long observed that unfertilized starfish eggs may begin to develop apparently without any outside 8stimulus10 and ,a4 ,p4 ,mathews found that slight mechanical agitation of these eggs in sea water increased the number which developed4 ,it has been shown in numerous experiments by ,delage1 ,r4 ,s4 ,lillie1 and the writer1 that the substances causing development in the starfish egg are identical or closely related to those which bring about this effect in the egg of the sea urchin and in both cases the development is preceded by a membrane formation4 ,but how can membrane formation be produced by mere agitation8 ,it seems to me that this can be understood if we suppose that it depends upon the destruction of an emulsion in the cortical layer of the egg4 ,it is conceivable that in the egg of certain forms the stability of this emulsion is so small that mere shaking would be enough to destroy it and thus induce membrane formation and development4#ib #ib ,loeb1 ,j41 ,artificial ,parthenogenesis and ,fertilization1 p4 #bee4 ,the durability of emulsions varies1 and where an emulsion is very durable shaking has no effect1 while where it is at the critical point of separating into two continuous phases a slight shaking will bring about the separation1 and where the emulsion is still less durable we observe the phenomenon of a 8spontaneous0 parthenogenesis4 ,eggs like those of most sea urchins belong to the former1 eggs like those of some starfish and annelids belong to the second or third type4 ,it is impossible to state at present whether the fertilization membrane is preformed in the fertilized egg and merely lifted off from the egg or whether its formation is due to the hardening of a colloidal substance separated from the emulsion 7or excreted7 and hardened in touch with sea water4 ,but we can be sure of one thing1 namely1 that the liquid between egg and membrane contains some colloidal substance which determines the tension and spherical shape of the membrane4 ,the membrane is obviously permeable not only to water but also to dissolved crystalloids1 while it is impermeable to colloids4 ,when we add some colloidal solution 7e4 g41 white of egg1 blood serum1 or tannic acid7 to the sea water containing fertilized eggs of purpuratus1 the membrane collapses and lies close around the egg2 while if the eggs are put back into sea water or a sugar solution the membrane soon assumes its spherical shape4 ,this is intelligible on the assumption that in the process of membrane formation 7or in the destruction of the emulsion in the cortical layer7 a colloidal substance goes into solution which cannot diffuse into the sea water since the membrane is impermeable to the colloidal particles4 ,the membrane is1 however1 permeable to the constituents of sea water or to sugar4 ,consequently sea water will diffuse into the space between membrane and egg until the tension of the membrane equals the osmotic pressure of the colloid dissolved in the space between egg and the membrane4 ,if we add enough colloid to the outside solution so that its osmotic pressure is higher than that of the colloidal solution inside the membrane the latter will collapse4 ,it should also be stated that the unfertilized eggs of many marine animals are surrounded by a jelly 7chorion7 which is dissolved when the egg is fertilized4#ic ,the writer has shown that the same chemical substances which will induce membrane formation and artificial parthenogenesis will as a rule also cause a swelling and liquefaction of the chorion4 #ic ,it has been stated by several writers that the eggs of the sea urchin can no longer form the fertilization membrane when the jelly surrounding the egg is dissolved4 ,the writer has found that if the jelly surrounding the eggs of ,strongylocentrotus purpuratus is dissolved by acid the eggs still form a fertilization membrane upon the entrance of a spermatozon4 ,we have devoted so much space to the mechanism of membrane formation since it is likely to give a clearer insight into the physicochemical nature of physiological processes than the phenomena of muscular stimulation and contraction or nerve stimulation1 upon which the majority of physiologists base their conclusions concerning the mechanism of life phenomena4 ,before we come to the discussion of the second factor in the activation of the egg it should be stated more definitely that for the eggs of some forms the first factor1 the process underlying membrane formation1 suffices for the development of the egg into a larva and that no second factor is required in these cases4 ,this is true for the eggs of starfish and certain annelids4 ,thus in #aija ,loeb#id and ,neilson showed that a short treatment with ,h,cl and ,,hno sufficed to cause some eggs of ,asterias in ,woods ,hole to develop into larv without a second treatment being needed1 and ,delage#ie showed the same for ,,co2 and in #aije the writer found that the eggs of the ,californian starfish ,asterina can be induced to form a membrane by butyric acid treatment and that ten per cent4 of these eggs developed into normal larv4 ,quite recently ,r4 ,s4 ,lillie observed that the eggs of ,asterias at ,woods ,hole can be caused to form membranes and develop into larv by a treatment with butyric acid and that the time of exposure required to get a maximal number of larv varies approximately inversely with the concentration of the acid1 within a range of #j4jjje to #j4jjf ,n butyric acid4 ,if the exposure is too short membrane formation will occur without normal development4#if #id ,loeb1 ,j41 ,artificial ,parthenogenesis and ,fertilization1 #aiac1 p4 #bej and ff4 #ie ,delage1 ,y41 ,arch4 d4 ,zol4 expr4 et gn41 #aijb1 x41 #bac2 #aijd1 ii41 #bg2 #aije1 iii41 #ajd4 #if ,lillie1 ,r4 ,s41 ,jour4 ,biol4 ,chem41 #aiaf1 xxiv41 #bcc4 ,all this leads us to the conclusion that the main effect of the spermatozon in inducing the development of the egg consists in an alteration of the surface of the latter which is apparently of the nature of a cytolysis of the cortical layer4 ,anything that causes this alteration without endangering the rest of the egg may induce its development4 ,the spermatozon1 therefore1 causes the development of the egg by carrying a substance into the latter which effects an alteration of its surface layer4 #e4 ,we will now discuss the action of the second1 corrective factor1 in the inducement of development4 ,when we cause membrane formation in a sea-urchin egg by the proper treatment with butyric acid it will commence to develop and segment but will disintegrate rapidly if kept at room temperature and the more rapidly the higher the temperature4 ,if1 however1 the eggs are treated afterward for a certain length of time 7from thirty-five to sixty minutes at #ae ,c4 for purpuratus and #ag-a_/b to #bb-a_/b minutes for ,arbacia at #bc ,c47 in a solution which is isosmotic with #ej c4c4 sea water #h c4c4 #b-a_/b m ,na,cl1#ig they will develop into larv1 many of which may be normal4 ,any hypertonic solution of this osmotic pressure1 sea water1 sugar1 or a single salt1 will suffice provided the solution does not contain substances that are too destructive for living matter4 ,the hypertonic solution produces its corrective effect only if the egg contains free oxygen2 and in a slightly alkaline medium more rapidly than in a neutral medium4 ,the time of exposure in the hypertonic solution diminishes in certain limits with the concentration of ,,oh ions in the solution4 #ig ,it is necessary to call attention to the fact that sugar solutions of a high concentration 7e4 g41 m solutions7 have a much higher osmotic pressure than that which they should have theoretically 7,lord ,berkeley and ,hartley74 ,delage by ignoring this fact has misinterpreted his experiments with sugar solutions4 ,see ,lloyd1 ,d4 ,j41 ,arch4 f4 ,entwcklngsmech41 #aiad1 xxxviii41 #djb4 ,it is strange that in the eggs of purpuratus the corrective effect can also be brought about by exposing the eggs after the artificial membrane formation for about three hours to normal sea water free from oxygen2 or to sea water in which the oxidations have been retarded by the addition of ,,kcn4 ,this method is not so reliable as the treatment with hypertonic solution4 ,what does the hypertonic solution do to prevent the disintegration of the egg after the artificial membrane formation8 ,the writer suggested in #aije that the artificial membrane formation alone starts the development but leaves the eggs usually in a sickly condition and that the hypertonic solution or the lack of oxygen allows them to recuperate from such a condition4 ,the second factor is1 according to this view1 merely a corrective or curative factor4 ,the following observations will explain the reasons for such an assumption4 ,the writer found that if we keep the unfertilized eggs after artificial membrane formation in sea water deprived of oxygen the disintegration of the egg following artificial membrane formation is prevented for a day at least4 ,the same result can be obtained by adding ten drops of #a_/aj per cent4 ,,kcn to #ej c4c4 of sea water1 and certain narcotics1 e4 g41 chloral hydrate1 act in the same way4 ,wasteneys and the writer found that chloral hydrate 7and other narcotics7 in the concentration required do not suppress or even lower the oxidations in the egg to any considerable extent1#ih but they prevent the processes of cell division4 ,hence it seems that the egg disintegrates so rapidly after artificial membrane formation because it is killed by those processes leading to nuclear division or cell division which are induced by the artificial membrane formation4 ,if we suppress these phenomena of development 7for not too long a time7 we give the egg a chance to recover and if now the impulse to develop is still active we notice a perfectly normal development4 ,if the egg is kept too long without oxygen it suffers for other reasons and cannot develop2 the writer has shown that if eggs fertilized by sperm are kept for too long a time without oxygen they also will no longer be able to develop normally4 ,the short treatment with a hypertonic solution supplies the corrective factor required1 so that the egg can then undergo cell division at room temperature without disintegrating4 #ih ,loeb1 ,j41 and ,wasteneys1 ,h41 ,jour4 ,biol4 ,chem41 #aiac1 xiv41 #eag2 ,biochem4 ,ztschr41 #aiac1 lvi41 #bie4 ,the correctness of this interpretation1 which is in reality mainly a statement of observations1 is proved by the two following groups of facts4 ,the older observers had already noticed that the unfertilized eggs of the sea urchin when lying in sea water will die after a day or more1 and that occasionally such eggs show nuclear division or even the beginning of cell division shortly before disintegration sets in4 ,the writer has studied this phenomenon in the unfertilized eggs of purpuratus and found that only the eggs of certain females show this cell division before disintegration and that the cell division is preceded by an atypical form of membrane formation2 the eggs surrounding themselves by a fine gelatinous film comparable to that produced in the egg of ,arbacia by a treatment with butyric acid4 ,it is difficult to state what induces the alteration of the surface in the eggs that lie so long in sea water4 ,it may be due to the ,,co formed by the eggs--since we know that ,,co may induce membrane formation--or it may be due to the alkalinity of the sea water or to a substance originating from the jelly surrounding the eggs4 ,it was found that if such eggs are kept without oxygen their disintegration 7and cell division7 will be delayed considerably4 ,the presumable explanation for this is that the lack of oxygen prevents the internal changes underlying cell division and thus prevents the disintegration of the egg4 ,the direct proof that an egg in the process of cell division is more endangered by abnormal solutions than an egg at rest has been furnished by numerous observations of the writer4 ,he showed in #aijf that the fertilized egg of purpuratus dies rather rapidly in a pure m_/#b ,na,cl or any other abnormal isotonic solution1 while the unfertilized egg can live for days in such solutions4#ii ,in a series of papers1 beginning in #aije1 he showed that the fertilized egg will live longer in hypertonic1 hypotonic1 and otherwise abnormally constituted solutions when the cell divisions are suppressed by lack of oxygen or by the addition of ,,kcn or of chloral hydrate4#ajj ,it is thus obvious that coincident with the changes underlying nuclear division or cell division alterations occur in the sensitiveness of the egg to salt solutions of abnormal concentration or constitution1 e4 g41 ,na,cl,ca,cl isotonic with sea water1 hypertonic1 or hypotonic solutions4 #ii ,loeb1 ,j41 ,biochem4 ,ztschr41 #aijf1 ii41 #ha4 #ajj ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijf1 cxiii41 #dhg2 ,biochem4 ,ztschr41 #aiaj1 xxvi41 #bgi1 #bhi2 xxvii41 #cjd2 xxix41 #hj2 ,arch4 f4 ,entwcklngsmech41 #aiad1 xl41 #cbb4 ,we must1 therefore1 conclude that artificial membrane formation induces development but that it leaves the egg in a sickly condition in which the very processes leading to cell division bring about its destruction2 that if it is given time it can recover from this condition and that the treatment with the hypertonic solution also brings about this recovery rapidly and reliably4 ,herlant#aja suggested that the corrective effect of the hypertonic solution consisted in the proper development of the astrospheres required for cell division4 ,according to this author mere membrane formation does not lead to the formation of sufficiently large astrospheres and hence cell division may remain impossible4#ajb ,the writer has no a priori objection to this suggestion which agrees with earlier observations by ,morgan except that it is at present difficult to harmonize it with all the facts4 ,why should it be possible to replace the treatment with the hypertonic solution by a suspension of the oxidations in the egg for three hours while we know that lack of oxygen suppresses the formation of astrospheres in the fertilized eggs8 ,what becomes of the astrospheres if the treatment with the hypertonic solution precedes the membrane formation by a number of hours or a day 7which is possible as we shall see71 and why do they not induce cell division1 if ,herlant's idea is correct8 ,nevertheless the suggestion of ,herlant deserves to be taken into serious consideration4 #aja ,herlant1 ,m41 ,arch4 de ,biol41 #aiac1 xxviii41 #eje4 #ajb ,it is also important to remember that the formation of astrospheres after mere membrane formation occurs considerably more slowly than if the egg has also received a treatment with a hypertonic solution4 #f4 ,how can an alteration of the surface of the egg--e4 g41 a cytolytic or other destruction of the cortical layer--lead to a beginning of development8 ,the answer is possibly given in the relation of oxidation to development4 ,the writer found in #ahie that if oxygen is withdrawn from the fertilized sea-urchin egg it can not segment and this seems to be the case for eggs in general4#ajc ,in #aijf he found that the rapid disintegration of the eggs of the sea urchin which follows artificial membrane formation could be prevented when the eggs were deprived of oxygen or when the oxidations were suppressed in the eggs by ,,kcn4 ,this suggested a connection between the disintegration of the egg after artificial membrane formation and the increase in the rate of oxidations2 and he found further that the formation of acid is greater in the fertilized than in the unfertilized egg4 ,he1 therefore1 expressed the view in #aijf that the essential feature 7or possibly one of the essential features7 of the process of fertilization was the increase of the rate of oxidations in the egg and that this increase was caused by the membrane formation alone4#ajd ,these conclusions have been since amply confirmed by the measurements of ,o4 ,warburg as well as those of ,loeb and ,wasteneys1 both showing that the entrance of the spermatozon into the egg raises the rate of oxidations from #djj to #fjj per cent41 and that membrane formation alone brings about an increase of similar magnitude4 ,loeb and ,wasteneys found that the hypertonic solution does not increase the rate of oxidations in a fertilized egg4 ,it does do so1 however1 in an unfertilized egg without membrane formation1 but merely for the reason that in such an egg the hypertonic solution brings about the cytolytic change in the cortex of the egg underlying membrane formation4#aje ,according to ,warburg it is probable that the oxidations occur mainly if not exclusively at the surface of the egg since ,na,o,h1 which does not diffuse into the egg1 raises the rate of oxidations more than ,,nh,,oh which does diffuse into the egg4 ,and finally1 the same author showed that the oxidations in the sea-urchin egg are due to a catalytic process in which iron acts as a catalyzer4#ajf ,in view of all these facts and their harmony with the methods of artificial parthenogenesis the suggestion is justifiable that the alteration or cytolysis of the cortical layer of the egg is in some way connected with the increased rate of oxidations4 #ajc ,the writer found that the eggs of ,fundulus will segment a number of times even if all the oxygen has apparently been removed4 #ajd ,loeb1 ,j41 ,biochem4 ,ztschr41 #aijf1 ii41 #ahc4 #aje ,thus the treatment of an unfertilized egg without membrane with a hypertonic solution combines two effects1 first the general cytolytic alteration of the cortical layer of the membrane and the corrective effect of the hypertonic solution4 ,the former effect raises the rate of oxidations in the egg1 the latter does not4 #ajf ,warburg1 ,o41 ,sitzungsber4 d4 ,heidelberger ,akad4 d4 ,wissnsch41 ,b4 #aiad4 ,the question remains then3 ,how can membrane formation or the alteration of the cortical layer underlying membrane formation cause an increase in the rate of oxidations8 ,one possibility is that the iron 7or whatever the nature of the catalyzer may be7 exists in the cortex of the egg in a masked condition--or in a condition in which it is not able to act--while the alteration of the cortical layer makes the iron active4 ,it might be that either the iron or the oxidizable substrate is contained in the lipoid layer in the unfertilized condition of the egg and that the destruction or cytolysis of the cortical layer brings both the iron and the oxidizable substrate into the watery phase in which they can interact4 ,another possibility is that the act of fertilization increases the permeability of the egg4 ,this idea1 which seems attractive1 was first suggested and discussed by the writer in #aijf4ajg ,he had found that when fertilized and unfertilized eggs were put into abnormal salt solutions1 e4 g41 pure solutions of ,na,cl1 the fertilized eggs died more rapidly than the unfertilized eggs and he pointed out that these experiments suggested the possibility that fertilization increases the permeability of the egg for salts4 ,the reason for his hesitation to accept this interpretation was1 that the fertilized egg is also more easily injured by lack of oxygen than the unfertilized egg and in this case the greater sensitiveness of the fertilized egg was obviously due to its greater rate of metabolism4 ,later experiments by the writer showed that the fertilized egg can be made more resistant to abnormal salt solutions if its development is suppressed by lack of oxygen or by ,,kcn or by certain narcotics4 ,with our present knowledge it does not seem very probable that lack of oxygen diminishes the permeability of the egg1 but we know that it inhibits the developmental processes4 ,warburg has made it appear very probable that the fertilized egg is impermeable for ,na,o,h and if this is the case it should also be impermeable for ,na,cl4#ajh #ajg ,loeb1 ,j41 ,biochem4 ,ztschr41 #aijf1 ii41 #hg4 #ajh ,unless the egg is left so long in the pure ,na,cl solution that its permeability is increased4 ,the idea that fertilization and membrane formation cause an increase in the permeability of the egg was later accepted and elaborated by ,r4 ,lillie4 ,this author assumes that the unfertilized egg cannot develop because it contains too much ,,co but that the ,,co can escape from the egg as soon as its permeability is increased through the destruction of the cortical layer of the egg4#aji ,after the ,,co has escaped1 the excessive permeability must be restored to its normal value and this is the rle of the hypertonic treatment4 ,it is1 however1 difficult to harmonize the assumption of an impermeability of the unfertilized egg for ,,co with the fact that if the unfertilized sea-urchin egg is cut into two1 as is done in merogony1 no development takes place1 while such pieces will develop when a spermatozon enters4 ,the cortical layer is removed along the cut surface and there is no reason why the ,,co should not escape4 ,besides1 the experiments of ,godlewski and the writer prove that the cortical layer of the unfertilized sea-urchin egg is apparently very permeable for ,,co since the latter causes membrane formation if contained in the sea water in sufficiently high concentration4 #aji ,lillie1 ,r4 ,s41 ,jour4 ,morphol41 #aiaa1 xxii41 #fie2 ,am4 ,jour4 ,physiol41 #aiaa1 xxvii41 #bhi4 ,lillie assumes that the hypertonic treatment restores the permeability raised to excess by the butyric acid treatment1 but this assumption is not in harmony with the following facts4 ,the writer has shown that it is immaterial whether the eggs are treated first with the hypertonic solution and then with butyric acid or the reverse1 if only the eggs remain longer in the hypertonic solution when the hypertonic treatment precedes the butyric acid treatment4 ,it was stated in the beginning of this chapter that the development of the egg can be induced by hypertonic sea water1 and we know the reason since hypertonic sea water is a cytolytic agency4 ,the writer found that when we expose unfertilized eggs of purpuratus for from two to two and a half-hours to hypertonic sea water they will often not develop and only a few eggs will undergo the first cell divisions1 then going into a condition of rest4 ,when these eggs1 both the segmented and unsegmented1 were treated twenty-four or thirty-six hours later with butyric acid1 so that they formed a membrane1 they all developed into larv without further treatment4 ,it is impossible to apply ,lillie's theory to these facts1 for the simple reason that the treatment with hypertonic sea water was just long enough to induce development in some eggs and hence according to ,lillie's ideas must have increased the permeability of these eggs4 ,yet these same eggs were induced to develop normally when subsequently treated with butyric acid1 which according to ,lillie also acts by increasing the permeability4 ,nothing indicates that the treatment of the eggs with a hypertonic solution diminishes their permeability2 the reverse would be much more probable4 ,lillie's theory also fails to explain that mere treatment of the eggs with a hypertonic solution can bring about their development into larv4 ,this1 however1 is intelligible on the assumption that the hypertonic solution in this case has two different effects1 first a cytolysis of the cortical layer of the egg and second an entirely different effect1 possibly upon the interior of the egg1 which represents the second or corrective effect4 ,mc,clendon#aaj has shown that the electrical conductivity of the egg is increased after fertilization1 and ,j4 ,gray#aaa has found that this increase in conductivity is only transitory and disappears in fifteen minutes4 ,this might indicate that the egg becomes transitorily more permeable for salts after the entrance of the spermatozon or after membrane formation2 although an increase in conductivity might be caused by other changes than a mere increase in permeability of the egg4 ,the writer is of the opinion that it is necessary to meet all these and other difficulties before we can state that the alteration of the cortical layer1 which is the essential feature of development1 acts chiefly or exclusively by an increase in the permeability of the egg4#aab #aaj ,mc,clendon1 ,j4 ,f41 ,publications of the ,carnegie ,institution1 ,no4 #ahc1 #abe2 ,am4 ,jour4 ,physiol41 #aiaj1 xxvii41 #bdj4 #aaa ,gray1 ,j41 ,proc4 ,cambridge ,philosophical ,society1 #aiac1 xvii41 #a4 #aab ,r4 ,lillie has recently shown that in a hypotonic solution water diffuses more rapidly into a fertilized than into an unfertilized egg4 ,this is exactly what one should expect since the unfertilized egg is not only surrounded by the cortical layer but also by a thick layer of jelly both of which are lacking in the fertilized egg4 ,it is difficult to understand how this observation can throw any light on the mechanism of development1 since water diffuses rapidly enough into the unfertilized egg4 #g4 ,when the experiments on artificial parthenogenesis were first published they aroused a good deal of antagonism not only among reactionaries in general but also among a certain group of biologists4 ,o4 ,hertwig had defined fertilization as consisting in the fusion of two nuclei1 the egg nucleus and the sperm nucleus4 ,no such fusion of two nuclei takes place in artificial parthenogenesis since no spermatozon enters the egg1 and it became necessary1 therefore1 to abandon ,hertwig's definition as wrong4 ,the objection raised that the phenomena are limited to a few species soon became untenable since it has been possible to produce artificial parthenogenesis in the egg of plants 7,fucus1 according to ,overton7 as well as of animals1 from echinoderms up to the frog2 and it may possibly one day be accomplished also in warm-blooded animals4 ,a second objection was that the eggs caused to develop by the methods of artificial parthenogenesis could never reach the adult stage and that hence the phenomenon was merely pathological4 ,there was no basis for such a statement1 except that it is extremely difficult to raise marine invertebrates4 ,delage#aac was courageous enough to make an attempt to raise parthenogenetic larv of the sea urchin beyond the larval stage and he succeeded in one case in carrying the animal to the mature stage4 ,it proved to be a male4 #aac ,delage1 ,y41 ,compt4 rend4 ,acad4 ,sc41 #aiji1 cxlviii41 #dec4 ,better opportunities were offered when a method was discovered which induced the development of the unfertilized eggs of the frog4 ,in #aijg1 ,guyer made the surprising observation that if he injected lymph or blood into the unfertilized eggs of frogs he succeeded in starting development and he even obtained two free-swimming tadpoles4 8,apparently the white rather than the red corpuscles are the stimulating agents which bring about development1 because injections of lymph which contains only white corpuscles produce the same effects as injections of blood40 ,curiously enough1 ,guyer thought that probably the cells which he introduced and not the egg were developing4 ,in #aiaj1 ,bataillon showed that a mere puncture of the egg with a needle could induce development but he believes that for the full development the introduction of a fragment of a leucocyte is required4 ,bataillon has called attention to the analogy with the writer's results on lower forms1 the puncturing of the egg corresponding to the cytolysis of the surface layer of the egg and the introduction of a leucocyte as the analogue of the second or corrective factor4 ,the method of producing artificial parthenogenesis by puncturing the egg has thus far been successful only in the egg of the frog4 ,the writer has tried it in vain on the eggs of many other forms4 ,he has at present seven parthenogenetic frogs over a year old1 produced by merely puncturing the eggs with a fine needle 7,fig4 #f74 ,these frogs have reached over half the size of the adult frog4 ,they can in no way be distinguished from the frogs produced by fertilization with a spermatozon4 ,this makes the proof conclusive that the methods of artificial parthenogenesis can result in the production of normal organisms which can reach the adult stage4 ,bancroft and the writer tried to determine the sex of a parthenogenetic tadpole and of a frog just carried through metamorphosis4 ,since in early life the sex glands of both sexes in the frog contain eggs it is not quite easy to determine the sex1 except that in the male the eggs gradually disappear and from this and other criteria we came to the conclusion that both parthenogenetic specimens1 which were four months old1 were males4 ,the writer has recently examined the gonads of a ten months old parthenogenetic frog4 ,here no doubt concerning the sex was possible since the gonads were well-developed testicles containing a large number of spermatozoa of normal appearance1 and no eggs4#aad 7,figs4 #g and #h47 ,this would indicate that the frog belongs to those animals in which the male is heterozygous for sex4 #aad ,since this was written1 two more of the parthenogenetic frogs over a year old died4 ,both were males4 #h4 ,the fact that the egg of so high a form as the frog can be made to develop into a perfect and normal animal without a spermatozon--although normally the egg of this form does not develop unless a spermatozon enters--corroborates the idea expressed in previous chapters that the egg is the future embryo and animal2 and that the spermatozon1 aside from its activating effect1 only transmits ,mendelian characters to the egg4 ,the question arises3 ,is it possible to cause a spermatozon to develop into an embryo8 ,the idea has been expressed that the egg was only the nutritive medium on which the spermatozon developed into an embryo1 but this idea has been rendered untenable by the experiments on artificial parthenogenesis4 ,nevertheless the question whether or not the spermatozon can develop into an embryo on a suitable culture medium remains1 and it can only be decided by direct experiments4 ,it was shown by ,boveri1 ,morgan1 ,delage1 ,godlewski1 and others1 that if a spermatozon enters an enucleated egg or piece of egg it can develop into an embryo1 but since the cytoplasm of the egg is the future embryo this experiment proves only that the egg nucleus may be replaced by the sperm nucleus2 and also that the sperm nucleus carries into the egg1 the substances which induce development4 ,incidentally these experiments on merogony also prove that the mere mechanical tearing of the cortical layer1--which must happen in the separation of the unfertilized egg into parts with and without a nucleus1--by dissection or by shaking1 is not sufficient to start development in the sea-urchin egg4 ,j4 de ,meyer put the spermatozoa of sea urchins into sea water containing an extract of the eggs of the same species but found only that the spermatozoa swell in such a solution4 ,loeb and ,bancroft made extensive experiments in cultivating spermatozoa of fowl in vitro on suitable culture media4 ,in yolk and white of egg the head of the spermatozon underwent transformation into a nucleus1 but no mitosis or aster formation was observed4#aae ,these experiments should be continued4 #aae ,loeb1 ,j41 ,artificial ,parthenogenesis and ,fertilization1 ,chicago1 #aiac4 ,,chapter ,,vi ,,determinism ,,in ,,the ,,formation ,,of ,,an ,,organism ,,from ,,an ,,egg #a4 ,the writer in a former book 7,dynamics of ,living ,matter1 #aijf1 p4 #a71 defined living organisms as chemical machines consisting chiefly of colloidal material and possessing the peculiarity of preserving and reproducing themselves4 ,some authors like ,driesch1 and v4 ,uexkll seem to find it impossible to account for the development of such machines from an undifferentiated egg on a purely physicochemical basis4 ,a study of ,driesch's very interesting and important book#aaf shows that he assumes the eggs of certain animals1 e4 g41 the sea urchin1 to consist of homogeneous material2 and he concludes that nature has solved1 in the formation of highly differentiated organisms from such undifferentiated material1 a problem which does not seem capable of a solution by physicochemical agencies alone4 ,but the supposition of a structureless egg is wrong1 since ,boveri has demonstrated the existence of a very simple but definite structure in the unfertilized egg of the sea urchin2 and a similar simple structure has been demonstrated by other authors1 especially ,conklin1 in the eggs of other forms4 #aaf ,driesch1 ,h41 ,science and ,philosophy of the ,organism4 ,london1 #aijh and #aiji4 ,in this chapter we shall attempt the task among others of showing how1 on the basis of the simple physicochemical structure of the unfertilized egg1 the main organ of self-preservation of the organism1 the intestine1 is formed through the mere process of cell division and growth4 ,cell division is the most general of the specific functions of living matter and it is the basis underlying the differentiation of the comparatively simple structure of the egg into a more complex organism4 ,if cell division and growth were equal in all parts of the egg no differentiation would be possible1 but the different regions of the unfertilized egg contain different constituents and these1 probably on account of their chemical difference1 do not all begin to grow or divide simultaneously and equally4 ,boveri#aag found that in the unfertilized egg of the sea urchin ,strongylocentrotus lividus at ,naples a definite structure is indicated by the fact that the yellowish-red pigment is not equally distributed over the whole surface of the egg but is arranged in a wide ring from the equator almost to one of the poles4 ,thus three zones can be recognized in the egg 7,fig4 #i71 a small clear cap ,a at one pole1 a pigmented ring ,b1 and the rest again unpigmented ,c4 ,observation has shown that each one of these regions gives rise to a definite constituent of the egg3 ,a furnishes the mesenchyme from which the skeleton and the connective tissue originate2 ,b is the material for the formation of the intestine1 and ,c gives rise to the ectoderm4 #aag ,boveri1 ,th41 ,verhandl4 d4 physik4-med4 ,gesellsch41 ,wrzburg1 #aija1 xxxiv41 #ade4 ,illustration3 ,,fig4 #i ,the pigment is only at the surface of the egg1 and its collection at ,b indicates only that the material in ,b differs physicochemically from ,a and ,c4 ,the real determiners of the three different groups of organs are three different groups of substances whose distribution is approximately but probably not wholly identical with the regions indicated by distribution of pigment4 ,the intestine-forming material is probably not entirely lacking in ,c but is contained here in a lower concentration and probably the more so the greater the distance from ,b2 and the same may probably be said for the substances determining mesenchyme and ectoderm formation4 ,hence the unfertilized egg contains already a rough preformation of the embryo inasmuch as the main axis of the embryo and the arrangement of its first organs are determined4 ,illustration3 ,,fig4 #aj ,illustration3 ,,fig4 #aa ,after the egg is fertilized the cell divisions begin4 ,the first division is as a rule at right angles to the stratification of the egg1 each of the two cells contains one-half of the pigment ring 7and of each of ,a and ,c7 7,fig4 #aj71 and after the next division each contains one-fourth of the pigmented part4 ,each of the four cells is a diminutive whole egg since each contains the three layers in the normal arrangement 7,fig4 #aa74 ,the next divisions bring about an unequal division of the material4 ,four cells will be formed of ectoderm material ,c and only little intestine material ,b1 the other four cells containing ,b and ,a4 ,these latter form at the next division four very small colourless cells1 the so-called micromeres1 ,a 7,fig4 #ab71 from which the mesenchyme1 skeleton1 and connective tissue are formed1 four larger cells1 ,b1 from which the intestine is formed1 and eight cells1 ,c1 from which the ectoderm will arise4 ,the separation of the three groups of substances is probably not as complete as our purely diagrammatic drawing 7,fig4 #ab7 indicates4 ,illustration3 ,,fig4 #ab ,the cell division proceeds and the cells become smaller and smaller and all gather at the surface of the egg1 thus forming a hollow sphere4 ,it is not known what brings about this gathering of the cells at the surface1 whether it is protoplasmic creeping or streaming or whether the cells are held by a jelly-like layer which covers the surface of the egg 7hyaline membrane7 7,fig4 #ac74 ,then the cilia are formed at the external surface of these cells and the egg begins to swim2 we say it has reached the first larval1 the so-called blastula stage4 ,this happens according to ,driesch after the tenth series of cell divisions1 when the number of cells is theoretically #ajbd1 in reality not quite so many 7between #hjj and #ijj74 ,the next step consists in the cells derived from the material ,a 7mesenchyme and micromeres7 gliding into the hollow sphere1 where they form a ring1 the physicochemical process responsible for this gliding being yet unknown4 ,at the opening of this ring an active growing of the cells of the entoderm into the hollow sphere takes place and the hollow cylinder formed by this growth is the intestine 7,fig4 #ad74 ,why the cells grow into the hollow sphere and not into the opposite direction is unknown4 ,the next step is the formation of a skeleton by the formation of crystals consisting of the ,ca,c,o by the mesenchyme cells surrounding the intestine4 ,for the establishment of the principle in which we are interested the description of morphogenesis need not be carried farther4 ,illustration3 ,,fig4 #ac ,illustration3 ,,fig4 #ad ,this principle which is under discussion here is the development of a purposeful arrangement of organs out of the egg4 ,if we assume that the egg consists of homogeneous material we are indeed confronted with a riddle4 ,since the facts contradict such an assumption but show1 as ,boveri has pointed out1 a prearrangement which allows us to indicate in the unfertilized egg already the exact spot where the intestine will grow into the blastula cavity1 we are on solid physicochemical ground1 although many questions of detail cannot yet be answered4 ,such a preformation as ,boveri has demonstrated is only conceivable if the material of the egg has not too high a degree of fluidity2 we may consider it as consisting essentially of a semi-solid gel which is not homogeneous throughout the egg but divided into three strata4 #b4 ,lyon#aah tried to ascertain whether by centrifuging the sea-urchin egg it was possible to modify its structure and thereby affect the later embryo4 ,he and subsequent experimenters found that it only is possible to change the position of the nucleus and the distribution of the pigment in the egg4 ,it follows from this that the nucleus and the pigment are suspended in rather fluid material1 the former in the centre1 the pigment at or near the surface4 ,the position of the nucleus determines the first plane of segmentation1 since the nuclear division precedes the division of the cytoplasm of the egg and the plane of nuclear division becomes also the plane of the division of the whole egg--a point which need not be discussed here4 ,it was found1 however1 by ,lyon and the subsequent investigators that the place where the micromeres are formed and where the intestine of the embryo later originates is little influenced by the centrifuging of the egg4 ,the localization of this spot must therefore be determined by a structure sufficiently solid not to be shifted by the centrifugal force4 ,the intestinal stratum in the egg contains the forerunners of the tissues which secrete hydrolyzing enzymes1 e4 g41 trypsin into the digestive tract4 #aah ,lyon1 ,e4 ,p41 ,arch4 f4 ,entwcklngsmech41 #aijg1 xxiii41 #aea2 ,morgan1 ,t4 ,h41 and ,spooner1 ,g4 ,b41 ibid41 #aiji1 xxviii41 #ajd2 ,morgan1 ,jour4 ,exper4 ,zol41 #aiaj1 ix41 #eid2 ,conklin1 ,e4 ,g41 ibid41 #aiaj1 ix41 #dag2 ,lillie1 ,f4 ,r41 ,biol4 ,bull41 #aiji1 xvi41 #ed4 ,when the surrounding solution is altered in constitution or when the temperature is too high1 the intestine instead of growing into the hollow sphere grows outside1 we get an evagination instead of an invagination of the intestine4 ,such larv may live for a few days but they cannot grow into a living organism4 ,the forces which make the intestine grow into the hollow sphere are unknown2 it may possibly be only the difference between the tension on the external and internal surfaces of the hollow sphere2 under normal conditions1 the resistance on the inner surface being smaller1 the intestine grows into the hollow sphere4 ,the intestine is one of the organs required for the self-preservation of a more complicated organism1 in fact a higher organism without a digestive tract is not capable of living for any length of time4 ,in the gastrula--i4 e41 the blastula with an intestine--we have an organism which is durable1 but the processes leading up to the formation of the intestine are so simple that it is difficult to understand why the assumption of a 8supergene0 should be required in this case4 #c4 ,driesch#aai was the first to show that if we isolate one of the first two cells of a dividing egg each develops into a whole embryo of half size4 ,this is perfectly intelligible1 since each of the two cells contains all the three layers in the normal arrangement 7,fig4 #aj74 ,the cells divide and the cells having the tendency to creep to the surface of the mass arrange themselves in a hollow sphere1 the blastula4 ,since micromeres and intestine material are present and in their normal position an intestine will grow into the blastula and a whole organism will result4 ,all of this is as necessary as is the formation of one embryo from the whole egg material4 ,yet the two half-embryos betray their origin from two cleavage cells of the same egg1 in that the two gastrul formed are often if not always symmetrical to each other 7,fig4 #ae71 as the writer had a chance to observe in the egg of ,strongylocentrotus purpuratus#abj in the following experiment4 ,the eggs of the sea urchin ,strongylocentrotus purpuratus are put soon after fertilization into solutions which differ from sea water in two points2 namely that they are neutral or very faintly acid 7through the ,,co absorbed from the air7 instead of being faintly alkaline1 and second1 that one of the following three constituents of the sea water is lacking2 namely3 ,k1 ,na1 or ,ca4 ,when the eggs are allowed to segment in such a solution the first two cleavage cells are as a rule in a large percentage of cases--often as many as ninety per cent4--separated from each other1 and when the eggs are put into normal sea water 7about twenty minutes after the cell division7 each cell develops into a normal embryo4 ,in a number of cases the embryos remained inside the egg membrane and did not move until after the invagination of the intestine was far advanced2 in such cases it was found quite often that the invagination began at the plane of cleavage at symmetrical points of the two embryos1 and the growth of the intestine was symmetrical in both embryos4 #aai ,driesch1 ,h41 ,ztschr4 f4 wissnsch4 ,zol41 #ahia1 liii41 #afj4 #abj ,loeb1 ,j41 ,arch4 f4 ,entwcklngsmech41 #aiji1 xxvii41 #aai4 ,illustration3 ,,fig4 #ae ,this symmetry is probably due to the following fact3 the first cleavage plane goes through that spot where the intestine grows into the blastula cavity4 ,if the micromere material does not change its position after the two cleavage cells are separated and the new blastul do not become completely spherical the symmetry which we observed is bound to occur4 ,the occurrence is a confirmation of ,boveri's observation4 ,it is natural that ,driesch also found that each cell in the four-cell stage should give rise to a full embryo1 since each of these cells is in reality a diminutive egg containing the three strata in the right arrangement4 ,when1 however1 the cells of the eight- or sixteen-cell stage were isolated ,driesch's results were different4 ,in this case the isolated cells from the ectoderm material did no longer all form a gastrula2 when such a cell still formed a gastrula it was probably due to the fact that it contained some entoderm material2 while the cells taken from the entoderm region all formed embryos and therefore contained ectoderm material4#aba ,the isolated ectoderm cells of a blastula could no longer form an intestine2 they were lacking the entoderm material4 ,it looks as if a gradual migration of all the entoderm material from the ectoderm into the entoderm took place during the blastula formation4 #aba ,driesch1 ,h41 ,arch4 f4 ,entwcklngsmech41 #aijj1 x41 #cfa4 ,when the contents of the egg are displaced by pressure the result will be determined by the location of the main mass of the intestine-forming material2 where the main mass of this body is located the invagination of the intestine will take place4 ,in his earlier work ,driesch assumed from pressure experiments that the egg had a great power of 8regulation40 ,in a later paper#abb he expressed to a large extent his agreement with ,boveri who denied this power of 8regulation0 and showed that the existence of the structure of the egg--i4 e41 a division into three strata1 one forming the ectoderm1 the second the entoderm1 and the third the mesoderm--was sufficient to explain the various phenomena of apparent 8regulation40 ,driesch's idea of a regulation in this case has often been used to insist upon the non-explicability of the phenomena of development from a purely physicochemical viewpoint4 ,it is1 therefore1 only fair to point out that ,boveri#abc has furnished the facts for a simpler explanation1 which seems to have escaped the notice of antimechanists4#abd #abb ,driesch1 ,h41 ,arch4 f4 ,entswcklngsmech41 #aijb1 xiv41 #ejj4 #abc ,boveri1 ,th41 ,verhandl4 d4 physik4 med4 ,gesellsch41 ,wrzburg1 ,n4,f41 #aija1 xxxiv41 #ade4 #abd v4 ,uexkll makes in his last book 7,bausteine zu einer biologischen ,weltanschauung1 ,mnchen1 #aiac1 p4 #bd7 the following statement3 8,driesch succeeded in showing that the germ cell has no trace of a machine-like structure but consists entirely of equivalent parts40 ,this is not correct4 ,the objection may be raised that in accepting ,boveri's facts and interpretation we pushed the miracle only one step farther and that we now have to explain the origin of the structure in the unfertilized egg4 ,this ,boveri has done by showing that the egg grows from the wall of the ovary and that that part of the egg which is connected with the wall of the ovary gives rise to the ectoderm layer1 while the opposite part gives rise to the mesenchyme and the intestine4 ,this shows a connection between the orientation of the egg in the wall of the ovary and its stratification4 ,while this does not solve the problem of stratification in the egg it gives the clue to its solution4 ,the ultimate origin of stratification probably goes back to the fact of the presence of watery and water-immiscible substances1 such as fats4 ,the experiments by ,beutner and the writer have shown that the electromotive forces which are observed in living tissues originate at the boundaries between a watery and a water-immiscible phase1 like oleic acid or lecithin4#abe ,in his earlier writings#abf the writer had thought that the colloids had special significance and this idea seems to prevail today2 but the actual observations have shown that the phase boundary fat-water is of greater importance4 ,needless to say the fats if not present in the cell from the beginning can be formed in the metabolism4 #abe ,loeb1 ,j41 and ,beutner1 ,r41 ,biochem4 ,ztschr41 #aiab1 xli41 #a2 xliv41 #cjc2 #aiac1 li41 #bhh2 li41 #cjj2 #aiad1 lix41 #aie4 #abf ,loeb1 ,j41 ,the ,dynamics of ,living ,matter4 ,new ,york1 #aijf4 ,introductory ,remarks4 #d4 ,all the 8regulation0 in the egg is of a purely physicochemical character2 it consists essentially of a flow of material4 ,if this idea is correct1 the apparent power of 8regulation0 of the blastomeres should differ according to the degree of fluidity and the possibility of different layers separating1 and this assumption is apparently supported by facts4 ,the first plane of segmentation of the egg is usually the plane of symmetry of the later organism and where the degree of fluidity is less than in the sea-urchin egg1 a separation of the two first blastomeres should easily result in the formation of two half-embryos instead of two whole embryos4 ,this is the case for the frog's egg as ,roux showed in a classical experiment4 ,roux destroyed one of the two first cleavage cells of a frog's egg with a hot needle and found that as a rule the surviving cell developed into only a half-embryo4#abg ,the frog's egg consists of two substances1 a lighter one which is on top and a heavier one below4 ,although viscous1 the two substances are not too viscous to prevent a flow if the egg is turned upside down4 ,o4 ,schultze found that if a normal egg is turned upside down in the two-cell stage and held in that position1 two full embryos arise1 one from each of the two blastomeres4 ,through the flow of the lighter liquid in the egg upwards the two halves of the protoplasm on top become separated and develop independently into two whole embryos instead of into two half-embryos4 ,in ,roux's experiment this flow of protoplasm was avoided4 ,morgan showed that if ,roux's experiment is repeated with the modification that the egg is put upside down after the destruction of the one cell1 the intact cell will give rise not to a half but to a whole embryo4#abh ,these experiments prove that each of the first two cleavage cells of the frog's egg represents one-half of the embryo and that a whole embryo can develop from each half only when a redistribution of material takes place1 which in the egg of the frog can be brought about by gravitation since the egg consists of a lighter and a heavier mass4 #abg ,roux1 ,w41 ,virchow's ,archiv1 #ahhh1 cxiv41 #aac4 #abh ,morgan1 ,t4 ,h41 ,embryology of the ,frog4 ,new ,york4 ,when1 therefore1 in the egg of the sea urchin each of the first two blastomeres naturally gives rise to a whole embryo it is due to a greater degree of fluidity of the protoplasm and not to a lack of preformation of the embryo in the cytoplasm4 ,this idea is confirmed by the observations on the egg of ,ctenophores whose cytoplasm seems to be more solid than that of most other eggs4 ,chun found that the isolated blastomere of the first cell division produced a half-larva1 possessing only four instead of the eight locomotor plates of the normal animal4 ,it seems that in the egg of molluscs1 also1 the simple symmetry relations of the body are already preformed4 ,it is well known that there are shells of snails which turn to the right while others turn in the opposite direction4 ,the shells of ,lymnus turn to the right1 those of ,planorbis to the left4 ,it was observed by ,crampton#abi1 ,kofoid1 and ,conklin that the eggs of right-wound snails do not segment in a symmetrical1 but in a spiral1 order1 and that in left-handed snails the direction of the spiral segmentation is the reverse of that of the segmentation in the right-handed snails4 ,conklin was able to show that the asymmetrical spiral structure is already preformed in the egg before cleavage4 ,the asymmetry of the body in snails is therefore already preformed in the egg4#acj #abi ,crampton1 ,h4 ,e41 ,new ,york ,academy of ,sciences1 #ahid2 ,kofoid1 ,c4 ,a41 ,proc4 ,am4 ,acad4 ,arts and ,sciences1 #ahid1 xxix4 #acj ,conklin1 ,e4 ,g41 ,anat4 ,anzeig41 #aijc1 xxiii41 #egg2 ,heredity and ,environment in the ,development of ,man4 ,princeton1 #aiae1 p4 #aga4 ,e4 ,b4 ,wilson#aca has found a marked differentiation in the eggs of some annelids and molluscs4 ,he isolated the first two blastomeres of the egg of ,lanice1 an ,annelid4 ,these two blastomeres are somewhat different in size2 from the larger one of the first two blastomeres1 the segmented trunk of the worm originates4 ,wilson found that when either cell of the two-cell stage is destroyed1 the remaining cell segments as if it still formed a part of an entire embryo4#acb ,the later development of the two cells differs in an essential respect1 and in accordance with what we should expect from a study of the normal development4 ,the posterior cell develops into a segmented larva with a prototroch1 an asymmetrical pre-trochal or head region1 and a nearly typical metameric seta-bearing trunk region1 the active movements of which show that the muscles are normally developed4 ,the pre-trochal or head region bears an apical organ1 but is more or less asymmetrical1 and1 in every case observed1 but a single eye was present1 whereas the normal larva has two symmetrically placed eyes4 ,the development of the anterior cell contrasts sharply with that of the posterior4 ,this embryo likewise produces a prototroch and a pre-trochal region1 with an apical organ1 but produces no post-trochal region1 develops no trunk or set1 and does not become metameric4 ,except for the presence of an apical organ1 these anterior embryos are similar in their general features to the corresponding ones obtained in ,dentalium4 ,none of the individuals observed developed a definite eye1 though one of them bore a somewhat vague pigment spot4 ,this result shows that from the beginning of development the material for the trunk region is mainly localized in the posterior cell2 and1 furthermore1 that this material is essential for the development of the metameric structure4 ,the development of this animal is1 therefore1 to this extent1 at least1 a mosaic work from the first cleavage onward--a result that is exactly parallel to that which ,i earlier reached in ,dentalium1 where ,i was able to show that the posterior cell contains the material for the mesoblast1 the foot1 and the shell2 while the anterior cell lacks this material4 ,i did not succeed in determining whether1 as in ,dentalium1 this early localization in ,lanice pre-exists in the unsegmented egg4 ,the fact that the larva from the posterior cell develops but a single eye1 suggests the possibility that each of the first two cells may be already specified for the formation of one eye2 but this interpretation remains doubtful from the fact that the larva from the anterior cell did not1 in the five or six cases observed1 produce any eye4 #aca ,wilson1 ,e4 ,b41 ,science1 #aijd1 xx41 #gdh2 ,jour4 ,exper4 ,zol41 #aijd1 i41 #a1 #aig4 #acb ,the reader will notice the absence of 8regulation40 ,conklin has established the existence of a definite structure in the unfertilized eggs of ,ascidians1 ,amphioxus1 and many molluscs4 ,in all cases the results of the isolation of the first blastomeres seem to agree with the demonstrable structure of the unfertilized egg4 #e4 ,these examples may suffice to show that the egg has from the beginning a simple structure1 and we will now point out by which means further differentiation may come about4 ,sachs suggested that all differentiation and the formation of every organ presupposes the previous existence of specific substances responsible for the formation4 ,these substances which are now called internal secretions or hormones develop gradually during embryonic development4 ,what exists first is a jelly-like block of protoplasmic material with a varying degree of viscosity and with just enough differentiation to indicate head and tail end1 a right and left1 and a dorsal and ventral side of the future embryo4 ,aside from such simple differences phenomena of protoplasmic streaming contribute to the further differentiation4 ,such streaming begins1 according to ,conklin1#acc in the egg just before fertilization when the surface layer of the egg protoplasm streams to the point of entrance of the sperm1 and these movements may lead to the segregation of different kinds of plasma in different parts of the egg and to the unequal distribution of these substances in different regions of the egg4 #acc ,conklin1 ,e4 ,g41 ,heredity and ,environment in the ,development of ,man4 ,princeton ,university ,press1 #aiae4 ,the reader is referred to this book for the literature and main facts on the structure of the egg2 it should also be stated that ,conklin's book is one of the best introductions to modern biology in the ,english literature4 ,one of the most striking cases of this is found in the ,ascidian ,styela in which there are four or five different kinds of substances in the egg which differ in colour1 so that their distribution to different regions of the egg and to different cleavage cells may be easily followed and even photographed while in the living condition4 ,the peripheral layer of protoplasm is yellow and when it gathers at the lower pole of the egg where the sperm enters it forms a yellow cap4 ,this yellow substance then moves following the sperm nucleus1 up to the equator of the egg on the posterior side and there forms a yellow crescent extending around the posterior side of the egg just below the equator4 ,on the anterior side of the egg a grey crescent is formed in a somewhat similar manner and at the lower pole between these two crescents is a slate-blue substance1 while at the upper pole is an area of colourless protoplasm4 ,the yellow crescent goes into cleavage cells which become muscle and mesoderm1 the grey crescent into cells which become nervous system and notochord1 the slate-blue substance into endoderm cells1 and the colourless substance into ectoderm cells4 ,thus within a few minutes after the fertilization of the egg and before or immediately after the first cleavage1 the anterior and posterior1 dorsal and ventral1 right and left poles are clearly distinguishable1 and the substances which will give rise to ectoderm1 endoderm1 mesoderm1 muscles1 notochord1 and nervous system are plainly visible in their characteristic positions4#acd #acd ,conklin1 ,e4 ,g41 loc4 cit41 p4 #aag4 ,we may finally allude briefly to the fact that when once a number of tissues are differentiated each one may influence the other by calling forth tropistic reactions4 ,thus the writer showed that in the yolk sac of the fish ,fundulus the pigment cells lie at first without any definite order but that they gradually are compelled to creep entirely on the blood-vessels and form a sheath around them with the result that the yolk sac assumes a tiger-like marking4#ace ,driesch#acf has pointed out that the mesenchyme cells are directed in their migration2 and it seems that the direction of the growth of the axis cylinder is determined by the tissues into which it grows4 ,the idea of tropistic reactions in the formation of organs has been discussed by ,herbst4#acg #ace ,loeb1 ,j41 ,jour4 ,morphol41 #ahic1 xiii41 #afa2 ,the ,mechanistic ,conception of ,life4 ,chicago1 #aiab1 p4 #ajf4 #acf ,driesch1 ,h41 ,science and ,philosophy of the ,organism1 i41 p4 #ajd4 #acg ,herbst1 ,c41 ,formative ,reize in der tierischen ,ontogenese4 ,leipzig1 #aija4 #f4 ,as a consequence of further changes definite anlagen or buds originate later in the embryo which are destined to give rise to definite organs4 ,thus in the tadpole early mesenchyme cells are formed which are the anlagen for the four legs1 which will grow out under the proper conditions4 ,these anlagen are specific inasmuch as from the anlage of a foreleg only a foreleg1 and from the anlage for a hindleg only a hindleg1 will develop4 ,braus#ach has proved this by transplanting the anlage of a foreleg to different parts of the body4 ,no matter into which part of the body they are transplanted the mesenchyme cells for the foreleg will give rise to a foreleg only2 even if they are transplanted into the spot from which the hindlegs grow out under natural conditions4 ,there is therefore nothing to indicate 8regulation40 #ach ,braus1 ,h41 ,mnchener ,med4 ,wochnschr41 #aijc1 #a 7,,ii471 ,no4 #dg1 p4 #bjgf4 ,the same is true for the formation of the eye and probably in general4 ,we have to consider the formation of the various organs of the body as being due to the development of specific cells in definite locations in the organisms which will grow out into definite organs no matter into which part of the organism they are transplanted4 ,it is at present unknown what determines the formation of these specific anlagen4 ,they may lie dormant for a long time and then begin to grow at definite periods of development4 ,we shall see later that we know more about the conditions which cause them to grow4 #g4 ,the fact that the egg1 and probably every cell1 has a definite structure should determine the limits of the divisibility of living matter4 ,in most cases the complete destruction of a cell means the cessation of life phenomena4 ,a brain or kidney which has been ground to a pulp is no longer able to perform its functions2 yet we know that such pulps can still perform some of the characteristic chemical processes of the organ2 e4 g41 the alcoholic fermentation characteristic of yeast can be caused by the press juice from yeast2 or characteristic oxidations can be induced by the ground pulp of organs4 ,the question arises as to how far the divisibility of living matter can be carried without interfering with the total of its functions4 ,are the smallest particles of living matter which still exhibit all its functions of the order of magnitude of molecules and atoms1 or are they of a different order8 ,the first step toward obtaining an answer to this question was taken by ,moritz ,nussbaum1#aci who found that if an infusorian be divided into two pieces1 one with and one without a nucleus1 only the piece with a nucleus will continue to live and perform all the functions of self-preservation and development which are characteristic of living organisms4 ,this shows that at least two different structural elements1 nucleus and cytoplasm1 are needed for life4 ,we can understand to a certain extent from this why an organ after being reduced to a pulp1 in which the differentiation into nucleus and protoplasm is definitely and permanently lost1 is unable to accomplish all its functions4#adj #aci ,nussbaum1 ,m41 ,arch4 f4 mikroscop4 ,anat41 #ahhf1 xxvi41 #dhe4 #adj ,it must not be overlooked that in bacteria and the blue alg no distinct differentiation into nucleus and protoplasm can be shown4 ,to these organisms1 therefore1 the experiments of ,nussbaum cannot be applied4 ,the observations of ,nussbaum and those who repeated his experiments showed that although two different structures are required1 not the whole mass of an infusorian is needed to maintain its life4 ,the question then arose3 ,how small a fraction of the original cell is required to permit the full maintenance of life8 ,the writer tried to decide this question in the egg of the sea urchin4 ,he had found a simple method by which the eggs of the sea urchin 7,arbacia7 can easily be divided into smaller fragments immediately after fertilization4 ,when the egg is brought from five to ten minutes after fertilization 7long before the first segmentation occurs7 into sea water which has been diluted by the addition of equal parts of distilled water1 the egg takes up water1 swells1 and causes the membrane to burst4 ,part of the protoplasm then flows out1 in one egg more1 in another less4 ,if these eggs are afterward brought back into normal sea water those fragments which contain a nucleus begin to divide and develop4#ada ,it was found that the degree of development which such a fragment reaches is a function of its mass2 the smaller the piece1 the sooner as a rule its development ceases4 ,the smallest fragment which is capable of reaching the pluteus stage possesses the mass of about one-eighth of the whole egg4 ,boveri has since stated that it was about one twenty-seventh of the whole mass4 ,inasmuch as only the linear dimensions are directly measurable1 a slight difference in measurement will cause a great discrepancy in the calculation of the mass4 ,driesch's results disagree with the statement of ,boveri and support the observation of the writer4 #ada ,loeb1 ,j41 ,arch4 d4 f4 ges4 ,physiol41 #ahic1 lv41 #ebe4 ,if we raise the question why such a limit exists in regard to the divisibility of living matter1 it seems probable that only those fragments of an egg are capable of development into a pluteus which contain a sufficient amount of material of each of the three layers4 ,if this be correct1 it would certainly not suffice to mix the chemical constituents of the egg in order to produce a normal embryo2 this would require besides the proper chemical substances a definite arrangement or structure of this material4 ,the limits of divisibility of a cell seem therefore to depend upon its physical structure and must for this reason vary for different organisms and cells4 ,the smallest piece of a sea-urchin egg that can reach the pluteus stage is still visible with the naked eye1 and is therefore considerably larger than bacteria or many alg1 which also may be capable of further division4 #h4 ,the most important fact which we gather from these data is that the cytoplasm of the unfertilized egg may be considered as the embryo in the rough and that the nucleus has apparently nothing to do with this predetermination4 ,this must raise the question suggested already in the third chapter whether it might not be possible that the cytoplasm of the eggs is the carrier of the genus or even species heredity1 while the ,mendelian heredity which is determined by the nucleus adds only the finer details to the rough block4 ,such a possibility exists1 and if it should turn out to be true we should come to the conclusion that the unity of the organism is not due to a putting together of a number of independent ,mendelian characters according to a 8pre-established plan10 but to the fact that the organism in the rough existed already in the cytoplasm of the egg before the egg was fertilized4 ,the influence of the hereditary ,mendelian factors or genes consisted only in impressing the numerous details upon the rough block and in thus determining its variety and individuality2 and this could be accomplished by substances circulating in the liquids of the body as we shall see in later chapters4 ,,chapter ,,vii ,,regeneration #a4 ,the action of the organism as a whole seems nowhere more pronounced than in the phenomena of regeneration1 for it is the organism as a whole which represses the phenomena of regeneration in its parts1 and it is the isolation of the part from the influence of the whole which sets in action the process of regeneration4 ,the leaf of the ,bermuda 8life plant0--,bryophyllum calycinum--behaves like any other leaf as long as it is part of a healthy whole plant1 while when isolated it gives rise to new plants4 ,the power of so doing was possessed by the leaf while a part of the whole1 and it was the 8whole0 which suppressed the formative forces in the leaf4 ,when a piece is cut from the branch of a willow it forms roots near the lower end and shoots at the upper end1 so that a tolerably presentable 8whole0 is restored4 ,how does the 8whole0 prevent the basal end of the shoot from forming roots as long as it is part of the plant8 ,a certain fresh-water flatworm has the mouth and pharynx in the middle of the body4 ,when a piece is excised between the head and the pharynx a new head is formed at the oral end1 a new tail at the opposite end1 and in the middle of the remaining old tissue a new mouth and pharynx is formed4 ,how does the 8whole0 suppress all this formative power in the part before the latter is isolated8 ,it almost seems as if the isolation itself were the emancipation of the part from the tyranny of the whole4 ,the explanation of this tyranny or of the correlation of the parts in the whole is to be found1 however1 in a different influence4 ,the earlier botanists1 ,bonnet1 ,dutrochet1 and especially ,sachs1#adb pointed out that the phenomena of correlation are determined by the flow of sap in the body of a plant4 ,these authors formulated the idea that the formation of new organs in the plant is determined by the existence of specific substances which are carried by the ascending or descending sap4 ,specific shoot-producing substances are carried to the apex1 while specific root-producing substances are carried to the base of a plant4 ,when a piece is cut from a branch of willow the root-forming substances must continue to flow to the basal end of the piece1 and since their further progress is blocked there they induce the formation of roots at the basal end4 ,goebel#adc and de ,vries have accepted this view and the writer made use of it in his first experiments on regeneration and heteromorphosis in animals4#add ,at that time the idea of the existence of such specific organ-forming substances was received with some scepticism1 but since then so many proofs for their existence have been obtained that the idea is no longer questioned4 ,such substances are known now under the name of 8internal secretions0 or 8hormones02 their connection with the theory of ,sachs was forgotten with the introduction of the new nomenclature4 #adb v4 ,sachs1 ,j41 8,stoff und ,form der ,pflanzenorgane10 ,gesammelte ,abhandlungen1 #ahib1 ii41 #aafj4 ,arbeiten a4 d4 bot4 ,inst4 ,wrzburg1 #ahhj-hb4 #adc ,goebel1 ,k41 ,einleitung in die experimentelle ,morphologie der ,pflanzen1 #aijh4 #add ,loeb1 ,j41 ,untersuchungen zur physiologischen ,morphologie der ,tiere4 ,i4 ,heteromorphose4 ,wrzburg1 #ahia4 ,,ii4 ,organbildung und ,wachsthum4 #ahib4 ,reprinted in ,studies in ,general ,physiology4 ,chicago1 #aijf4 ,it may be well to enumerate some of the cases in which the influence of specific substances circulating in the blood upon phenomena of growth has been proven4 ,one of the most striking observations in this direction is the one made by ,gudernatsch on the growth of the legs of tadpoles of frogs and toads4#ade ,the young tadpoles have no legs1 but the mesenchyme cells from which the legs are to grow out later are present at an early stage4 ,from four months to a year or more may elapse before the legs begin to grow4 ,gudernatsch found that legs can be induced to grow in tadpoles at any time1 even in very young specimens1 by feeding them with the thyroid gland 7no matter from what animal74 ,no other material seems to have such an effect4 ,the thyroid contains iodine1 and ,morse#adf states that if instead of the gland1 iodized amino acids are fed to the tadpole the same result can be produced4 ,we must1 therefore1 draw the conclusion that the normal outgrowth of legs in a tadpole is due to the presence in the body of substances similar to the thyroid in their action 7it may possibly be thyroid substance7 which are either formed in the body or taken up in the food4 #ade ,gudernatsch1 ,j4 ,f41 ,zentralbl4 f4 ,physiol41 #aiab1 xxvi41 #cbc2 ,arch4 f4 ,entwcklngsmech41 #aiab1 xxxv41 #deg2 ,am4 ,jour4 ,anat41 #aiad1 xv41 #dca4 #adf ,morse1 ,m41 ,jour4 ,biol4 ,chem41 #aiad1 xix41 #dba4 ,thus we see that the mesenchyme cells giving rise to legs may lie dormant for months or a year but will grow out when a certain type of substances1 e4 g41 thyroid1 circulates in the blood4 ,there may exist an analogy between the activating effect of the thyroid substance and the activating effect of the spermatozon or butyric acid 7or other parthenogenetic agencies7 upon the egg1 but we cannot state that the thyroid substance activates the mesenchyme cells by altering their cortical layer4 ,the fact that the substance of the thyroid may induce general growth in the human is too well known to require more than an allusion in this connection4 ,when growth stops in children as a consequence of a degeneration of the thyroid1 feeding of the patient with thyroid again induces growth4 ,it may also suffice merely to call attention to the connection between acromegaly and the hypophysis4 ,it was formerly believed that the nervous system acted as a regulator of the phenomena of metamorphosis in animals1 but it was possible to show by simple experiments that the central nervous system does not play this rle and that the regulator must be the blood or substances contained therein4 ,in the metamorphosis of the ,amblystoma larva the gills at the head and tail undergo changes simultaneously1 the gills being absorbed completely4 ,the writer showed that in larv in which the spinal cord was cut in two1 no matter at which level1--the sympathetic nerves were in all probability also cut--the two organs continued to undergo metamorphosis simultaneously4#adg ,uhlenhuth found that if the eye of a salamander larva is transplanted into another larva the transplanted eye undergoes its metamorphosis into the typical eye of the adult form1 simultaneously with the normal eyes of the individual into which it was transplanted4#adh ,these and other observations of a similar character leave no doubt that substances circulating in the blood and not the central nervous system are responsible for the phenomena of growth and metamorphosis4 #adg ,loeb1 ,j41 ,arch4 f4 ,entwcklngsmech41 #ahig1 iv41 #ejb4 #adh ,uhlenhuth1 ,e41 ibid41 #aiac1 xxxvi41 #baa4 ,an interesting observation on the rle of internal secretion in growth was made by ,leo ,loeb4#adi ,when the fertilized ovum comes in contact with the wall of the uterus it calls forth a growth there1 namely the formation of the maternal placenta 7decidua74 ,this author showed that the corpus luteum of the ovary gives off a substance to the blood which alters the tissues in the uterus in such a way that contact with any foreign body induces this deciduoma formation4 ,the case is of interest since it indicates that the substance given off by the corpus luteum does not induce growth directly1 but that it allows mechanical contact with a foreign body to do so while without the intervention of the corpus luteum substance no such effect of the mechanical stimulus would be observable4 ,the action of the substance of the corpus luteum is independent of the nervous system1 since in a uterus which has been cut out and retransplanted the same phenomenon can be observed4 #adi ,loeb1 ,leo1 ,zentralbl4 f4 allg4 ,path4 u4 path4 ,anat41 #aijg1 xviii41 #efc2 ,zentralbl4 f4 ,physiol41 #aijh1 xxii41 #dih2 #aiji1 xxiii41 #gc2 #aiaj1 xxiv41 #bjc2 ,arch4 f4 ,entwcklngsmech41 #aiji1 xxvii41 #hi1 #dfc2 ,jour4 ,am4 ,med4 ,assoc41 #aijh1 l41 #ahig2 #aiji1 liii41 #adga4 ,bouin and ,ancel#aej have shown that the corpus luteum1 which in the case of pregnancy continues to exist for a long time1 is responsible for the changes in the mammary gland in the first half of pregnancy1 when an active cell proliferation takes place in the gland4 ,this process can be interrupted by destroying the corpus luteum artificially4 ,during the second half of gravidity no further cell proliferation takes place1 but the cells begin to secrete milk while during the period of cell proliferation such secretions do not occur4 #aej ,quoted from ,m4 ,caullery1 ,les ,problmes de la ,sexualit1 ,paris1 #aiac1 p4 #abf4 ,claude ,bernard and ,vitzou had shown that the period of growth and moulting of the higher crustacea is accompanied by a heaping up of glycogen in the liver and subdermal connective tissue4 ,smith#aea found that during the period between two moultings1 when there is no growth1 the storage cells are seen to be filled with large and numerous fat globules instead of with glycogen4 ,he also found that in the ,cladocera 8the period of active growth is accompanied by glycogen--as opposed to fat--metabolism40 ,he observed1 moreover1 that if ,cladocera are crowded at a low temperature the fat metabolism 7with inhibition to growth7 is favoured1 while at high temperatures and with no crowding of individuals the glycogen metabolism is favoured4 ,in the latter case a purely parthenogenetic mode of propagation is observed1 while in the former sexual reproduction takes place4 ,the effect of crowding of individuals is possibly due to products of excretion1 which then act on growth and reproduction indirectly by changing the 8glycogen metabolism0 to 8fat metabolism40 #aea ,smith1 ,geoffrey1 ,proc4 ,roy4 ,soc41 ,b4 #aiae1 lxxxviii41 #dah4 ,all these cases agree in this1 that apparently specific substances induce or favour growth1 not in the whole body1 but in special parts of the body4 ,sachs suggested that there must be in each organism as many specific organ-forming substances as there are organs in the body4 ,we will now show that the assumption of the existence of such 8organ-forming0 substances 7which may or may not be specific7 and of their flow in definite channels explains the inhibitory influence of the whole on the parts as well as the unbridled regeneration of the isolated parts4 #b4 ,we have seen that the resting egg can be aroused to development and growth by substances contained in a spermatozon or by certain other substances mentioned in the preceding chapter4 ,we will assume that plants contain a large number of cells or buds which are comparable to the resting egg cell1 but which can be aroused to action by certain substances circulating in the sap2 and that the same is effected for animal cells by substances in the blood4 ,in plants the cells which can be aroused to new growth have very often a rather definite location while in lower animals they are more ubiquitous4 ,for experimental purposes organisms where these buds have a definite location are more favourable1 since we are better able to study the mechanism underlying the process of activation and inhibition 7correlation74 ,when a leaf of the plant ,bryophyllum calycinum is cut off and put on moist sand or into water or even into air saturated with water vapour1 new plants will arise from notches of the leaf4 ,this is the usual way of propagating the plant and in no other part of the leaf except the notches will new plants arise4 ,these notches therefore contain cells comparable to seeds or to unfertilized eggs or to the mesenchyme cells which give rise to legs in the tadpole of the frog4 ,the question arises3 ,why do notches in the leaf never begin to grow while the leaf is attached to an intact plant1 and why do they grow when the leaf is isolated8 ,to this we are inclined to give an answer in the sense of ,bonnet1 ,sachs1 de ,vries1 and ,goebel1 namely that the flow of 7specific87 substances in the plant determines when and where dormant buds or anlagen shall begin to grow4 ,such substances may originate or may be present in the leaf2 but as long as it is connected with a normal plant they will be carried by the circulation to the growing points of the stem and of the roots and they cannot reach the notches2 while when we detach the leaf1 either a new distribution or a new flow of liquids will be established whereby the substances reach some of the notches2 and in these notches new roots and a new shoot will be formed4 ,when we cut off a leaf and put it into moist air1 not all but only a few of the notches will1 as a rule1 grow out 7,fig4 #af72 but when we isolate each notch leaving as much of the rest of the leaf as possible attached to it1 each notch will give rise to a new plant4#aeb 7,fig4 #ag47 ,we see1 therefore1 that it does not even require a whole plant to cause inhibition but that we may observe the tyranny of the whole over the parts in a single leaf4 ,the explanation is as follows3 ,when we isolate a leaf1 some of the notches will commence to grow into new plants and this growth will arrest the development of the other notches of the leaf in the same way as their development was suppressed by the whole plant4 #aeb ,loeb1 ,j41 ,bot4 ,gazette1 #aiae1 lx41 #bdi4 ,illustration3 ,,fig4 #af4 ,growth of roots and shoots in a few notches of an isolated leaf of ,bryophyllum calycinum ,illustration3 ,,fig4 #ag4 ,if all the notches of a leaf are isolated from each other each notch will give rise to roots and a shoot1 but the growth will be less rapid than in ,fig4 #af4 ,figs4 #af and #ag were two leaves taken from the same node of a plant4 ,the explanation is the same2 those notches which begin to grow first will attract the flow of substances to themselves1 thus preventing the other notches from getting those substances4 ,this idea is supported by the fact that if all the notches are isolated from the leaf each notch will give rise to a slowly growing plant1 while if the leaf is not cut into pieces1 and a few notches only grow out1 their growth is much more rapid4 ,in all these experiments the idea that the 8isolation0 in itself is responsible for the growth still presents itself4 ,it can be disposed of by the following experiment which never fails4 ,three leaves of ,bryophyllum calycinum are suspended in an atmosphere saturated with water vapour but their tips are submersed in water 7,figs4 #ah1 #ai1 #bj74 ,the first leaf1 ,fig4 #bj1 is entirely separated from its stem1 the second leaf1 ,fig4 #ai1 remains connected with the adjacent piece of stem1 and the third leaf1 ,fig4 #ah1 remains also connected with this piece of stem but the latter still possesses both leaves4 ,the first leaf1 ,fig4 #bj1 produces new roots and shoots in the submerged part in a few days2 the second leaf1 ,fig4 #ai1 produces no roots or shoots for a long time4 ,this might find its explanation by the assumption that the first leaf1 being more isolated than the second1 regenerates more quickly4 ,but this explanation becomes untenable owing to the fact that the third leaf1 ,fig4 #ah1 being less isolated than both 7possessing a second leaf in addition to the stem71 forms new roots and shoots also more quickly than the second leaf4 ,the phenomena become intelligible in the following way4 ,the fact that in the second leaf shoots and roots are formed very late1 if at all1 finds its explanation not in the lessened isolation of this leaf1 but in the fact that the formation of a new shoot or of a callus in the piece of stem takes place more quickly than the formation of roots and shoots in the notches of a completely isolated leaf4 ,the stem acts therefore as a centre of suction for the flow of substances from the leaf and this prevents or retards the formation of roots and shoots in the notches4 ,in the isolated leaf of ,bryophyllum calycinum no callus formation takes place and hence no flow of the sap away from the leaf will occur4 ,this will allow one or more of the notch buds of this leaf to grow out and then a flow will be established towards these growing buds4 ,illustration3 ,,fig4 #ah ,,fig4 #ai ,,fig4 #bj ,in the third specimen1 ,fig4 #ah1 the presence of two leaves suppresses or1 as a rule1 retards the growth of a shoot on the stem and possibly also the flow from one leaf may block to some extent the flow from the opposite leaf if the piece of stem is very short4 ,this puts the leaves in a condition not as good as that in leaf ,fig4 #bj1 but better than in leaf ,fig4 #ai4aec #aec ,with larger leaves the experiment may also succeed in moist air4 ,in the normal plant the buds in the notches of the leaf remain dormant since the flow of the 8stimulating0 substances takes place towards the tips of the stem and root1 and because these substances are retained there in excess4 ,this is probably the real basis of the mysterious dominance of the 8whole0 over its 8parts0 or of the anlagen of the tip of the stem over those farther below4 ,when a piece of the stem of ,bryophyllum is cut off and its leaves are removed1 the two apical buds will grow out first4 ,this 8dominance0 finds its explanation probably in the anatomical structure and the mechanism of sap flow which tend to bring the 8stimulating0 substances first to the anlagen in the tip4 ,in ,laminaria ,setchell has been able to show directly that regeneration always starts from that tissue which conducts nutritive material4 ,when we cut out a piece of a stem of ,bryophyllum1 and remove all the leaves1 new shoots will be formed from the two apical buds of the stem1 and roots will arise from the most basal nodes2 provided that the stem is suspended in air saturated with water vapour4 ,the growth in such a stem deprived of all leaves is slow4 ,if we remove all the leaves on such a piece of stem except the two at the apical end1 the stem will form only roots1 but these will develop much more rapidly than on a stem without leaves4 ,if we remove all the leaves except the two at the basal end1 the stem will only form shoots 7at the apical end7 but these will develop much more rapidly than in a leafless stem4 ,hence the leaves accelerate the growth of roots towards the basal end and inhibit it towards the apical end2 and they favour the growth of shoots towards the apical end and inhibit it in the nodes located nearer the base4 ,we thus see that while the stem inhibits the growth of the leaves connected with it1 the latter accelerate the growth in the stem4 ,both facts can probably be explained on the same basis2 namely1 on the assumption that it is the flow of substances from the leaf to the stem which inhibits the growth of the notches and accelerates the growth of the buds in the stem4 ,on this assumption it would also follow that the leaves send root-forming substances towards the basal and shoot-forming substances towards the apex of the stem4 ,it also seems to follow from recent as yet unpublished experiments by the writer that the root-forming substances are associated or identical with the substances which cause geotropic curvature in the stem4 ,these observations show that the phenomena of correlation or of the influence of the whole over the parts is due to peculiarities of circulation or the flow of sap2 and that the isolation prevents the sap from flowing away to other parts of the plant4 ,there is no need for assuming the existence of a mysterious force which directs the piece to grow into a whole4 ,illustration3 ,,fig4 #ba #c4 ,phenomena of inhibition or correlation such as we have described in ,bryophyllum are not lacking in the regeneration of animals1 as experiments on ,tubularia show4#aed ,tubularia mesembryanthemum 7,fig4 #ba7 is a hydroid consisting of a long stem terminating at one end in a stolon which attaches itself to solid bodies such as rocks1 at the other end in a polyp4 ,the writer found that if we cut a piece from a stolon and suspend it in an aquarium it forms as a rule a polyp at either end 7,fig4 #bb71 but the velocity with which the two polyps are formed is not the same1 the polyp at the oral end of the piece being formed much more rapidly--a day or one or two weeks sooner--than the aboral polyp4 ,the process of polyp regeneration at the aboral pole could1 however1 be accelerated and its velocity made equal to that of the regeneration of the oral polyp by suppressing the formation of the latter4 ,this was accomplished by depriving the oral pole of the oxygen necessary for regeneration1 e4 g41 by merely putting the oral end of the piece of stem into the sand4 ,it was1 therefore1 obvious that the formation of the oral polyp retarded the formation of the aboral polyp4 ,this inhibition might have been due to the fact that a specific organ-forming material needed for the formation of a polyp existed in sufficient quantity in the stem for the formation of one polyp only at a time4 ,this idea1 however1 was found to be incorrect since when the stem was cut into two or more pieces each piece formed a polyp at once at its oral pole and regenerated the aboral polyps also1 but again with the usual delay4 ,it seemed more probable then that the cause of the difference in the rapidity of polyp formation at both ends lay in the fact that certain material flowed first to the oral pole and induced polyp formation here but that this flow was reversed as soon as the polyp at the oral pole was formed or as soon as the formation of the oral polyp was inhibited by lack of oxygen4 ,the partial or full completion of the formation of the oral polyp acted as an inhibition to the further flow of material to this pole4 ,this idea was supported by an observation made independently by ,godlewski and the writer that if a piece of stem be cut out of a ,tubularia1 and if the piece be ligatured somewhere between the two ends1 the oral and the aboral polyps are formed simultaneously4 ,this would be comprehensible on the assumption that the retarding effect which the formation of the oral has on the aboral polyp was indeed of the nature of a flow of material towards the oral pole4 #aed ,loeb1 ,j41 ,untersuchungen zur physiologischen ,morphologie4 ,i4 ,heteromorphose4 #ahia4 ,,ii4 ,organbildung und ,wachsthum4 ,wrzburg1 #ahib4 ,illustration3 ,,fig4 #bb ,illustration3 ,,fig4 #bc ,miss ,bickford#aee found that the difference in time between the formation of the two polyps disappears also when the piece cut from the stem becomes so small that it is of the order of magnitude of a single polyp4 ,in that case two incomplete polyps are formed simultaneously at each end 7,fig4 #bc74 ,the new head in the regeneration of ,tubularia arises1 as ,miss ,bickford observed1 from the tissue near the wound4 ,at some distance from the wound in the old tissue two rows of tentacles arise1 which are noticeable as rows of longitudinal lines inside the stem before the head is formed4 ,driesch noticed that the newly formed head is the smaller the smaller the whole piece4 7,this is true1 however1 only in rather small pieces47 ,there is1 therefore1 in small pieces a rough proportionality between size of head and size of regenerating piece4 ,driesch#aef uses this interesting fact to prove the existence of an entelechy1 while we are inclined to see in it an analogue to the observation of ,leo ,loeb1 that the velocity of the process of healing in the case of a deficiency of the epithelium decreases when the size of the uncovered area diminishes4 ,while we do not wish to offer any suggestion concerning the mechanism of these quantitative phenomena--they may be related in some way with the velocity of certain chemical reactions--we see no reason for assuming that they cannot be explained on a purely physicochemical basis4 #aee ,bickford1 ,e4 ,e41 ,jour4 ,morphol41 #ahid1 ix41 #dag4 #aef ,driesch1 ,h41 ,science and ,philosophy of the ,organism1 i41 #abg4 ,the writer noticed that certain pigmented cells from the entoderm of the organism always gather at that end where a new polyp is about to be formed4 ,these red or yellowish cells always collect first at the oral end of a piece of stem4 ,it may be that certain substances given off by the pigmented cells at the cut end are responsible for the polyp formation1 but this is only a surmise4 ,another suggestion made by ,child1#aeg is that there exists an axial gradient in the stem whereby the cells regenerate the more quickly the nearer they are to the oral pole4 ,if this were correct1 and we cut a long piece from the stem of a ,tubularia and bisect the piece1 the oral pole of the anterior half should regenerate more quickly than the oral pole of the posterior half4 ,according to the writer's observations on a ,tubularian 7,t4 crocea7 growing in the estuaries near ,oakland1 ,california1 both oral ends regenerate equally fast in such cases4 #aeg ,child1 ,c4 ,m41 8,die physiologische ,isolation von ,teilen des ,organismus10 ,roux's ,vortrge und ,aufstze1 ,leipzig1 #aiaa4 #d4 ,the phenomena of regeneration in ,cerianthus membranaceus1 a sea anemone1 can be easily understood from the experiments on ,tubularians1 if we imagine the body wall of ,cerianthus to consist of a series of longitudinal elements running parallel to the axis of symmetry of the animal from the tentacles to the foot4 ,the number of these elements may be supposed to correspond to the number of tentacles in the outer row of the normal animal4 ,each such element behaves like a ,tubularian1 with this difference1 however1 that the elements in ,cerianthus are more strongly polarized than in ,tubularia1 and that each one is able to form a tentacle at its oral pole only4 ,this fact can be nicely illustrated in the following way3 if a square or oblong piece 7a b c d1 ,fig4 #bd7 be cut from the body wall of a ,cerianthus in such a way that one side1 a c1 of the oblong is parallel to the longitudinal axis of the animal1 tentacles will grow on one of the four sides only2 namely1 on the side a b4#aeh 7,fig4 #be47 ,the other three free edges are not able to produce tentacles4 ,if an incision be made in the body wall of a ,cerianthus1 tentacles will grow on the lower edge of the incision 7,fig4 #bf74 #aeh ,loeb1 ,j41 8,untersuchungen zur physiologischen ,morphologie der ,tiere40 ,illustration3 ,,fig4 #bd ,illustration3 ,,fig4 #be ,illustration3 ,,fig4 #bf ,the writer tried whether or not by tying a ligature around the middle of a piece of an ,actinian this polarity could be suppressed2 but the experiments did not succeed1 inasmuch as the cells compressed by the ligature died1 and were liquefied through bacterial action so that the pieces in front and behind the ligature fell apart4 ,it is therefore impossible to decide whether or not a current or a flow of substances in a certain direction through these elements is responsible for this polarity1 though this may be possible4 ,the writer found1 however1 that one condition is necessary for the growth and regeneration of tentacles which also plays a rle in the corresponding phenomena in plants1 namely turgidity4 ,the tentacles of ,cerianthus are hollow cylinders closed at the tip1 and by liquid being pressed into them they can be stretched and appear turgid4 ,if1 however1 an incision is made in the body1 the tentacles above the incision can no longer be stretched out4 ,in one experiment the oral disk of a ,cerianthus was cut off2 very soon new tentacles began to grow at the top1 and after having reached a certain size1 an incision was made in the animal4 ,the tentacles above the incision collapsed in consequence and ceased to grow1 while growth of the others continued4 ,on the lower edge of the incision new tentacles began to grow4 ,illustration3 ,,fig4 #bg ,it seems also possible that ,morgan's well-known experiment on regeneration in ,planaria can be explained by a flow of substances4 ,he#aei found that if a piece a c d b be cut out of a fresh-water ,planarian at right angles to the longitudinal axis 7,fig4 #bg71 at the front end a new normal head1 at the back end a new tail1 will be regenerated 7,fig4 #bh72 but that if a piece a c d b be cut from a ,planarian obliquely 7,fig4 #bi7 instead of at right angles to the longitudinal axis a tiny head is formed at the foremost corner of the piece a and a tiny tail at the hindmost corner b 7,fig4 #cj74 ,why is it that in the oblique piece the head is formed in the corner and not all along the cut surface as is the case when the cut is made at right angles to the longitudinal axis8 ,the writer is inclined to believe that the right answer to this question has been given by ,bardeen4#afj ,this author has pointed out the apparent rle that the circulatory 7or so-called digestive7 canals in ,planarians play in the localization of the phenomena of regeneration1 inasmuch as the new head always forms symmetrically at the opening of the circulatory vessel or branch which is situated as much as possible at the foremost end of the regenerating piece of worm4 ,he assumes that through muscular action the liquids of the body are forced to stream toward this end1 and that this fact has some connection with the formation of a new head4 ,there can be no doubt that the facts here mentioned agree with ,bardeen's suggestion4 ,the oblique pieces in ,morgan's experiments which at first have the heads and tails outside the line of symmetry of the middle piece1 gradually assume a normal position 7,figs4 #ca1 #cb74 ,the writer is inclined to believe that this is due to mechanical conditions4 ,the head a e c of such an oblique piece is asymmetrical1 the one side a e being less stretched than the other e c4 ,the higher tension of the piece e c will have the effect of bringing e nearer c1 since we know that acid formation and hence energy production increases in proportion to surface1 i4 e41 it must be the greater the more it is stretched4 ,the reverse is true for the tail d f b1 and the effect here will be that f will be pulled nearer d4 ,in this way purely mechanical conditions are responsible for the fact that the soft tissues of the animal are gradually restored to their true orientation4 #aei ,morgan1 ,t4 ,h41 ,regeneration1 ,new ,york1 #aija4 #afj ,bardeen1 ,c4 ,r41 ,am4 ,jour4 ,physiol41 #aija1 v41 #a2 ,arch4 f4 ,entwcklngsmech41 #aijc1 xvi41 #a4 ,illustration3 ,,fig4 #bh ,illustration3 ,,fig4 #bi ,illustration3 ,,fig4 #cj ,illustration3 ,,fig4 #ca ,illustration3 ,,fig4 #cb ,as a final possible example of the influence of internal secretion or substances contained in the blood may be mentioned the following curious observation of ,przibram4#afa ,in a crustacean1 ,alpheus1 the two chel 7pincers7 are not equal in size and form1 one being very much larger than the other4 ,przibram found that when he cut off the larger pincer in such crustaceans the remaining pincer assumes in the next moulting the size and shape of the removed large pincer2 while in place of the removed pincer one of the small type is produced4 ,hence a reversal of the two pincers is thus brought about4 ,if later on the large pincer is again cut off the process is repeated and the original dissymmetry is restored4 ,przibram was able to show that the nervous system has no connection with this phenomenon4 #afa ,przibram1 ,h41 ,arch4 f4 ,entwcklngsmech41 #aija1 xi41 #cbi4 ,the elements which have entered into the discussion thus far are1 first1 the flow of substances in preformed channels2 second1 the existence of general or specific substances required for the growing or regenerating organ4 ,a third element is to be added2 namely the 8suction0 effect upon these substances of a developing organ4 ,thus we see that if one or a few of the notches in a leaf of ,bryophyllum grow out the other notches of the leaf are inhibited from growing4 ,there is enough material present in the leaf for all the notches to grow into shoots as is proved by the fact that all will grow out if they are isolated from each other4 ,this was explained on the assumption that the notches of a whole which happen to develop first1 create a flow of these substances from the rest of the leaf to themselves and thus prevent any getting to the other notches4 ,we stated that this is supported by the fact that the few notches growing out in an undivided leaf grow more rapidly than the many shoots growing from each notch of a divided leaf4 ,but why should a growing shoot or a growing point in general produce such a suction8 ,i think this may be possible on the assumption that the consumption of these substances by the growing organs causes a low osmotic pressure of these substances in the growing region and this fall of osmotic potential will act as a cause for the further flow4 ,this brings about the apparent 8suction0 effect of the growing elements upon the flow of substances4 #e4 ,we mentioned that when a piece is cut from a ,planaria between pharynx and head a new mouth is formed in the middle4 ,it should also be mentioned that according to ,child the piece after regeneration is smaller than it was before4#afb ,this indicates that material in the old cells has been digested or has undergone hydrolysis in order to furnish the nutritive material for the new head and tail1 since the piece cannot take up any food from the outside before a mouth is formed4 ,these phenomena of autodigestion--the process itself will be discussed in the last chapter--seem to occur in many 7if not all7 phenomena of regeneration4 ,it may be that the collecting of red cells at the end in a ,tubularian where regeneration is about to begin has to do with the furnishing of material by self-digestion1 since these cells are partly at least destroyed in the process4 ,it is of interest to look for more examples of autodigestion accompanying phenomena of regeneration4 #afb ,child1 ,c4 ,m41 ,senescence and ,rejuvenescence4 ,chicago1 #aiae4 ,illustration3 ,,fig4 #cc ,the writer has observed more closely the transformation of an organ into more undifferentiated material in ,campanularia 7,fig4 #cc71 a hydroid4#afc ,this organism shows a remarkable stereotropism4 ,its stolons attach themselves to solid bodies1 and the stems appear on the side of the stolon exactly opposite the point or area of contact with the solid body4 ,the stems grow1 moreover1 exactly at right angles to the solid surface element to which the stolon is attached4 ,if such a stem be cut and put into a watch glass with sea water1 it can be observed that those polyps which do not fall off go through a series of changes which make it appear as if the differentiated material of the polyp were transformed into undifferentiated material4 ,the tentacles are first put together like the hairs of a camel's-hair brush 7,fig4 #cd71 and gradually the whole fuses to a more or less shapeless mass which flows back into the periderm 7,fig4 #ce74 ,it follows from this that in this process certain solid constituents of the polyp1 e4 g41 the cell walls1 must be liquefied4 ,this undifferentiated material formed from the polyp may afterward flow out again1 giving rise to a stolon or a polyp2 to the former where it comes in contact with a solid body1 to the latter where it is surrounded by sea water4 ,these observations suggest the idea of reversibility of the process of differentiation of organs and tissues1 in certain forms at least4 ,we have to imagine that some of the cells or interstitial tissue is digested and that as a consequence the organ loses its characteristic shape4 #afc ,loeb1 ,j41 ,am4 ,jour4 ,physiol41 #aijj1 iv41 #fj4 ,illustration3 ,,fig4 #cd ,illustration3 ,,fig4 #ce ,giard and ,caullery have found that a regressive metamorphosis occurs in ,synascidians1 and that the animals hibernate in this condition4 ,the muscles of the gills of these animals are decomposed into their individual cells4 ,the result is the formation of a parenchyma which consists of single cells and of cell aggregates resembling a morula4#afd #afd ,the writer quotes this after ,driesch4 ,driesch1#afe experimenting on the regeneration of an ,ascidian1 found that when he cut off the gills and siphons of the animal the portion removed was able to regenerate a whole animal4 ,the gill-piece excised contained no heart1 no intestine1 and no stolon1 and all these organs were regenerated from the gills4 ,in a number of cases the regeneration took place by bud formation at the edge of the wound1 but in other cases the gills were transformed into an undifferentiated mass of tissue from which the missing parts of the animals arose by budding and new gills were formed4 #afe ,driesch1 ,h41 ,arch4 f4 ,entwcklngsmech41 #aijb1 xiv41 #bdg4 ,it is probable that the two cases are only quantitatively different4 ,in both1 autodigestion of certain cell constituents and possibly of whole cells must take place in order to obtain material for the formation of the lost part of the ,ascidian4 ,if an interstitial tissue is digested it becomes a question of how much of this tissue undergoes hydrolysis4 ,if there is little destroyed the old shape of the gills remains1 if too much is digested the old gills become a shapeless mass in which a certain number of the old cells are maintained and give rise to the new animal by cell division4 ,the material for the new organs must of course be furnished from old cells which have been digested4 ,if regeneration takes place in pieces which take up no food the newly formed organs must originate from material absorbed from cells of the animal which are hydrolyzed and whose material serves as food for those cells which grow4 ,very often this process of digestion takes place without loss of the total form of the organ and is overlooked by the pure morphologists4 ,in ,campanularia also the process of collapse described above is only apparent in a fraction of the cases as in ,driesch's observations on ,clavellina4#aff ,it is also possible that the red and yellow entoderm cells which gather at the end where the new polyp forms furnish the material which is utilized for the process of growth of the cells from which the tentacles arise 7with or without giving off specific 8hormones0 besides74 #aff ,one author1 ,miss ,thatcher1 in trying to repeat these observations1 did not notice the total collapse of the tissues and concluded that my observations must have been wrong4 ,the writer is fairly certain that his observations were correct4 #f4 ,we have mentioned the ideas concerning a design1 or 8entelechy10 acting as a guide to the developing egg and have shown that this revival of ,platonic and ,aristotelian philosophy in biology was due to a misconception2 namely1 that the egg consisted of homogeneous material which was to be differentiated into an organism4 ,for this supernatural task supernatural agencies seemed required4 ,but we have seen that the unfertilized egg is already differentiated in a way which makes the further differentiation a natural affair4 ,this idea of a quasi superhuman intelligence presiding over the forces of the living is met with in the field of regeneration1 and here again it is based upon a misconception4 ,the lens of the eye is formed in the embryo from the epithelium lying above the so-called optic cup 7the primitive retina74 ,where this retina touches the epithelium the latter begins to grow into the cup1 the ingrowing piece of epithelium is cut off and forms the lens1 which probably under the influence of substances secreted by the optic cup becomes transparent4 ,certain animals like the salamander are able to form a new lens when the old one has been removed by operation1 but the new lens is formed in an entirely different way2 namely1 from the upper edge of the iris4 ,g4 ,wolf1 who observed this regeneration used it to endow the organism with a knowledge of its needs2 the idea of a ,platonic preconceived plan or an ,aristotelian purpose suggested itself4 ,but it can be shown that the organism does in this case what it is compelled to do by its physical and chemical structure4 ,uhlenhuth#afg has shown by way of tissue culture that the cells of the iris cannot grow and divide as long as they are full of pigment granules as they normally are4 ,when the fine superficial membrane of the iris is torn the pigment granules fall out and the cells can now grow and multiply4 ,if the lens is taken out of the eye of the salamander the fine membrane of the iris is torn and the pigment cells at the edge 7especially the upper edge7 lose their pigment granules which fall down on account of their specific gravity4 ,as soon as this happens the cells will proliferate4 ,a spherical mass of cells is formed which become transparent and which will cease to grow as soon as they reach a certain size4 ,the unanswered question is3 ,why does the mass of cells become transparent so that it can serve as a lens8 ,the answer is that young cells when put into the optic cup always become transparent no matter what their origin2 it looks as if this were due to a chemical influence exercised by the optic cup or by the liquid it contains4 ,lewis has shown that when the optic cup is transplanted into any other place under the epithelium of a larva of a frog the epithelium will always grow into the cup where the latter comes in contact with the epithelium2 and that the ingrowing part will always become transparent4 ,this leaves us then with one puzzle still3 ,why is the growth of the lens limited8 ,the limitation in the growth of organs is one of the most important problems in growth and organ formation1 though unfortunately our knowledge of this topic is inadequate4 #afg ,not yet published4 #g4 ,the botanist ,j4 ,sachs was the first to definitely state that in each species the ultimate size of a cell is a constant1 and that two individuals of the same species but of different size differ in regard to the number1 but not in regard to the size of their cells4#afh ,amelung1 a pupil of ,sachs1 determined the correctness of ,sachs's theory by actual counts4 ,sachs1 in addition1 recognized that wherever there were large masses of protoplasm1 e4 g41 in siphone and other cloblasts1 many nuclei were scattered throughout the protoplasm4 ,he inferred from this that 8each nucleus is only able to gather around itself and control a limited mass of protoplasm40#afi ,he points out that in the case of the animal egg the reserve material--fat granules1 proteins1 and carbohydrates--are partly transformed into the chromatin substances of the nuclei1 and that the cell division of the egg results in the cells reaching a final size in which each nucleus has gathered around itself that mass of protoplasm which it is able to control4 ,morgan#agj and ,driesch#aga tested and confirmed the idea of ,sachs for the eggs of ,echinoderms4 ,we stated in the previous chapter that ,driesch produced artificially larv of sea urchins of one-eighth1 one-fourth1 and one-half their normal size by isolating a single cleavage cell in one of the first stages of segmentation of the fertilized sea-urchin egg4 ,he counted in each of the dwarf gastrul resulting from these partial eggs the number of mesenchyme cells and found that the larv from a one-half blastomere possessed only one-half1 those from a one-fourth blastomere only one-fourth1 and those from a one-eighth blastomere only one-eighth of the number of cells which a normal larva developing from a whole egg possessed4 ,moreover1 he could show that when two eggs were caused to fuse so as to produce a single larva of double size1 the gastrul of such larv had twice the number of mesenchyme cells4 ,driesch drew the conclusion from his observations that each morphogenetic process in an egg reaches its natural end when the cells formed in the process have reached their final size4 #afh v4 ,sachs1 ,j41 8,physiologische ,notizen10 vi41 ,flora1 #ahic4 #afi ,ibid41 ix41 #dbe1 ,flora1 #ahie4 #agj ,morgan1 ,t4 ,h41 ,arch4 f4 ,entwcklngsmech41 #ahie1 ii41 #ha2 #aija1 xiii41 #daf2 #aijc1 xvi41 #aag4 #aga ,driesch1 ,h41 ,arch4 f4 ,entwcklngsmech41 #ahih1 vi41 #aih2 #aijj1 x41 #cfa4 ,since each daughter nucleus of a dividing blastomere has the same number of chromosomes as the original nucleus of the egg1 it is clear that in a normally fertilized egg each nucleus has twice the mass of chromosomes that is contained in the nucleus of a merogonic egg1 i4 e41 an enucleated fragment of protoplasm into which a spermatozon has entered and which is able to develop4 ,such a fragment has only the sperm nucleus4 ,this phenomenon of merogony was discovered by ,boveri and was elaborated by ,delage4#agb ,boveri1 in comparing the final size of the cells in normal and merogonic eggs after the cell divisions had come to a standstill1 found that this size is always in proportion to the original mass of the chromatin contained in the egg2 the cells of the merogonic embryo1 e4 g41 the mesenchyme cells1 are only half the size of the same cells in the normally fertilized embryo4 ,driesch furnished a further proof of ,boveri's law1 that the final ratio of the mass of the chromatin substance in a nucleus to the mass of protoplasm is a constant in a given species4 ,driesch compared the size of the mesenchyme cells in a sea-urchin embryo produced by artificial parthenogenesis with those of a normally fertilized egg and found them half of the size of the latter4 ,when the fertilized eggs and the parthenogenetic eggs are equal in size from the start1--which is practically the case if eggs of the same female are used1--the process of the formation of mesenchyme cells comes to a standstill when their number in the normally fertilized eggs is half as large as the final number in the parthenogenetic egg4#agc ,boveri's results as well as those of ,driesch were obtained by counting the cells formed by eggs of equal size and not by simply measuring the size of the cells4 ,it is most remarkable that certain apparent exceptions to ,boveri's law which ,driesch has actually found had been predicted by ,boveri4 #agb ,delage1 ,y41 ,arch4 ,zol4 expr41 #ahii1 vii41 #chc4 #agc ,driesch1 ,h41 ,arch4 f4 ,entwcklngsmech41 #aije1 xix41 #fdh4 ,these facts show that the growth of an organ comes to a standstill when a certain size is reached or a certain number of cells are formed4 ,we cannot yet state why this should be1 but we are able to add that the formation of a lens of normal size in the regeneration of the eye is in harmony with the phenomena in the embryo4 ,there seems therefore no reason for stating that the regeneration of the lens cannot be explained on a purely physicochemical basis4 ,the only justification for such a statement on the part of ,wolf is that he was not in possession of the more complete set of facts now available through the work of ,fischel and ,uhlenhuth4 ,the healing of a wound is a process essentially similar to the regeneration of the lens4 ,normally the cells which begin to proliferate after a wound is made in the skin lie dormant1 inasmuch as they neither grow nor divide4 ,when a wound is made certain layers of epidermal cells undergo rapid cell division4 ,leo ,loeb#agd has studied this case extensively4 ,he found that if the skin is removed anywhere1 epidermis cells from the wound edge creep upon the denuded spot and form a covering4 ,this may be a tropism 7stereotropism7 or it may be a mere surface tension phenomenon4 ,next a rapid process of cell division begins in the cells adjacent to the wound these cells having been heretofore dormant4 ,he is inclined to attribute this increase in the rate of cell division to the stretching of the epithelial cells1 and he is supported in this reasoning by the observation that the larger the wound the more rapid the process of healing4#age ,during wound healing the mitoses first increase markedly in the old epithelium4 ,with the closure of the wound a sudden fall in the mitoses takes place4 ,the closure of the wound causes an increase in the number of epithelial rows over the defect4 ,this increase is therefore reached at an earlier period in the larger wound since the process of mitosis is more rapid here4 ,leo ,loeb thinks that the pressure of the epithelial cells upon each other leads to a rapid diminution in the mitotic proliferation4#agf #agd ,loeb1 ,leo1 ,arch4 f4 ,entwcklngsmech41 #ahih1 vi41 #big4 #age ,spain1 ,k4 ,c41 and ,loeb1 ,leo1 ,jour4 ,exper4 ,med41 #aiaf1 xxiii41 #ajg2 ,loeb1 ,l41 and ,addison1 ,w4 ,h4 ,f41 ,arch4 f4 ,entwcklngsmech41 #aiaa1 xxxii41 #dd2 #aiac1 xxxvii41 #fce4 #agf ,the excessive formation of epithelial cells in the healing of wounds has led the older pathologists to the generalization that if something is removed in the body an excessive compensation will take place4 ,the formation of antibodies has even been explained on this basis by ,weiggert and ,ehrlich in their side-chain theory4 ,as a matter of fact1 this generalization is entirely incorrect and in regeneration of starfish1 actinians1 flatworms1 annelids1 and possibly in all forms the reverse is true2 e4 g41 if we cut off the anterior half of the body in ,cerianthus less is reproduced than was cut away namely only tentacles and the mouth1 but not the missing piece of the body4 ,weiggert's conception of regeneration was probably based on the phenomenon of the healing of wounds1 but the excessive epithelium formation in this case is not the expression of a general law of regeneration but of the peculiar mechanical conditions which lead to mitoses4 ,it would be a very strange coincidence indeed if a theory of antibody formation based on such an erroneous generalization should be correct4 ,should it be possible that this is more generally the case1 e4 g41 also in the lens after it has reached a certain size8 ,the conditions limiting growth require further investigation4 ,it is hardly necessary to point out that in these cases we are seemingly dealing with cases of the inhibition of growth which cannot be explained by the tyranny of the whole over the parts1 and that there must be conditions at work other than the mere flow of substances which can cause a cessation of growth4 ,this can be illustrated by certain observations on the egg4 #h4 ,the history of the egg shows a reversible condition of rest and of activity4 ,the primordial egg cell multiplies actively until a large number of eggs are formed in the ovary which may reach into the millions in the case of sea urchins or certain annelids4 ,these cell divisions then stop and the egg goes into the resting stage in which it deposits the reserve material for the development of the embryo4 ,from this condition it can only be called into activity again by the spermatozon or the agencies of artificial parthenogenesis4 ,it seemed of interest to find out whether or not the development of the egg may be reversed once more after it has been activated4 ,from all that has been said in the chapter on artificial parthenogenesis1 such a reversal should take place in the cortical layer4 ,the result of these experiments seems to be that if a complete destruction or change in the cortical layer has once taken place--such as that caused by the entrance of a spermatozon into the egg--no reversal is possible2 although the development of the fertilized egg may be suppressed for a long time by either low temperature or lack of oxygen1 or1 in the case of seeds and spores1 by lack of water4 ,but as soon as the conditions for the chemical reactions in the egg are normal again1 the development may go on unless the egg has suffered by the methods used to prevent development or by the long duration of the suppression4 ,with an incomplete destruction of the cortical layer both development as well as reversal of development are possible4 ,thus the writer has shown that in the egg of ,arbacia the effect of the cortical alteration of the egg induced by the butyric acid treatment or by the treatment with bases can be reversed4 ,when unfertilized eggs of ,arbacia are put for from two to five minutes into #ej c4c4 sea water #b4j c4c4 ,n_/#aj butyric acid they will all form a gelatinous1 somewhat atypical fertilization membrane2 when put back into normal sea water all will perish in a few hours unless they are submitted to the short treatment with a hypertonic solution mentioned in the previous chapter1 while if submitted to this treatment they will develop4 ,if1 however1 these eggs are transferred from the butyric acid sea water not into normal sea water but into sea water containing some ,na,c,n 7#aj drops of #a_/aj per cent4 ,na,c,n or ,,kcn in #ej c4c4 sea water71 and if they remain here for some time 7e4 g4 overnight7 they will not perish when subsequently transferred back to normal sea water4 ,such eggs will develop when fertilized with sperm4 ,the activating effect of the membrane formation has1 therefore1 been reversed and the eggs have gone back into the resting stage4#agg ,wasteneys has found that the rate of oxidation which was raised considerably by the artificial membrane formation goes back to the value characteristic for the resting eggs after the reversal of their developmental tendency4#agh ,similar results were obtained in eggs activated with ,,nh,,oh4 ,it appears from this as though the change in the cortical layer which leads to the development of the egg and the increase in the rate of oxidations were reversible in the egg of ,arbacia4#agi #agg ,loeb1 ,arch4 f4 ,entwcklngsmech41 #aiad1 xxxviii41 #bgg4 #agh ,wasteneys1 ,h41 ,jour4 ,biol4 ,chem41 #aiaf1 xxiv41 #bha4 #agi ,f4 ,lillie thinks that the ,,kcn in this experiment merely inhibits the change of the cortical layer necessary for development4 ,this is contradicted by two facts3 first1 the writer has shown in #aijf that ,,kcn does not inhibit the membrane formation1 and1 second1 the eggs will not return to the resting stage when put back into sea water too soon2 in that case they will disintegrate4 ,this shows that in the ,,kcn something more happens than the mere block to disintegration4 ,the writer had previously noticed that eggs of ,strongylocentrotus purpuratus1 which had been treated for two hours with hypertonic sea water1 not infrequently began to divide into two1 four1 or eight cells 7and sometimes more7 and then went back into the resting state 7except that they possessed the second factor required for development as stated in ,chapter ,v74 ,it may be remarked incidentally that such eggs at the time of cell division contained the centrosomes and astrospheres1 and yet went back into a resting state1 thus showing that the centrosomes are only transitory organs or organs which are only active under certain conditions4 ,it is quite possible that in these phenomena of reversal not the whole of the cortical layer has undergone alteration4 ,the writer must leave it undecided whether the changes from the resting to the active state in body cells can also be explained in analogy with these experiments4 #i4 ,in the formation of the lens we have already noticed an instance where the adjacent organ influences growth inasmuch as the optic cup controlled the formation of the lens4 ,such influences are quite commonly observed4 ,a piece of ,tubularia when cut out from a stem and suspended in water will regenerate at the aboral pole not a stolon but a polyp1 so that we have an animal terminating at both ends of its body in a head4 ,the writer called such cases in which an organ is replaced by an organ of a different kind heteromorphosis4 ,contact with a solid body favours the formation of stolons4 ,fig4 #cf shows a piece of a stem of ,pennaria another hydroid1 which was lying on the bottom of an aquarium and which formed stolons at both ends a and b4 ,in ,margelis1 another hydroid1 the writer observed that without any operation the apical ends of branches which were in contact with solid bodies continued to grow as stolons1 while those surrounded by sea water continued to grow as stems4 ,illustration3 ,,fig4 #cf ,herbst discovered a very interesting form of heteromorphosis in certain crustaceans2 namely1 that in the place of an eye which was cut off1 an entirely different organ could be formed1 namely1 an antenna4 ,he showed that the experimenter has it in his power to determine whether the crustacean shall regenerate an eye or an antenna in place of the eye4 ,the latter will take place when the optic ganglion is removed with the eye1 the former when it is not removed4 ,these experiments were carried out successfully on ,palmon1 ,palmonetes1 ,sicyonia1 ,palinurus1 and other crustaceans4 ,the influence of gravitation is very familiar in plants2 in stems of ,bryophyllum placed horizontally the roots usually come out from the lower end of the callus4 ,such phenomena are not often found in animals but they exist here too as the following observation shows4 ,illustration3 ,,fig4 #cg ,if we cut a piece a b 7,fig4 #cg71 from the stem s s of ,antennularia antennina 7,fig4 #ch71 a hydroid1 and put it into the water in a horizontal position1 new stems c d 7,fig4 #cg7 may arise on its upper side4 ,the small branches on the under side of the old stem a b begin suddenly to grow vertically downward4#ahj ,in appearance and function these downward-growing elements are entirely different from the branches of the normal ,antennularia2 they are roots4 ,in order to understand better the transformation which thus occurs in these branches1 it may be stated that under normal conditions they have a limited growth 7see ,fig4 #ch71 are directed upward1 and have polyps on their upper side4 ,the parts which grow down 7,fig4 #cg7 have no polyps1 but attach themselves like true roots to solid bodies4 ,thus the changed position of the stem alone1 without any operation1 suffices to transform the lateral branches1 whose growth is limited1 into roots with unlimited growth4 ,the lateral branches on the upper side of the stem do not undergo such a transformation into roots except in the immediate surroundings of the place where a new stem arises4 ,it seems that the formation of a new stem also causes an excessive growth of roots1 possibly because the formation of new branches causes the removal of substances which naturally inhibit the formation of roots4 ,if a piece from the stem be put vertically into the water with top downward1 the uppermost point may continue to grow as a stem1 while the lowest point may give rise to roots4 ,in this case1 therefore1 a change in the orientation of organs has the effect of changing the character of organs4 #ahj ,loeb1 ,j41 ,untersuchungen zur physiologischen ,morphologie der ,tiere4 ,,ii4 ,organbildung und ,wachsthum4 ,wrzburg1 #ahib4 ,illustration3 ,,fig4 #ch ,there are only two ways by which we can account for these influences of gravitation4 ,either certain substances flow to the lowest level and collecting there induce growth and possibly changes in the character of growth 7as in ,antennularia7 or if the cells have elements of different specific gravity the relative position of these elements may possibly change and influence in this way the conditions for growth4 ,the influence of gravitation as well as of contact upon life phenomena are at present little understood4 ,in all these cases of heteromorphosis the original form is not restored4 ,it is needless to say that they are incompatible with the theory of natural selection4 ,the reader will have noticed that in this chapter one term has not been mentioned which is commonly met with in the literature1 namely the 8wound stimulus40 ,as the writer had indicated in a former publication1#aha the word 8stimulus0 is generally used to disguise our ignorance of 7and also our lack of interest in7 the causes which underlie the phenomena which we investigate4 ,regeneration very often does not take place near the wound but at some distance from it4 ,but even when the regeneration takes place at the edge of the wound the latter only serves to create conditions for regeneration1 and these conditions cannot be expressed by the word 8stimulus40 #aha ,loeb1 ,j41 ,die chemische ,entwicklungserregung des tierischen ,eies4 ,berlin1 #aiji4 ,while our knowledge of the rle of the whole in regeneration is incomplete in a great many details it seems that the known facts warrant the statement that the phenomena of regeneration belong as much to the domain of determinism as those of any of the partial phenomena of physiology4 ,,chapter ,,viii ,,determination ,,of ,,sex1 ,,secondary ,,sexual ,,characters1 ,,and ,,sexual ,,instincts ,i4 ,the ,cytological ,basis of ,sex ,determination #a4 ,it is a general fact that both sexes appear in approximately equal numbers1 provided a sufficiently large number of cases are examined4 ,this fact has furnished the clue for the discovery of the mechanism which determines the relative number of the two sexes4 ,the honour of having pointed the way to the solution of the problem belongs to ,mc,clung4#ahb ,it has been known that certain insects1 e4 g41 ,hemiptera and ,orthoptera1 possess two kinds of spermatozoa but only one kind of eggs4 ,the two kinds of spermatozoa differ in regard to a single chromosome1 which is either lacking or different in one-half of the spermatozoa4 #ahb ,mc,clung1 ,c4 ,e41 8,the ,accessory ,chromosome--,sex ,determinant80 ,biol4 ,bull41 #aijb1 iii41 #dc4 ,the first one to recognize the existence of two kinds of spermatozoa was ,henking1 who stated that in ,pyrrhocoris 7a ,hemipteran7 one-half of the spermatozoa of each male possessed a nucleolus1 while in the other half it was lacking4 ,montgomery afterward showed that ,henking's nucleolus was an accessory chromosome4 ,mc,clung was the first to recognize the importance of this fact for the problem of sex determination4 ,he observed an accessory chromosome in one-half of the spermatozoa of two forms of ,orthoptera1 ,brachystola and ,hippiscus1 and reached the following conclusion3 ,a most significant fact1 and one upon which almost all investigators are united in opinion1 is that the element is apportioned to but one-half of the spermatozoa4 ,assuming it to be true that the chromatin is the important part of the cell in the matter of heredity1 then it follows that we have two kinds of spermatozoa that differ from each other in a vital matter4 ,we expect1 therefore1 to find in the offspring two sorts of individuals in approximately equal numbers1 under normal conditions1 that exhibit marked differences in structure4 ,a careful consideration will suggest that nothing but sexual characters thus divides the members of a species into two well-defined groups1 and we are logically forced to the conclusion that the peculiar chromosome has some bearing upon the arrangement4 ,n4 ,m4 ,stevens and ,e4 ,b4 ,wilson#ahc have not only proved the correctness of this idea for a number of animals but have laid the foundation of our present knowledge of the subject4 ,wilson showed that in those cases where there are two types of spermatozoa1 one with and one without an accessory or as it is now called an ,x chromosome1 all the cells of the female have one chromosome more than the cells of the male4 ,from this he concludes correctly that in such species a female is produced when the egg is fertilized by a spermatozon containing an ,x chromosome1 while a male is produced when a spermatozon without an ,x chromosome enters the egg4 #ahc ,wilson1 ,e4 ,b41 8,studies on ,chromosomes10 ,jour4 ,exper4 ,zol41 #aije1 ii41 #cga1 #ejg2 #aijf1 iii41 #a2 #aiji1 vi41 #fi1 #adg2 #aiaj1 ix41 #ec2 #aiab1 xiii41 #cde4 8,croonian ,lecture10 #aiad1 ,proc4 ,roy4 ,soc41 ,b4 lxxxviii41 #ccc4 ,such a form is ,protenor1 one of the ,hemiptera4 ,wilson made sure that all the eggs are alike in the number of chromosomes1 each egg containing an ,x chromosome in addition to the six chromosomes characteristic of the species ,protenor4 ,there are two types of spermatozoa in equal numbers in this species1 each with six chromosomes1 but one with1 the other without1 an ,x chromosome4 ,the two possible chromosome combinations between egg and spermatozoa are therefore as follows 7see the diagrammatic ,fig4 #ci73 ,egg ,spermatozon ,result 7#a7 #f ,x #f #ab ,x ,male 7#b7 #f ,x #f ,x #ab #b,x ,female ,the egg which receives a spermatozon without an ,x chromosome has after fertilization #ab,x chromosomes and develops into a male2 while the egg into which a spermatozon with an ,x chromosome enters gives rise to a female4 ,since all the body cells arise from the fertilized egg by nuclear division and the chromosomes remain constant in number in all cells1 the consequence is that all the cells of a female ,protenor have two ,x chromosomes2 while all the cells of a male ,protenor have only one ,x chromosome4 ,illustration3 ,,fig4 #ci ,the chromosome situation in ,protenor is a somewhat extreme case1 inasmuch as one ,x chromosome is entirely lacking in the male4 ,in other forms of ,hemiptera1 e4 g41 ,lygus1 there are also two types of spermatozoa appearing in equal numbers differing in regard to the ,x chromosome1 but here it is only a difference in size2 one-half of the spermatozoa having a large ,x chromosome1 the other half instead a smaller chromosome4 ,calling this latter the ,y chromosome1 the sex determination in this form is as follows3 leaving aside the chromosomes which are equal in both egg and spermatozon we may say that there is one type of egg containing one large ,x chromosome2 there are two types of spermatozoa in equal numbers1 one possessing a large ,x chromosome1 the other possessing a small ,y chromosome4 ,wilson showed by a study of the chromosomes in males and females that when one of the spermatozoa containing a large ,x chromosome enters the egg1 the egg will develop into a female2 while when one of the spermatozoa containing a small ,y chromosome enters it will give rise to a male4 ,leaving aside the common chromosomes of both sexes1 a fertilized egg containing ,,xx gives rise to a female1 while one containing ,,xy gives rise to a male4 ,there is in this case as in that of ,protenor a preponderance of chromosome material in the female1 but this quantitative difference is not essential for the determination of sex1 since in some species the ,y chromosome may be as large as the ,x chromosome4 ,the main fact is that the female cells have the chromatin composition ,,xx1 the male cells the composition ,,xy1 where ,y is apparently qualitatively different and often1 but not necessarily1 smaller than ,x1 or entirely lacking4 ,it may be mentioned in passing that indirect evidence exists indicating that in man there are also two kinds of spermatozoa and one kind of egg1 and that sex depends on whether a male determining or a female determining spermatozon enters the egg4 #b4 ,this mode of sex determination holds only for those animals in which there is one type of egg and two types of spermatozoa4 ,experimental evidence furnished first by ,doncaster in #aijh on a moth1 ,abraxas1 indicated that a number of other forms exists in which matters are reversed1 inasmuch as there are two types of eggs and one type of spermatozoa4 ,this condition of affairs exists not only in the moth ,abraxas1 but also in the fowl as shown by ,pearl4 ,in these forms it is assumed that all the spermatozoa have one sex chromosome ,x1 while there are two types of eggs1 one possessing the sex chromosome ,x1 the other possessing ,y4 ,when a spermatozon enters an egg with an ,x chromosome1 the egg will give rise to a male1 while if it enters a ,y egg1 a female will arise4 ,the evidence pointing toward this result is chiefly contained in experiments on sex-limited or more correctly sex-linked heredity2 i4 e41 a form of heredity which follows the sex in a peculiar way4 ,thus colour-blindness is a case of sex-linked inheritance1 since this abnormality appears overwhelmingly in the male offspring of a colour-blind person4 ,doncaster crossed two varieties of ,abraxas differing in one character which was sex-linked1 and the results of his crossings indicated that in this form there are two types of eggs and one type of spermatozoa4#ahd #ahd ,doncaster1 ,l41 ,the ,determination of ,sex4 ,cambridge1 #aiad4 ,these observations on sex-linked heredity confirm the idea that the sex chromosomes determine the sex4 ,the most extensive and conclusive experiments along this line are those by ,morgan on the fruit fly ,drosophila4 ,in this form there are two kinds of spermatozoa and one kind of eggs2 the egg has one ,x chromosome1 while one-half of the spermatozoa has an ,x the other a ,y chromosome2 the entrance of the latter into an egg gives rise to a male1 of the former to a female4 ,while the eyes of the wild fruit fly ,drosophila ampelophila are red1 ,morgan#ahe noticed in one of his cultures a male that had white eyes4 ,this white-eyed male was mated to a red-eyed female4 ,the offspring1 the ,f generation1 were all red eyed1 males as well as females4 ,these were inbred and now gave in the ,f generation the following three types of offspring3 #ahe ,morgan1 ,t4 ,h41 ,heredity and ,sex4 ,new ,york1 #aiac4 7#a7 #ej per cent4 females1 all with red eyes4 7#b7 #ej per cent4 males #be per cent4 with red eyes4 #be per cent4 with white eyes4 ,the character white eye was therefore transmitted only to half the grandsons2 it was a sex-linked character4 ,it is known from a study of the pedigrees of colour-blind individuals that if the corresponding experiment had been carried out with them1 instead of with white-eyed flies1 the same proportions of normal and colour-blind would have been found3 namely1 normal colour vision in the ,f generation1 in both males and females1 and half of the males of the ,f generation colour-blind1 the other half and all the females with normal vision4 ,of course1 in man1 intermarriage between two different ,f strains would have been required in place of the inbreeding of the ,f generation1 which took place in ,morgan's experiments4 ,morgan interprets his experiments as follows4 ,the normal red-eyed ,drosophila has one kind of eggs1 each possessing one ,x chromosome4 ,this ,x chromosome has also the factor for the development of red-eye pigment4 ,the white-eyed male has two kinds of spermatozoa1 one with an ,x chromosome1 the other with a ,y chromosome1 both lacking the factor for red-eye pigment4 ,if we designate the ,x chromosome with the factor for red-eye pigment by ,x and the ,x and ,y chromosomes lacking the factor for redness with ,x and ,y the following combinations must result if we cross a normal red-eyed female with a white-eyed male3 ,eggs ,sperm ,result ,x ,x ,x,x red-eyed female ,x ,y ,x,y red-eyed male ,it is obvious that all the offspring of the first generation 7the ,f generation7 must be red eyed1 since all the eggs have one ,x chromosome with the factor for red4 ,according to the results obtained from cytological studies which will be explained in the next chapter1 the females with the chromatin constitution ,x,x will form two types of eggs in equal numbers3 namely1 eggs with an ,x and eggs with an ,x1 i4 e41 all eggs have one ,x chromosome1 but in fifty per cent4 of the eggs the ,x has the factor for red1 in fifty per cent4 this factor is lacking 7,x74 ,the males having the chromosome constitution ,x,y form two types of spermatozoa1 one with an ,x possessing the factor for red pigment and one1 the ,y chromosomes1 lacking this factor4 ,if inbred the next ,f generation will give rise to the following four types of offspring3 7#a7 ,x,x1 7#b7 ,x,x1 7#c7 ,x,y1 7#d7 ,,xy1 all four types in equal numbers4 7#a7 and 7#b7 give females1 both red eyed1 since both contain a red-factored ,x chromosome4 7#c7 and 7#d7 give males1 7#c7 giving rise to red-eyed males1 since it contains a red-factored ,x chromosome1 7#d7 producing males with white eyes since this ,x chromosome is lacking the factor for red eyes4 ,since all four combinations must appear in equal numbers 7provided the experimental material is ample enough1 which was the case in these experiments71 in the ,f generation both males and females should have red eyes and in the ,f generation all the females should have red eyes and half of the males should have red1 half white eyes4 ,these results were obtained4 ,the experiments were carried further4 ,no white-eyed females had appeared thus far4 ,on the same assumptions of the relation of the ,x1 ,x1 and ,y chromosomes to the heredity of sex as well as to eye colour it was possible to predict under what conditions and in which proportions white-eyed females should arise4 ,thus if a red-eyed female of the ,f generation 7a cross between white-eyed male and normal female7 be mated with a white-eyed male the result should be an equal number of white-eyed males and white-eyed females if the chromosome theory of sex determination were correct4 ,the reasoning would be as follows3 ,the red-eyed female1 having the chromosome constitution ,x,x should form two kinds of eggs in equal numbers with the constitution ,x and ,x2 the white-eyed male having the chromosome constitution ,,xy should form two kinds of spermatozoa ,x and ,y4 ,the following four types of individuals must then be produced in equal numbers3 7#a7 ,x,x1 7#b7 ,,xx1 7#c7 ,x,y1 and 7#d7 ,,xy4 ,in this case 7#b7 must give rise to white-eyed females and 7#d7 to white-eyed males1 while 7#a7 must give rise to red-eyed females and 7#c7 to red-eyed males4 ,hence white-eyed males and females and red-eyed males and females are to be expected in this case in equal numbers1 and this was actually observed4 ,the numerical agreement in this and the other experiments between the expected and observed result cannot well be an accident4 ,the fact that the inheritance of sex-linked characters in man follows the same laws as in ,drosophila is a strong argument in favour of the assumption that in man1 also1 sex is determined by two kinds of spermatozoa4 ,morgan and his students discovered no less than thirty-six sex-linked characters in ,drosophila1 and each behaved in a similar way to the red and white eye colour in regard to sex-linked inheritance1 so that the chromosome theory of sex determination rests on a safe basis4 ,that sex is merely determined by the number of ,x chromosomes1 not by the ,y chromosome1 is proved by the facts that the ,y chromosome may be completely absent as in ,protenor and that ,bridges#ahf has found a type of female ,drosophila with a chromosome formula ,,xxy whose sex was not affected by the supernumerary ,y4 #ahf ,bridges1 ,c4 ,b41 ,genetics1 #aiaf1 i41 #a4 #c4 ,on the basis of all these experiments and theories it is comparatively easy to explain a number of phenomena concerning sex ratios which before had been very puzzling4 ,in bees it had been shown many years ago by ,dzierzon that the males develop from unfertilized eggs while the females1 queens and workers1 develop from fertilized eggs4 ,this is intelligible on the assumption that the unfertilized egg contains only one ,x chromosome while the spermatozon carries into the egg the second ,x chromosome4 ,but if the male bee produces two types of spermatozoa we should expect that only one-half of the fertilized eggs should be females1 the other half males4 ,but it happens that of the two types of spermatozoa only one is formed since in one of the cell divisions which lead to the formation of spermatozoa one viable spermatozon only is formed while the other one perishes4 ,it is1 therefore1 quite possible that it is the female-producing spermatozon which survives while the male-producing spermatozon dies4 ,it is occasionally observed that an insect shows one sex on one side of its body and the opposite sex on the other side4 ,boveri suggested that this phenomenon of gynandromorphism is due to the fact that the spermatozon for some unknown reason does not fuse with the egg nucleus until after the egg has undergone its first cell division4 ,in this case it fuses with the nucleus of one of the two cells into which the egg divides 7or in some cases even one of the later cells874 ,as a consequence the one-half of the embryo which arises from the cell which was not fertilized would have only one ,x chromosome and in a case like the bee would develop parthenogenetically1 while the other half of the body1 developing from the cell into which a spermatozon has penetrated1 would be fertilized4 ,the latter half of the body would be female1 the former male4 ,in his last paper before his untimely death1 ,boveri has given proof for the correctness of this interpretation as far as gynandromorphism in the bee is concerned4#ahg #ahg ,boveri1 ,th41 ,arch4 f4 ,entwcklngsmech41 #aiae1 xlii41 #bfd4 ,it seems to be generally true that where sexual reproduction leads only to the formation of females the case finds its explanation in the fact that the male-producing spermatozoa perish and only the female-producing spermatozoa survive4 ,such an observation was made by ,morgan on a certain species of phylloxerans4 ,the slight preponderance in the number of one sex which is occasionally found--an excess of six per cent4 males over females in the human race--may well find its explanation on the assumption of a slightly greater mortality of the female-determining spermatozoa4 ,in certain forms parthenogenetic and sexual reproduction may alternate in a cycle1 e4 g41 in plant lice1 ,daphnia1 and rotifers4 ,in plant lice it has been observed for a long time that when the plant is normal and the weather warm the aphides remain wingless1 reproduce parthenogenetically1 and only females exist1 and this may last for years and for more than fifty generations2 but that when the plant is allowed to dry out both sexes appear4 ,here we are dealing with a limited determination of sex inasmuch as the experimenter has it in his power to prevent or allow the production of males4 ,the facts do not in all probability contradict the statements made concerning the rle of the ,x chromosomes in the determination of sex4 ,we have seen that where sex is determined by two types of spermatozoa one type of eggs is produced which possesses only one ,x chromosome4 ,such eggs might produce males if not fertilized 7as they do in bees71 but they cannot produce females because for that purpose they must have two ,x chromosomes4 ,it has been shown for certain cases1 and it may be true generally1 that if eggs of this type give rise to parthenogenetic females they may do so because they have for some reason two ,x chromosomes4 ,usually such an egg loses one of the ,x chromosomes in a process of nuclear division 7the so-called reduction division7 which usually precedes fertilization4 ,if this reduction division is omitted the egg has two ,x chromosomes and if such an egg develops parthenogenetically it gives rise to a female4 ,these cases do not1 therefore1 contradict the connection between ,x chromosomes and sex determination established by cytological observations and breeding experiments1 on the contrary1 they confirm it4 ,the question remains3 ,how can external conditions bring it about that the reduction division is omitted8 ,to this question no definite answer can be given at present4 ,we may in passing mention the well-known observation that twins which originate from the same egg always have the same sex2 while twins arising from different eggs show the usual variation as to sex4 ,twins coming from one egg have the same chorion and can thereby be diagnosed as such4 ,they can be produced as we have stated in ,chapter ,v by a separation of the first two cleavage cells of the egg1 each one giving rise to a full embryo4 ,it harmonizes with all that has been said above that the sex of two such individuals must be the same since they have the same number of ,x chromosomes1 the latter being determined in the human race by the nature of the spermatozon which enters the egg4 #d4 ,while thus far all the facts agree with the dominating influence of certain chromosomes upon sex determination1 one group of facts has not yet been explained3 namely1 hermaphroditism4 ,by hermaphroditism is meant the existence of complete and separate sets of female and male gonads in the same individual4 ,this condition exists regularly not only in definite groups of animals1 e4 g41 certain snails1 leeches1 tape-worms1 but also1 as everybody knows1 in flowering plants4 ,while in some forms both kinds of sex cells1 male and female1 are formed and mature simultaneously1 as1 e4 g41 in the ,ascidian ,ciona 7see ,chapter ,,iv71 in others they are formed successively1 very often the spermatozoa appearing first 7protandric hermaphroditism74 ,in the long tapeworm ,tnia each ring has testes and ovaries1 but the young rings are only male while in the older rings the testes disappear and the ovaries are formed4 ,the same ring is in succession male and female4 ,how can we reconcile the facts of hermaphroditism with the chromosome theory of sex determination8 ,rhabdonema nigrovenosum1 a parasite living in the lungs of the frog1 is hermaphroditic1 but its eggs produce not a hermaphroditic generation but one with the two separate sexes2 this generation is not parasitic and lives in the soil4 ,the generation produced by these separate males and females gives rise again to a hermaphrodite which migrates into the lungs of the frogs4 ,according to ,boveri and ,schleip#ahh the cells of the hermaphrodite have twelve chromosomes4 ,it produces two types of spermatozoa with six and five chromosomes respectively 7one-half of the cells losing one chromosome which is left at the line of cleavage between the two cells72 and one type with six chromosomes4 ,in this way separate males and females are produced by the hermaphrodite1 females with twelve and males with eleven chromosomes4 #ahh ,boveri1 ,th41 ,verhand4 d4 phys4-med4 ,gesellsch4 ,wrzburg1 #aiaa1 xli41 #he4 ,schleip1 ,w41 ,ber4 d4 naturf4 ,gesellsch41 ,freiburg i4 ,br41 #aiaa1 xix4 ,the males produce again two kinds of spermatozoa1 male and female producing1 but the male-producing spermatozoa become functionless4 ,this fusion of the other spermatozon containing six chromosomes with an egg having six chromosomes leads again to the formation of the hermaphrodite with twelve chromosomes4 ,it is obvious that in this case the cause for the hermaphroditism is not disclosed4 ,if chromosomes have anything to do with hermaphroditism there must be an undiscovered element in the chromosomes which may explain why the female as well as the hermaphrodite have the same chromosome constitution2 or we are forced to look for another determinant outside the ,x chromosomes or the chromosomes altogether4 ,this seems to be the only cytological work on the problem of hermaphroditism4 ,experimental work has been begun by ,correns#ahi and by ,shull on the determination of hermaphroditism in plants but lack of space forbids us to give details4 #ahi ,correns1 ,c41 ,biol4 ,centralbl41 #aiaf1 xxxvi41 #ab4 ,,ii4 ,the ,physiological ,basis of ,sex ,determination #e4 ,as stated at the beginning of this chapter1 the chromosome theory of sex determination explained only one feature of the problem1 namely1 the relative numbers in which both sexes or only one sex1 as the case may be1 are produced2 and in this respect the evidence is so complete that we must accept it4 ,but with all this1 the problem of sex determination is not exhausted1 since a physiological solution of the problem of sex determination demands an account of how the sex chromosomes can induce the formation not only of ovaries and testes but also of the other sex characters4 ,for the solution of this problem biology will have to depend largely on experiments in which it is possible to influence the formation of sex characters and of the sex glands themselves4 ,the most striking observations in this direction were made by ,baltzer on a marine worm1 ,bonellia4 ,in this animal the two sexes are very different1 the male being a tiny parasite1 a few millimetres in length1 which spends its life in the uterus of the female1 whose size is about five centimetres4 ,a female carries as a rule several and often a large number of the male parasites in its uterus1 which indicates that the males prevail numerically4 ,the fertilized eggs of the animals are laid in the sea water where the larv hatch4 ,at the time of hatching all larv are alike4 ,the differentiation of the larv into the dwarf males and the giant females can be determined at will4 ,the larv have a tendency to attach themselves to the proboscis of the female as soon as they hatch4 ,if given a chance to do so and if they stick to the proboscis for more than three days they will develop into males1 which soon afterwards creep into the female where they continue their parasitic existence4 ,if1 however1 no adult female ,bonellia is put into the aquarium in which the larv hatch1 about ninety per cent4 of the larv will1 after a period of rest1 develop into females2 the rest develop into males4 ,those which develop into females will often show a primary maleness which may manifest itself in the production of sperm or of other secondary male sexual characters4 ,this tendency is stronger the longer the period of rest lasts4 ,if the larv are allowed to settle on the proboscis of the adult female but are removed too early hermaphrodites are produced having male and female characters mixed4 ,baltzer has suggested on the basis of some observations that the larv while on the proboscis of the female absorb some substance secreted by the proboscis1 and this substance accelerates the further development into a male and suppresses the female tendency4 ,if this substance from the proboscis does not reach the larv the tendency to become males is gradually suppressed in the majority and only a few develop into pure males or protandric hermaphrodites1 while the female characters are given a chance to develop4 ,baltzer assumes1 therefore1--as it seems to us correctly--that in all larv the tendency for both sexual characters is present1 that they are1 in other words1 hermaphrodites1 but the chance for the suppression of one and the development of the other group of characters can be influenced by certain chemical substances which the larva may take up4#aij #aij ,baltzer1 ,f41 ,mitteil4 d4 zolog4 ,station1 ,neapel1 #aiad1 xxii4 ,giard has studied the effects of a curious form of castration brought about by parasites1 which is followed by a change in the sexual character of the castrated animal4 ,the phenomenon is very striking in certain forms of crabs when they are attacked by a parasitic crustacean1 ,sacculina4 ,the two sexes differ in the crab ,carcinus mnas by the form of the abdomen1 but when a male is attacked by the parasite its abdomen assumes the female shape4 ,smith observed in another crab that in such cases even the abdominal appendages of the male may be transformed into those of a female4 ,the transformation is so complete that the older observers had reached the conclusion that the parasite attacked only the females1 since they overlooked the fact that the castration by the parasite transformed the secondary sexual characters of the male into those of a female4 ,giard observed that in a dicious plant1 ,lychnis dioica1 a parasitic fungus brings about the transformation of the host into a hermaphrodite4 ,g4 ,smith has discovered a fact which shows that chemical changes must underlie these morphological transformations of primary or secondary sexual characters4 ,he noticed that in male crabs the presence of the parasite ,sacculina changes the contents of the fatty constituents in the blood1 making them equal to that of the female4 ,vaney and ,meignon had previously shown that during the chrysalid stage the female silkworms have always more glycogen and less fat than the males4 ,the castration by parasites is paralleled by what ,caullery calls the castration by senility4#aia ,in certain birds and also in mammals at the time when the sexual glands cease to function certain secondary sexual characters of the other sex make their appearance4 ,the most common case is that certain secondary male characters appear in the old female 7exceptionally also in the young female with abnormal ovaries7 7arrhenoidy74 ,thus old female pheasants assume the plumage of the male1 and in the human female after the menopause and especially among sterile women a beard may begin to grow4 ,the opposite phenomenon1 the old male assuming female characters1 is not so common4 ,very interesting observations on changes in the plumage of castrated fowl have recently been made by ,goodale4#aib #aia ,caullery1 ,m41 ,les ,problmes de la ,sexualit4 ,paris1 #aiac4 #aib ,goodale1 ,h4 ,d41 ,biol4 ,bull41 #aiaf1 xxx41 #bhf4 ,it had long been observed by cattle breeders that in the case of twins of different sex the female--the so-called free-martin--is usually sterile4 ,f4 ,lillie#aic has recently discovered the cause of this interesting phenomenon4 ,such twins originate from two different eggs since the mother has two corpora lutea1 one in each ovary4 ,in normal single pregnancies in cattle there is never more than one corpus luteum present4 ,the two eggs begin to develop separately in each horn of the uterus4 #aic ,lillie1 ,f41 ,science1 #aiaf1 xliii41 #faa4 ,the rapidly elongating ova meet and fuse in the small body of the uterus at some time between the #aj mm4 and the #bj mm4 stage4 ,the blood-vessels from each side then anastomose in the connecting part of the chorion2 a particularly wide arterial anastomosis develops1 so that either fetus can be injected from the other4 ,the arterial circulation of each also overlaps the venous territory of the other1 so that a constant interchange of blood takes place4 ,if both are males or both are females no harm results from this2 but if one is male and the other female1 the reproductive system of the female is largely suppressed1 and certain male organs even develop in the female4 ,this is unquestionably to be interpreted as a case of hormone action4 ,the reproductive system of these sterile females is for the most part of the female type1 though greatly reduced4 ,the gonad is the part most affected2 so much so that most authors have interpreted it as testis4 ,it should be added1 however1 that this result cannot at present be generalized1 since in the hermaphrodites the specific hormones of both sexes must circulate without suppressing each other's efficiency4 ,all these facts indicate that certain substances secreted by the ovaries or testes may inhibit the development of certain sexual characters of the opposite sex4 ,when these inhibitions are partly or entirely removed the secondary sexual characters of the opposite sex may appear4 ,this fact may also be interpreted as an indication of a latent hermaphroditism and if this be correct the real and latent hermaphrodites differ only by the degree of inhibition for one sex1 this inhibition being lacking or less complete in the real than in the latent hermaphrodite4 ,in the light of this conclusion the observations on the regeneration of both ovaries and testicles which ,janda observed in a hermaphroditic worm1 ,criodrilus lacuum1#aid is no longer so mysterious4 ,this worm normally possesses in the segments near the head a pair of ovaries and several pairs of testes4 ,janda found that if the anterior parts containing the gonads of these worms are cut off a complete regeneration takes place1 including both types of gonads1 ovaries as well as testes4 ,as a rule1 more than one pair of ovaries appear in the regenerated piece4 ,this important experiment shows that in a hermaphrodite both types of sex organs can be produced from body cells or from latent buds resembling body cells4 ,this phenomenon would be intelligible on the assumption that in the body of a hermaphrodite substances circulate which favour the development of both types of sex organs1 while in a dician animal probably only one type of sex organ would be developed2 the formation of the other being inhibited4 #aid ,janda1 ,v41 ,arch4 f4 ,entwcklngsmech41 #aiab1 xxxiii41 #cde2 xxxiv41 #eeg4 ,richard ,goldschmidt has discovered in his breeding experiments on the gipsy-moth 7,lymantria dispar7 a phenomenon which will probably throw much light on the physiology of sex determination4 ,he found that certain crosses between the ,japanese and the ,european gipsy-moth do not give pure sexes1 males or females1 but mixtures of the sexual characters of both sexes1 and this mixture is a very definite one for definite crosses4 ,these differences are such that it is possible to grade the hybrids according to their manifestations of maleness or femaleness1 both in morphological characters and instincts4 ,goldschmidt calls this peculiar phenomenon intersexualism1 and its essential feature is that the various degrees of intersexualism can be produced at will by the right combination of races4 ,female intersexualism begins with animals which show feathered antenn of medium size 7feathered antenn are a male character71 but which are otherwise entirely female in appearance except that they produce a smaller number of eggs which are fertilized normally4 ,in the next stage patches of the brown male pigment appear on the white female wings in steadily increasing quantity4 ,the instincts are still female1 the males are attracted and copulate4 ,but the characteristic egg sponge laid by the animal contains nothing but anal hairs in spite of the fact that the abdomen is filled with ripe eggs4 ,in the next stage whole sections of the wings show male colouration1 with cuneiform female sectors between1 the abdomen becomes smaller1 contains fewer ripe eggs1 the instincts are only slightly female1 the males are attracted very little1 and reproduction is impossible4 ,in the next stage the male pigment covers practically the whole wing1 the abdomen is almost male1 but still contains ovaries with a few ripe eggs1 the instincts are intermediate between male and female4 ,then follow very male-like animals which still show in different organs their female origin and have rudimentary ovaries4444 ,the end of the series is formed by males1 which show in some minor characters1 such as the shape of wings1 still some traces of their female origin4 ,the series of the male intersexes starts with males showing a few white female spots on their wings4 ,these become larger and larger1 the amount of brown pigment correspondingly decreasing4444 ,hand in hand with this the abdomen increases in size1 reaching in the most extreme cases two-thirds of the female size 7without containing eggs74 ,the same is true for the instincts which become more and more female4 7,and also for the copulatory organs which also become more and more female47 ,as stated above1 the main fact that every desired degree of intersexualism can be produced at will by properly combining the races for breeding1 and the intersexual potencies of the different races has been worked out by ,goldschmidt4#aie #aie ,goldschmidt1 ,r41 ,proc4 ,nat4 ,acad4 ,sc41 #aiaf1 ii41 #ec2 ,ztschr4 induct4 ,abstammungslehre1 #aiab1 vii41 and #aiad1 xi4 #f4 ,the relation between chemical substances circulating in the body--either derivatives of food taken up from without or of chemical compounds formed naturally inside the body--and the production of sexual characters is best shown in the polymorphism found among the social ants1 bees1 and wasps4 ,here we have1 as a rule1 in addition to the two sexes a third one1 the workers1 which are in reality rudimentary and for that reason sterile females4 ,they differ more or less markedly from both the typical male and female in their external form1 and1 as a rule cannot copulate owing to their deficient structure4 ,this third sex1 the sterile neuters1 can be transformed at desire into sexual females in certain species1 as ,p4 ,marchal has demonstrated4 ,he worked with a form of social wasps in which the workers are sterile and smaller than the real females4 ,in such a society of wasps all the males and workers die in the fall and only the fertilized females survive1 each one founding a new nest in the following spring4 ,from the first eggs laid1 workers arise1 small in stature and sterile2 these workers are nourished by their mother4 ,then these workers take care of the feeding of all those larv which arise from the eggs which their mother continues to lay4 ,throughout the spring only workers arise from the eggs4 ,the males appear in the summer1 the real females towards the end of the season when the sexes copulate4 ,marchal isolated a number of the sterile workers1 providing them with food but giving them no larv to raise4 ,he found that the workers which thus far had been sterile became fertile1 producing1 however1 only males4 ,this latter fact is easily understood from what has been said regarding the bees1 namely1 that the female produces only one type of eggs1 hence the unfertilized egg can give rise only to males4 ,the astonishing or important point is that the ovaries of the workers begin to develop as soon as they no longer have a chance to nourish the larv1 provided the food which would have been given to the larv is now at their disposal4 ,in other words1 the development of their ovaries is the outcome of eating the food which under normal conditions they would have given to the larv4 ,the food must1 therefore1 contain a substance which induces the development of eggs4 ,the natural sterility of the neuters or workers is1 therefore1 to use ,p4 ,marchal's expression1 a case of 8food castration10 78castration nutriciale074#aif ,the workers originate from fertilized eggs and are therefore females1 but for the full development of the ovaries and the other sexual characters something else besides the ,,xx chromosomes is needed and this is supplied in this case by the quantity or quality of the food4 ,may we not conclude that the same thing may happen generally1 except that these substances are formed by the body under the normal conditions of nutrition through the influence of constituents of the second ,x chromosome8 #aif ,this account of ,marchal's beautiful experiments is taken from ,caullery1 ,m41 ,les ,problmes de la ,sexualit4 ,paris1 #aiac4 ,it is known that the future queens among the bees receive also a special type of food which the workers do not receive4 ,again the idea of 8food castration0 of the latter is suggested4 ,in rotifers ,whitney#aig has shown that the cycle in the production of males and females can be regulated by the food4 ,in some species a scanty supply of green flagellates produced purely female offspring1 while a copious diet of the same green flagellates produced a predominance of male grandchildren1 sometimes as high as ninety-five per cent4 ,this was confirmed by ,shull and ,ladoff4#aih #aig ,whitney1 ,d4 ,d41 ,science1 #aiaf1 xliii41 #agf4 #aih ,shull1 ,a4 ,f41 and ,ladoff1 ,s41 ,science1 #aiaf1 xliii41 #agg4 #g4 ,the effects of the removal of the ovaries or testes upon the development of secondary sexual characters differ for different species4 ,in insects the secondary sexual characters are not altered by an operative removal of the sexual glands as in the caterpillar1 e4 g41 ,ocneria dispar1 according to ,oudemans4 ,this result has been invariably confirmed by all subsequent workers1 especially by ,meisenheimer4 ,crampton grafted the heads of pup of butterflies upon the bodies of other specimens of the opposite sex1 but the sexual characters of the head remained unaltered4 ,in vertebrates1 however1 there exists a distinct influence of a secretion from the sexual glands upon the development of certain of the secondary sexual characters1 which do not develop until sexual maturity4 ,in a way the observations on arrhenoidy and thelyidy referred to above are indications of this influence4 ,bouin and ,ancel had already suggested that the sexual glands of mammals have two independent constituents1 the sexual cells and the interstitial tissue2 and that the latter tissue is responsible for the development of the secondary sexual character4 ,this has been proved definitely by ,steinach1#aii who showed that when young rats are castrated certain secondary sexual characters are not fully developed4 ,the seminal vesicles and the prostate remain rudimentary and the penis develops incompletely4 ,such animals when adult recognize the female and seem to follow it1 but do not persist in their attention and neither erection nor cohabitation occurs4 ,when1 however1 the testes are retransplanted into the muscles of the castrated young animal 7so that they are no longer connected with their nerves7 seminal vesicles1 prostate1 and penis develop normally1 and these animals show normal sexual ardour and cohabitate with a female although the female cannot become pregnant since the males cannot ejaculate any sperm4 ,when the retransplanted testes were examined it was found that all the sperm cells had perished1 only the interstitial tissue of the testes remaining4 ,it was1 therefore1 proved that the development of the seminal vesicles1 the prostate1 the penis1 and the normal sexual instincts and activities depends upon the internal secretions from this interstitial tissue and not upon the sex cells proper4 ,this agrees with the conclusions at which ,bouin and ,ancel had arrived by ligaturing the vasa deferentia of male animals4 #aii ,steinach1 ,e41 ,zentralbl4 f4 ,physiol41 #aiaj1 xxiv41 #eea2 ,arch4 f4 d4 ges4 ,physiol41 #aiab1 cxliv41 #gb4 ,steinach in another series of experiments castrated young male rats and transplanted into them the ovaries of young females4 ,these ovaries did not disintegrate1 the eggs remaining1 and corpora lutea were formed4 ,in such feminized individuals the seminal vesicles1 prostate1 and penis did not reach their normal development1 and it was thereby proved that the internal secretions from the ovary do not promote the growth of the secondary sexual male characters4 ,on the contrary1 ,steinach was able to show that the growth of the penis was directly inhibited by the ovary1 since in the feminized males this organ remained smaller than in the merely castrated animals4 ,on the other hand the infantile uterus and tube when transplanted into the young male with the ovaries grow in a normal way1 and ,steinach thinks that pregnancy in such feminized males is possible if sperm be injected into the uterus4 ,in some regards the feminized males showed the morphological habitus of females4 ,soon after the transplantation of ovaries into a castrated male the nipples of its mammary glands begin to grow to the large size which they have in the female and by which the two sexes can easily be discriminated4 ,in addition the stronger longitudinal growth of the body in the male does not occur in the feminized specimens1 the body growth becomes that of a female2 and likewise the fat and hair of the feminized male resemble that of a real female4 ,while the castrated males show an interest in the females1 the feminized males are absolutely indifferent to females and behave like them when put together with normal males2 and1 what is more interesting1 they are treated by normal males like normal females4 ,the sexual instincts have1 therefore1 also been reversed in the feminized males by the substitution of ovaries for testes4 ,the inhibition of the growth of the penis by the ovary is of importance2 it supports the idea already expressed that in hermaphrodites this inhibition of the growth of the secondary organs of the other sex is only feeble or does not exist at all4 ,we may finally ask whether there is any connection between the cytological basis of sex determination by special sex chromosomes and the physiological basis of sex determination by specific substances or internal secretions4 ,it is possible that the sex chromosomes determine or favour1 in a way as yet unknown1 the formation of the specific internal secretion discussed in the second part of this chapter4 ,in this way all the facts of sex determination might be harmonized1 and it may become clear that when it is possible to modify secretions by outside conditions or to feed the body with certain as yet unknown specific substances the influence of the sex chromosomes upon the determination of sex may be overcome4 ,,chapter ,,ix ,,mendelian ,,heredity ,,and ,,its ,,mechanism#bjj ,i #a4 ,the scientific era of the investigation of heredity begins with ,mendel's paper on plant hybridization which was not appreciated by his contemporaries4 ,mendel invented a method for the quantitative study of heredity which consisted essentially in crossing two forms of peas differing only in one well-defined hereditary character2 and in following statistically and separately the results of this crossing and that of the inbreeding of the second and third generations of hybrids4 ,this led him to the recognition of one essential feature of heredity2 namely1 that while the hybrids of the first generation are all alike1 each hybrid produces two types of sex cells in equal numbers1 one for each of the pure breeds which has been used for the crossing4 ,this takes place not only when the forms used for the crossing differ in regard to one character only but also if they differ for two or more characters4 ,the statement made is ,mendel's law of heredity1 or1 more correctly1 ,mendel's law of the segregation of the hereditary characters of the parents in the sex cells of the hybrids4#bja ,mendel's law allows us to tabulate and calculate beforehand the relative number of different forms which appear if the offspring of a mating of two varieties are bred among themselves4 #bjj ,for the literature on the subject the reader is referred to ,morgan1 ,t4 ,h41 ,sturtevant1 ,a4 ,h41 ,muller1 ,h4 ,j41 and ,bridges1 ,c4 ,b41 ,the ,mechanism of ,mendelian ,heredity4 ,new ,york1 #aiae4 #bja ,mendel1 ,g41 8,experiment in ,plant-,hybridization10 translated in ,w4 ,bateson's classical book on ,mendel's ,principles of ,heredity4 ,cambridge1 #aiji4 ,in order to do this it must be remembered also that while in some cases the hybrid is an intermediate between the two parent forms1 in other cases it cannot be discriminated from one of the two parent forms4 ,in such cases the character which appears in the hybrid was called by ,mendel the dominant character and the one which disappeared the recessive character4 ,according to ,bateson1 who was the first to systematize the phenomena of ,mendelian heredity1 recessiveness means generally the absence of a character which is present in the dominant type4 ,when1 e4 g41 the cross between a tall and a dwarf form of pea gives in the first generation only tall peas1 on the basis of the presence and absence theory the dominant form contains a factor for growth which is lacking in the dwarf form4 ,while this theory fits many cases it meets with difficulties in others4 ,thus the presence of a factor for pigment should be dominant over the absence of such a factor1 which is usually the case1 inasmuch as the cross of a coloured rat or rabbit with an albino is black or coloured4 ,there is1 however1 also a case where whiteness is dominant over colour1 as we shall see later4 ,this fact does not necessarily contradict the presence and absence theory4#bjb #bjb ,the reader will find a critical discussion of the presence and absence theory on page #bbj of ,morgan1 ,sturtevant1 ,muller1 and ,bridges1 ,the ,mechanism of ,mendelian ,heredity4 ,new ,york1 #aiae4 ,when two pure breeds of parents differ in one character1 e4 g41 two varieties of beans1 one with a violet the other with a white flower1 the cross between the two species 7the ,f generation7 has pale violet flowers1 approximately intermediate between the two parents4 ,if these hybrids are bred among themselves the offspring is called the ,f generation4 ,according to ,mendel's law the hybrids of the first ,f generation all have two kinds of eggs in equal numbers1 one kind representing the pure breed of the parents with violet1 the other of the pure breed with white flowers4 ,the same is true for the pollen cells4 ,hence the following possible combinations must appear in the offspring when the pale violet hybrids are inbred3 violet white 4444 eggs _/ ,x _/ violet white 4444 pollen ,the four possible combinations are3 7#a7 violet--violet2 7#b7 violet--white2 7#c7 violet--white2 7#d7 white--white4 ,the first will result in pure violet flowers1 the fourth in pure white1 and the second and third in pale violet flowers4 ,since all four combinations will appear in equal numbers when the number of crossings is sufficiently large the numerical result will be3 violet3 pale violet3 white #a3b3a ,fifty per cent4 of the ,f generation will be pale violet1 #be per cent4 violet1 and #be per cent4 white4 ,the violets and whites each will breed true when bred among themselves since they are pure1 and produce only one type of eggs and pollen4 ,the pale violets are hybrids and will again produce the two types of eggs and pollen1 that is1 if bred among themselves will again give violets1 pale violets1 and whites in the ratio #a3b3a4 ,this the experiment confirms4 ,as has been stated1 it not infrequently happens that all the hybrids of the first generation are alike4 ,in such cases the one character is 8recessive10 i4 e41 overshadowed or covered by the other the 8dominant0 character1 which alone appears in the hybrids4 ,thus when ,mendel crossed peas having round seeds with peas having angular seeds all the hybrids had round seeds4 ,the round form is dominant1 the angular recessive1 i4 e41 all the hybrids have round seeds4 ,when these hybrids were bred among themselves the next generation produced round and angular seeds in the ratio of #c3a 7#edgd round to #ahej angular74 ,the explanation is as follows4 ,let ,r denote round1 ,a angular character2 the pure breeds of parents have the gametic constitution ,,rr and ,,aa respectively4 ,when crossed1 all the offsprings have the constitution ,,ra and since ,a is recessive this hybrid generation resembles the pure ,,rr parents4 ,the ,f generation produces two kinds of eggs ,r and ,a and two kinds of pollen ,r and ,a in equal numbers1 and these if inbred give the following four combinations in equal numbers3 ,,rr1 ,,ra1 ,,ar1 ,,aa4 ,since ,,ra1 ,,ar1 and ,,rr all give round seeds the ,f generation produces round seeds to angular seeds in the ratio of #c3a4 ,the two organisms with the gametic constitution ,,rr and ,,ra look alike1 yet they are different in regard to heredity4 ,the gametically pure form ,,rr is called homozygous1 the impure form ,,ra heterozygous4 #b4 ,w4 ,s4 ,sutton#bjc was the first to show that the behaviour of the chromosomes furnishes an adequate basis on which to account for ,mendel's law of the segregation of the characters in the sex cells of the hybrids4 ,if we disregard the cases of parthenogenesis and the ,x chromosomes1 we may state that each species is characterized by a definite number of chromosomes1 e4 g4#bjd #bjc ,sutton1 ,w4 ,s41 8,the ,chromosomes in ,heredity10 ,biol4 ,bull41 #aijd1 iv41 #bca4 #bjd ,morgan1 ,t4 ,h41 ,sturtevant1 ,a4 ,h41 ,muller1 ,h4 ,j41 and ,bridges1 ,c4 ,b41 ,mechanism of ,mendelian ,heredity4 ,new ,york1 #aiae1 p4 #bf4 man 7probably7 #bd corn #bj mouse #bj evening primrose #g snail 7,helix hortensis7 #bb nightshade #cf potato beetle #ah tobacco #bd cotton #bh tomato #ab four o'clock #af wheat #h garden pea #g ,in the fertilization of the egg the number of chromosomes is doubled 7if we disregard for the moment the complication caused by the ,x and ,y chromosomes which was considered in the previous chapter74 ,it was noticed by ,montgomery that each chromosome had a definite size and individuality1 and he suggested that homologous chromosomes existed in sperm and egg and that in fertilization the homologous chromosomes of egg and sperm always joined and fused in the special stage designated as synapsis1 which will interest us later4 ,on the basis of this suggestion ,sutton developed the chromosome theory of the mechanism of ,mendelian heredity or segregation4 ,according to this theory1 all the cells of an individual 7inclusive of the egg cells and sperm cells7 have two sets of homologous chromosomes1 one from the father1 the other from the mother4 ,before the egg and sperm are ready for the production of a new individual1 each loses one set of homologous chromosomes in the so-called reduction division1 but the lost set is made up indiscriminately of maternal as well as paternal chromosomes1 so that while one egg retains the maternal chromosome ,a the other will retain the paternal one1 and so on4 ,if before the reduction division all the eggs had the chromosome constitution ,,aa1 ,,bb1 ,,cc1 ,,dd 7where ,a ,b ,c ,d are the paternal and ,a ,b ,c ,d the maternal chromosomes71 after the reduction division each daughter cell has a full set of four chromosomes1 but maternal and paternal mixed4 ,thus the one cell may have ,,ab,,cd1 the other ,a,b,c,d1 etc4 ,this1 according to ,sutton1 is the basis of the ,mendelian heredity4 ,suppose the determiner of a certain character 7violet colour of flower in the bean7 is located in a chromosome ,a of this species4 ,the homologous chromosome in beans with white colour may be designated as a4 ,according to the chromosome theory of ,mendelian heredity a differs from ,a in one point1 though this difference is probably only of a chemical character and not visible4 ,if an egg with ,a is fertilized by a pollen with a 7or vice versa71 after fertilization the chromosome constitution of the fertilized egg is ,aa4 ,all the other homologous chromosomes are identical and therefore need not be considered4 ,all the nuclei of the ,f generation have the chromosome constitution ,aa4 ,all will form eggs and pollen with nuclei of the same chromosome constitution ,aa1 but all these sex cells will go through the maturation division before they are fertilized2 and this reduction division leads to the existence of two kinds of eggs in equal numbers1 one containing only the ,a1 the other only the a chromosome2 and the same happens in the pollen4 ,when therefore the hybrids ,f are mated among themselves1 the following four chromosome combinations will be produced3 ,eggs ,pollen ,a a ,a a ,transcriber's note3 ,diagram illustrating the four possible pairings of chromosomal characters ,possible combinations in fertilized eggs ,,aa1 ,aa1 aa1 in the ratio #a3b3a4 ,now this is exactly the ratio of ,mendelian heredity in the ,f generation4 ,the plant with the chromosome constitution ,,aa will form violet flowers1 those with the chromosome constitution ,aa will form pale violet flowers1 and those with the chromosome constitution aa will form white flowers4 ,to quote ,sutton's words3 ,the result would be expressed by the formula ,,aa3 ,aa3 aa which is the same as that given for any character in a ,mendelian case4 ,thus the phenomena of germ cell division and of heredity are seen to have the same essential features viz41 purity of units 7chromosomes1 characters7 and the independent transmission of the same2 while as a corollary it follows in each case that each of the two antagonistic units 7chromosomes1 characters7 is contained by exactly half the gametes produced4 ,it is obvious that ,sutton by this idea did for heredity in general what ,mc,clung had done for sex determination or sex heredity1 that is1 he showed that the numerical results obtained in ,mendelian heredity can be accounted for on the basis that factors for hereditary characters are carried by definite chromosomes4 ,the cytological basis of sex determination becomes only a special case of the cytological basis of ,mendelian heredity4 ,in the examples quoted the plants giving rise to violet and to white flowers are homozygous for the colour of flower having the chromosome constitution ,,aa and aa respectively2 while the plants with pale violet flowers are heterozygous1 having the chromosome constitution ,aa in their nuclei4 ,the former give rise to identical sex cells ,a and ,a or a and a2 while the heterozygous plants give rise to different sex cells ,a and a4 ,from this point of view in ,drosophila 7and very probably also in man7 the female is homozygous for sex having in all its cells the critical chromosome constitution ,,xx and giving rise to one type of eggs only1 each with one ,x chromosome2 while the male in these forms is heterozygous for sex having in all its cells the chromosome constitution ,,xy and forming two different types of spermatozoa in equal numbers ,x and ,y4 ,in ,abraxas and in the fowl the female is heterozygous for sex and the male homozygous4 #c4 ,if the chromosomes are the vehicle for ,mendelian heredity it should be possible to show that the various hereditary characters which follow ,mendel's law must be distributed over the various chromosomes2 and it should be possible to find out which characters are contained in the same chromosome4 ,it has already been stated that sex-linked heredity is intelligible on the assumption that the ,x chromosome carries the sex-linked characters4 ,t4 ,h4 ,morgan and his pupils have shown with the greatest degree of probability that corresponding linkages occur in the other chromosomes and that there are in ,drosophila exactly as many groups of linkage as there are different chromosomes1 namely four4#bje #bje ,morgan1 ,t4 ,h41 ,sturtevant1 ,a4 ,h41 ,muller1 ,h4 ,j41 and ,bridges1 ,c4 ,b41 ,the ,mechanism of ,mendelian ,heredity4 ,new ,york1 #aiae4 ,mendel had found that when he crossed two species of peas differing in regard to two pairs of characters1 he obtained in the ,f generation results which he calculated on the assumption that the segregation of the two pairs of characters in the sex cells of the hybrids took place independently of each other4 ,to illustrate by an example3 ,when crossing a yellow round pea with a green wrinkled variety in which the characters round and yellow are dominant1 green and wrinkled recessive1 all the hybrids of the ,f generation had the characters round and yellow4 ,when these were inbred the ,f generation produced four types of seed in the ratio #i3 #c3 #c3 #a1 namely3 7#a7 yellow round 7#cae seeds7 7#b7 yellow wrinkled 7#aja seeds7 7#c7 green round 7#ajh seeds7 7#d7 green wrinkled 7#cb seeds7 ,the explanation according to ,mendel's theory is as follows3 ,since the segregation of each pair of characters occurs independently1 there must be #c yellow to #a green and also #c round to #a wrinkled in the ,f generation4 ,the yellow will1 therefore1 be round and wrinkled in the ratio of #c3a1 which will give #i yellow round to #c yellow wrinkled4 ,the green will also be round and wrinkled in the ratio of #c3a1 which will give #c green round to #a green wrinkled1 which is the ratio of #i3 #c3 #c3 #a found by ,mendel4 ,on the basis of the chromosome theory the following explanation could be given of this numerical relation4 ,the peas with yellow round seeds have sex cells with a factor for both yellow and for round in two different chromosomes2 these two different chromosomes we will designate with ,y and ,r4 ,the peas with green and wrinkled seeds will have in their sex cells factors for these characters in two homologous chromosomes g and w1 where g is the homologue of ,y and w of ,r4 ,the cells of the hybrids of the ,f generation will have the chromosome constitution ,yg ,rw1 where ,y and g and ,r and w are homologous chromosomes which will lie alongside each other ,y,rgw,transcriber's note3 displayed in the text as ,,yr over gw1 i4e4 like a fraction but without a dividing bar4 ,in the formation of sex cells a reduction of these four chromosomes to two takes place whereby1 according to the theory of ,sutton1 the following two types of separation can take place3 ,,yr and gw1 or g,r and ,yw4 7,a separation into ,yg and ,rw is impossible since the division takes place only between homologous chromosomes47 ,hence there will be four types of eggs1 ,,yr1 gw1 g,r1 and ,yw and the same four types of pollen cells4 ,the ,f generation will produce the sixteen possible combinations in equal numbers3 namely1 ,,yryr ,y,rgw ,y,rg,r ,y,r,yw gw,y,r gwgw gwg,r gw,yw g,r,y,r g,rgw g,rg,r g,r,yw ,yw,y,r ,ywgw ,ywg,r ,yw,yw ,since w and g are recessives and therefore disappear when in combination with their respective dominants ,y and ,r the result will be #i ,,yr 7yellow round71 #c ,yw 7yellow wrinkled71 #c ,rg 7round green71 and #a gw 7green wrinkled7 as ,mendel actually observed and as all investigators since have confirmed4 ,bateson made the discovery that these ,mendelian ratios #i3 #c3 #c3 #a did not always occur when forms differing in two characters were crossed4 ,he found typical and very constant deviations from this ratio in definite cases and these cases he interpreted as being due to 8gametic coupling40 ,these phenomena demonstrate the existence of a complex interrelation between the factorial units4 ,this interrelation is such that certain combinations between factors may be more frequent than others4 ,the circumstances in which this interrelation is developed and takes effect we cannot as yet distinguish1 still less can we offer with confidence any positive conception as to the mode in which it is exerted4#bjf #bjf ,bateson1 ,w41 loc4 cit41 p4 #aeg4 ,morgan has given an ingenious explanation of these deviations on the basis of the chromosome theory of ,mendelian heredity4 ,he assumes that they occur in those cases where the two or more characters are contained in the same chromosome4 ,in that case the two factors lying in the same chromosome should generally be found together4 ,such was the case for instance in the experiments with flies having red eyes and yellow body colour versus white eyes and grey body colour1 the character for white eyes and yellow body being located in the ,x chromosome 7see preceding chapter71 or in the experiments on ,abraxas4 ,these phenomena are called linkage1 and the numerical results of linkage were given in the preceding chapter in connection with the crossing of sex-linked characters4 ,we have already mentioned that before the maturation division occurs the homologous maternal and paternal chromosomes fuse--the so-called synapsis of the cytologists--and afterward separate again4 ,it had been observed by ,janssens that in this stage of fusion and subsequent separation a partial twisting and a partial exchange between two chromosomes may take place4 ,morgan assumes that this exchange accounts for certain deviations in the ratio of linkage4 ,if in ,fig4 #dj the white and black signify two homologous chromosomes ,i and ,i containing the two pairs of homologous factors ,,ab and ab respectively1 the synapsis state would be as in ,fig4 #da4 ,if the separation were complete1 either ,i or its homologue ,i might be lost in the maturation division of the egg4 ,if1 however1 the synapsis is slightly irregular1 as in ,fig4 #db1 where the chromosomes are slightly twisted1 ,i and ,i will not separate completely but an exchange will take place1 part of ,i and ,i becoming exchanged4 ,this would result in the formation of two mixed chromosomes ,ab and a,b 7,fig4 #db74 ,this partial exchange of homologous chromosomes1 which ,morgan calls 8crossing over10 occurs1 as he found in ,drosophila1 in the egg only1 not in the maturation division of the sperm4 ,he informs me that in the silkworm moth ,tanaka found that it occurs only in the male1 while in ,primula it takes place both in the ovules and in the pollen as shown by ,gregory4 ,illustration3 ,,fig4 #dj ,illustration3 ,,fig4 #da ,illustration3 ,,fig4 #db ,morgan and his fellow-workers have put this theory to numerous tests by breeding experiments and the results have fully supported it4 ,according to the chromosome theory linkage should occur only when factors lie in the same chromosome4 ,hence it should be possible1 on the basis of this linkage theory1 to foretell how many linkage groups there may occur in a species2 namely1 as many as there are chromosomes4 ,in ,drosophila there are four pairs of chromosomes1 and ,morgan and his fellow-workers found only four groups of linked characters4#bjg ,this agreement can be no mere accident4 #bjg ,the number of hereditary characters examined to test the theory was over #acj4 ,carrying the assumption still farther1 these authors were able to show that each individual character has in all probability a definite location in the chromosome1 so that it seems as if each individual chromosome consisted of a series of smaller chromosomes1 each of which may be a factor in the determination of a hereditary character which is transmitted according to ,mendel's law of segregation4 ,biology has thus reached in the chromosome theory of ,mendelian heredity an atomistic conception1 according to which independent material determiners for hereditary characters exist in a linear arrangement in the chromosomes4 ,,ii #d4 ,we are not concerned in this volume with the many applications of the theory of heredity to the breeding of plants1 animals1 and man2 the reader will find a discussion of these topics in the numerous writings of the special workers on genetics4#bjh ,we are1 however1 interested in the bearing this work has on the conception of the organism4 ,two questions present themselves3 ,is the organism nothing but a mosaic of hereditary characters determined essentially by definite elements located in the chromosomes2 and if this be true1 what makes a harmonious whole organism out of this kaleidoscopic assortment8 ,we call it a kaleidoscopic assortment since a glance at the list of hereditary characters found in one chromosome1 according to ,morgan1 shows that there is apparently no physiological or chemical connection between them1 and second3 ,how can a factor contained in the chromosome determine a hereditary character of the organism8 ,to the first question we venture to offer the answer which has been already suggested in various chapters of this book1 that the cytoplasm of the egg is the future embryo in the rough2 and that the factors of heredity in the sperm only act by impressing the details upon the rough block4 ,this metaphor will receive a more definite meaning by the answer to the second question4 ,the characters which follow ,mendelian heredity are morphological features as well as instincts4 ,for the former we have already had occasion to show in previous chapters to what extent they depend upon the internal secretions or the existence of specific compounds in the circulation1 and the same is true for the instincts 7,chapters ,,viii and ,x74 ,this then leads us to the suggestion that these determiners contained in the chromosomes give rise each to the formation of one or more specific substances which influence various parts of the body4 ,we probably do not notice all the effects in each case1 but when a special organ is affected in a conspicuous way1 we connect the factor with this organ or the special feature of the organ which is altered1 and speak of a determiner or factor for that organ1 or for one of its characters4 ,we also understand in this way why outside conditions should be able to overcome the hereditary tendency in certain cases1 for instance why the influence of certain hereditary factors for pigmentation should depend upon temperature as ,e4 ,baur observed4 #bjh ,bateson1 ,w41 ,mendel's ,principles of ,heredity1 #c;d ed41 #aiac2 ,davenport1 ,chas4 ,b41 ,heredity in ,relation to ,eugenics1 #aiaa4 ,pearl1 ,r41 ,modes of ,research in ,genetics4 ,the view1 according to which the determiners in the chromosomes only tend to give special characters to the embryo or to the adult while the cytoplasm of the egg may be considered the real embryo1 receives some support from the fact that the first development of the egg is purely maternal1 even if the egg nucleus has been replaced by sperm of a different species4 ,if an egg of a sea urchin be cut into two pieces1 one with and one without a nucleus1 and the enucleated piece be fertilized with the sperm of a different species of sea urchin1 the blastula and gastrula stages are purely maternal and only the skeleton of the pluteus stage begins to betray the influence of the foreign sperm inasmuch as this skeleton is purely paternal1 according to ,boveri4 ,in all experiments on hybridization it has been found that the rate of cell division of the egg is a purely maternal character4 ,thus when fish eggs of a species1 in which the rate of first segmentation of the egg is about eight hours1 are fertilized with sperm of a species for which the same process requires about thirty minutes or less at the same temperature1 the rate of segmentation is again about eight hours4 ,there is then no chromosome influence noticeable in the early development4 ,when two forms of sea urchins1 ,strongylocentrotus franciscanus and purpuratus1#bji are crossed1 certain features of the skeleton of the embryo1 e4 g41 the so-called cross-bars1 are a dominant1 inasmuch as they are found in purpuratus and both the crosses1 while they are absent in franciscanus4 ,the development prior to the formation of the skeleton is purely maternal4 ,these observations again lend support to the idea that the ,mendelian factors of heredity must have the embryo to work on and that the organism is not to be considered a mere mosaic of ,mendelian factors4 ,this is further supported by the idea that the species specificity resides in the proteins of the unfertilized egg 7see ,chapter ,,iii71 and it is quite likely that this species specificity decides which type of animal should arise from an egg4 #bji ,loeb1 ,j41 ,king1 ,w4 ,o4 ,r41 and ,moore1 ,a4 ,r41 ,arch4 f4 ,entwcklngsmech41 #aiaj1 xxix41 #ced4 ,these experiments have been repeated at different seasons of the year and in different years and have been found to be constant4 ,the idea had been suggested that the factors which determine the future character might be ferments or enzymes1 or substances from which such ferments develop4 ,a4 ,r4 ,moore#baj pointed out that the cross-bars in the skeleton of the hybrid between ,s4 purpuratus and franciscanus develop more slowly than in the pure breed and that this should be expected if the determiners were enzymes4 ,since the pure purpuratus has two determiners for the development of the cross-bars 7from both egg and sperm71 the hybrids only one 7from either egg or sperm71 the pure purpuratus should have twice the enzyme mass of the hybrid4 ,it is known that the velocity of a chemical reaction increases in proportion with the mass 7or in some cases in proportion with the square root of the mass7 of the enzyme2 the cross-bars should therefore develop faster in the pure than in the hybrid breeds1 as was observed by ,moore4 ,it was1 however1 not possible to obtain quantitative data4 #baj ,moore1 ,a4 ,r41 ,arch4 f4 ,entwcklngsmech41 #aiab1 xxxiv41 #afh4 ,on the other hand1 it is obvious that this reasoning would not hold for all cases4 ,thus when beans with violet flowers are crossed with white-flowered beans the hybrids are pale blue1 which indicates that the hybrids have less pigment than the pure violet4 ,now we know that the mass of enzyme does not influence the chemical equilibrium but only the velocity of the reaction4 ,the hybrids and pure violets differ1 however1 in the mass of violet pigment formed1 that is to say1 in regard to the equilibrium4 ,hence the idea that the determiners are enzymes or give rise to enzymes is probably not applicable to cases of this type4 ,the experiments on the heredity of pigments are at present almost the only ones which can be used for an analysis of the chemical nature of the character and its possible determiner4 ,the important work of ,g4 ,bertrand#baa and of ,chodat#bab on the production of black pigment in the cells of animals and plants with the aid of enzymes has paved the way for such work4 ,bertrand has shown that tyrosine 7p-oxyphenylaminopropionic acid7 is transformed into a black pigment by an enzyme tyrosinase which occurs in numerous organisms and is obviously the cause of pigment and colouration in a great number of species4 ,this discovery was utilized in the study of the heredity of pigments by ,miss ,durham1 ,gortner1#bac and very recently by ,onslow4#bad ,the latter showed that from the skins of certain coloured rabbits and mice a peroxidase can be extracted which behaves like a tyrosinase toward tyrosine in the presence of hydrogen peroxide4 ,this peroxidase was found in the skins of black agouti1 chocolate and blue rabbits1 but not in yellow or orange rabbits4 ,the recessive whiteness in rabbits and mice according to this author is due to the lack of the peroxydase4 ,there exists a dominant whiteness in the ,english rabbit which is due to a tyrosinase inhibitor which destroys the activity of the tyrosinase 8and the dominant white bellies of yellow and agouti rabbits are due to the same cause40 8,variations in coat colour are probably due to a quantitative rather than to a qualitative difference in the pigment present40 #baa ,bertrand1 ,g41 ,ann4 d4 l',inst4 ,pasteur1 #aijh1 xxii41 #cha2 ,bull4 ,soc4 ,chim41 #ahif1 xv41 #gia4 #bab ,chodat1 ,r41 ,arch4 d4 ,sc4 phys4 et nat41 #aiae1 xxxix41 #cbg4 #bac ,gortner1 ,r4 ,a41 ,trans4 ,chem4 ,soc41 #aiaj1 xcvii41 #aaj4 #bad ,onslow1 ,h41 ,proc4 ,roy4 ,soc41 #aiae1 ,b4 lxxxix41 #cf4 ,one point might still be mentioned since it may help to overcome a difficulty in visualizing the connection between the localization of a factor in the chromosome and the production of a comparatively large quantity of a specific chemical compound1 e4 g41 a chromogen or a tyrosinase4 ,we must remember that all the cells of an organism have identical chromosomes1 so that a factor for an enzyme like tyrosinase is contained in every cell throughout the whole body4 ,it is likely1 however1 that the same factor 7which we may conceive to be a definite chemical compound7 will find a different chemical substrate to work on in the cells of different organs of the body1 since the different organs differ in their chemical composition4 ,thus it is conceivable that in the production of tyrosinase or of tyrosine not a single chromomere of one single cell is engaged1 but the sum total of all these individual chromomeres of all the cells in one or several organs of the body4 ,the writer has added this remark especially in consideration of the fact that some authors seem to feel that the chromosome conception of heredity is incompatible with a physicochemical view of this process4 ,since we have mentioned this difficulty which some writers seem to find in the chromosome theory of ,mendelian heredity1 it may be added that a single factor may suffice to determine a series of complicated reflexes4 ,thus the heliotropic reactions of animals are due to the presence of photosensitive substances1 and it suffices for the hereditary transmission of the complicated purposeful reactions based on these tropisms that a factor for the formation of the photosensitive substance should exist4#bae #bae ,loeb1 ,j41 8,egg ,structure and the ,heredity of ,instincts10 ,the ,monist1 #ahig1 vii41 #dha4 #e4 ,another point should be emphasized1 namely that for ,mendelian heredity it is immaterial whether the character is introduced by the spermatozon or by the egg4 ,this fact which ,mendel himself already recognized is in full harmony with the conclusion that the chromosomes and not the cytoplasm are the bearers of ,mendelian heredity1 since only in respect to the chromosome constitution are egg and sperm alike1 while they differ enormously in regard to the mass of protoplasm they carry4 ,we can1 therefore1 be tolerably sure that wherever we deal with a hereditary factor which is determined by the egg alone the cytoplasm of the latter is partly or exclusively responsible for the result4 ,we have already mentioned the fact that the rate of segmentation of the egg is such a character4 ,yet this character is as definite as any ,mendelian character1 and it would be as easy to discriminate two species of eggs by the time required from insemination to the beginning of cell division as it would be by any ,mendelian character of their parents4 ,the application of our modern knowledge of heredity to human affairs has been discussed in a very original way by ,bateson in his address before the ,british ,association in ,sydney to which the reader may be referred4#baf #baf ,bateson1 ,w41 ,nature1 #aiaf1 xciii41 #fgd4 ,,chapter ,x ,,animal ,,instincts ,,and ,,tropisms#bag #a4 ,the idea that the organism as a whole cannot be explained from a physicochemical viewpoint rests most strongly on the existence of animal instincts and will4 ,many of the instinctive actions are 8purposeful10 i4 e41 assisting to preserve the individual and the race4 ,this again suggests 8design0 and a designing 8force10 which we do not find in the realm of physics4 ,we must remember1 however1 that there was a time when the same 8purposefulness0 was believed to exist in the cosmos where everything seemed to turn literally and metaphorically around the earth1 the abode of man4 ,in the latter case1 the anthropo- or geocentric view came to an end when it was shown that the motions of the planets were regulated by ,newton's law and that there was no room left for the activities of a guiding power4 ,likewise1 in the realm of instincts when it can be shown that these instincts may be reduced to elementary physicochemical laws the assumption of design becomes superfluous4 #bag ,ideas similar to those expressed in this chapter may be found in the writer's former book ,comparative ,physiology of the ,brain and ,comparative ,psychology1 ,new ,york1 #aijj1 and in the books by ,george ,bohn1 ,la ,naissance de l',intelligence1 ,paris1 #aiji1 and ,la nouvelle ,psychologie animale1 ,paris1 #aiaa4 ,if we look at the animal instincts purely as observers we might well get the impression that they cannot be explained in mechanistic terms4 ,we need only consider what mysticism apparently surrounds all those instincts by which the two sexes are brought together and by which the entrance of the spermatozon into the egg is secured2 or the remarkable instincts which result in providing food and shelter for the young generation4 ,we have already had occasion to record some cases of instincts which suggest the possibility of physicochemical explanation2 for example the curious experiment of ,steinach on the reversal of the sexual instincts of the male whose testes had been exchanged for ovaries4 ,there is little doubt that in this case the sexual activities of each sex are determined by specific substances formed in the interstitial tissue of the ovary and testes4 ,the chemical isolation of the active substances and an investigation of their action upon the various parts of the body would seem to promise further progress along this line4 ,marchal's observations on the laying of eggs by the naturally sterile worker wasps are a similar case4 ,the fact that such workers lay eggs when the queen is removed or when they are taken away from the larv may be considered as a manifestation of one of those wonderful instincts which form the delight of readers of ,maeterlinck's romances from insect life4 ,imagine the social foresight of the sterile workers who when the occasion demands it 8raise0 eggs to preserve the stock from extinction6 ,and yet what really happens is that these workers1 when there are no larv1 can consume the food which would otherwise have been devoured by the larv2 and some substance contained in this food induces the development of eggs in the otherwise dormant ovaries4 ,what appeared at first sight as a mysterious social instinct is revealed as an effect comparable to that of thyroid substance upon the growth of the legs of tadpoles in ,gudernatsch's experiment 7,chapter ,,vii74 #b4 ,if we wish to show in an unmistakable way the mechanistic character of instincts we must be able to reduce them to laws which are also valid in physics4 ,that instinct1 or rather that group of instincts1 for which this has been accomplished are the reactions of organisms to light4 ,the reader is familiar with the tendency of many insects to fly into the flame4 ,it can be shown that many species of animals1 from the lowest forms up to the fishes1 are at certain stages--very often the larval stage--of their existence1 slaves of the light4 ,when such animals1 e4 g41 the larv of the barnacle or certain winged plant lice or the caterpillars of certain butterflies1 are put into a trough or test-tube illuminated from one side only1 they will rush to the side from which the light comes and will continue to do this whenever the orientation of the trough or test-tube to the light is changed2 while they will be held at the window side of the vessel if the light or the position of the vessel remains unchanged4 ,this instinct to get to the source of light is so strong that1 e4 g41 the caterpillars of ,porthesia chrysorrha die of starvation on the window side of the vessel1 with plenty of food close behind4 ,this powerful 8instinct0 is1 as we intend to show1 in the last analysis1 the expression of the ,bunsen-,roscoe law of photochemical reactions4 ,a large number of chemical reactions are induced or accelerated by light1 and the ,bunsen-,roscoe law shows that the chemical effect is in these cases1 within certain limits1 equal to the product of the intensity into the duration of illumination4 ,the 8attraction0 or 8repulsion0 of animals by the light had been explained by the biologists in an anthropomorphic way by ascribing to the animals a 8fondness0 for light or for darkness4 ,thus ,graber1 who had made the most extensive experiments1 gave as a result the statement that animals which are fond of light are also fond of blue while they hate the red1 and those which are fond of the 8dark0 are fond of red and hate the blue4#bah ,in #ahhh the writer published a paper in which he pointed out that the so-called fondness of animals for light and blue and for dark and red was simply a case of an automatic orientation of animals by the light comparable to the turning of the tips of a plant towards the window of the room in which the plant is raised4#bai #bah ,graber1 ,v41 ,grundlinien zur ,erforschung des ,helligkeits- und ,farbensinnes der ,tiere4 ,prag1 #ahhd4 #bai ,loeb1 ,j41 ,sitzungsber4 d4 physik4-med4 ,gesellsch4 ,wrzburg1 #ahhh4 ,der ,heliotropismus der ,tiere und seine bereinstimmung mit dem ,heliotropismus der ,pflanzen4 ,wrzburg1 #ahhi4 ,arch4 f4 d4 ges4 ,physiol41 #ahig1 lxvi41 #dci4 ,the phenomenon of a plant bending or growing to the source of light is called positive heliotropism 7while we speak of negative heliotropism in all cases in which the plant turns away from the light1 as is observed in many roots74 ,the writer pointed out that animals which go to the light are positively heliotropic 7or phototropic7 and do so because they are compelled automatically by the light to move in this direction1 while he called those animals which move away from the light negatively heliotropic2 they are automatically compelled by the light to move away from it4 ,what the light does is to direct the motions of the animals and to explain this the following theory was proposed4 ,animals possess photosensitive elements on the surface of their bodies1 in the eyes1 or occasionally also in epithelial cells of their skin4 ,these photosensitive elements are arranged symmetrically in the body and through nerves are connected with symmetrical groups of muscles4 ,the light causes chemical changes in the eyes 7or the photosensitive elements of the skin74 ,the mass of photochemical reaction products formed in the retina 7or its homologues7 influences the central nervous system and through this the tension or energy production of the muscles4 ,if the rate of photochemical reaction is equal in both eyes this effect on the symmetrical muscles is equal1 and the muscles of both sides of the body work with equal energy2 as a consequence the animal will not be deviated from the direction in which it was moving4 ,this happens when the axis or plane of symmetry of the animal goes through the source of light1 provided only one source of light be present4 ,if1 however1 the light falls sidewise upon the animal1 the rate of photochemical reaction will be unequal in both eyes and the rate at which the symmetrical muscles of both sides of the body work will no longer be equal2 as a consequence the direction in which the animal moves will change4 ,this change will take place in one of two ways1 according as the animal is either positively or negatively heliotropic2 in the positively heliotropic animal the resulting motion will be toward1 in the negatively heliotropic from1 the light4 ,where we have no central nervous system1 as in plants or lower animals1 the tension of the contractile or turgid organs is influenced in a different way1 which we need not discuss here4 ,the reader will perceive that according to the writer's theory two agencies are to be considered in these reactions3 first1 the symmetrical arrangement of the photosensitive and the contractile organs1 and second1 the relative masses of the photochemical reaction products produced in both retin or photosensitive organs at the same time4 ,if a positively heliotropic animal is struck by light from one side1 the effect on tension or energy production of muscles connected with this eye will be such that an automatic turning of the head and the whole animal towards the source of light takes place2 as soon as both eyes are illuminated equally the photochemical reaction velocity will be the same in both eyes1 the symmetrical muscles of the body will work equally1 and the animal will continue to move in this direction4 ,in the case of the negatively heliotropic animal the picture is the same except that if only one eye is illuminated the muscles connected with this eye will work less energetically4 ,the theory can be nicely tested for negatively heliotropic animals in the larv of the blowfly when they are fully grown1 and for positively heliotropic animals on the larv of ,balanus1 and many other organisms4 ,one of the difficulties in identifying the motions of animals to or from the light with the positive and negative heliotropism of plants consisted in the fact that plants are mostly sessile 7and respond to a one-sided illumination with heliotropic curvatures to or from the light71 while most animals are free moving and respond to the one-sided illumination by being turned and compelled to move to or from the light4 ,this difficulty was overcome by the observation that sessile animals like the hydroid ,eudendrium 7,fig4 #dc7 or the tube worm ,spirographis 7,fig4 #dd7 react to a one-sided illumination also with heliotropic curvatures like sessile plants4#bbj ,on the other hand1 it had been found before by ,strassburger that free-swimming plant organisms like the swarmspores of alg move to or from the source of light as do free-swimming animals4 #bbj ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #ahij1 xlvii41 #cia2 #ahif1 lxiii41 #bgc4 ,illustration3 ,,fig4 #dc ,illustration3 ,,fig4 #dd #c4 ,the writer suggested in #ahigbba that the light acts chemically in the heliotropic reactions and in #aiab that the heliotropic reactions probably follow the law of ,bunsen and ,roscoe1#bbb and it was possible to confirm this idea by direct experiments4#bbc ,this law states that the photochemical effect of light equals i t where i is the intensity of the light and t the duration of illumination4 ,the experiments were carried out on young regenerating polyps of ,eudendrium by measuring the time required to cause fifty per cent4 of the polyps to bend to the source of light4 ,the intensity of light was varied by altering the distance of the source of light from the polyps4 ,table ,,vi gives the result4 #bba ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #ahig1 lxvi41 #dci4 #bbb ,loeb1 ,j41 ,the ,mechanistic ,conception of ,life1 ,chicago1 #aiab1 p4 #bg4 #bbc ,loeb1 ,j41 and ,ewald1 ,w4 ,f41 ,zentralbl4 f4 ,physiol41 #aiad1 xxvii41 #aafe4 ,,table ,,vi ---------------------------------------- ------------------ ,distance ,time ,required to ,cause ,fifty ,per ,cent4 of the between ,polyps to ,bend towards the ,source of ,light ,polyps and ---------------------------------------- ----- ,source of ,observed ,calculated from ,light ,bunsen-,roscoe ,law ---------------------------------------- ----------------- ,metres ,minutes ,minutes ---------------------------------------- ----------------- #j4be #aj #j4ej between #ce and #dj #dj #a4jj #aej #afj #a4ej between #cfj and #dbj #cfj ---------------------------------------- ----------------- ,we must therefore conclude that the heliotropic curvature of the polyps is determined by a photochemical action of the light4 ,the light brings about or accelerates a chemical reaction which follows the ,bunsen-,roscoe law4 ,as soon as the product of this reaction on one side of the polyp exceeds that on the other by a certain quantity1 the bending occurs4 ,when the product it is the same for symmetrical spots of the organism no bending can result4 ,this is what our theory suggested4 ,it is very difficult to prove directly the applicability of the ,bunsen-,roscoe law for free-moving animals1 but it can be shown that intermittent light is as effective as constant light of the same intensity1 provided that the total duration of the illumination by the intermittent light is equal to that of the constant light1 and the duration of the intermission is sufficiently small 7,talbot's law74 ,talbot's law is in reality only a modification of the ,bunsen-,roscoe law4 ,ewald has proved in a very elegant way the applicability of ,talbot's law to the orientation of the eyestalk of ,daphnia4#bbd ,this makes it probable that the law of ,bunsen-,roscoe underlies generally the heliotropic reaction of animals4 #bbd ,ewald1 ,w4 ,f41 ,science1 #aiac1 xxxviii41 #bcf4 ,it is of importance for the theory of the identity of the heliotropism of animals and plants that in the latter organisms the law of ,bunsen and ,roscoe is also applicable4 ,this had been shown previously by ,frschel#bbe and by ,blaauw4#bbf ,in the following table are given the results of ,blaauw's experiments on the applicability of the ,bunsen-,roscoe law for the heliotropic curvature of the seedlings of oats 7,avena sativa74 ,the time required to cause heliotropic curvatures for intensities of light varying from #j4jjjag to #bfebj metre-candles was measured4 ,the product i t1 namely metre-candles-seconds1 varies very little 7between #af and #bf74 #bbe ,frschel1 ,p41 ,sitzungsber4 d4 k4 ,akad4 d4 ,wissensch41 ,wien1 #aijh1 cxvii4 #bbf ,blaauw1 ,h4 ,a41 ,rec4 d4 travaux botaniques ,nerlandais1 #aiji1 v41 #bji4 ,,table ,,vii --------------------------------------- ,i ,,ii ,,iii ,duration of ,metre- ,metre- ,illumination ,candles ,candles- ,seconds --------------------------------------- #dc hours #j4jjjag #bf4c #ac #j4jjjdci #bj4f #aj #j4jjjfji #ba4i #f #j4jjjhee #ah4f #c #j4jjagfi #ai4a #ajj minutes #j4jjbgjf #af4b #fj #j4jjdggc #ag4b #cj #j4jajah #ah4c #bj #j4jafdj #ai4g #ae #j4jbdi #bb4d #h #j4jdih #bc4i #d #j4jhih #ba4f #dj seconds #j4faef #bd4h #be seconds #a4jiih #bg4e #h #c4jbhac #bd4b #d #e4def #ba4h #b #h4dec #af4i #a #ah4id #ah4i #b_/e #de4je #ah4j #b_/be #cjh4g #bd4g #a_/be #eaa4d #bj4e #a_/ee #abee #bb4h #a_/ajj #aijb #ai4j #a_/djj #gije #ai4h #a_/hjj #acjid #af4d #a_/ajjj #bfebj #bf4e --------------------------------------- ,it is1 therefore1 obvious that the blind instinct which forces animals to go to the light1 e4 g41 in the case of the moth1 is identical with the instinct which makes a plant bend to the light and is a special case of the same law of ,bunsen and ,roscoe which also explains the photochemical effects in inanimate nature2 or in other words1 the will or tendency of an animal to move towards the light can be expressed in terms of the ,bunsen-,roscoe law of photochemical reactions4 ,the writer had shown in his early publications on light effects that aside from the heliotropic reaction of animals1 which as we now know depends upon the product of the intensity and duration of illumination1 there is a second reaction which depends upon the sudden changes in the intensity of illumination4 ,these latter therefore obey a law of the form3 ,effect f 7di_/dt74#bbg ,jennings has maintained that the heliotropic reactions of unicellular organisms are all of this kind1 but investigations by ,torrey and by ,bancroft#bbh on ,euglena have shown that ,jennings's statements were based on incomplete observations4 #bbg ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #ahic1 liv41 #ha2 ,jour4 ,exper4 ,zol41 #aijg1 iv41 #aea4 #bbh ,bancroft1 ,f4 ,w41 ,jour4 ,exper4 ,zol41 #aiac1 xv41 #chc4 #d4 ,in these experiments only one source of light was applied4 8,when two sources of light of equal intensity and distance act simultaneously upon a heliotropic animal1 the latter puts its median plane at right angles to the line connecting the two sources of light40#bbi ,this fact has been amply verified by ,bohn1 by ,parker and his pupils1 and especially by ,bradley ,patten1 who used it to compare the relative efficiency of two different lights4 #bbi ,loeb1 ,j41 ,studies in ,general ,physiology1 ,chicago1 #aije1 p4 #b4 ,the behaviour of the animals under the influence of two lights is a confirmation of our theory of heliotropism inasmuch as the animal moves in such a direction that the symmetrical elements of the surface of the body are struck by light of the same intensity at the same angle1 so that as a consequence equal masses of photosensitive substances are produced in symmetrical elements of their eyes or skin in equal times4 ,the effect on the symmetrical muscles will be identical4 ,as soon as one of the lights is a little stronger the animal will deviate towards this light1 in case it is positively heliotropic and towards the weaker light if it is negatively heliotropic4 ,this deviation again is not the product of chance but follows a definite law as ,patten#bcj has recently shown4 ,he used the negatively heliotropic larv of the blowfly4 ,these larv were made to record their trail while moving under the influence of the two lights4 ,the results of the measurements of #bejj trails showing the progressive increase in angular deviation of the larv 7from the perpendicular upon the line connecting the two lights71 with increasing differences between the lights1 are given in the following table4 ,since the deviation or angular deflection of the larv is towards the weaker of the two lights it is marked negative4 #bcj ,patten1 ,bradley ,m41 ,am4 ,jour4 ,physiol41 #aiae1 xxxviii41 #cac4 ,,table ,,viii ---------------------------------------- -------------- ,percentage ,difference ,average ,angular ,deflection of in the ,intensity the ,two ,paths of the ,larv of the ,two ,lights towards the ,weaker ,light ---------------------------------------- -------------- ,per ,cent4 ,degrees #j -#j4ji #h-a_/c -#b4gg #af-b_/c -#e4ge #be -#h4hf #cc-a_/c -#aa4ib #ej -#bj4bh #ff-b_/c -#cj4ij #hc-a_/c -#df4ha #ajj -#gg4ef ---------------------------------------- -------------- ,let us assume that the negatively heliotropic animal is at an equal distance from the two unequal lights and placed so that at the beginning of the experiment its median plane is at right angles to the line connecting the two lights1 but with its head turned away from them4 ,in that case the velocity of reaction in the symmetrical photosensitive elements of the eyeless larv is greater on the side of the stronger light4 ,since the animal is negatively heliotropic this will result in a greater relaxation or a diminution of the energy production of the muscles turning the head of the animal towards the side of the stronger light4 ,hence the animal will automatically deviate from the straight line towards the side of the weaker light4 ,by the alteration of the position of its body the photosensitive elements exposed to the stronger of the two lights will be put at a less efficient angle and hence the rate of photochemical reaction on this side will be diminished4 ,the deviation from the perpendicular in which the animal will ultimately move will be such that as a consequence1 the rate of photochemical reaction in symmetrical elements is again equal4 ,the ultimate direction of motion will1 according to our theory always be such that the mass of chemical products formed under the influence of light in symmetrical photosensitive elements during the same time is equal4 ,patten also investigated the question whether the same difference of percentage between two lights would give the same deviation1 regardless of the absolute intensities of the lights used4 ,the absolute intensity was varied by using in turn from one to five glowers4 ,the relative intensity between the two lights varied in succession by #j1 #h-a_/c1 #af-b_/c1 #be1 #cc-a_/c1 and #ej per cent4 ,yet the angular deflections were within the limits of error identical for each relative difference of intensity of the two lights no matter whether1 #a1 #b1 #c1 #d1 or #e glowers were used4 ,the following table shows the result4 ,,table ,,ix ,a ,,table ,,based ,,on ,,the ,,measurements ,,of #bgjj ,,trails ,,showing ,,the ,,angular ,,deflections ,,at ,,five ,,different ,,absolute ,,intensities ---------------------------------------- ---------------------------- ,difference of ,intensity between the ,two ,lights ,number ---------------------------------------- -------------- of #j #h-a_/c #af-b_/c #be #cc-a_/c #ej ,glowersper cent4per cent4per cent4per cent4per cent4per cent4 ---------------------------------------- ----------------------- ,deflection in ,degrees #a -#j4ee -#b4cb -#e4bg -#i4jd -#aa4hf -#ai4df #b -#j4aj -#c4je -#f4ab -#h4ee -#aa4ib -#bb4bh #c #j4de -#b4fj -#e4fe -#h4gc -#ac4ae -#bj4eb #d -#j4jbe -#b4ih -#f4fj -#i4ff -#aa4gf -#ai4hh #e -#j4bbe -#b4ib -#e4abe -#h4cj -#aj4ib -#ai4bh ---------------------------------------- ----------------------- ,average -#j4ji -#b4gg -#e4ge -#h4hf -#aa4ib -#bj4bh ---------------------------------------- ----------------------- ,such constancy of quantitative results is only possible where we are dealing with purely physicochemical phenomena or where life phenomena are unequivocally determined by purely physicochemical conditions4 #e4 ,it seems difficult for some biologists1 even with the validity of the ,bunsen-,roscoe law proven1 to imagine that the movements of the animals under the influence of light are not voluntary 7or not dictated by the mysterious 8trial and error0 method of ,jennings74#bca ,but one wonders how it is possible on such an assumption to account for the fact that the angle of deflection of the larva of the fly when under the influence of two lights of different intensities should be always the same for a given difference in intensity2 or why the time for curvature in ,eudendrium should vary inversely with the intensity of illumination4 ,it is1 however1 possible to complete the case for the purely physicochemical analysis of these instincts4 ,john ,hays ,hammond1 ,jr41 has succeeded in constructing heliotropic machines which in the dark follow a lantern very much in the manner of a positively heliotropic animal4 ,the eyes of this heliotropic machine consist of two lenses in whose focus is situated the 8retina0 consisting of selenium wire4 ,the two eyes are separated from each other by a projecting piece of wood which represents the nose and allows one eye to receive light while the other is shaded4 ,the galvanic resistance of selenium is altered by light2 and when one selenium wire is shaded while the other is illuminated1 the electric energy 7supplied by batteries inside the machine7 which makes the wheels turn 7these take the place of the legs of the normal animal7 no longer flows symmetrically to the steering wheel1 and the machine turns towards the light4 ,in this way the machine follows a lantern in a dark room in a way similar to that of a positively heliotropic animal4 ,here we have a model of the heliotropic animal whose purely mechanistic character is beyond suspicion1 and we may be sure that it is not 8fondness0 for light or for brightness nor will-power nor a method of 8trial and error0 which makes the machine follow the light4 #bca ,according to this theory the animal is not directly oriented by the outside force1 e4 g4 the light1 but selects among its random movements the one which is most 8suited0 and keeps on moving in this direction4 ,this idea is untenable for most if not all the cases of tropisms and has been refuted by practically all the workers in this field1 e4 g41 ,parker and his pupils1 ,bohn1 ,h4 ,b4 ,torrey1 ,holmes1 ,bancroft1 ,ewald1 and others4 ,it is only upheld by ,jennings and ,mast2 and is accepted among those to whom the idea of a physicochemical explanation of life phenomena does not appeal4 ,torrey and ,bancroft 7for the literature the reader is referred to ,bancroft's paper1 ,jour4 ,exper4 ,zol41 #aiac1 xv41 #chc7 have shown directly that the theory of trial and error is not even correct for the organism for which ,jennings has developed this idea2 namely ,euglena4 #f4 ,it may also be of interest to know that in heliotropism the motions of the legs are automatically controlled by the chemical changes taking place in symmetrical elements of the retina4 ,in order to prove this point we will turn to the phenomenon of galvanotropism4 ,the galvanic current forces certain animals to move in the direction of one of the two electrodes just as the light forces the heliotropic animals to move towards 7or from7 the source of light4 ,the change in the concentration of the ions at the boundary of the various organs1 especially the nerves1 determines the galvanotropic reactions4 ,when the shrimp ,palmonetes is put into a trough with dilute salt solution through which a current of a certain intensity flows1 the animal is compelled to move towards the anode4#bcb ,it can walk forwards1 backwards1 or sidewise4 ,here we can observe directly that the effect of the current consists in altering the tension of the muscles of the legs in such a way as to make it easy for the animal to move toward the anode and difficult to move toward the cathode4 ,thus if the current be sent sidewise through the animal1 say from left to right 7,fig4 #de71 the legs of the left side assume the flexor position1 those of the right the extensor position4 ,with this position of its legs the animal can easily move to the left1 i4 e41 the anode1 and only with difficulty to the right1 i4 e41 the cathode4 ,this change in the position of the legs occurs when the animal is not moving at all1 thus showing that the galvanotropic movements take place not because the animal intends to go to the anode1 but that the animal goes to the anode because its legs are practically prevented by the galvanic current from working in any other way4 ,this is exactly what happens in the heliotropic motions of animals4#bcc #bcb ,loeb1 ,j41 and ,maxwell1 ,s4 ,s41 ,arch4 f4 d4 ges4 ,physiol41 #ahif1 lxiii41 #aba4 #bcc ,that the mechanisms by which heliotropic and galvanotropic orientation is brought about are identical was shown by ,bancroft in ,euglena 7,bancroft1 loc4 cit474 ,illustration3 ,,fig4 #de ,to understand what happens when the current goes lengthwise through the body it should be stated that ,palmonetes uses the third1 fourth1 and fifth pairs of legs for its locomotion4 ,the third pair pulls in the forward movement1 and the fifth pair pushes4 ,the fourth pair generally acts like the fifth1 and requires no further attention4 ,if a current be sent through the animal longitudinally1 from tail to head1 and the strength be increased gradually1 a change soon takes place in the position of the legs 7,fig4 #df74 ,in the third pair the tension of the flexors predominates1 in the fifth the tension of the extensors4 ,the animal can thus move easily with the pulling of the third and the pushing of the fifth pairs of legs1 that is to say1 the current changes the tension of the muscles in such a way that the forward motion is rendered easy1 the backward motion is difficult4 ,hence it can easily move toward the anode1 but only with difficulty toward the cathode4 ,if a current be sent through the animal in the opposite direction1 namely1 from head to tail1 the third pair of legs is extended1 the fifth pair bent2 that is1 the third pair can push1 and the fifth pair pull4 ,the animal will thus move backward easily and forward with difficulty1 and it is thus driven to the anode again4 ,illustration3 ,,fig4 #df ,the explanation which ,loeb and ,maxwell proposed for this influence of the current on the legs assumes that there are three groups of ganglion cells in the central nervous system of these animals which are oriented according to the three main axes of the body2 7#a7 right-left and left-right1 7#b7 backward1 and 7#c7 forward4 ,it depends upon whether the ganglion cells or the nerve elements are in anelectrotonus1 which muscles are bent and which relaxed4 ,it would lead us too far to recapitulate the theory in this place1 and the reader who is interested in it is referred to ,loeb and ,maxwell's paper4#bcd ,the importance of the observations lies in the fact that they show that any element of will or choice on the part of the animal in these motions is eliminated1 that the animal moves where its legs carry it1 and not that the legs carry the animal where the latter 8wishes0 to go4 #bcd ,loeb1 ,j41 and ,maxwell1 ,s4 ,s41 ,arch4 f4 d4 ges4 ,physiol41 #ahif1 lxiii41 #aba4 #g4 ,this may be the place to dispel an error which has sometimes crept into the discussion of the tropistic reactions of animals4 ,it has been stated occasionally that it is the energy gradient and not the automatic orientation of the animal by the light which makes the positively heliotropic animal move towards the source of light and the negatively heliotropic away from it4 ,thus the positively heliotropic animal would be compelled to move towards the source of light as a consequence of the fact that the intensity of the light increases the more the nearer the animal approaches the source of light4 ,if the source of light be the reflected sky-light the difference of intensity at both ends of a microscopic organism is so slight that it is beneath the limit capable of influencing the motions4 ,illustration3 ,,fig4 #dg ,a simple experiment published by the writer in #ahhi suffices to dispel the idea that the energy gradient determines the direction of the motion of an animal in tropistic reactions4 ,let direct sunlight 7,s1 ,fig4 #dg7 fall through the upper half of a window 7w w7 upon a table1 and diffused daylight 7,d7 through the lower half of the window on the same table4 ,a test-tube a c is placed on the table in such a way that its long axis is at right angles to the plane of the window2 and one half a b is in the direct sunlight1 the other half in the shade4 ,if at the beginning of the experiment the positively heliotropic animals are in the direct sunlight at a1 they promptly move toward the window1 gathering at the window end c of the tube1 although by so doing they go from the sunshine into the shade4#bce ,this experiment is in harmony with our idea that the effect of light consists in turning the head of the animal and subsequently its whole body toward the source of light4 ,by going from the strong light into the shade the reaction velocity in both eyes is diminished equally and hence there is no reason for the animal to change its orientation1 though its progressive motion may be stopped for an instant by the change4 ,but at the boundary between sunlight and daylight a sudden change from strong to weak light occurs4 ,if the energy gradient determined the direction of the positively heliotropic animal1 the motion should stop at the boundary from strong to weak light1 which may happen for an instant but which will not interfere with the progressive motion of the animal4 #bce ,loeb1 ,j41 ,dynamics of ,living ,matter1 p4 #abf4 #h4 ,graber had found that when animals are put into a trough covered half with blue and half with red glass1 those that are 8fond0 of light go under the blue1 those that are 8fond0 of darkness go under the red glass4 ,the writer pointed out that this result should be expected on the basis of his theory of heliotropism1 if the assumption be correct that the red light is considerably less efficient than light which goes through blue glass 7such glass also allows green rays to go through74 ,the botanists had already shown that red glass is impermeable for the rays which cause heliotropic reactions of plants1 and the writer was able to show the same for the heliotropic reactions of animals4 ,red glass acts1 therefore1 almost like an opaque body for these animals4 ,a closer examination of the most efficient rays for the heliotropic reactions of different organisms has revealed the fact that for some organisms a region in the blue #dfj-dij 1 for others a region in the yellowish-green1 near about #ebj-ecj is the most efficient4#bcf ,for many plants and for some animals1 like ,eudendrium and the larv of the worm ,arenicola1 a region in the blue is most efficient2 for certain1 if not most1 animals a region in the yellow-green is most efficient4 ,among unicellular green alg1 ,chlamydomonas1 has its maximal efficiency in the yellowish-green and ,euglena in the blue4 ,according to observations by ,mast1 some green unicellular organisms like ,pandorina1 ,eudorina1 and ,spondylomorum seem to behave more like ,chlamydomonas1 while certain others behave more like ,euglena4#bcg ,wasteneys and the writer suggested that there are two groups of heliotropic substances1 one with a maximum of photosensitiveness in the blue1 the other in the yellowish-green2 and that the latter group may or may not be related or identical with the visual purple which is most rapidly bleached by light of a wave length near #ebj-ecj 4 #bcf ,loeb1 ,j41 and ,maxwell1 ,s4 ,s41 ,univ4 ,cal4 ,pub41 #aiaj1 ,physiol41 iii41 #aie2 ,loeb and ,wasteneys1 ,proc4 ,nat4 ,acad4 ,sc41 #aiae1 i41 #dd2 ,science1 #aiae1 xli41 #cbh2 ,jour4 ,exper4 ,zol41 #aiae1 xix41 #bc2 #aiaf1 xx41 #bag4 #bcg ,mast1 ,s4 ,o41 ,proc4 ,nat4 ,acad4 ,sc41 #aiae1 i41 #fbb4 ,the ophthalmologist ,hess#bch has utilized the heliotropic reactions of animals in an attempt to prove that all animals from the lowest invertebrates up to the fishes inclusive suffer from total colour-blindness4 ,this statement was based on the observation that for most positively heliotropic animals the region in the yellowish-green near #ebj seems the most efficient4 ,since this region of the spectrum appears also as the brightest to a totally colour-blind man1 he concluded that all these animals are totally colour-blind4 ,there is no reason why heliotropic reactions should be used as an indicator for colour sensations2 if totally colour-blind human beings were possessed of an irresistible impulse to run into a flame ,hess's assumption might be considered1 but no such phenomenon exists in colour-blind man4 ,moreover1 v4 ,frisch#bci has shown by experiments on the influence of the background on the colouration of fish as well as by experiments on bees and on ,daphnia that the reactions of these animals to light of different wave-lengths indicate different effects besides those of mere intensity4 ,thus v4 ,frisch could train bees to go to a blue piece of cardboard distributed among many cardboards of different shades of grey4 ,bees thus trained would alight on any blue object even if it contained no food4 ,it would be impossible to do this with totally colour-blind organisms4 #bch ,hess1 ,c41 8,gesichtssinn10 ,winterstein's ,handb4 d4 vergl4 ,physiol41 #aiac1 iv4 #bci v4 ,frisch1 ,k41 8,der ,farbensinn und ,formensinn der ,biene10 ,zol4 ,jahrb4 ,abt4 f4 allg4 ,zol4 u4 ,physiol41 #aiad1 xxxv4 ,see also ,ewald1 ,w4 ,f41 ,ztschr4 f4 ,sinnesphysiol41 #aiad1 xlviii41 #bhe4 #i4 ,heliotropic reactions play a great rle in the preservation of individuals as well as of species4 ,in order to understand this rle it must be stated that the photosensitive substances appear often only under certain conditions and that their effect is inhibited under other conditions4 ,thus among ants the winged males and females alone show positive heliotropism1#bdj while the wingless workers are free from this reaction4 ,this positive heliotropism becomes violent at the time of the nuptial flight and this phenomenon itself seems to be a heliotropic phenomenon since it takes place in the direction of the light4 ,when the queen founds her nest she loses her wings and becomes negatively heliotropic again4 ,kellogg#bda has shown that the nuptial flight of the bees is also a purely heliotropic phenomenon4 ,when a part of the hive remote from the entrance is illuminated the bees rush to the light and can thus be prevented from swarming4 ,these phenomena suggest that the presence of some substance secreted by the sex glands may cause the intensification of the heliotropism which leads to the nuptial flight4 #bdj ,loeb1 ,j41 ,der ,heliotropismus der ,tiere1 #ahhi4 #bda ,kellogg1 ,v4 ,l41 ,science1 #aijc1 xviii41 #fic4 ,in certain species of ,daphnia1 fresh-water copepods1 and of ,volvox1 a trace of ,,co suffices to make negatively heliotropic or indifferent specimens violently positively heliotropic4#bdb ,certain forms of marine copepods and the larv of ,polygordius can be made positively heliotropic by lowering the temperature#bdc and the larv of the barnacle can be made negatively heliotropic by strong light4#bdd ,it is quite possible that a change in the sense of heliotropism by temperature and light is to some extent at least responsible for the periodic depth migrations of heliotropic animals4 ,many if not all positively heliotropic animals can be made negatively heliotropic by exposure to ultraviolet light4#bde #bdb ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijf1 cxv41 #efd4 #bdc ,ibid41 #ahic1 liv41 #ha4 #bdd ,groom1 ,theo4 ,t41 and ,loeb1 ,j41 ,biol4 ,centralbl41 #ahij1 x41 #afj2 ,ewald1 ,w4 ,f41 ,jour4 ,exper4 ,zol41 #aiab1 xiii41 #eia4 #bde ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijf1 cxv41 #efd2 ,moore1 ,a4 ,r41 ,jour4 ,exper4 ,zol41 #aiab1 xiii41 #egc4 ,a most interesting example of the rle of heliotropism in the preservation of a species is shown in the caterpillars of ,porthesia chrysorrha4 ,the butterfly lays its eggs upon a shrub4 ,the larv hatch late in the fall and hibernate in a nest on the shrub1 as a rule not far from the ground4 ,as soon as the temperature reaches a certain height1 they leave the nest2 under natural conditions1 this happens in the spring when the first leaves have begun to form on the shrub4 7,the larv can1 however1 be induced to leave the nest at any time in the winter provided the temperature is raised sufficiently47 ,after leaving the nest1 they crawl directly upward on the shrub where they find the leaves on which they feed4 ,should the caterpillars move down the shrub1 they would starve1 but this they never do1 always crawling upward to where they find their food4 ,what gives the caterpillar this never-failing certainty which saves its life1 and for which a human being might envy the little larva8 ,is it a dim recollection of experiences of former generations8 ,it can be shown that it is the light reflected from the sky which guides the animal upward4 ,when we put these animals into a horizontal test-tube in a room1 they all crawl toward the window1 or toward a lamp2 the animal is positively heliotropic4 ,it is this positive heliotropism which makes them move upward where they find their food1 when the mild air of the spring calls them forth from their nest4 ,at the top of the branch1 they come in contact with a leaf1 and chemical or tactile influences set the mandibles of the young caterpillar into activity4 ,if we put these larv into closed test-tubes which lie with their longitudinal axes at right angles to the window1 they will all migrate to the window end1 where they stay and starve1 even if their favourite leaves are close behind them4 ,they are slaves of the light4 ,the few young leaves on top of a twig are quickly eaten by the caterpillar4 ,the light1 which saved its life by making it creep upward where it finds food1 would cause it to starve could it not free itself from the bondage of positive heliotropism4 ,the animal1 after having eaten1 is no longer a slave of the light1 but can and does creep downward4 ,it can be shown that a caterpillar1 after having been fed1 loses its positive heliotropism almost completely and permanently4 ,if we submit unfed and fed caterpillars of the same nest contained in two different test-tubes to the same artificial or natural source of light1 the unfed will creep to the light and stay there until they die1 while those that have eaten will pay little or no attention to the light4 ,their sensitiveness to light has disappeared2 after having eaten they become independent of light and can creep in any direction4 ,the restlessness which accompanies the condition of hunger makes the animal creep downward--which is the only direction open to it--where it finds new young leaves on which it can feed4 ,the wonderful hereditary instinct1 upon which the life of the animal depends1 is its positive heliotropism in the unfed condition and its loss of this heliotropism after having eaten4 ,the latter phenomenon is in harmony with the experiments which show that the heliotropism of certain species of ,daphnia disappears when the water becomes neutral4 ,and finally it may be pointed out that the majority of green plants could not exist if their stems were not positively1 their roots negatively1 heliotropic4 ,it is the positive heliotropism which makes the top grow toward the light1 which enables the leaves to get the light necessary for assimilation1 and the roots to grow into the soil where they find the water and nutritive salts4 #aj4 ,while we do not wish to deal here with the different tropisms it should be stated that aside from heliotropism1 chemotropism as well as stereotropism play the most essential rle in the so-called instinctive actions of animals4 ,it is a problem of orientation by the diffusion of molecules from a centre when a male butterfly is deviated from its flight and alights on the wooden box in which is enclosed a female of the same species4 ,we have already alluded to certain phenomena of chemotropism in ,chapter ,,iv4 ,certain organisms have a tendency to bring their bodies as much as possible on all sides in contact with solid bodies2 thus the butterfly ,amphipyra1 which is a fast runner1 will come to rest under a glass plate when the plate is put high enough above the ground so that it touches the back of the butterfly4 ,the animals which live under stones or underground or in caves are as a rule both negatively heliotropic and positively stereotropic4 ,their tropisms predestine or force them into the life they lead4 ,the sensitive area which forms the basis of tropisms is as a rule developed not in the whole organism but only in certain segments of the body4 ,thus the eyes are located in the head4 ,but when the action of one segment becomes overpowering the whole organism follows the segment4 ,it has been customary among physiologists to speak of reflexes in such cases4 ,thus1 e4 g41 the arms of the male frog develop a powerful positive stereotropism on their ventral surface during the spawning season4 ,it would avoid confusion to realize that there is nothing gained in applying to this tropism the meaningless term 8reflex02 it is better to call them tropisms since the organism as a whole is involved4 ,if necessary we might speak of segmental tropisms4 ,the act of seeking the female as well as that of cohabitation are in many cases combinations of chemotropism and stereotropism4 ,the development of these tropisms depends upon the presence of certain specific substances in the body1 a fact emphasized already in the case of heliotropism4 ,in case of the development of the segmental stereotropism of the male frog at the time of spawning it has been shown that it depends on an internal secretion from the testes4 ,it has been suggested by some authors that the tropistic reactions are determined by some feeling or emotion on the part of the organism4 ,we have no means of judging the emotions of lower animals 7except by 8intuition074 ,the writer suggested in #ahii in his book on brain physiology that emotions may be determined by specific substances which also determine the tropistic reaction 7as well as phenomena of organ formation1 although this latter phenomenon has nothing to do with the subject of instincts72 and the excellent work of ,cannon#bdf has shown the rle of adrenalin in the expression of fear4 ,it is1 therefore1 both unwarranted and unnecessary to state that hypothetical emotions determine the tropistic reactions4 #bdf ,cannon1 ,w4 ,b41 ,bodily ,changes in ,pain1 ,hunger1 ,fear1 and ,rage1 ,new ,york1 #aiae4 ,,chapter ,,xi ,,the ,,influence ,,of ,,environment #a4 ,the term environment in relation to an organism may easily assume a mystic rle if we assume that it can modify the organisms so that they become adapted to its peculiarities4 ,such ideas are difficult to comprehend from a physicochemical viewpoint1 according to which environment cannot affect the living organism and non-living matter in essentially different ways4 ,of course we know that proteins will as a rule coagulate at temperatures far below the boiling point of water and that no life is conceivable for any length of time at temperatures above #ajj ,c41 but heat coagulation of proteins occurs as well in the test-tube as in the living organism4 ,if we substitute for the indefinite term environment the individual physical and chemical forces which constitute environment it is possible to show that the influence of each of these forces upon the organism finds its expression in simple physicochemical laws and that there is no need to introduce any other considerations4 ,we select for our discussion first the most influential of external conditions1 namely temperature4 ,the reader knows that there is a lower as well as an upper temperature limit for life4 ,setchell has ascertained that in hot springs whose temperature is #dc ,c41 or above1 no animals or green alga are found4#bdg ,in hot springs whose temperature is above #dc he found only the ,cyanophyce1 whose structure is more closely related to that of the bacteria than to that of the alg1 inasmuch as they have neither definitely differentiated nuclei nor chromophores4 ,the highest temperature at which ,cyanophyce occurred was #fc ,c4 ,not all the ,cyanophyce were able to stand temperatures above #dc ,c41 but only a few species4 ,the other ,cyanophyce were found at a temperature below #dj ,c41 and were no more able to stand higher temperatures than the real alg or animals4 ,the ,cyanophyce of the hot springs were as a rule killed by a temperature of #gc4 ,from this we must conclude that they contain proteins whose coagulation temperature lies above that of animals and green plants1 and may be as high as #gc4 ,among the fungi many forms can resist a temperature above #dc or #de2 the spores can generally stand a higher temperature than the vegetative organs4 ,duclaux found that certain bacilli 7,tyrothrix7 found in cheese are killed in one minute at a temperature of from #hj to #ij2 while for the spores of the same bacillus a temperature of from #aje to #abj was required4#bdh #bdg ,setchell1 ,w4 ,a41 ,science1 #aijc1 xxvii41 #icd4 #bdh ,duclaux1 ,e41 ,trait de microbiol41 #ahih1 i41 #bhj4 ,duclaux has called attention to a fact which is of importance for the investigation of the upper temperature limit for the life of organisms4 ,according to this author it is erroneous to speak of a definite temperature as a fatal one2 instead we must speak of a deadly temperature zone4 ,this is due to the fact that the length of time which an organism is exposed to a higher temperature is of importance4 ,duclaux quotes as an example a series of experiments by ,christen on the spores of soil and hay bacilli4 ,the spores were exposed to a stream of steam and the time determined which was required at the various temperatures to kill the spores4 ,it took at #ajj over sixteen hours #aje-aaj two to four hours #aae thirty to sixty minutes #abe-acj five minutes or more #ace one to five minutes #adj one minute ,in warm-blooded animals #de is generally considered a temperature at which death occurs in a few minutes2 but a temperature of #dd1 #dc1 or #db is also to be considered fatal with this difference only1 that it takes a longer time to bring about death4 ,this fact is to be considered in the treatment of fever4 ,it is generally held that death in these cases is due to an irreversible heat coagulation of proteins4 ,according to ,duclaux1 it can be directly observed in micro-organisms that in the fatal temperature zone the normally homogeneous1 or finely granulated1 protoplasm is filled with thick1 irregularly arranged bodies1 and this is the optical expression of coagulation4 ,the fact that the upper temperature limit differs so widely in different forms is explained by ,duclaux through differences in the coagulation temperature of the various proteins4 ,it is1 e4 g4 known that the coagulation temperature varies with the amount of water of the colloid4 ,according to ,cramer1 the mycelium of ,penicillium contains #hg4f water to #ab4d dry matter1 while the spores have #ch4i water and #fa4a dry substance4 ,this may explain why the mycelium is killed at a lower temperature than the spores4 ,according to ,chevreul1 with an increase in the amount of water1 the coagulation temperature of albuminoids decreases4 ,the reaction of the protoplasm influences the temperature of coagulation1 inasmuch as it is lower when the reaction is acid1 higher when the reaction is alkaline4 ,the experiments of ,pauli show also a marked influence of salts upon the temperature of coagulation of colloids4 ,the process of heat coagulation of colloids is also a function of time4 ,if the exposure to high temperature is not sufficiently long1 only part of the colloid coagulates2 in this case an organism may again recover4 ,inside of these upper and lower temperature limits we find that life phenomena are influenced by temperature in such a way that their rate is about doubled for an increase of the temperature of #aj ,c41 and that this temperature coefficient for #aj1 ,q1 very often steadily diminishes from the lower to the higher temperature2 so that near the lower temperature limit it becomes often considerably greater than #b and near the higher temperature limit it becomes very often less than #b4bdi ,this influence of temperature is so general that we are bound to associate it with an equally general feature of life phenomena2 and such a feature would be most likely the chemical reactions4 ,it is known through the work of ,berthelot1 van't ,hoff1 and ,arrhenius that the temperature coefficient for the velocity of chemical reactions is also generally of about the same order of magnitude2 namely #b for a difference of #aj4 ,in chemical reactions there is also a tendency for ,q to become larger for lower temperature1 and coefficients of ,q about #e or #f have repeatedly been found for purely chemical reactions between #j and #aj1 e4 g41 for the inversion of cane sugar by the hydrogen ion4 ,the temperature coefficient for the reaction velocity of ferments shows the same diminution of ,q with rising temperature which is also noticed in most life phenomena4 ,thus ,van ,slyke and ,cullen#bej found that the reaction rate of the enzyme urease 8is nearly doubled by every #aj rise in temperature between #aj and #ej4 ,within this range the temperature coefficient is nearly constant and averages #a4ia4 ,from ,o to #aj it is #b4hj1 from #ej to #fj it is only #a4ji4 ,the optimum is at about #ee40 ,the rapid fall of the temperature coefficient for enzyme action at the upper temperature limit has been ascribed by ,tammann to a progressive destruction of the active mass of enzyme by the higher temperature 7by hydrolysis74 ,this will1 however1 not account for the high value of the coefficient near the lower limit4 ,but is it not imaginable that at low temperature an aggregation of the enzyme particles exists which is also equivalent to a diminution of the active mass of the enzyme and that this aggregation is gradually dispersed by the rising temperature8 ,this would account for the fact that at a temperature near #j;,c life phenomena stop because the enzymes are all in a state of aggregation or gelation2 that then more and more are dissolved and the rate of chemical reaction increases since the mass of enzyme particles increases until all the enzyme molecules are dissolved or rendered active4 ,under this assumption three processes are superposed in the variation of the value of ,q with temperature3 7#a7 the supposed increase in the number of available ferment molecules with increasing temperature near the lower temperature limit2 7#b7 the temperature coefficient of the reaction velocity which is nearly #b for #aj;,c42 7#c7 the diminution of the number of available ferment molecules by hydrolysis or some other action of the increasing temperature4 ,this latter is noticeable near the upper temperature limit4 ,the reason that #a and #c interfere more strongly in life phenomena than in the chemical reactions of crystalloid substances may possibly be accounted for by the fact that the enzymes and most of the constituents of living matter are colloidal1 i4 e41 consist of particles of a considerably greater order of magnitude than the molecules of crystalloids4#bea #bdi ,a full discussion of the literature on temperature coefficients is given in ,a4 ,kanitz's book on ,temperatur and ,lebensvorgnge1 ,berlin1 #aiae4 #bej ,van ,slyke1 ,d4 ,d41 and ,cullen1 ,g4 ,e41 ,jour4 ,biol4 ,chem41 #aiad1 xix41 #ada4 #bea ,these considerations may meet the objections of ,krogh to the application of the van't ,hoff rule of temperature effect on reaction velocity to life phenomena4 ,see also the discussion of this subject in ,kanitz's book4 ,we will now show the rle of the temperature coefficient upon phenomena of development4 ,f4 ,r4 ,lillie and ,knowlton#beb first determined the influence of temperature upon the development of the egg of the frog and showed that it was of the same nature as that of a chemical reaction4 ,these experiments were repeated a year later by ,o4 ,hertwig4#bec #beb ,lillie1 ,f4 ,r41 and ,knowlton1 ,e4 ,p41 ,zol4 ,bull41 #ahig1 i4 #bec ,hertwig1 ,o41 ,arch4 mikrosk4 ,anat41 #ahih1 li41 #cai4 ,see also ,e4 ,cohen1 ,vortrge fr ,aerste ber physikalische ,chemie4 #b;d ed4 ,leipzig1 #aijg4 ,the time required for the eggs to reach definite stages was measured for different temperatures and it was found that the temperature coefficient ,q between #b4e and #f was equal to #aj or more2 between #f and #ae it was between #b4f and #d4e2 between #aj and #bj it was #b4i to #c4c1 and between #bj and #bd it was between #a4d and #b4j4 ,to anybody who has worked on this problem it is obvious that no exact figures can be obtained in this way1 since the point when a certain stage of development is reached is not so sharply defined as to exclude a certain latitude of arbitrariness4 ,the writer found that very exact figures can be obtained on the influence of temperature upon development of the sea-urchin egg by measuring the time from insemination to the first cell division4 ,such experiments were carried out in a cold-water form ,strongylocentrotus purpuratus and a form living in warmer water1 ,arbacia4#bed ,the figures on ,arbacia have been verified by different observers in different years4 #bed ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijh1 cxxiv41 #daa2 ,loeb ,j41 and ,wasteneys1 ,h41 ,biochem4 ,ztschr41 #aiaa1 xxxvi41 #cde2 ,loeb ,j41 and ,chamberlain1 ,m4 ,m41 ,jour4 ,exper4 ,zol41 #aiae1 xix41 #eei4 ,,table ,x ,,influence ,,of ,,temperature ,,upon ,,the ,,time 7,,in ,,minutes7 ,,required ,,from ,,insemination ,,to ,,the ,,first ,,cell ,,division ---------------------------------------- ---------------- ,arbacia ,temperature------------------------,str ongylocentrotus ,loeb and ,loeb and purpuratus ,wasteneys ,chamberlain #aiaa #aiae ---------------------------------------- --------------- ,c4 ,minutes ,minutes ,minutes #c #ecb #d #dfi #e #ceb #f #bge #g #dih #bia #h #daj #daa #baj #i #cjh #big4e #aei #aj #bag #bjh #adc #aa #age #age #ab #adg #adh #aca #ac #abi #ad #aaf #aba #ae #ajj #ajj #ajj #af #he4e #ag #gj4e #ah #fh #fh #hg #ai #fe #gh #bj #ef #ef #ge #ba #ec4c #gh #bb #dg #df #ge #bc #de4e ,upper temperature #bd #db limit #be #dj #ci4e #bf #cc4e #bg4e #cd #cj #cc #ca #cg ---------------------------------------- --------------- ,these figures permitted the determination of the temperature coefficients ,q with a sufficient degree of accuracy 7see next table74 ,it seemed of importance to attempt to decide what the chemical reaction underlying these reaction velocities is 7if it is a chemical reaction74 ,loeb and ,wasteneys#bee investigated the temperature coefficient for the rate of oxidations in the newly fertilized egg of ,arbacia and found that the temperature coefficient ,q for that process does not vary in the same way as the temperature coefficient for cell division4 #bee ,loc4 cit4 ,,table ,,xi ,,temperature ,,coefficients ,q ,,for ,,the ,,rate ,,of ,,segmentation ,,and ,,oxidations ,,in ,,the ,,eggs ,,of ,strongylocentrotus ,,and ,arbacia ---------------------------------------- ------------------ ,q for ,rate of ,segmentation in ,q for ,rate of ,temperature---------------------------- --- ,oxidations in ,strongylocentrotus ,arbacia ,arbacia ---------------------------------------- ------------------ ,c4 #c-ac #c4ia #b4ah #d-ad #c4hh #e-ae #c4eb #b4af #g-ag #c4bg #g4c #b4jj #h-ah #f4j #i-ai #b4jd #d4g #aj-bj #a4ij #c4h #b4ag #aa-ba #c4c #ab-bb #a4gd #c4a #ac-bc #b4h #b4de #ae-be #b4e #b4bd #af-bf #b4f #ag4e-bg4e #b4b #b4jj #bj-cj #a4g #a4if ---------------------------------------- ------------------ ,it is obvious that the temperature coefficient of the rate of oxidations is remarkably constant1 about #b for #aj1 for various temperatures and does not show the variation from #g or more to #b4b for ,q for the rate of segmentation4 ,kanitz#bef has shown that in a graph in which the logarithms of the segmentation velocities are drawn as ordinates and the temperatures as absciss the logarithms form two straight lines which are joined at an angle4 ,according to the law of van't ,hoff and ,arrhenius concerning the influence of temperature upon velocities of chemical reactions the logarithms should lie in a straight line4 ,we are dealing therefore in these cases with two exponential curves1 one representing in ,arbacia the interval #g-ac and the second from #ac-bf2 in ,strongylocentrotus between #c-i and #i-bj4 #bef ,kanitz1 ,a41 loc4 cit41 p4 #abc4 ,it was found in these experiments that if measurements of the ,q of later stages of development are attempted the variations due to unavoidable difficulties become too great to permit an equal degree of reliability in the determinations4 ,the vast importance of this influence of temperature upon the rate of development is seen in the fact that in addition to the food supply the rate of the maturing of plants and animals depends on this factor4 #b4 ,this influence of temperature upon development has been used to find the conditions determining fluctuating variation4 ,the reader knows that by this expression are understood the differences between individuals of a pure strain or breed4 ,these variations are not inherited1 a fact contrary to the idea of ,darwin1 who assumed that by the selection of extreme cases of fluctuating variation new varieties could develop4 ,what is the basis of this fluctuating variation8 ,the writer concluded that if fluctuating variations were due to a slight variation in the quantity of a specific substance--in some cases an enzyme--required for the formation of a hereditary character1 the temperature coefficient might be used to test the idea4 ,we have just seen that the time required from insemination until the cell division of the first egg occurs is very sharply defined for each temperature4 ,if a large number e4 g4 one hundred or more eggs are under observation simultaneously in a microscopic field it can be seen that they do not all segment at the same time but in succession2 this is the expression of fluctuating variation4 ,miss ,chamberlain and the writer have measured the time which elapses between the moment the first egg of such a group segments and the moment the last egg begins its segmentation1 and found that this latitude of variation is also very definite for each temperature1 and that its temperature coefficient is for each interval of #aj practically identical with the temperature coefficient of the segmentation for the same interval4#beg ,the slight deviations are practically all in the same sense and accounted for by a slight deficiency in the nature of the experiments4 ,the two following tables give the latitude of variations for different temperatures for the first segmentation in ,arbacia and the temperature coefficient for this latitude and the rate of segmentation4 ,these two latter coefficients are practically identical4 #beg ,loeb1 ,j41 and ,chamberlain1 ,m4 ,m41 ,jour4 ,exper4 ,zol41 #aiae1 xix41 #eei4 ,,table ,,xii ---------------------------- ,latitude ,temperature of ,variation ---------------------------- ,c4 ,minutes #i #eb4e #aj #ci4e #aa #bf4j #ab #bb4e #ac #ai4b #ad #ag4e #ae #ac4j #ah #ab4j #ai #ab4e #bj #i4f #ba #h4j #bb #g4h #bc #h4j #bd #h4j #be #e4j ---------------------------- ,,table ,,xiii ---------------------------------------- ---- ,,temperature ,,coefficient ,,of ----------------------------- ,temperature ,latitude ,interval of ,segmentation ,variation ---------------------------------------- --- ,c4 #i-ai #d4b #d4g #aj-bj #c4i #c4h #aa-ba #c4b #c4c #ab-bb #b4h #c4a #ac-bc #b4d #b4h #ad-bd #b4c #b4h #ae-be #b4f #b4e ---------------------------------------- --- ,if we assume that the temperature coefficient for the segmentation of the egg is that of a chemical reaction 7other than oxidation7 underlying the process of segmentation1 the fluctuating variation in the time of the segmentations of the various eggs fertilized at the same time is due to the fact that the mass of the enzyme controlling that reaction varies within definite limits in different eggs4 ,the first egg segmenting at a given temperature has the maximal1 the last egg segmenting has the minimal mass of enzyme4 ,it should be added that the time of the first segmentation is determined by the cytoplasm and is not a ,mendelian character1 as was stated in a previous chapter4 #c4 ,the point of importance to us is that the influence of temperature upon the organism is so constant that if disturbing factors are removed it would be possible to use the time from insemination to the first segmentation of an egg of ,arbacia as a thermometer on the basis of the table on page #bie4 ,facts of this character should dispose of the idea that the organism as a whole does not react with that degree of machine-like precision which we find in the realm of physics and chemistry4 ,such an idea could only arise from the fact that biologists have not been in the habit of looking for quantitative laws1 chiefly1 perhaps1 because the difficulties due to disturbing secondary factors were too great4 ,the worker in physics knows that in order to discover the laws of a phenomenon all the disturbing factors which might influence the result must first be removed4 ,when the biologist works with an organism as a whole he is rarely able to accomplish this since the various disturbing influences1 being inseparable from the life of the organism1 can often not be entirely removed4 ,in this case the biologist must look for an organism in which by chance this elimination of secondary conditions is possible4 ,the following example may serve as an illustration of this rather important point in biological work4 ,although all normal human beings have about the same temperature1 yet if the heart-beats of a large number of healthy human beings are measured the rate is found to vary enormously4 ,thus v4 ,krsy found among soldiers under the most favourable and most constant conditions of observations--the soldiers were examined early in the morning before rising--variations in the rate of heart-beat between #db and #ajh4 ,in view of this fact1 those opposed to the idea that the organism as a whole obeys purely physicochemical laws might find it preposterous to imagine that the rate of heart-beat could be used as a thermometer4 ,yet if we observe the influence of temperature on the rate of the heart-beat of a large number of embryos of the fish ,fundulus1 while the embryos are still in the egg1 we find that at the same temperature each heart beats at the same rate1 the deviations being only slight and such as the fluctuating variations would demand4#beh ,this constancy is so great that the rate of heart-beat of these embryos could in fact be used as a rough thermometer4 ,the influence of temperature upon the rate of heart-beat is completely reversible so that when we measure the rate for increasing as well as for decreasing temperatures we get approximately the same values as the following table shows4 #beh ,loeb1 ,j41 and ,ewald1 ,w4 ,f41 ,biochem4 ,ztschr41 #aiac1 lviii41 #agi4 ,,table ,,xiv ---------------------------------------- ------------------- ,temperature ,time ,required for ,nineteen ,heart-beats in the ,embryo of ,fundulus ---------------------------------------- ------------------- ,c4 ,seconds #cj #f4be #be #h4e #bj #aa4e #ae #ai4j #aj #cb4e #e #fa4j #aj #cc4e #ae #ah4h #bj #ab4j #be #aj4j #cj #f4j ---------------------------------------- ------------------- ,why does each embryo have the same rate of heart-beat at the same temperature in contradistinction to the enormous variability of the same rate in man8 ,the answer is1 on account of the elimination of all secondary disturbing factors4 ,in the embryo of ,fundulus the heart-beat is a function almost if not exclusively of two variables1 the mass of enzymes for the chemical reactions underlying the heart-beat and the temperature4 ,by inheritance the mass of enzymes is approximately the same and in this way all the embryos beat at the same rate 7within the limits of the fluctuating variation7 at the same temperature4 ,this identity exists1 however1 only as long as the embryo is relatively quiet in the egg4 ,as soon as the embryo begins to move this equality disappears since the motion influences the heart-beat and the motility of different embryos differs4 ,in man the number of disturbing factors is so great that no equality of the rate for the same temperature can be expected4 ,differences in emotions or the internal secretions following the emotions1 differences in previous diseases and their after-effects1 differences in metabolism1 differences in the use of narcotics or drugs1 and differences in activity are only some of the number of variables which enter4 #d4 ,as stated above the temperature influences practically all life phenomena in a similar characteristic way1 e4 g41 the production of ,,co in seeds#bei and the assimilation of ,,co by green plants4#bfj ,the writer would not be surprised if even the aberrations in the colour of butterflies under the influence of temperature turned out to be connected with the temperature coefficient4 ,the experiments of ,dorfmeister1 ,weismann1 ,merrifield1 ,standfuss1 and ,fischer1 on seasonal dimorphism and the aberration of colour in butterflies have so often been discussed in biological literature that a short reference to them will suffice4 ,by seasonal dimorphism is meant the fact that species may appear at different seasons of the year in a somewhat different form or colour4 ,vanessa prorsa is the summer form1 ,vanessa levana the winter form of the same species4 ,by keeping the pup of ,vanessa prorsa several weeks at a temperature of from #j to #a ,weismann succeeded in obtaining from the summer chrysalids specimens which resembled the winter variety1 ,vanessa levana4 #bei ,clausen1 ,h41 ,landwirtschaftl4 ,jahrb41 #ahij1 xix41 #hic4 #bfj ,matthaei1 ,g4 ,l4 ,c41 ,trans4 ,philosoph4 ,soc41 #aijd1 cxcvii41 #dg2 ,blackman1 ,f4 ,f41 ,ann4 of ,bot41 #aije1 xix41 #bha4 ,if we wish to get a clear understanding of the causes of variation in the colour and pattern of butterflies1 we must direct our attention to the experiments of ,fischer1 who worked with more extreme temperatures than his predecessors1 and found that almost identical aberrations of colour could be produced by both extremely high and extremely low temperatures4 ,this can be seen clearly from the following tabulated results of his observations4 ,at the head of each column the reader finds the temperature to which ,fischer submitted the pup1 and in the vertical column below are found the varieties that were produced4 ,in the vertical column ,a are given the normal forms3 ,,table ,,xv ---------------------------------------- ------------------------------------- #j to #j to ,a #ce to #cf to #db to -#bj;,c4 #aj;,c4 7,normal #cg;,c4 #da;,c4 #df;,c4 ,forms7 ---------------------------------------- ------------------------------------- ichnusoidespolaris urtic ichnusa polaris ichnusoides 7nigrita7 7nigrita7 antigone fischeri io ---- fischeri antigone 7iokaste7 7iokaste7 testudo dixeyi polychloroserythromelasdixeyi testudo hygia artemis antiopa epione artemis hygia elymi wiskotti cardui ---- wiskotti elymi klymene merrifieldiatalanta ---- merrifieldiklymene weismanni porima prorsa ---- porima weismanni ---------------------------------------- ------------------------------------- ,the reader will notice that the aberrations produced at a very low temperature 7from #j to -#bj;,c47 are absolutely identical with the aberrations produced by exposing the pup to extremely high temperatures 7#db to #df;,c474 ,moreover1 the aberrations produced by a moderately low temperature 7from #j to #aj;,c47 are identical with the aberrations produced by a moderately high temperature 7#cf to #da;,c474 ,from these observations ,fischer concludes that it is erroneous to speak of a specific effect of high and of low temperatures1 but that there must be a common cause for the aberration found at the high as well as at the low temperature limits4 ,this cause he seems to find in the inhibiting effects of extreme temperatures upon development4 ,if we try to analyse such results as ,fischer's from a physicochemical point of view1 we must realize that what we call life consists of a series of chemical reactions1 which are connected in a catenary way2 inasmuch as one reaction or group of reactions 7a7 7e4 g41 hydrolyses7 causes or furnishes the material for a second reaction or group of reactions 7b7 7e4 g41 oxidations74 ,we know that the temperature coefficient for physiological processes varies slightly at various parts of the scale2 as a rule it is higher near #j and lower near #cj4 ,but we know also that the temperature coefficients do not vary equally for the various physiological processes4 ,it is1 therefore1 to be expected that the temperature coefficients for the group of reactions of the type 7a7 will not be identical through the whole scale with the temperature coefficients for the reactions of the type 7b74 ,if therefore a certain substance is formed at the normal temperature of the animal in such quantities as are needed for the catenary reaction 7b71 it is not to be expected that this same perfect balance will be maintained for extremely high or extremely low temperatures2 it is more probable that one group of reactions will exceed the other and thus produce aberrant chemical effects1 which may underlie the colour aberrations observed by ,fischer and other experimenters4 ,it is important to notice that ,fischer was also able to produce aberrations through the application of narcotics4 ,wolfgang ,ostwald has produced experimentally1 through variation of temperature1 dimorphism of form in ,daphnia4 #e4 ,next or equal in importance with the temperature is the nature of the medium in which the cells are living4 ,it has often been pointed out that the marine animals and the cells of the body of metazoic animals are surrounded by a medium of similar constitution1 the sea water and the blood or lymph1 both media being salt solutions differing in concentration but containing the three salts ,na,cl1 ,k,cl1 and ,ca,cl in about the same relative concentration1 namely #ajj molecules ,na,cl3 #b4b molecules of ,k,cl3 #a4e molecules of ,ca,cl4 ,this has suggested to some authors the poetical dream that our home was once the ocean1 but we cannot test the idea since unfortunately we cannot experiment with the past4 ,plants1 unicellular fresh-water alg1 and bacteria do not demand such a medium for their existence4 ,herbst had shown that when sea-urchin larv were raised in a medium in which only one of the constituents of the sea water was lacking 7not only ,na,cl1 ,k,cl1 or ,ca,cl1 but also ,na,,so1 ,na,h,c,o1 or ,na,,hpo71 the eggs could not develop into plutei2 from which he concluded that every constituent of the sea water was necessary4 ,this would indicate a case of extreme adaptation to all the minuti of the external medium4 ,experiments on a much more favourable animal for this purpose1 namely1 the eggs of the marine fish ,fundulus1 gave altogether different results4 ,the eggs of this marine fish develop naturally in sea water but they develop just as well in fresh or in distilled water1 and the young fish when they are made to hatch in distilled water will continue to live in this medium4 ,this proves that these eggs require none of the salts of the sea water for their development4 ,when these eggs are put immediately after fertilization into a pure solution of ,na,cl of that concentration in which this salt exists in the sea water practically all the eggs die without forming an embryo2 but if a small quantity of ,ca,cl is added every egg is able to form one1 and these embryos will develop into fish and the latter will hatch4 ,this led the writer to the conclusion that these fish 7and perhaps marine animals in general7 need the ,ca of the sea water only to counteract the injurious effects which a pure ,na,cl solution has if it is present in too high a concentration4#bfa ,when we raise the eggs in a pure ,na,cl solution of a concentration m_/#h practically every egg will develop2 and even in a m_/#d or #c_/h m many or some eggs will form embryos without adding ,ca2 it may be that a trace of ,ca present in the membrane of the egg may suffice to counter-balance the injurious action of a weak salt solution4 #bfa ,loeb1 ,j41 8,the ,poisonous ,character of a ,pure ,na,cl ,solution40 ,am4 ,jour4 ,physiol41 #aijj1 iii41 #cbi2 ,arch4 f4 d4 ges4 ,physiol41 #aija1 lxxxviii41 #fh2 ,am4 ,jour4 ,physiol41 #aijb1 vi41 #daa2 ,biochem4 ,zischr41 #aijf1 ii41 #ha4 ,the concentration of the ,na,cl in the sea water at ,woods ,hole 7where these experiments were made7 is about m_/#b1 and as soon as this concentration of ,na,cl is reached the eggs are all killed as a rule before they can form an embryo1 unless a small but definite amount of ,ca is added4 ,it was found that the eggs can be raised in much higher concentrations of ,na,cl1 but in that case more ,ca must be added4 ,the following table gives the minimal amount of ,ca,cl which must be added in order to allow fifty per cent4 of the eggs to form embryos4 7,the eggs were put into the solution an hour or two after fertilization47 ,,table ,,xvi -------------------------------------- ,concentration ,cc4 m_/#af ,ca,cl of ,required for #ej c4c4 ,na,cl ,na,cl ,solution -------------------------------------- m4 #c_/h #j4a #d_/h #j4c #e_/h #j4e #f_/h #j4f #g_/h #j4i #h_/h #a4b-a4d #i_/h #a4h-b4j #aj_/h #b4j-b4e #aa_/h #b4j8 #ab_/h #c4j-c4e #ac_/h #f4j -------------------------------------- ,this indicates that the quantity of ,ca,cl required to counteract the injurious effects of a pure solution of ,na,cl increases approximately in proportion to the square of the concentration of the ,na,cl solution4#bfb ,the reader will notice that the eggs can survive and develop in a solution of three times the concentration of sea water1 provided enough ,ca is added4 #bfb ,loeb1 ,j41 ,jour4 ,biol4 ,chem41 #aiae1 xxiii41 #dbc4 ,it was found also that not only ,ca but a large number of other bivalent metals were able to counteract the injurious action of an excessive ,na,cl solution2 namely ,mg1 ,sr1 ,ba1 ,mn1 ,co1 ,zn1 ,pb1 and ,fe2#bfc only ,hg and ,cu could not be used since they are themselves too toxic4 ,the antagonistic efficiency of the bivalent cations other than ,ca was1 however1 smaller than that of ,ca4 ,the following table gives the highest concentration of ,na,cl solution in which the newly fertilized eggs of ,fundulus can still form an embryo4#bfd #ej c4c4 #aj_/h m ,na,cl#d c4c4 m_/#a ,mg,cl #ej c4c4 #ad_/h m ,na,cl#a c4c4 m_/#a ,ca,cl #ej c4c4 #aa_/h m ,na,cl#a c4c4 m_/#a ,sr,cl #ej c4c4 #g_/h m ,na,cl#a c4c4 m_/#a ,ba,cl #bfc ,loeb1 ,j41 8,on the ,physiological ,effects of the ,valency and ,possibly the ,electrical ,charges of ,ions10 ,am4 ,jour4 ,physiol41 #aijb1 vi41 #daa4 #bfd ,loeb1 ,j41 ,jour4 ,biol4 ,chem41 #aiad1 xix41 #dca4 ,on the other hand it was seen that in all the chlorides with a univalent cation1 ,li,cl1 ,k,cl1 ,rb,cl1 ,cs,cl1 ,,nh,cl1 the eggs could form embryos up to a certain concentration of the salt2 but that this concentration could be raised by the addition of ,ca4 ,,table ,,xvii ,,concentrations ,,at ,,which ,,the ,,eggs ,,no ,,longer ,,are ,,able ,,to ,,form ,,embryos ---------------------------------------- -------- ,in the ,in the ,same ,salts with the ,pure ,salts ,addition of #a c4c4 m ,ca,cl to #ej c4c4 ,solution ---------------------------------------- -------- ,li,cl about #f_/cbm #e_/h m ,na,cl m_/#b #ad_/h m ,k,cl #aa_/af m #h_/h m #f_/h m ,rb,cl #h_/h m #i_/h m #g_/h m ,cs,cl #c_/h m #h_/h m #d_/h m ---------------------------------------- -------- ,in short it turned out that the injurious action of the pure solution of any chloride 7or any other anion7 with a univalent metal could be counteracted to a considerable extent by the addition of small quantities of a salt with a bivalent metal4 ,it was also found in the early experiments of the writer that the bivalent or polyvalent anions had no such antagonistic effect upon the injurious action of the salts with a univalent cation4 ,we therefore see that what at first sight appeared in the experiments of ,herbst a necessity1 namely1 the presence of each constituent of the sea water1 turns out as a special case of a more general law2 the salts with univalent ions are injurious if their concentration exceeds a certain limit and this injurious action is diminished by a trace of a salt with a bivalent cation4 ,why was it not possible to prove this fact for the eggs of the sea urchin8 ,before we answer this question1 we wish to enter upon the discussion of the nature of the injurious action of a pure ,na,cl solution of a certain concentration and of the annihilation of this action by the addition of a small quantity of ,ca4 ,the writer suggested in #aije that the injurious action of a pure ,na,cl solution consisted in rendering the membrane of the egg permeable for ,na,cl1 whereby the germ inside the membrane is killed2 while the addition of a small amount of ,ca 7or any other bivalent metal7 prevents the diffusion of ,na into the egg1#bfe possibly1 as ,t4 ,b4 ,robertson#bff suggested1 by forming a precipitate with some constituent of the membrane1 whereby the latter becomes more impermeable4 ,the correctness of this idea can be demonstrated in the following way4 ,when eggs of ,fundulus1 which are three or four days old and contain an embryo1 are put into a test-tube containing #c m ,na,cl they will float on this solution for about three or four hours2 after that they will sink to the bottom4 ,before this happens the egg will shrink and when it ceases to float the embryo is usually dead4 ,this is intelligible on the assumption that the ,na,cl solution entered the egg1 increased its specific gravity so that it could not float any longer and killed the embryo4 ,when we add1 however1 #a c4c4 #aj_/h m ,ca,cl to #ej c4c4 #c m ,na,cl the eggs will float1 the heart will continue to beat normally and the embryo will continue to develop for three days or more1 because the calcium prevents the ,na,cl from entering into the egg4#bfg ,for if we put a newly hatched embryo into #ej c4c4 #c m ,na,cl#a c4c4 #aj_/h m ,ca,cl it will die almost instantly2 hence the membrane must have acted for three or more days as a shield which prevented the ,na,cl from diffusing into the egg in the presence of ,ca,cl4 #bfe ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aije1 cvii41 #beb4 #bff ,robertson1 ,t4 ,b41 ,ergeb4 d4 ,physiol41 #aiaj1 x41 #baf4 #bfg ,loeb1 ,j41 ,biochem4 ,ztschr41 #aiab1 xlvii41 #abg4 ,the same experiments cannot be demonstrated in the sea-urchin egg1 first1 because it can live neither in distilled water nor in very dilute nor very concentrated solutions2 and second1 because it is not separated as is the germ of the ,fundulus egg from the surrounding solution by a membrane which is under proper conditions practically impermeable for water and salts4 ,nevertheless it can be shown that the results at which we arrived in our experiments on ,fundulus are of a general application4 ,osterhout#bfh has shown that plants which grow in the soil or in fresh water are readily killed by a pure ,na,cl solution of a certain concentration1 while they can resist the same concentration of ,na,cl if some ,ca,cl is added4 ,wo4 ,ostwald#bfi has shown the same for a species of ,daphnia4 ,we1 therefore1 come to the conclusion that the injurious action following an alteration in the constitution of the sea water is in some of the cases due to an increase in the permeability of the membranes of the cell1 whereby substances can diffuse into the cell which when the proper balance prevails cannot diffuse4 ,for this balance the ratio of the concentration of the salts with univalent cation ,na and ,k over those with bivalent cation ,ca and ,mg ,c,na,k salts_/,c,ca,mg salts is of the greatest importance4 #bfh ,osterhout1 ,w4 ,j4 ,v41 ,bot4 ,gazette1 #aijf1 xlii41 #abg2 #aijg1 xliv41 #beg2 ,jour4 ,biol41 ,chem41 #aijf1 i41 #cfc4 #bfi ,ostwald1 ,wo41 ,arch4 f4 d4 ges4 ,physiol41 #aije1 cvi41 #efh4 #f4 ,the importance of this quotient appears in the so-called 8behaviour0 of marine animals4 ,we have mentioned the newly hatched larv of the barnacle in connection with heliotropism4 ,these larv swim in a trough of normal sea water at the surface1 being either strongly positively or negatively heliotropic4 ,they collect as a rule in two dense clusters1 one at the window and one at the room side of the dish4 ,if such animals are put into a solution of ,na,cl,k,cl 7in the proportion in which these salts exist in the sea water71 they will fall to the bottom unable to rise to the surface4 ,they will1 however1 rise to the surface and swim energetically to or from the window if a certain quantity of any of the chlorides of a bivalent metal1 ,mg1 ,ca1 or ,sr1 is added1 but these movements will last only a few minutes when only one of these three salts is added2 and then the animals will fall to the bottom again4 ,if1 however1 two salts1 e4 g41 ,mg,cl and ,ca,cl1 are added the animals will stay permanently at the surface and react to light as they would have done in normal sea water4 ,these animals also can resist comparatively large changes in the concentration of the sea water1 and it seemed of interest to find out whether the quotient ,c,na,cl,k,cl_/,c,mg,cl,ca,cl1 which just allowed all the animals to swim at the surface1 had a constant value4 ,the ,mg,cl,ca,cl solution was #c_/h m and contained the two metals in the proportion in which they exist in the sea water2 namely1 #aa4h molecules ,mg,cl to #a4e molecules ,ca,cl4 ,the next table gives the result4#bgj ,since these experiments lasted a day or more each1 usually two different concentrations of ,na,cl,k,cl of the ratio #a3b or #a3d were compared in one experiment4 #bgj ,loeb1 ,j41 ,jour4 ,biol4 ,chem41 #aiae1 xxiii41 #dbc4 ,,table ,,xviii ---------------------------------------- ---------- ,number ,concentration ,c4c4 #c_/h m ,value of of of ,ca,cl,mg,cl ,c,na,k_/ ,experiment ,na,cl,k,cl ,required ,c,mg,ca ---------------------------------------- ---------- #a m_/#af #j4c #bg4h m_/#h #j4d-j4e #cg4j #b m_/#h #j4e #cc4c m_/#d #j4i-a4j #ce4a #c #c_/af m #j4g #ce4g #c_/h m #a4c #ch4e #d m_/#h #j4e #cf4j m_/#b #a4h-a4i #ci4b #e m_/#d #j4h-j4i #ci4b m_/#b #a4f-a4g #dj4c #f #e_/af m #j4i #df4c #e_/h m #a4g #di4j #g #c_/af m #j4f #da4g #f_/h m #b4d #da4g ---------------------------------------- ---------- ,these experiments indicate that the ratio of ,c,na,k_/,c,ca,mg remains very nearly constant with varying concentrations of ,c,na,k4 ,in former experiments on jellyfish the writer had shown that there exists an antagonism between ,mg and ,ca#bga1 and this observation was subsequently confirmed by ,meltzer and ,auer#bgb for mammals4 ,it was observed that in a solution of ,na,cl,k,cl,mg,cl the larv of the barnacle were also not able to remain at the surface for more than a few minutes1 while an addition of some ,ca,cl made them swim permanently at the surface4 ,various quantities of ,mg,cl were added to a mixture of m_/#d or m_/#b ,na,cl,k,cl1 to find out how much ,ca,cl1 was required to allow them to swim permanently at the surface4 #bga ,loeb1 ,j41 ,jour4 ,biol4 ,chem41 #aije-jf1 i41 #dbg4 #bgb ,meltzer1 ,s4 ,j41 and ,auer1 ,j41 ,am4 ,jour4 ,physiol41 #aijh1 xxi41 #djj4 ,,table ,,xix ---------------------------------------- -------------------------- ,c4c4 of m_/#af ,ca,cl ,necessary to ,induce the ,majority of the ,larv to ,swim in --------------------------- m_/#b 7,na,k7 m_/#d 7,na,k7 ---------------------------------------- ------------------------- #ej c4c4 ,na,cl,k,cl#j4ge c4c4 #c_/h m ,mg,cl #j4b #ej c4c4 ,na,cl,k,cl #a4e c4c4 #c_/h m ,mg,cl #j4d #j4c #ej c4c4 ,na,cl,k,cl #b4e c4c4 #c_/h m ,mg,cl #j4d #j4d #ej c4c4 ,na,cl,k,cl #e4j c4c4 #c_/h m ,mg,cl #j4g-j4h #j4g-j4h #ej c4c4 ,na,cl,k,cl#aj4j c4c4 #c_/h m ,mg,cl #a4f #a4f #ej c4c4 ,na,cl,k,cl#ae4j c4c4 #c_/h m ,mg,cl #a4h #ej c4c4 ,na,cl,k,cl#bj4j c4c4 #c_/h m ,mg,cl #a4h ---------------------------------------- ------------------------- ,in order to interpret these figures correctly we must remember that we are dealing with two different antagonisms1 one between the salts with univalent and bivalent metals and the other between ,mg and ,ca4 ,the former antagonism is satisfied by the addition of ,mg1 inasmuch as enough ,mg was present for this purpose in all solutions4 ,what was lacking was the balance between ,mg and ,ca4 ,the experiments in ,table ,,xix therefore answer the question of the ratio between ,mg and ,ca4 ,if we consider only the concentrations of ,mg between #b4e and #aj4j c4c4 #c_/h m ,mg,cl--which are those closest to the normal concentration of ,mg in the sea water--we notice that ,c,ca must vary in proportion to ,c,mg4 ,if we now combine the results of this and the previous paragraph we may express them in the form of the theory of physiologically balanced salt solutions1 by which we mean that in the ocean 7and in the blood or lymph7 the salts exist in such ratio that they mutually antagonize the injurious action which one or several of them would have if they were alone in solution4#bgc ,this law of physiologically balanced solutions seems to be the general expression of the effect of changes in the constitution of the salt solutions for marine or all aquatic organisms4 #bgc ,this theory was first expressed by the writer in ,am4 ,jour4 ,physiol41 #aijj1 iii41 #dcd4 ,this chapter would not be complete without an intimation of the rle of buffers in the sea water and the blood1 by which the reaction of these media is prevented from changing in a way injurious to the organism4 ,these buffers are the carbonates and phosphates4 ,instead of saying that the organisms are adapted to the medium1 ,l4 ,henderson has pointed out the fitness of the environment for the development of organisms and one of these elements of fitness are the buffers against alterations of the hydrogen ion concentration4#bgd ,the ratio in which the salts of the different metals exist in the sea water is another4 ,it is obvious that the quantitative laws prevailing in the effect of environment upon organisms leave no more room for the interference of a 8directing force0 of the vitalist than do the laws of the motion of the solar system4 #bgd ,henderson1 ,l41 ,the ,fitness of the ,environment4 ,see also ,michaelis1 ,l41 ,die ,wasserstoffionenconzentration4 ,berlin4 #aiad4 ,,chapter ,,xii ,,adaptation ,,to ,,environment #a4 ,it is assumed by certain biologists that the environment influences the organism in such a way as to increase its adaptation4 ,were this correct it would not contradict a purely physicochemical conception of life2 it would only call for an explanation of the mechanism by which the adaptation is brought about4 ,there are striking cases on record which warn us against the universal correctness of the view that the environment causes an adaptive modification of the organism4 ,thus the writer pointed out in #ahhi that positive heliotropism occurs in organisms which have no opportunity to make use of it1#bge e4 g41 ,cuma rathkii1 a crustacean living in the mud1 and the caterpillars of the willow borer living under the bark of the trees4 ,we understand today why this should be so1 since heliotropism depends upon the presence of photosensitive substances1 and it can readily be seen that the question of use or disuse has nothing to do with the production of certain harmless chemical compounds in the body4 ,a much more striking example is offered in the case of galvanotropism4 ,many organisms show the phenomenon of galvanotropism1 yet1 as the writer pointed out years ago1 galvanotropism is purely a laboratory product and no animal has ever had a chance or will ever have a chance to be exposed to a constant current except in the laboratory of a scientist4 ,this fact is as much of a puzzle to the selectionist and to the ,lamarckian 7who would be at a loss to explain how outside conditions could have developed this tropism7 as to the vitalist who would have to admit that the genes and supergenes indulge occasionally in queer freaks and lapses4 ,the only consistent attitude is that of the physicist who assumes that the reactions and structures of animals are consequences of the chemical and physical forces1 which no more serve a purpose than those forces responsible for the solar systems4 ,from this viewpoint it is comprehensible why utterly useless tropisms or structures should occur in organisms4 #bge ,loeb1 ,j41 ,der ,heliotropismus der ,tiere and seine bereinstimmung mit dem ,heliotropismus der ,pflanzen4 ,wrzburg1 #ahij 7appeared in #ahhi74 #b4 ,a famous case for the apparent adaptation of animals to environment has been the blind cave animals4 ,it is known that in caves blind salamanders1 blind fishes1 and blind insects are common1 while such forms are comparatively rare in the open4 ,this fact has suggested the idea that the darkness of the cave was the cause of the degeneration of the eyes4 ,a closer investigation leads1 however1 to a different explanation4 ,eigenmann has shown that of the species of salamanders living habitually in ,north ,american caves1 two have apparently quite normal eyes4 ,they are ,spelerpes maculicauda and ,spelerpes stejnegeri4 ,two others living in caves have quite degenerate eyes1 ,typhlotriton spelus and ,typhlomolge rathbuni4 ,if disuse is the direct cause of blindness we must inquire why ,spelerpes is not blind4 ,another difficulty arises from the fact that a blind fish ,typhlogobius is found in the open 7on the coast of southern ,california7 in shallow water1 where it lives under rocks in holes occupied by shrimps4 ,the question must again be raised3 ,how can it happen that in spite of exposure to light ,typhlogobius is blind8 ,the most important fact is perhaps the one found by ,eigenmann in the fishes of the family of ,amblyopsid4 ,six species of this group live permanently in caves1 are not found in the open1 and have abnormal eyes1 while one lives permanently in the open1 is never found in caves1 and one comes from subterranean springs4 ,the one form which is found only in the open1 ,chologaster cornutus1 has a simplified retina as well as a comparatively small eye1 in other words1 its eye is not normal4 ,this indicates the possibility that the other representatives which are found only in caves also might have abnormal eyes even if they had never lived in caves4 ,through these facts the old idea becomes questionable1 namely1 that the cave animals had originally been animals with normal eyes which owing to disuse had undergone a gradual hereditary degeneration4 ,recent experiments made on the embryos of the fish ,fundulus have yielded the result that it is possible to produce blindness in fish by various means other than lack of light4#bgf ,thus the writer found that by crossing the egg of ,fundulus with the sperm of a widely different species1 namely1 ,menidia1 blind embryos were produced very frequently2 that is to say such embryos had the degenerate eyes characteristic of blind cave fishes4 ,very often no other external trace of an eye1 except a gathering of pigment1 could be found1 while a close histological examination would possibly have resulted in the demonstration of rudiments of a lens and other tissues of the eye4 #bgf ,loeb1 ,j41 ,biol4 ,bull41 #aiae1 xxix41 #ej4 ,another method of producing blind fish embryos consists in exposing the egg immediately1 or soon after fertilization1 to a temperature between #j and #b ,c4 for a number of hours4 ,many embryos are killed by this treatment1 but those which survive behave very much like the hybrids between ,fundulus and ,menidia1 i4 e41 a number of them have quite degenerated eyes4 ,if the eggs have once formed an embryo they can be kept at the temperature of #j for a month or more without giving rise to blind animals4 ,occasionally such rudimentary eyes were also observed when eggs were kept in a solution containing a trace of ,,kcn4 ,stockard has succeeded in producing cyclopean eyes in ,fundulus by adding an excess of magnesium salt to the sea water in which the eggs developed or by adding alcohol1 and ,mc,clendon has confirmed and added to these results4 ,the writer tried repeatedly1 but in vain1 to produce ,fundulus with deficient eyes by keeping the embryos in the dark4 ,sperm and egg were not allowed to be exposed to the light yet the embryos without exception had normal eyes4 ,f4 ,payne raised sixty-nine successive generations of a fly ,drosophila in the dark1 but the eyes and the reaction of the insects to light remained perfectly normal4 ,uhlenhuth has recently demonstrated in a very striking way that the development of the eyes does not depend upon the influence of light or upon the eyes functioning4 ,he transplanted the eyes of young salamanders into different parts of their bodies where they were no longer connected with the optic nerves4 ,the eyes after transplantation underwent a degeneration which was followed by a complete regeneration4 ,he showed that this regeneration took place in complete darkness and that the transplanted eyes remained normal in salamanders kept in the dark for fifteen months4 ,hence the eyes which were no longer in connection with the central nervous system1 which had received no light1 and could not have functioned1 regenerated and remained normal4 ,the degeneration which took place in the eyes immediately after being transplanted was apparently due to the interruption of the circulation in the eye1 and the regeneration commenced in all probability with the re-establishment of the circulation in the transplanted organ4 ,in our own experiments it can be shown that the circulation in the embryo was deficient in all cases where the eyes degenerated4 ,the hybrids between ,fundulus and ,menidia have often a beating heart but rarely a circulation 7although they form blood72 and the same phenomenon occurred in the embryos which were exposed to a low temperature at an early period of their lives4 ,hence all the facts agree that conditions which lead to an abnormal circulation 7and consequently also to an abnormal or inadequate nutrition of the embryonic eye7 may prevent development and lead to the formation of blind fishes4 ,eigenmann states that no blood-vessels enter the eye of the blind cave salamander ,typhlotriton4 ,the presence or absence of light does not usually interfere with the circulation or nutrition of the embryonic eye1 and hence does not as a rule lead to the formation of degenerated eyes4 ,this would lead us to the assumption that the blind fish owe their deficiency not to lack of light but to a condition which interferes with the circulation in the embryonic eye4 ,such a condition might be brought about by an anomaly in the germ plasm or in one chromosome1 the nature and cause of which we are not able to determine at present2 but which1 since it occurs in the germ plasm or the chromosomes1 must be hereditary4 ,this would explain why it is1 that animals with perfect eyes may occur in caves and why perfectly blind animals may occur in the open4 ,it leaves1 however1 one point unexplained2 namely1 the greater frequency of blind species in caves or in the dark and the relative scarcity of such forms in the open4 ,eigenmann has shown that all those forms which live in caves were adapted to life in the dark before they entered the cave4#bgg ,these animals are all negatively heliotropic and positively stereotropic1 and with these tropisms they would be forced to enter a cave whenever they are put at the entrance4 ,even those among the ,amblyopsid which live in the open have the tropisms of the cave dweller4 ,this eliminates the idea that the cave adapted the animals for the life in the dark4 #bgg ,cunot has proposed the term preadaptation for such cases and this term expresses the situation correctly4 ,cunot1 ,l41 ,la ,gnse des ,espces animales4 ,paris1 #aiaa4 ,only those animals can thrive in caves which for their feeding and mating do not depend upon visual mechanisms2 and conversely1 animals which are not provided with visual mechanisms can hold their own in the open1 where they meet the competition of animals which can see1 only under exceptional conditions4 ,this seems to account for the fact that in caves blind species are comparatively more prevalent than in the open4 ,in other words1 the adaptation of blind animals to the cave is only apparent2 they were adapted to cave life before they entered the cave4 ,many animals are obviously burdened with a germinal abnormality giving rise to imperfection and smallness of the eye--the hereditary factor involved may have to do with the development of the blood-vessels and lymphatics of the eye4 ,such mutants can survive more easily in the cave1 where they do not have to meet the competition of seeing forms1 than in the open4 ,in man also an hereditary form of blindness is known1 the so-called hereditary glaucoma4 ,it has nothing to do with light1 but the disease seems to be due to an hereditary anomaly of the circulation in the eye4 ,kammerer#bgh has recently reported that by keeping the blind ,european cave salamander ,proteus anguinus under certain conditions of illumination he succeeded in producing two specimens with larger eyes4 ,according to him the eyes of ,proteus may develop to a certain point and then retrogress again4 ,he states that by keeping young salamanders alternately for a week or two in sunlight and in a dark room where they were exposed to red incandescent light1 two males formed somewhat larger eyes4 ,the first year no alteration was visible4 ,in the second year a slight increase in the size of the eyes was noticeable under the skin4 ,in the third year the eye protruded slightly and this increased somewhat in the fourth year4 #bgh ,kammerer1 ,p41 ,arch4 f4 ,entwcklngsmech41 #aiab1 xxxiii41 #cdi4 ,there is thus far only one case on record in animal biology in which the light influences the formation of organs4 ,the writer found that the regeneration of the polyps of the hydroid ,eudendrium does not take place if the animals are kept in the dark1 while the polyps will regenerate if exposed to the light2#bgi and the time of exposure may be rather short according to ,goldfarb4#bhj ,it is possible that ,proteus resembles in this respect ,eudendrium2 it should be stated1 however1 that of many different forms tried by the writer over a number of years1 ,eudendrium was the only one which gave evidence of such an influence of light4 ,of course it is not impossible that the light might influence reflexly the development of blood-vessels in the eyes of certain animals1 e4 g41 ,proteus1 and thus allow the eyes of ,proteus to grow a little larger4 #bgi ,loeb1 ,j41 ,arch4 d4 f4 ges4 ,physiol41 #ahif1 lxiii41 #bgc4 #bhj ,goldfarb1 ,a4 ,j41 ,jour4 ,exper4 ,zol41 #aijf1 iii41 #abi2 #aiaj1 viii41 #acc4 ,we therefore come to the conclusion that it is not the cave that made animals blind but that animals with a hereditary tendency towards a degeneration of the eyes can survive in a cave while they can only exceptionally survive in the open4 ,the cause of the degeneration is a disturbance in the circulation and nutrition of the eye1 which is as a rule independent of the presence or absence of light4 ,we may by way of a digression stop for a moment to consider the most astonishing and uncanny case of adaptation2 namely1 the formation of the transparent refractive media1 especially the lens in front of the retina4 ,it is due to these media that the rays which are sent out by a luminous point can be united to an image point on the retina4 ,one part of this process is understood2 namely1 the formation of a lens4 ,wherever the optic cup of the embryo is transplanted under the epithelium the latter will be transformed into a transparent lens4 ,when the upper edge of the iris is injured in the salamander so that the cells can multiply1 the mass of newly formed cells also becomes transparent and a lens is formed4 ,this indicates the existence of a substance in the optic cup which makes the epithelial cells transparent2 and which also limits the size of the lens which is formed4 ,the lens is not always a perfect optical instrument1 on the contrary1 it is as a rule somewhat defective4 ,of course1 a great many details concerning the process of lens regeneration have still to be worked out4 #c4 ,it is well known that most marine animals die if put into fresh water and vice versa2 and in salt lakes or ponds with a concentration of salt so high that most marine animals would succumb if suddenly transferred to such a solution we have a limited fauna and flora4 ,the common idea is that marine animals become adapted to fresh water or vice versa2 or to the conditions in salt lakes2 especially if the changes take place gradually4 ,yet it can be shown that the existence of these different faunas can be explained without the assumption of an adaptive effect of the environment4 ,the writer has worked with a marine fish ,fundulus whose eggs develop naturally in sea water which1 however1 will develop just as well in distilled water2 and the young fish hatching in distilled water live and grow in this medium4 ,most of the adult fish die after several days1 when put suddenly into distilled water1 but they can live in fresh water which contains only a trace of salt4 ,they can also live in very concentrated sea water1 e4 g41 twice the normal concentration4 ,suppose that a bay of the ocean containing such fish should suddenly become landlocked and the concentration of the sea water be thus raised to twice its natural amount2 the majority of forms would die and only ,fundulus and possibly a few other species with the same degree of resistance would survive4 ,an investigator examining the salinity of the water and not knowing the natural resistance of ,fundulus to changes in concentration would be inclined to assume that he had before him an instance of a gradual adaptation of the fish to a higher concentration of the sea water2 whereas the fish was already immune to this high concentration before coming in contact with it4 ,this fish seemed a favourable object from which to find out how far an adaptation to the environment really existed2 and the result was surprising4 ,by changing the concentration of the sea water gradually it is possible to raise the natural resistance of the fish only a trifle1 not much over ten per cent4 ,the concentration of the natural sea water is a little over that of a m_/#b solution of ,na,cl,k,cl,ca,cl in the proportion in which these three salts exist in the sea water4 ,when adult ,fundulus are put into a #aj_/h m solution of ,na,cl,k,cl,ca,cl in the proportion in which these salts occur in sea water they die in less than a day1 but when put from sea water directly into a #h_/h m or #i_/h m solution they can live indefinitely4 ,it was found#bha that if the concentration of the sea water was raised gradually 7by m_/#h a day7 the fish on the fifth day could resist a #aj_/h m solution of ,na,cl,k,cl,ca,cl for a month 7or possibly indefinitely2 the experiment was discontinued after that period74 ,when a #aj_/h m solution was allowed to become more concentrated slowly by evaporation 7at room temperature7 all the fish died rapidly when the concentration was #ab_/h m or even below4 ,in higher concentrations they can live only a day or two4 ,these experiments show that while the fish is naturally immune to a #i_/h m ,na,cl,k,cl,ca,cl solution1 by the method of slowly raising the concentration it may be made to tolerate a #aj_/h m or #aa_/h m solution1 but not more4 ,these fish when once adapted to a #aj_/h m solution can be put suddenly into a very weak solution1 e4 g41 a m_/#hj ,na,cl1 without suffering and when brought back into a #aj_/h m solution of ,na,cl,k,cl,ca,cl they will continue to live4 ,if they remain for several days in the weak solution their power of resistance to #aj_/h m ,na,cl,k,cl,ca,cl solution is weakened4 #bha ,loeb1 ,j41 ,biochem4 ,ztschr41 #aiac1 liii41 #cia4 ,what change takes place when the fish is made more resistant and why is its normal resistance so great8 ,the answer based on the writer's experiments seems to be as follows3 ,fundulus is comparatively resistant to sudden changes in the concentration of the sea water between m_/#hj and #i_/h m because it possesses a comparatively impermeable skin whose permeability is not seriously altered by sudden changes within these limits of concentration2 while if these limits are exceeded and the fish are brought suddenly into too high a concentration the skin becomes permeable and the fish dies1 the gills becoming unfit for use or nerves being injured by the salt which diffuses into the fish4 ,the fact1 that by slowly raising the concentration to #aj_/h m the fish may resist this limit1 is in reality no adaptation4 ,there is no sharp limit between the injurious and non-injurious concentration4 ,we have seen that the fish is naturally immune to a #i_/h m solution4 ,it is also naturally immune to a #aj_/h m or #aa_/h m solution if we give it time to compensate the injurious effects of a #aj_/h m solution by the repairing action of its blood or kidneys4 ,beyond this no rise is possible4 ,in reality adaptation does not exist in this case4 ,in former experiments the writer had shown that a pure ,na,cl solution of that concentration in which this fish naturally lives kills it very rapidly1 while it lives in such a solution indefinitely if a little ,ca,cl is added4 ,the explanation of this fact is that the pure ,na,cl solution is able to diffuse into the tissues of the animal while the addition of a trace of ,ca,cl renders the membrane practically impermeable to ,na,cl4 ,the question then arose whether it was possible to make the fish more resistant to a pure ,na,cl solution of sufficiently high concentration and how this could be done4 ,on the basis of the idea of an adaptive effect of the environment we should expect that by gradually raising the concentration of a pure ,na,cl solution the latter would gradually alter the animal and make it more resistant4 ,the method of procedure suggested was therefore to put the fish first in low and gradually into increasing concentrations of ,na,cl4 ,this method was tried and found futile for the purpose4 ,fundulus when put from sea water 7after having been washed7 into a #f_/h m ,na,cl solution die in about four hours4 ,when kept previously in a weaker ,na,cl solution they die if anything more quickly4 ,but it is possible to make them live longer in a #f_/h m solution of ,na,cl2 we have to proceed1 however1 by a method which is in contrast with the ideas of the adaptive influence of the environment4 ,when the fish are first treated with sea water 7or with a mixture of ,na,cl,k,cl,ca,cl7 of a higher concentration so that they become adapted to a #aj_/h m solution of ,na,cl,k,cl,ca,cl or to #aj_/h m sea water1 they become also more resistant to an otherwise toxic solution of ,na,cl4 ,fish taken directly from sea water were killed in less than four hours when put into a #f_/h m ,na,cl solution1 while fish of the same lot previously adapted to #aj_/h m sea water in the manner described above lived two or three days in a #f_/h m ,na,cl solution4#bhb #bhb ,loeb1 ,j41 ,biochem4 ,ztschr41 #aiac1 liii41 #cia4 ,it is not impossible that it was the high concentration of calcium in the #aj_/h m sea water which rendered the fish more immune to a subsequent treatment with ,na,cl4 ,we know why a pure ,na,cl solution kills them and we also know why the addition of ,ca,cl protects them against this pernicious effect4 ,it is rather strange that where the conditions of the experiments are clear we find nothing to indicate an adaptive effect of the environment4 #d4 ,ehrlich's work on trypanosomes seems to indicate a remarkable power of adaptation on the part of organisms to certain poisons4 ,if the writer understands these experiments correctly they consisted in infecting a mouse with a certain strain of trypanosomes1 and treating it with a certain arsenic compound1 which inhibited somewhat the propagation of the parasites but did not kill them all4 ,four or five days later trypanosomes from this mouse were transmitted to another mouse and after twenty-four hours this mouse was treated with a stronger dose of the same arsenic compound2 and this process was repeated4 ,after the third transmission or later1 the trypanosomes can resist considerably higher doses of the same poison than at first and this resistance is retained for years4 ,ehrlich seems to have taken it for granted that he had succeeded in transforming the surviving trypanosomes into a type which is permanently more resistant to the arsenic compound than was the original strain4 ,the writer is not entirely convinced that in these experiments a possibility was sufficiently considered which is suggested by ,johannsen's experiments on the importance of pure lines in work on heredity4 ,according to this author a strain of trypanosomes taken at random should1 in all likelihood1 contain a population consisting of strains with different degrees of resistance4 ,if a high but not the maximal concentration of an arsenic compound is repeatedly injected into the infected mice the weaker populations of trypanosomes are killed and only the more resistant survive4 ,these of course continue to retain their resistance if transplanted to hosts of the same species4 ,according to this interpretation the arsenic-fast strain may possibly have existed before the experiments were made1 and ,ehrlich's treatment consisted only in eliminating the less resistant strains4 ,on the other hand1 it has been shown that if an arsenic-fast strain of trypanosomes is carried through a tsetse fly it loses its arsenic-fastness4 ,this fact may possibly eliminate the applicability of the pure line theory to a discussion of the nature of the arsenic-fastness1 but it seems that further experiments are desirable4 #e4 ,dallinger stated that he succeeded in adapting certain protozoans to a temperature of #gj ,c4 by gradually raising their temperature during several years4 ,it is desirable that this statement be verified2 until this is done doubts are justified4 ,schottelius found that colonies of ,micrococcus prodigiosus when transferred from a temperature of #bb to that of #ch no longer formed pigment and trimethylamine4 ,after the cocci had been cultivated for ten or fifteen generations at #ch they failed to form pigment even when transferred back to #bb ,c4 ,dieudonn#bhc used ,bacillus fluorescens for similar purposes4 ,at #bb it forms a fluorescing pigment and trimethylamine1 but not at #ce4 ,by constantly cultivating this bacillus at #ce ,dieudonn found that after the fifteenth generation had been cultivated at #ce the bacillus produced pigment and trimethylamine at #ce4 ,davenport and ,castle#bhd found that tadpoles of a frog kept at #ae went into heat rigour at #dj4c ,c41 while those kept for twenty-eight days at #be were not affected by this temperature but went into heat rigour at #dc4e4 ,when the latter tadpoles were put back for seventeen days to a temperature of #ae they had lost their resistance to high temperature partially1 but not completely1 since they went into heat rigour at #da4f4 ,the authors suggest that this adaptation to a higher temperature is due to a loss of water on the part of protoplasm1 whereby the latter becomes more resistant to an increase in temperature4 ,this idea was put to a test by ,kry#bhe1 who found that the coagulation temperature of their muscle plasm is not altered by keeping cold-blooded animals at different temperatures4 #bhc ,dieudonn1 ,a41 ,arb4 a4 d4 kais4 ,gesndhtsmt41 #ahid1 ix41 #dib4 #bhd ,davenport1 ,c4 ,b41 and ,castle1 ,w4 ,e41 ,arch4 f4 ,entwcklngsmech41 #ahif1 ii41 #bbg4 #bhe ,kry1 ,f41 ,arch4 f4 ,entwcklngsmech41 #aijg1 xxiii41 #efj4 ,loeb and ,wasteneys#bhf found that ,fundulus taken from a low temperature of #aj ,c4 die in less than two hours when suddenly transferred to sea water of #bi ,c42 and in a few minutes if suddenly transferred to a temperature of #ce ,c4 ,if1 however1 the fish were transferred to a temperature of #bg ,c4 for forty hours they could live indefinitely in sea water of #ce4 ,by exposing the fish each day two hours to a gradually rising temperature they could render them resistant to a temperature of #ci4 ,the remarkable fact was that fish if once made resistant to a high temperature 7#ce7 did not lose this resistance when kept for four weeks at from #aj to #ad ,c4 ,control fish taken from the same temperature died in from two to four minutes2 immunized fish taken from #aj and put directly to #ce ,c4 lived for many hours or indefinitely4 ,they will even retain this immunity when kept for two weeks at a temperature of #j4d ,c4 #bhf ,loeb1 ,j41 and ,wasteneys1 ,h41 ,jour4 ,exper4 ,zol41 #aiab1 xii41 #edc4 ,why is it that an animal can in general resist a high temperature better if the latter is raised gradually than when it is raised suddenly8 ,physics offers us an analogy to this phenomenon in the experience that glass vessels which burst easily when their temperature is raised suddenly1 remain intact when the temperature is raised gradually4 ,glass is a poor conductor of heat and when the temperature is raised suddenly inside a glass cylinder the inner layer of the cylinder expands while the outer layer on account of the slowness of conduction of heat does not expand equally and the cylinder may burst4 ,we might assume that the sudden increase in temperature brings about certain changes in the cells 7e4 g41 an increase in permeability or destruction of the surface layer874 ,if the rise of temperature occurs gradually the blood or lymph or the cell sap may have time to repair the damage1 and this repair seems to be irreversible1 at least for some time1 as the experiments on ,fundulus seem to indicate4 ,if the temperature rises too rapidly the damage cannot be repaired quickly enough by the cell or body liquids4 ,it is also to be considered that substances might be formed in the body at a higher temperature which do not exist at a lower temperature1 and vice versa1 and this might explain results like those of ,schottelius or ,dieudonn and many others4 #f4 ,the theory of an adapting effect of the environment has often been linked with the assumption of the inheritance of acquired characters4 ,the older claims of the hereditary transmission of acquired characters1 such as ,brown-,squard's epilepsy in guinea pigs after the cutting of the sciatic nerve1 have been shown to be unjustified or have found a different and more rational explanation4 ,recently ,p4 ,kammerer has claimed to have proven by new experiments that by environmental changes1 hereditary changes can be produced4 ,it has been mentioned already that the mature male frogs and toads possess during the breeding season lumps on the thumbs or arms which are pigmented and which bear numerous minute horny black spines2 these secondary sexual characters serve the male frog in holding the females in the water during copulation4 ,there is one species which does not possess this sexual character1 namely the male of the so-called midwife toad 7,alytes obstetricans74 ,in this species the animals copulate on land1 and it is natural to connect the lack of this secondary sexual character in the male with its different breeding habit4 ,kammerer now forced such toads to copulate in water instead of on land 7by keeping the animals in a terrarium with a high temperature74 ,he makes the statement that by forcing the parents to lay their eggs during successive spawning periods in water he finally obtained offspring which under normal temperature conditions lay their eggs naturally in water2 in other words1 they have changed their habits4 ,we will not discuss this part of his statement since the breeding habits of animals in captivity are liable to be abnormal4 ,but ,kammerer makes the further important statement#bhg that the male offspring of such couples will in the third generation produce the swelling on the thumb and the usual roughness1 and in the fourth generation black pads and hypertrophy of the muscles of the forearm will appear4 ,in other words1 he reports having succeeded in producing an inheritance of an acquired morphological character which has never been known to occur in this species4 ,bateson1 on account of the importance of the case1 wished to examine it more closely and ,i will quote his report4 ,the systematists who have made a special study of ,batrachia appear to be agreed that ,alytes in nature does not have these structures2 and when individuals possessing them can be produced for inspection it will1 ,i think1 be time to examine the evidence for the inheritance of acquired characters more seriously4 ,i wrote to ,dr4 ,kammerer in ,july1 #aiaj1 asking him for the loan of such a specimen and on visiting the ,biologische ,versuchsanstalt in ,september of the same year ,i made the same request1 but hitherto none has been produced4 ,in matters of this kind much generally depends on interpretations made at the time of observation2 here1 however1 is an example which could readily be attested by preserved material4#bhh #bhg ,kammerer1 ,p41 ,arch4 f4 ,entwcklngsmech41 #aiji1 xxviii41 #ddh4 #bhh ,bateson1 ,w41 ,problems of ,genetics1 pp4 #bja-bjb4 ,yale ,university ,press1 #aiac4 ,more recently the same author has reported another hereditary morphological change brought about by outside conditions4#bhi ,a certain salamander 7,salamandra maculosa7 has yellow spots on a generally dark skin4 ,kammerer states that if such salamanders are kept on a yellow ground they become more yellow1 not by an extension of the chromatophores 7which would not be surprising7 but by actual multiplication and growth of the yellow pigment cells2 while the black skin is inhibited in its growth4 ,the reverse is true if these salamanders are kept on black soil2 in this case according to ,kammerer the growth of the yellow cells of the skin is inhibited while the black part of the skin grows4 ,curiously enough1 according to him1 these induced changes are hereditary4 ,here again we are dealing with the inheritance of an acquired morphological character4 #bhi ,kammerer1 ,p41 ,arch4 f4 ,entwcklngsmech41 #aiac1 xxxvi41 #d4 ,megusar#bij has repeated ,kammerer's experiments on salamanders but contradicts him by stating that the colour of the soil has no influence on the colouration of salamanders4 ,of course1 we know the phenomenon of colour adaptation in which the animal changes its colour pattern according to the environment4 ,this is an effect of the retina image on the skin and has been interpreted by the writer as a case of colour telephotography1 for which no physical explanation has yet been found4#bia ,this phenomenon1 however1 does not lead to any hereditary change of colour4 #bij ,werner1 ,f41 ,biol4 ,centralbl41 #aiae1 xxxv41 #agf4 #bia ,loeb1 ,j41 ,the ,mechanistic ,conception of ,life4 ,chicago1 #aiab4 ,kammerer makes many statements on the heredity of acquired modifications of instinct2 indeed he claims that an interest in music on the part of parents produces offspring with musical talent4 ,in such claims much depends upon the subjective interpretation of the observer4 ,the writer is not aware that there is at present on record a single adequate proof of the heredity of an acquired character4 ,we have records of changes in the offspring by poisoning the germ plasm by alcohol given to parents--as in ,stockard's well-known experiments--or by exposing butterflies to extreme temperatures1 but in these cases the germ cells were poisoned or altered by the alcohol or by chemical compounds produced at very low or very high temperatures4 ,this is of course an entirely different thing from stating that by inducing the midwife toad to lay its eggs in the water the male offspring acquires the pads and horns of other species of frogs on its thumb2 or that by keeping black salamanders on yellow paper the offspring is more yellow4 ,yet if there is an inheritance of acquired characters which can in any way throw light on the so-called phenomena of adaptation it must consist in results such as ,kammerer claims to have obtained4 ,while the writer does not decline to accept ,ehrlich's interpretation of the arsenic-fast strains of trypanosomes or ,kammerer's statements in regard to the inheritance of acquired character1 he feels that more work should be done before they can be used for our problem4 #g4 ,this attitude leaves us in a quandary4 ,the whole animated world is seemingly a symphony of adaptation4 ,we have mentioned already the eye with its refractive media so well curved and placed that a more or less perfect image of the outside objects is focussed exactly on the retina2 and this in spite of the fact that lens and retina develop independently2 we have mentioned and discussed the cases of instincts or automatic arrangements which are required to perpetuate life--the attraction of the two sexes and the automatic mechanisms by which sperm and egg are brought together2 the maternal instincts by which the young are taken care of2 and all those adaptations by which animals get their food and the suitable conditions of preservation4 ,can we understand all these adaptations1 without a belief in the heredity of acquired characters8 ,as a matter of fact the tenacity with which some authors cling to such a belief is dictated by the idea that this is the only alternative to the supra-naturalistic or vitalistic ideas4 ,the writer is of the opinion that we do not need to depend upon the assumption of the heredity of acquired characters1 but that physiological chemistry is adequate for this purpose4 ,the earlier writers explained the growth of the legs in the tadpole of the frog or toad as a case of an adaptation to life on land4 ,we know through ,gudernatsch that the growth of the legs can be produced at any time even in the youngest tadpole1 which is unable to live on the land1 by feeding the animal with the thyroid gland4 ,as we have stated in ,chapter ,,vii1 it is quite possible that in nature the legs of the tadpole begin to grow when enough of the thyroid or a similar compound has been formed or is circulating in the animal4 ,it might justly be claimed as a case of adaptation that the egg attaches itself to the wall of the uterus and calls forth the formation of the decidua4 ,we have mentioned the observation of ,leo ,loeb that the corpus luteum of the ovary gives off a substance to the blood which alters the tissues in the uterus in such a way that contact with any foreign body 7e4 g41 the egg7 induces this decidua formation4 ,again what appeared as adaptation when unknown turns out to be a result of the action of a definite chemical substance circulating in the body4 ,it appears as a case of adaptation that the eggs of the majority of animals cannot develop without a spermatozon1 and yet we can imitate the activating effect of a spermatozon on the egg by definite chemical compounds1 which leads to the suggestion that the activating effect of the spermatozon on the egg might be due to the fact that it carries such a compound4 ,the wonderful adaptations exhibited in the mating instincts seem to be due to definite substances secreted by the sex glands1 as was shown by ,steinach 7,chapter ,,vii74 ,here1 again1 the process as popularly conceived1 is the reverse of the truth2 those survive that have the equipment1--they did not acquire the equipment under the influence of environment4 ,it is absolutely imperative for green plants that their stems and leaves be exposed to the light since only in this way are they able to form carbohydrates2 and it is equally essential that the roots should grow into the soil so that the plant may get the nitrates and phosphates required to build up its proteins and nucleins4 ,this result is1 in the language of adaptationists1 brought about by an adaptive response of the plant to the light4 ,in reality this adaptive response is due 7,chapter ,x7 to the presence of a photosensitive substance present in almost all green plants4 ,lewis has shown that if the optic cup is transplanted under the skin of a young larva into any part of the body the skin in contact with the optic cup will form a lens2 it looks as if a chemical substance from the optic cup were responsible for the formation of the lens4 ,these examples might be multiplied indefinitely4 ,they all indicate that apparent morphological and instinctive adaptations are merely caused by chemical substances formed in the organism and that there is no reason for postulating the inheritance of acquired characters4 ,we must not forget that there are just as many cases where chemical substances circulating in the body lead to indifferent or harmful results4 ,as an example of the first type1 we may mention the existence of heliotropism in animals living in the dark1 of the latter type1 the inheritance of deficiencies like colour-blindness or glaucoma4 ,while it is possible for forms with moderate disharmonies to survive1 those with gross disharmonies cannot exist and we are not reminded of their possible existence4 ,as a consequence the cases of apparent adaptation prevail in nature4 ,the following observation may serve to give an idea how small is the number of existing or durable forms compared with the number of forms incapable of existence4 ,we have mentioned the fact observed by ,moenkhouse1 the writer1 and ,newman1 that it is possible to fertilize the eggs of each marine bony fish with the sperm of practically every other marine bony fish4 ,the number of teleosts at present in existence is about ten thousand4 ,if we accomplish all possible hybridizations1 one hundred million different crosses will result4 ,of these only a small fraction of one per cent4 can live 7see ,chapter ,i71 and it is generally the lack of a proper circulation which inhibits them from reaching maturity4 ,it is1 therefore1 no exaggeration to state that the number of species existing today is only an extremely small fraction of those which can and possibly do originate1 but which escape our notice and disappear because they cannot live or reproduce4 ,if we consider these facts we realize that the mere laws of chance are adequate to account for the fact of the apparently purposeful adaptations2 as they are adequate to account for the ,mendelian numbers4 ,,chapter ,,xiii ,,evolution ,darwin's work has been compared to that of ,copernicus and ,galileo inasmuch as all these men freed the mind from the incubus of ,aristotelian philosophy which1 with the efficient co-operation of the church and the predatory system of economics1 caused the stagnation1 squalor1 immorality1 and misery of the ,middle ,ages4 ,copernicus and ,galileo were the first to deliver the intellect from the idea of a universe created for the purpose of man2 and ,darwin rendered a similar service by his insistence that accidental and not purposeful variations gave rise to the variety of organisms4 ,in this struggle for intellectual freedom the names of ,huxley and ,haeckel must be gratefully remembered1 since without them ,darwin's idea would not have conquered humanity4 ,darwin assumed that the small fluctuating variations could accumulate to larger variations and thus cause new forms to originate4 ,it was the merit of de ,vries#bib to have pointed out that fluctuating variations are not hereditary and hence could not have played the rle assigned to them by ,darwin1 while discontinuous variations as they appear in the so-called 8sports0 or mutations are inherited4 ,this was an important step in the history of the theory of evolution4 ,it did not touch the foundation of ,darwin's work1 namely the substitution of the idea of an accidental evolution for that of a purposeful creation2 it only modified the conception of the possible mechanism of evolution4 ,according to de ,vries1 there are special species or groups of species which are in a state of mutation4 ,he considers the evening primrose on which he made his observations as one of these forms4 ,morgan and his pupils have observed over #acj mutations in a fly ,drosophila4 ,from our present limited knowledge we must admit the possibility that the tendency toward the production of mutants is not equally strong in different forms4 ,whether this part of de ,vries's idea is or is not correct there can be no doubt that variations occur which consist in the loss and apparently1 though in rarer cases1 in the gain or a modification of a ,mendelian factor4 ,if we wish to visualize the basis of such a change we may do so by imagining well-defined chemical constituents in one or more of the chromomeres undergoing a chemical change4 #bib de ,vries1 ,h41 ,the ,mutation ,theory1 translated by ,farmer1 ,j4 ,b41 and ,darbishire1 ,a4 ,d41 ,chicago1 #aiji4 ,species and ,varieties4 ,chicago1 #aijf4 ,gruppenweise ,artbildung4 ,berlin1 #aiac4 ,this way of looking at the origin of variation has had the effect of putting an end to the vague speculations concerning the evolution of one form from another4 ,we demand today the experimental test when such a statement is made and as a consequence the amount of mere speculation in this field has diminished considerably4 ,it is possible that any further progress concerning evolution must come by experimental attempts to bring about at will definite mutations4 ,such attempts have been reported but they are not all beyond the possibility of error4#bic ,the most remarkable among them are those by ,tower who by a very complicated combination of effects of temperature and moisture claims to have produced definite mutations in the potato beetle4 ,the conditions for these experiments are so expensive and complicated that a repetition by other investigators has not yet been possible4 #bic ,for a critical discussion of the details1 see ,bateson1 ,w41 ,problems of ,genetics1 ,new ,haven1 #aiac1 ,chapter ,x4 ,it is1 however1 still uncertain whether the mere addition or loss of ,mendelian characters can lead to the origin of new species4 ,species specificity is determined by specific proteins 7,chapter ,,iii471 while some ,mendelian characters at least seem to be determined by hormones or substances which need neither be proteins nor specific for the species4 ,,chapter ,,xiv ,,death ,,and ,,dissolution ,,of ,,the ,,organism #a4 ,it is an old saying that we cannot understand life unless we understand death4 ,the dead body1 if its temperature is not too low and if it contains enough water1 undergoes rapid disintegration4 ,it was natural to argue that life is that which resists this tendency to disintegration4 ,the older observers thought that the forces of nature determined the decay1 while the vital force resisted it4 ,this idea found its tersest expression in the definition of ,bichat1 that 8life is the sum total of the forces which resist death40 ,science is not the field of definitions1 but of prediction and control4 ,the problem is3 first1 how does it happen that as soon as respiration has ceased only for a few minutes the human body is dead1 that is to say1 will commence to undergo disintegration1 and second1 what protects the body against this decay while the respiration goes on1 although temperature and moisture are such as to favour decay8 ,the earlier biologists had already raised the question why it was that the stomach and intestine did not digest themselves4 ,the hydrochloric acid and the pepsin in the stomach and the trypsin in the intestine digest proteins taken in in the form of food2 why do they not digest the proteins of the cells of the stomach and the intestine8 ,they will promptly digest the stomach as soon as the individual is dead1 but not during life4 ,a self-digestion may also be caused if the arteries of the stomach are ligatured4 ,claude ,bernard and others suggested that the layer of mucus protected the cells of the stomach and of the intestine from the digestive enzymes2 or that the epithelial layer had a protective effect4 ,pavy suggested that the alkali of the blood had a protective action4 ,all these theories became untenable when ,fermi showed that all kinds of living organisms1 protozoans1 worms1 arthropods1 are not digested in solutions of trypsin as long as they are alive1 while they are promptly digested in the same solution when dead4#bid ,this is in harmony with the fact that many parasites live in the intestine without being digested as long as they are alive4 ,fermi concluded that the living cell cannot be attacked by the digestive ferments1 while with death a change occurs by which they can be attacked4 ,but what is this change8 ,fermi seems to be inclined to think that the 8living molecule0 of protein is not hydrolysable 7perhaps because the enzyme cannot attach itself to it871 while a change in the constitution or configuration of the proteins takes place after respiration has ceased4 ,the fact that the living cell resists the digestive action of trypsin and pepsin has found two other modes of explanation1 first1 that the cells are surrounded by a membrane or envelope through which the enzyme cannot diffuse1 and second1 that the living cells possess antiferments4 ,but the so-called antiferments are also said to exist after the death of the cell1 whereas after death the cell is promptly digested4 ,frdricq1 as well as ,klug1 has shown that worms which are not attacked by trypsin are digested by this enzyme when they are cut into small pieces2 although the pieces of course contain the antienzyme4 ,the other suggestion that a membrane impermeable for trypsin protects the cells would explain why living protozoa are not digested by trypsin1 but it leaves another fact unexplained1 namely1 the autodigestion of all the cells after death by enzymes contained in the cells themselves4 #bid ,fermi1 ,c41 ,centralbl4 f4 ,bacteriologie1 ,abt4 #a1 #aiaj1 lvi41 #ee4 #b4 ,the disintegration of the body after death is not caused exclusively or even chiefly by the digestive enzymes of the intestinal tract or the micro-organisms entering the dead body from the outside1 but by the enzymes contained in the cells themselves4 ,this phenomenon of autolysis#bie was first characterized by ,hoppe-,seyler4#bif ,all organs suffering death within the organism1 in the absence of oxygen1 undergo softening and dissolution in a manner resembling that of putrefaction4 ,in the course of that process1 albuminous matter gives rise to leucin and tyrosin1 fat to free acids and soaps4 ,this maceration1 identical with the pathological conception of softening1 is accomplished without giving rise to ill odour and is a process similar to the one resulting from the action of water1 acids1 and digestive enzymes4 #bie ,levene1 ,p4 ,a41 ,autolysis4 ,the ,harvey ,lectures1 #aije-aijf1 p4 #gc1 gives a full account of the work on this subject up to #aije4 #bif ,hoppe-,seyler1 ,f41 ,tbinger med4-chem4 ,untersuchungen1 #ahga1 ,p4 #dii4 ,in work of this kind1 rigid asepsis is required to exclude the possibility of bacterial infection and this was first done by ,salkowski1 who showed that in aseptically kept tissues like liver and muscle the amount of substances that can be extracted with hot water increases considerably4 ,by the work of others1 especially ,martin ,jacoby and ,levene1 it was established that the power of self-digestion is shared by all organs4 ,analysis of the products of the autodigestion of tissues shows that1 e4 g41 the amino acids1 which constitute the proteins1 are produced4 ,dakin1 ,jones1 and ,levene demonstrated the hydrolytic products of the nucleins1 in the case of the self-digestion of tissues4#big #big ,levene1 ,p4 ,a41 ,am4 ,jour4 ,physiol41 #aijd1 xii41 #bgf4 ,again the question arises3 ,why do the tissues not undergo autolysis during lifetime and what protects them1 and the answer is that self-digestion is a consequence of the lack of oxidations4 ,the presence of antiferments must continue after death and cannot be the cause which prevents the self-digestion during life1 since nothing indicates the destruction of the hypothetical antidigestive enzymes through lack of oxygen4 ,the recent work of ,bradley and ,morse#bih and of ,bradley#bii has thrown some light on the problem4 ,these authors found that proteins of the liver which are indigestible can be made digestible by the liver enzymes if an acid salt or a trace of acid is added to the mixture4 ,a m_/#bjj ,h,cl solution gives marked acceleration of the autodigestion of the liver4 ,this would explain why autodigestion takes place after oxidations cease4 ,in many if not all the cells1 acids are constantly formed during lifetime1 e4 g41 lactic acid1 which through oxidation are turned to ,,co1 and this diffuses into the blood so that the ,h ion concentration in the cells does not rise materially4 ,if1 however1 the oxidations cease1 as is the case after death1 the formation of lactic acid continues1 but the acid is not oxidized to ,,co and thus removed1 and as a consequence the ,h ion concentration increases in the cells and the self-digestion of proteins1 which the digestive enzymes contained in the cells themselves could not attack formerly1 becomes possible4 ,acid increases the digestibility of a protein1 probably by salt formation4 ,theoretically we should not be surprised that while in the liver an increase in the ,c,h favours autolysis in other tissues the same result is produced by the reverse effect4 ,we might say that the preservation of a certain ,c,h probably at or near the point of neutrality during life prevents self-digestion1 while the gross alteration of the ,c,h in either direction after death 7or after the cessation of oxidations in the tissues7 induces autolysis4 ,bradley indeed suggests that many of the phenomena of autolysis during lifetime1 such as atrophy1 necrosis1 involution1 might be due to an increase in the ,c,h in the tissues4 #bih ,bradley1 ,h4 ,c41 and ,morse1 ,m41 ,jour4 ,biol4 ,chem41 #aiae1 xxi41 #bji4 #bii ,bradley1 ,h4 ,c41 ibid41 #aiae1 xxii41 #aac4 ,these facts agree with the suggestion of ,fermi that in the living cell the proteins cannot be attacked by the digestive enzymes but relieves us of the necessity of making the monstrous assumption of a 8living molecule0 of proteins as distinct from a 8dead0 molecule4 ,the difference between life and death is not one between living and dead molecules1 but more likely between the excess of synthetic over hydrolytic processes4 ,in the second chapter we mentioned the interesting idea of ,armstrong that when a synthesis is brought about by a digestive enzyme 7e4 g41 maltase7 not the original substrate is formed 7e4 g41 maltose7 but an isomer1 in this case isomaltose2 and this isomer is not attacked by the enzyme maltase4 ,we thus get a rational understanding of the statement which ,claude ,bernard used to make but which remained at his time mysterious3 la vie1 c'est la cration4 ,during life1 when nutritive material is abundant1 through the reversible action of certain enzymes1 synthetic compounds are formed from the building stones furnished by the blood4 ,these synthetic isomers cannot be hydrolyzed by the enzymes by which they are formed and hence on account of the isomeric structure are immune against destruction4 ,it is not impossible that the increase of the concentration of acid in the cells after death transforms the isomers into that form in which they can be digested by the enzymes contained in the cell4 ,another possibility is that the increase in digestibility brought about by an increase in ,c,h in the cell is due to the hydrating effect of acids on proteins with a subsequent increase in digestibility4 ,whatever the answer may be1 the work done since ,claude ,bernard has removed that cloud of obscurity which in his days surrounded the prevalence of synthetic action in the living and of disintegration in the dead tissues4 #c4 ,we have already referred to the connection between the lack of oxygen and the onset of autolysis and disintegration of tissues in the body4 ,it is of interest that there are cells in which the disintegration under the influence of lack of oxygen is so rapid that it can be followed under the microscope4 ,the writer has observed that certain cells undergo complete irreversible dissolution in a very short time under the influence of lack of oxygen1 e4 g41 the first segmentation cells of the egg of a teleost fish ,ctenolabrus4#cjj #cjj ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #ahie1 lxii41 #bdi4 ,illustration3 ,,fig4 #dh ,illustration3 ,,fig4 #di ,illustration3 ,,fig4 #ej ,illustration3 ,,fig4 #ea ,when these eggs are deprived of oxygen at the time they reach the eight- or sixteen-cell stage1 it can be noticed that the membranes of the blastomeres are transformed into small droplets within half an hour or more1 according to the temperature4 ,these droplets begin to flow together1 forming larger drops4 ,figures #dh to #ea show the successive stages of this process4 ,when the eggs are exposed to the air in time1 segmentation can begin again2 but if a slightly longer time is allowed to elapse1 the process becomes irreversible and life becomes extinct4 ,such clear structural changes cannot often be observed in the eggs of other animals under the same conditions4 ,are these changes of structure 7apparently liquefaction of solid elements7 responsible for death under such conditions8 ,in order to obtain an answer to this question1 the writer investigated the effect of the lack of oxygen upon the heart-beat of the embryo of the same fish ,ctenolabrus4 ,this egg is perfectly transparent and the heart-beat can easily be watched4 ,when these eggs are put into an ,engelmann gas chamber and a current of pure hydrogen is sent through1 the heart may cease to beat in fifteen or twenty minutes2 it stops beating suddenly1 before the number of heart-beats has diminished noticeably1 and ceases beating before all the free oxygen can have had time to diffuse from the egg4 ,in one case the heart beat ninety times per minute before the hydrogen was sent through2 four minutes after the current of hydrogen had passed through the gas chamber1 the rate of the heart-beat was eighty-seven per minute1 three minutes later it was seventy-seven1 and then the beats stopped suddenly4 ,it is hard to believe that this cessation could have been caused by lack of energy4 ,hydrolytic processes alone could furnish sufficient energy to maintain the heart-beat for some time1 even if all the oxygen had been used up4 ,the suddenness of the standstill at a time when the rate had hardly diminished seems to be more easily explained by a sudden collapse of the machine2 it might be that liquefaction or some other change of structure occurs in the heart or its ganglion cells1 comparable to that which we mentioned before4 ,in another fish ,fundulus1 where the cleavage cells undergo no visible changes in the case of lack of oxygen1 the heart of the embryo can continue to beat for about twelve hours in a current of hydrogen4 ,in this case the rate of the heart-beat sinks during the first hour in the hydrogen current from about one hundred to twenty or ten per minute2 then it continues to beat at this rate for ten hours or more4 ,in this case one might believe that during the period of steady diminution of the tension of oxygen in the heart 7during the first hour71 the heart-beat sinks steadily while it keeps up at a low but steady rate as long as the energy for the beat is supplied solely by hydrolytic processes2 but there is certainly no change in the physical structure of the cells noticeable in ,fundulus1 and consequently there is no sudden standstill of the heart4 ,budgett has observed that in many infusorians visible changes of structure occur in the case of lack of oxygen#cja2 as a rule the membrane of the infusorian bursts or breaks at one point1 whereby the liquid contents flow out4 ,hardesty and the writer found that ,paramcium becomes more strongly vacuolized when deprived of oxygen1 and at last bursts4 ,amb likewise become vacuolized and burst under these conditions4 ,budgett found that a number of poisons1 such as potassium cyanide1 morphine1 quinine1 antipyrine1 nicotine1 and atropine1 produce structural changes of the same character as those described for lack of oxygen4 ,as far as ,,kcn is concerned1 ,schoenbein had already observed that it retards the oxidation in the tissues1 and ,claude ,bernard and ,geppert confirmed this observation4 ,for the alkaloids1 ,w4 ,s4 ,young has shown that they are capable of retarding certain processes of autoxidation4 ,this accounts for the fact that the above-mentioned poisons produce changes similar to those observed in the case of lack of oxygen4#cjb #cja ,budgett1 ,s4 ,p41 ,am4 ,jour4 ,physiol41 #ahih1 i41 #baj4 #cjb ,loeb1 ,j41 ,the ,dynamics of ,living ,matter1 ,new ,york1 #aijf1 pp4 #ai-ba4 ,the phenomenon of rapid disintegration when deprived of oxygen 7or in the presence of ,,kcn7 seems to be general as ,child#cjc has shown in extensive experiments4 ,child has used it to show that younger animals disintegrate more rapidly than older or larger ones1 and he uses this fact for a theory of senescence4 ,he connects the more rapid disintegration of the young animal with a greater metabolism4#cjd ,without wishing to doubt ,child's interesting observations the writer is not quite certain whether the more rapid disintegration of the younger forms is not a result of the fact that the walls of membranes in the young are softer than those of the older animals1 and hence are more readily liquefied4 ,such a difference could be due to mere chemical constitution1 e4 g41 the increase in ,ca in the membrane with the increase in age4 ,in old age in man the deposit of ,ca in the blood-vessels is a frequent occurrence4 #cjc ,child1 ,c4 ,m41 ,senescence and ,rejuvenescence1 ,chicago1 #aiae4 #cjd ,it is a fact that in the early cells of ,ctenolabrus the dissolution of the cell walls through lack of ,o precedes death1 since when oxygen is admitted early enough the cells recover again4 ,in infusorians the bursting of the animal due to lack of ,o occurs suddenly1 while the animal is still moving1 and this bursting is the cause of death1 and not the reverse4 ,these facts may help us to understand the nature of death and dissolution of the body in higher animals4 ,death in these animals is due to cessation of oxidations1 but the surprising fact is that if the oxidations have been interrupted but a few minutes life cannot be restored even by artificial respiration4 ,this suggests that the respiratory ganglia in the medulla oblongata suffer an irreparable injury or an irreversible change 7comparable to that just described in the cells of ,ctenolabrus7 even when deprived of oxygen for only a short time4 ,as a consequence of the irreversible injury to the medulla the respirations cease permanently1 the heart-beat must also cease1 and gradually the different tissues must undergo the dissolution characteristic of death4 ,while all the cells may be immortal they are only so in the presence of oxygen and the nutritive solution which the circulating blood furnishes4 ,with the proper supply of oxygen cut off they can no longer live4 #d4 ,it is an unquestionable fact that each form has a quite definite duration of life4 ,unicellular organisms are immortal2 but for the higher organisms with sexual reproduction the duration of life is almost as characteristic as any morphological peculiarity of a species4 ,no species can exist unless the natural life of its individuals outlasts the period of sexual maturity2 and unless the average duration of life is long enough to allow as many offspring to be brought into the world as will compensate for loss by death4 ,the male bee dies before it is a year old1 while the queen may live several years4 ,in a certain species of butterflies1 the ,psychid1 the parthenogenetic female lays its eggs while still in the cocoon and then dies without ever leaving the cocoon4 ,the imago of the ephemera leaves the water in the evening1 copulates1 lets its eggs fall into the water1 and is dead the next morning4 ,the imperfect condition of their mandibles and alimentary canal makes them unfit for a long duration of life4 ,the males of the rotifers which are devoid of organs of digestion live but a few days4 ,in the ,zological ,station at ,naples in #aijf1 an actinian1 ,actinia equina1 was alive after having been in captivity fifteen years1 and another one1 ,cerianthus1 had been observed for twenty-four years4 ,korschelt kept earthworms for as long as ten years4 ,the fresh-water mussel may reach the age of sixty years or more and crayfish may live for over twenty years4 ,the differences in the duration of life of mammals are too well known to need discussion4 ,if the cells and tissues are immortal1 how does it happen that the duration of life is so characteristic for each species8 ,metchnikoff#cje has recently investigated the cause of 8natural0 death in the butterfly of the silkworm4 ,the butterfly in this species lacks the organs necessary for taking up food1 like the male rotifer or the ephemerid and hence is already1 by this fact1 condemned to a short life4 ,metchnikoff observed that these butterflies could live twenty-three days1 but the average duration of life was #ae4f for the males and #af4f days for the females2 and that seventy-five per cent4 of them contained no parasitic fauna or flora in their intestine4 ,they lose considerably in weight during their lives1 but the males still contain the fat body at the time of death4 ,none of the changes accompanying 8old age0 in man are found in the tissues of these butterflies before death4 ,metchnikoff is inclined to believe that the animal is poisoned by some excretion retained in the body2 namely1 the urine1 and that this poison also causes the symptoms of weakness which characterize the animal4 ,he could prove the toxic character of their urine on other animals4 ,this combined with starvation could sufficiently account for the short duration of life4 ,the facts of the case show that it is due to an imperfection in the construction of the organism such as one would expect to find more or less in each animal if one discards the idea of purposefulness and divine wisdom in nature4 ,only a slight1 perhaps an infinitesimal1 fraction1 of those species which are theoretically possible and which at one time or another arise can survive4 ,those which are durable show all transitions from the grossest disharmonies to an apparent lack of such shortcomings4 #cje ,metchnikoff1 ,e41 ,ann4 d4 l',inst4 ,pasteur1 #aiae1 xxix41 #dgg4 #e4 ,minot had tried to prove that the death of metazoa is due to the greater differentiation and specialization of their tissues4 ,admitting the immortality of the unicellular organisms he argues that death is the price metazoa pay for the higher differentiation of their cells4 ,this is of course purely metaphorical1 but we may put it into a form in which it is capable of discussion in physicochemical terms1 by assuming that death is a necessary stage in the development of a species4 ,we are inclined1 however1 to follow ,metchnikoff and suspect some poison accidentally or unavoidably formed in the body or some structural shortcoming as the cause of 8natural0 death4 ,an unusually favourable object for the study of natural death is the animal egg4 ,the egg of the starfish ,asterias forbesii when taken out of the body is usually immature1 but in the spawning season it ripens in sea water4 ,the writer#cjf observed that eggs which ripen disintegrate very rapidly when not fertilized4 ,this disintegration may be due to a process of autolysis1 which sets in only after the egg has extruded the two polar bodies4 ,the writer found that by preventing the maturation of the egg either by withdrawing the oxygen or by replacing the alkaline sea water by a neutral solution or by exposing the eggs for some time to acidulated sea water1 the disintegration could also be prevented4 #cjf ,loeb1 ,j41 ,biol4 ,bull41 #aijb1 iii41 #bie4 ,further experiments showed that even in the mature egg rapid disintegration could be prevented by lack of oxygen1 and similar results were obtained by ,mathews4 ,when the egg is fertilized it does not disintegrate in the presence of oxygen but it gradually dies in the absence of oxygen4 ,one is almost tempted to say that while the fertilized egg is a strict arobe the mature unfertilized egg is an anarobe4 ,this latter statement1 however1 becomes doubtful since the presence of oxygen may help the disintegration only indirectly by allowing certain changes to go on in the egg4 ,the important points for us are that duration of life in the mature unfertilized egg is comparatively short and that the entrance of a spermatozon or the process of artificial parthenogenesis saves the life of the egg4 ,loeb and ,lewis found that the life of the unfertilized sea-urchin egg 7which is usually mature when removed from the ovaries7 can also be prolonged when its oxidations are suppressed4 ,the decay of the unfertilized egg seems to be due to the fact that those alterations in the cortical layer which underlie the membrane formation and which are responsible for the starting of development gradually take place4 ,in such a condition the egg will die quickly unless deprived of oxygen4 ,this view is supported by the observation of ,wasteneys that unfertilized eggs of ,arbacia show an increased rate of oxidations when allowed to remain for some time in sea water2 we have seen in ,chapter ,v that such an increase also accompanies artificial membrane formation4 #f4 ,if the limited duration of life of an organism is determined by one or more definite harmful chemical processes1 we should expect to find a temperature coefficient for the duration of life or at least be able to show that if all other conditions are the same the duration of life is for a given organism a function of temperature4 ,the writer#cjg investigated the duration of life of fertilized and unfertilized eggs of ,strongylocentrotus purpuratus for the upper temperature limits4 #cjg ,loeb1 ,j41 ,arch4 f4 d4 ges4 ,physiol41 #aijh1 cxxiv41 #daa4 ,,table ,,xx ---------------------------------------- -------------------- ,duration of life of the eggs of ,s4 purpuratus ---------------------------------------- ------------------- ,temperature ,unfertilized ,fertilized ---------------------------------------- ------------------- ,c4 ,minutes ,minutes #cb #a-a_/f #a-a_/b #b #ca #b-a_/d #c #cj #c #d #e #e #bi #f #g #bh #h #aa #aj #ac #bg about #ah #bj #bb #bf #ce #ce #dj #dj #be #gf #ha #bd #afh #aib #bjj #bji ,hours #bb #aj-a_/e #ba #bd #bj #gb ---------------------------------------- ------------------- ,these observations show a very high temperature coefficient near the upper temperature limit1 and this may account at least partly for the fact that in tropical seas the pelagic fauna is so much more limited than in polar seas4#cjh ,it is quite probable that the high temperature coefficients at the utmost limits are only an expression of the coagulation time of certain proteins4 #cjh ,k4 ,brandt 78ber den ,nitratgehalt des ,ozeanwassers and seine biologische ,bedeutung10 ,abh4 d4 kais4 ,leop4 ,carol4 deutsch4 ,akad4 d4 ,naturfoscher41 #aiae7 accounts for this fact by the assumption that through the greater activity of the denitrifying bacteria in the tropical waters the amount of available nitrates is here comparatively smaller than in the polar oceans4 ,the writer fully appreciates the importance of this fact but nevertheless is inclined also to see a limiting factor in the enormously rapid decline of the duration of life at the upper temperature limits4 ,p4 and ,n4 ,rau state that in the cold certain butterflies live longer1 and similar statements exist for the silkworm1 but these statements are not based on exact experiments1 which are difficult4 ,dr4 ,northrop and the writer have started experiments on the influence of temperature on the duration of life of the fly ,drosophila4 ,newly hatched flies were kept first without food except water and air at #cd1 #bh1 #bd1 #ai1 #ad1 and #aj1 and second with cane sugar4 ,the average duration of life was as follows3 ,with water days ,with cane sugar days #cd #b4a #f4b #bh #b4d #g4b #bd #b4d #i4d #ai #d4a #ab4c #ad #h4c #aj #aa4i ,these experiments show that there is a definite temperature coefficient for the duration of life and that this coefficient is of the order of magnitude of that of a chemical reaction4 ,we are continuing these experiments with animals in the presence of food4 ,it should1 however1 be remembered that the fly carries with it a good deal of reserve material from the larval period4 ,we have carried on simultaneously determinations of the temperature coefficients of the duration of the larval and pupa stage of these organisms at the same temperatures and found ratios similar to those given above for the duration of life with water only4 #g4 ,metchnikoff#cji has furnished the scientific facts for our understanding of senescence4 ,he has demonstrated that the changes in tissue which give rise to phenomena of senility are due to the action of phagocytes4 ,thus the ganglion cells are altered 7digested87 and destroyed by 8neuronophags0 and this is the main cause of mental senility4 ,definite phagocytic cells1 the osteoclasts1 slowly dissolve the bones 7by the excretion of an acid87 and this leads to the known fragility of the bones in old age4 ,the whiteness of the hair is due to the action of phagocytes2 in the muscles in old age the contractile elements are destroyed by the sarcoplasm1 and so on4 ,it agrees with these facts that where organs are absorbed in the embryonic development of an animal1 as e4 g41 the tail of the tadpole in metamorphosis1 the phenomenon is due to a process of phagocytosis 7and autolysis74 ,we have mentioned the fact that in the larva of the ,amblystoma the absorption of the gills and of the tail occurs simultaneously and that both must be caused by a constituent of the blood4 ,such a constituent may be responsible for phagocytosis and autolysis in the organs undergoing absorption4 ,metchnikoff calls attention to the fact that certain infectious diseases1 e4 g41 syphilis1 may bring about precocious senility2 and he mentions also the senile appearance of young cretins which is due to the diseased thyroid4 8,it is no mere analogy to suppose that human senescence is the result of a slow but chronic poisoning of the organism40 ,he assumes that in man this poisoning is caused by the products of fermentation in the large intestine and that the micro-organisms responsible for these fermentations may therefore be regarded as the real cause of senility in man4 ,parrots which are long-lived birds have a limited flora of microbes in their intestine1 while cows and horses which are short-lived in comparison with man possess an extraordinary richness of the intestinal flora4 ,but1 needless to say1 it is not the quantity of microbes alone which is to be considered1 the nature of the microbes is of much greater importance4 #cji ,metchnikoff1 ,e41 ,the ,prolongation of ,life4 ,new ,york1 #aijg4 ,certain plants like the ,californian ,sequoia gigantea may be considered as practically immortal since they live several thousands of years2 other plants1 the annuals1 die after fructification4 ,metchnikoff quotes from a letter by de ,vries that this author prolonged the life of notheras by cutting the flowers before fertilization4 ,under ordinary conditions the stem dies after producing from forty to fifty flowers1 but if cutting be practised new flowers are produced until the winter cold intervenes4 ,by cutting the stem sufficiently early the plants are induced to develop new buds at the base and these buds survive winter and resume growth in the following spring4 ,metchnikoff suggests that it is a poison formed in the plant 7in connection with fructification87 which kills the annuals1 while it is not formed or is less harmful in the perennials4 ,he compares the situation to the death of the lactic acid bacilli if the lactic acid is allowed to accumulate4 ,this hypothesis is certainly worthy of consideration1 and it is quite possible that in addition to structural shortcomings poisons formed by certain organs of the body as well as poisons formed by bacteria account for the phenomenon of death in metazoa4 ,,index ,abraxas1 #bjc1 #bch1 #bda ,acquired characters1 inheritance of1 #ccg ff4 ,actinia equina1 #cfa ,adaptation1 #ab1 #cah ff42 to life in caves1 #cai ff42 fresh and salt water1 #cbg ff42 poisons1 #ccb ff42 temperature1 #ccd ff42 caused by hormones1 #cdb ,addison1 ,w4 ,h4 ,f41 #ahh ,agglutination1 of corpuscles by sera1 #fg ff42 of sperm1 #gh1 #hb ff4 ,allolobophora terrestris1 #df ,alpheus1 #agf ,alytes obstetricans1 #ccg1 #cch ,amanita phalloides1 #fc ,amblystoma1 #aeg1 #cfh ,amelung1 #ahd ,amphipyra1 #bhc ,analogies between living and dead matter1 #ad ff4 ,anaphylaxis reaction1 #fa ff4 ,ancel1 #aeh1 #bbe ff4 ,antagonistic salt action4 ,see ,balanced salt solutions4 ,antennularia antennina1 #aid1 #aif ,apes1 blood relationship to man1 #ed1 #ef ff4 ,apolant1 #de ,arbacia1 #ge ff41 #if1 #ii1 #aja1 #aaa1 #aad1 #aej1 #aij ff41 #bic ff41 #bih1 #bii1 #cfd ,arenicola1 #bgg ,armstrong1 ,e4 ,f41 #bf1 #bh1 #ced ,arrhenius1 ,s41 #cc ff41 #hh1 #bij1 #bif ,arrhenoidy1 #bah1 #bbe ,artificial parthenogenesis1 #ie ff42 in sea urchins1 #ie ff42 new method of1 #ih1 #ii2 by blood1 #aja ff42 by sperm extract1 #ajc2 by acids1 #aje2 by mechanical agitation1 #ajg2 in starfish1 #aaj2 rle of hypertonic solution1 #aab1 #aae1 #aaf2 and oxidation1 #aaf1 #aag1 #aah2 and permeability1 #aai ff42 in frogs1 #abd2 and determination of sex1 #abe ,artificial production of life1 #ch-ci ,assimilation of ,,co without chlorophyll1 #ag ff4 ,asterias1 #di1 #ha1 #aaj1 #cfc2 ochracea1 #gc ff42 capitata1 #gd ,asterina1 #ge1 #ha1 #aaj ,astrospheres1 #aae ff41 #aib ,auer1 ,j41 #cae ,autolysis1 #cea ff4 ,avena1 #bfc ,b4 coli communis1 #cf2 typhosus1 #cf2 fluorescens1 #ccd ,bacteria1 growth of1 #ae ff41 #bi1 #ga ff42 specificity in1 #da ff4 8,bacterio-purpurin10 #da ,balanced salt solutions1 #cjg-cag2 theory of1 #cag2 and adaptation1 #cca ff4 ,balanus1 #bei ,baltzer1 ,f41 #bae ff4 ,bancroft1 ,f4 ,w41 #gj1 #abe1 #abg1 #bfd1 #bfi ff4 ,bang1 #fc ,bardeen1 ,c4 ,r41 #agd ff4 ,barnacle1 larv of1 #cac ff4 ,bataillon1 #abd ,bateson1 ,w41 #bcj1 #bdj ff41 #cch1 #cdh ,batrachia1 #cch ,baur1 ,e41 #dh1 #bdf ,bayliss1 #fc ,becquerel1 ,p41 #cf ff4 ,beggiatoa1 #ai ,beijerinck1 ,m41 #bj ,berkeley1 ,lord1 #aaa ,bernard1 ,claude1 #b ff41 #bf1 #aei1 #cej1 #ced1 #cee1 #ceh ,berthelot1 #bij ,bertrand1 ,g41 #bdh ff4 ,beutner1 ,r41 #adj ,bichat1 #b1 #cdi ,bickford1 ,e4 ,e41 #afi ,blaauw1 ,h4 ,a41 #bfc ,blackman1 ,f4 ,f41 #cjb ,blastomeres1 #ada ff4 ,blind animals1 #cai ff4 ,blood1 transfusion of1 #ec ff4 ,blood relationship1 established by transfusion1 #ec1 #ed ff42 precipitin reaction1 #ee ff42 anaphylaxis reaction1 #fa ff42 hemoglobin crystals1 #fd ff4 ,blood serum1 precipitin reaction of1 #ed ff42 effect of1 on unfertilized eggs1 #aja ff41 #abd ,blowfly1 heliotropism of larv of1 #bfe ff4 ,bohn1 ,g41 #bec1 #bfd1 #bfi ,bombinator igneus1 #df ,bonellia1 #bae ,bonnet1 #aed1 #afa ,bordet1 #ed ff41 #fj ,bouin1 #aeh1 #bbe ff4 ,boveri1 ,th41 #h1 #abf1 #abh ff41 #acd1 #ach ff41 #aej ff41 #ahf ff41 #bji ff41 #bdf ,brachystola1 #aii ,bradley1 ,h4 ,c41 #bg1 #fd1 #cec1 #ced ,brandt1 #cff ,braus1 ,h41 #adg ,bridges1 ,c4 ,b41 #bjh1 #bbi1 #bca ff4 ,brown1 ,a4 ,p41 #fd ff4 ,bruchmann1 ,h41 #ic ,bryophyllum calycinum1 #aec1 #afj ff41 #agg ,buchner1 #bd ,budgett1 #ceh ,buller1 #ic ,bunsen-,roscoe1 law of1 #aa1 #bef ff41 #bfa1 #bfc1 #bfd ,burrows1 #ca ,campanularia1 #agh1 #aha ,cannon1 ,w4 ,b41 #bhe ,carcinus mnas1 #bag ,cardamine pratensis1 #ij ,carrel1 #ca ,cassia bicapsularis1 #cg ,castle1 ,w4 ,e41 #hi ff41 #cce ,caullery1 ,m41 #aeh1 #ahj1 #bag ,cave animals1 #cai ff4 ,cell division1 #ae1 #bi1 #abi ff42 suppression of1 #aac ff4 ,cells1 nutritive media of1 #ae ff2 immortality of1 #cj ff42 migrating1 #dd2 mesenchyme1 #ea ff41 #acj ff41 #adg1 #aee ff4 ,cerianthus membranaceus1 #aga ff41 #ahh1 #cfa ,chtopterus1 #gh ff4 ,chamberlain1 ,m4 ,m41 #bic1 #big ,chapman1 ,h4 ,g41 #fj ,chemotropism of spermatozoa1 #ib ff4 ,chevreul1 #bhi ,child1 ,c4 ,m41 #g1 #agj1 #agg1 #ceh ,chlamydomonas1 #bgg ,chodat1 ,r41 #bdh ,chologaster1 #cbj ,christen1 #bhh ,chromosomes1 rle of1 in sex determination1 #aih ff42 theory of ,mendelian heredity1 #bcc ,chun1 #adb ,ciona intestinalis1 #hi ff41 #bab ,cladocera1 #aei ,clausen1 ,h41 #cjb ,clavellina1 #aha ,cohen1 ,e41 #bib ,cohn1 #da ff4 ,compton1 #ij ,conklin1 ,e4 ,g41 #abi1 #acd1 #adc1 #ade ff4 ,constancy of species1 #dj-dc ,copernicus1 #cdf ,corpus luteum1 action of1 #aeg-aeh ,correlation1 #aed1 #afg ,correns1 ,c41 #ij ff41 #bad ,cramer1 #bhi ,crampton1 ,h4 ,e41 #adc1 #bbe ,criodrilus lacuum1 #bai-bbj ,crossing over of chromosomes1 #bda ff4 ,crystals1 differences between living organisms and1 #ad ff4 ,ctenolabrus1 #cee1 #ceg1 #cei ,ctenophores1 #adb ,cunot1 ,l41 #ab1 #cbd ,cullen1 ,g4 ,e41 #bd1 #bia ,cuma rathkii1 #cah ,cyanophyce1 #bhg ,cytisus biflorus1 #cg ,cytoplasm of eggs as future embryo1 #h1 #i1 #gj1 #abf1 #aea ff4 ,dakin1 #ceb ,dallinger1 #ccd ,daphnia1 #baj1 #bfb1 #bgi1 #bhj1 #bhb1 #cjf1 #cab ,darbishire1 ,a4 ,d41 #cdg ,darwin1 #ij1 #big1 #cdf ff4 ,darwinian theory1 #e ff4 ,davenport1 ,c4 ,b41 #bdd1 #cce ,death1 #cdi ff42 natural1 cause of1 #cfd1 #cfi ,decidua formation induced by corpus luteum1 #aeg-aeh ,delage1 ,y41 #ajg1 #aaj1 #aaa1 #abc1 #abf1 #ahf de la ,rive1 #bd de ,meyer1 ,j41 #abg ,dendrostoma1 #aja ,dentalium1 #add ,design1 #d1 #e ,determination of sex1 in bees1 #bjh ff42 in phylloxerans1 #baj2 in ,bonellia1 #bae ,development of egg1 #abg ff4 de ,vries1 ,h41 #f1 #db1 #aed1 #afa1 #cdg1 #cfi ,dewitz1 #ic ,dieudonn1 ,c41 #ccd1 #ccg 8,directive force10 #b ,disharmonies1 #g ,divisibility of living matter1 limits of1 #adh-aea ,dominance1 #bcj ,doncaster1 ,l41 #bjc ,dorfmeister1 #cjc ,driesch1 ,h41 #d ff41 #abh1 #acc1 #acf1 #ach ff41 #adg1 #aej1 #afi ff41 #ahj ff41 #ahd ff4 ,drosophila ampelophila1 #bjd ff41 #bcg1 #bdc1 #cbb1 #cdg1 #cff ,duclaux1 ,e41 #bhh1 #bhi v4 ,dungern1 #hj ,duration of life1 #cfj ff4 ,durham1 #bdi ,dutrochet1 #aed ,dzierzon1 #bjh ,ectoderm formation1 #acj ff4 ,egg1 as the future embryo1 #h1 #i1 #gj1 #abf1 #aea2 artificial parthenogenesis of1 #ie ff42 organisms from1 #abh ff42 determining unity of organism1 #aea-aeb2 chromosomes in1 #aih ff4 ,egg structure1 #abi ff42 influence of centrifugal force on1 #ace2 and regulation1 #aci1 #adj1 #ada2 and fluidity of protoplasm1 #ada ,ehrlich1 #de1 #cbb1 #ccb ff41 #cda2 side-chain theory of1 #hh1 #ahh ,eigenmann1 #cbj1 #cbc ff4 ,electromotive forces1 origin in living organs1 #adj ,engelmann1 #ceg ,engler1 #bd ,entelechy1 #d1 #agj1 #ahb ,environment1 influence of1 #bhf ff42 temperature1 #bhh ff41 #cdd ff42 salinity1 #cjf2 adaptation to1 #cai ,enzyme action1 #bc ff41 #big1 #cjb ,ernst1 ,a41 #ba ,eternity of life1 #cd ff41 #cfj ,eudendrium1 #bfj1 #bfa1 #bfi1 #bgg1 #bgh1 #cbf ,eudorina1 #bgg ,euglena1 #bfd1 #bfi1 #bgb1 #bgg ,euler1 ,h41 #ba ,evolution1 #cdf ff42 and mutation1 #cdh ,ewald1 ,w4 ,f41 #bfa ff41 #bfi1 #bhj1 #cja ,farmer1 ,j4 ,b41 #cdg ,fermi1 #cej1 #ced ,fertilization1 heterogeneous1 #dh ff41 #ea1 #gc ff42 specificity in1 #ga ff42 and oxidation1 #aag ff42 and permeability1 #aai ff4 8,fertilizin10 #hd1 #hg ff41 #ic ,fischel1 #ahg ,fischer1 #cjc ff4 ,fish1 #ee ,fitness of environment1 #cag ,fitzgerald1 ,j4 ,g41 #fc ,flow of substances and regeneration in ,bryophyllum1 #afa ff4 ,fluctuating variations1 #f1 #big ff41 #cdf ff4 ,folin1 #bb ,food1 influence on polymorphism in wasps1 #bbb ff4 ,food castration1 #bbd2 influence on sexual cycle in rotifers1 #bbd2 on metamorphosis in tadpoles1 #aee ,ford1 #fc ,forssmann1 #fc ,frdricq1 #cea ,free-martin1 cause of sterility1 #bah-bai ,friedenthal1 ,h41 #ec ff41 #fj ,frisch1 ,k41 #bgh1 #bgi ,frschel1 ,p41 #bfc ,fuchs1 ,h4 ,m41 #ij ,fucus1 #abc ,fundulus heteroclitus1 #ea1 #aaf1 #adg1 #cjj1 #cja1 #cjb1 #cjg ff41 #cba ff41 #cbh ff41 #cce1 #ccg1 #ceg ff4 ,galileo1 #cdf ,galvanotropism1 #aa1 #bgj ff41 #cai ,gay1 ,f4 ,p41 #fb ff4 ,generation1 spontaneous1 #ad ff41 #cd ,genes1 #d ff41 #aeb1 #cai ,genus and species1 chemical basis of1 #dj ff4 ,geppert1 #ceh ,germination in seeds1 #ce ff4 ,giard1 #ahj1 #baf ff4 ,godlewski1 ,e41 #dh1 #ge1 #gh1 #abj1 #abf1 #afi ,godlewski1 ,e41 ,sr41 #ah ,goebel1 ,k41 #aed1 #afa ,goldfarb1 ,a4 ,j41 #cbf ,goldschmidt1 ,r41 #bbj ff4 ,goodale1 ,h4 ,d41 #bah ,gortner1 ,r41 #bdi ,graber1 ,v41 #bef1 #bgf ,grafting1 heteroplastic1 in animals1 #df2 in plants1 #dg ,gravitation1 influence on organ formation in ,antennularia1 #aid ff42 on the egg of the frog1 #ada ,gray1 ,j41 #abb ,gregory1 #bdc ,groom1 ,t4 ,t41 #bhj ,growth1 termination of1 #ahd2 influence of cell size1 #ahg ,gudernatsch1 ,j4 ,f41 #aee1 #bee1 #cdb ,guyer1 #abd ,gynandromorphism1 #bji ,haeckel1 #cdf ,half-embryos and whole embryos1 #ada1 #adb ,hammond1 ,j4 ,h41 ,jr41 #bfi ,harden1 #af ,hardesty1 #ceh ,harmonious character of organism1 #e1 #f1 #cah ff41 #cda ff4 ,harrison1 #ca ,hartley1 #aaa ,healing of wound1 #ahg ,hektoen1 #ff ,heliotropism1 #aa ff41 #beg ff41 #cah2 heredity of1 #bej ff42 change of1 #bgi1 #bhj ff42 and adaptation1 #cah ,helmholtz1 #cd ,hemoglobins1 crystallographic measurements of1 #fd ff4 ,henderson1 ,l41 #cag ,henking1 #aih ff4 ,herbst1 ,c41 #ig1 #adg1 #aic1 #cjf1 #caj ,heredity1 of genus and species1 #dj ff41 #gj1 #aea1 #aeb2 ,mendelian1 #gj1 #aea ff41 #bbi ff41 #cdh2 of sex1 #aih2 sex-linked1 #bjc ff41 #bch ff42 and evolution1 #cdh ,herlant1 ,m41 #gh ff41 #aae ff4 ,hermaphroditism1 #hi ff41 #bab ff41 #baf1 #bai ff4 ,see also ,inhibition and ,regeneration4 ,hertwig1 ,o41 #ig1 #abc1 #bib ,hertwig1 ,r41 #ie1 #ig ,hess1 ,c41 #bgh ,heterogeneous hybrids1 purely maternal1 #di1 #ej ,heterogeneous transplantation1 ,murphy's experiments on1 #dd ff42 limitation of1 #df ,heteromorphosis1 #aee1 #aic-aif ,hill1 ,c41 #be ,hippiscus1 #aii ,holmes1 ,s4 ,j41 #bfi ,hoppe-,seyler1 #cea ,hormones1 #ade1 #aee1 #aha1 #bai2 and ,mendelian heredity1 #bde ff41 #cdh2 and adaptation1 #cdb4 ,see also ,organ-forming substances4 ,huxley1 #cdf ,hybridization1 heterogeneous1 in sea urchins1 #dh ff41 #gc ff42 in fishes1 #ea2 in plants 7,mendel's71 #bcj ff4 ,hydrolytic enzymes1 action of1 #bd2 reversible action of1 #bd ff4 ,hypertonic solution1 #ii1 #aaa ff4 ,imitation of cell structures by colloids1 #ci ,immortality1 of cancer cells1 #cj2 of somatic cells1 #cj ff42 of life in general1 #cd ff4 ,inheritance1 of colour-blindness1 #bjc1 #bjd1 #bje2 of eye pigment in ,drosophila1 #bjd ff42 of pigments1 #bdh ff42 of acquired characters1 #ccg ff4 ,inhibition of regeneration in ,bryophyllum1 #afb ff4 ,inhibition of sexual characters of opposite sex1 in pheasants1 #bah2 lack of in hermaphrodites1 #bai2 in ,bonellia1 #bbf ,instincts1 #aj ff41 #bec ff42 sexual1 #aih ff4 ,intersexualism1 #bba ,intestine1 formation of1 #acj ff4 ,isoagglutinins1 #ff ff41 #ib ,isolation of blastomeres1 #acf ff4 ,jacoby1 #ceb ,janda1 ,v41 #bai ff4 ,jansky1 #fg ,janssens1 #bdb ,jennings1 ,h4 ,s41 #bfd ff4 ,jensen1 #de ,joest1 #df ,johannsen1 ,w41 #db1 #ccc ,jones1 #ceb ,jost1 #ij ,kammerer1 ,p41 #cbe1 #ccg ff4 ,kanitz1 ,a41 #bij1 #bib1 #bif ,kastle1 ,j4 ,h41 #bf ff4 ,kellogg1 ,v4 ,l41 #bgi ,kelvin1 #cd ,king1 ,w4 ,o4 ,r41 #ej1 #bdg ,klug1 #cea v4 ,knaffl1 ,e41 #ajf ,knowlton1 ,e4 ,p41 #bib ,kofoid1 ,c4 ,a41 #adc v4 ,krsy1 #cjj ,korschelt1 #cfa ,krakatau1 #ba ,kraus1 #ed ff4 ,krogh1 #bib ,kry1 ,f41 #cce ,kupelwieser1 ,h41 #ge ,lack of oxygen1 influence on disintegration of tissue1 #cee ff4 ,ladoff1 ,s41 #bbd ,lamarck1 #f ,laminaria1 #afe ,landois1 ,l41 #ec ,landsteiner1 #ff ,lanice1 #adc ff4 ,lankester1 ,e4 ,r41 #da ,leathes1 ,j4 ,b41 #fc ,leucna leucocephala1 #cg ,levene1 #cea1 #ceb ,lewis1 #ahc1 #cdd1 #cfd ,light1 influence on organ formation1 in cave animals1 #cai ff42 in ,proteus1 #cbe2 in ,eudendrium1 #cbf4 ,see also ,heliotropism4 ,lillie1 ,f4 ,r41 #hj1 #hb ff41 #hg ff41 #ic1 #acd1 #aia1 #bah1 #bib ,lillie1 ,r4 ,s41 #aja1 #ajg1 #aaj1 #abj ff4 ,lipase1 synthetic action of1 #bf ,living and dead matter1 specific differences between1 #ad ff4 ,lloyd1 ,d4 ,j41 #aaa ,localization of ,mendelian characters in individual chromosomes1 #bdc1 #bdd ,loeb1 ,leo1 #cj ff41 #de1 #aeg1 #agj1 #ahg ff41 #cdb ,loevenhart1 ,a4 ,s41 #bf ff4 ,lumbricus rubellus1 #df ,lychnis dioica1 #bag ,lycopodium1 #ic ,lygus1 #bja ,lymantria dispar1 #bbj ,lymnus1 #adb ,lymphocytes1 rle of1 #de ff4 ,lyon1 ,e4 ,p41 #acd ff4 ,macfadyen1 ,a41 #cf ,maeterlinck1 #bee ,magnus1 ,w41 #fj ,maltase1 synthetic action of1 #be ,marchal1 ,p41 #bbb ff41 #bed ,margelis1 #aib ,mass of chromatin and of cytoplasm1 #ahf ,mast1 #bfi1 #bgg ,mathews1 ,a4 ,p41 #ajg1 #cfc ,matthaei1 ,g4 ,l4 ,c41 #cjb ,maxwell1 ,s4 ,s41 #bgj1 #bgd1 #bgg ,mc,clendon1 ,j4 ,f41 #abb1 #cbb ,mc,clung1 ,c4 ,e41 #fh1 #aih ff41 #bcg ,megusar1 #cdj ,meignon1 #bag ,meisenheimer1 #bbe ,meltzer1 ,s4,j41 #cae ,membrane formation1 #hf ff42 artificial1 #ih ff4 ,mendel1 ,g41 #bc1 #bbi ff4 ,mendelian characters1 and evolution1 #gj1 #cdh2 and internal secretions1 #bdc1 #cdh2 and enzymes1 #bdg1 #bdh1 #bdi ,mendelian1 factors of heredity1 #d ff41 #fh1 #aea ff42 mutation1 #ff2 dominant1 #ij2 segregation1 #bbi ff4 ,see also ,non-,mendelian inheritance4 ,mendelian heredity1 mechanism of1 #bbi ff42 and chromosomes1 #bcc ff42 and hormones1 #bde ff41 #cdh2 and enzymes1 #bdg ff4 ,menidia1 #ea1 #cba1 #cbc ,merogony1 #abj1 #abf1 #ahf ,merrifield1 #cjc ,mesenchyme formation1 #acj ff4 ,metamorphosis of tadpoles induced by thyroid1 #aee1 #aef ,metchnikoff1 #cfa ff41 #cfg ff4 ,michaelis1 ,l41 #fb1 #cag ,micrococcus prodigiosus1 #ccd ,micromeres1 #acb ff4 ,minot1 #cfb ,moenkhaus1 ,w4 ,j41 #ea1 #cdd ,molisch1 #bj ,montgomery1 #aii1 #bcd ,moore1 ,a4 ,r41 #ej1 #bdg ff41 #bhj ,morgan1 ,t4 ,h41 #df1 #fh1 #hi ff41 #ie1 #aaf1 #abf1 #acd1 #ada ff41 #agc1 #age1 #ahd1 #bjd ff41 #bbi ff41 #bda ff41 #bdd1 #cdg ,morse1 ,m41 #aef1 #cec ,morton1 ,j4 ,j41 #dd ,moss1 ,w4 ,l41 #fg ,muller1 ,h4 ,j41 #bbi1 #bca ff4 ,murphy1 ,j4 ,b41 #dd ff4 ,mutation1 #f1 #db1 #bdc2 and evolution1 #cdg1 #cdh ,myers1 #ee ,nathanson1 #ai ,natural death1 #cfa ff4 ,neilson1 #aaj ,newman1 #cdd ,newton's ,law1 #bec ,nitrifying bacteria1 #af ff4 ,non-,mendelian inheritance1 genus and species characters1 #gj1 #aea1 #bea2 rate of segmentation1 #bdf2 first development1 #bdg ,northrop1 #cff ,nostocace1 #ba ,nussbaum1 ,m41 #adi ,nuttall1 ,g4 ,h4 ,f41 #ef ff4 ,ocneria dispar1 #bbe notherus1 #cfi ,onslow1 ,h41 #bdi ,organ-forming substances or hormones in regeneration1 #aed ff42 causing metamorphosis in tadpoles1 #aee-aeg2 decidua formation1 #aeh2 development of milk glands1 #aeh2 ,sachs's theory of1 #aei ,organisms from eggs1 #abh ff4 ,origin of life1 #ad ff41 #cc ff4 ,osborne1 #bc ,osterhout1 ,w4 ,j4 ,v41 #cab ,ostwald1 ,wo41 #bi1 #cje1 #cab ,oudemans1 #bbe ,overton1 #abc ,palmon1 #aic ,palmonetas1 #aic2 geotropism of1 #bgj ,palinurus1 #aic ,pandorina1 #bgg ,parker1 ,g4 ,h41 #bfd1 #bfi ,parthenogenesis1 artificial1 #ie ff42 8spontaneous10 #ajg ,pasteur1 #ad ff41 #bd1 #cc1 #ch ,patten1 ,b41 #bfd ff ,pauli1 ,w41 #bhi ,pavy1 #cej ,payne1 ,f41 #cbb ,pearl1 ,r41 #bjc1 #bdd ,penicillium1 #bhi ,pennaria1 #aib ,pepsin1 synthetic action of1 #bh1 #fb1 #fc ,pfeffer1 #ib ff4 ,phagocytosis1 #cfg ,planaria1 #agc ff41 #agg ,planorbis1 #adb ,plants1 heteroplastic grafting in1 #dg ff42 regeneration in1 #afj ff4 ,polygordius1 #bhj ,polymorphism1 #bbb ,porthesia1 #bef1 #bhj ff4 ,preadaptation1 #ab1 #cbd ,precipitin reaction1 #ed ff4 ,preformation of organism in egg1 #abh ff41 #adb-ade ,presence and absence theory1 #bcj ff4 ,primula1 #bdc ,proteins1 specific reactions of1 #ed ff42 and species specificity1 #fh2 and evolution1 #gj1 #cdh ,protenor1 #bjj ff41 #bjh ,proteus1 #cbe ff4 ,przibram1 ,h41 #agf ,pure lines1 #ccc1 #ccd ,pycnopodia spuria1 #gd ,pyrrhocoris1 #aih ,radiation pressure1 rle in transmission of spores through interstellar space1 #cd ff4 ,rana1 esculenta1 #df2 palustris1 #df2 virescens1 #df ,rate of segmentation1 a non-,mendelian hereditary character1 #bdf ,rau1 #cff ,reaction1 tropistic1 #aa ff41 #ib ff41 #adg1 #agh1 #ahg1 #bee ff42 precipitin1 #ed ff42 anaphylaxis1 #fa ff4 ,regeneration1 #i ff41 #aec ff42 in plants1 #afj ff42 in ,bryophyllum1 #afa-afg2 in animals1 #afg ff42 in ,tubularia1 #afg-agj2 in ,cerianthus1 #aga ff42 in ,planarians1 #agc-agf2 in ,alpheus1 #agf2 and autolysis1 #agh-aha2 of lens1 #ahb1 #ahc2 external influences on1 #aib ff42 of gonads in hermaphrodites1 #bai ,regulation1 #aci1 #adj1 #ada2 in regeneration1 see ,regeneration4 ,reichert1 ,e4 ,t41 #fd ff4 ,reseda1 #ij ,resistance of spores1 #cf2 seeds1 #cf ff4 ,reversibility of development1 in ,campanularia1 #agh ff42 in ,ascidians1 #ahj2 in egg1 #ahi ff42 in ,antennularia1 #aid ,rhabdonema nigrovenosum1 #bac ,richet1 ,c41 #fa ,richter1 #cd ,ringer solution1 #ii ,robertson1 ,t4 ,b41 #bh ff41 #fb ff41 #ajd1 #caa ,roentgen rays1 #de ,roscoe1 see ,bunsen ,rotifers1 determination of sexual cycle by food1 #bbd ,roux1 ,w41 #ada ff4 ,saccharomyces1 #cf2 cerevisi1 #fj ,sacculina1 #baf ff4 ,sachs1 #hh v4 ,sachs1 ,j41 #ade1 #aed ff41 #aei1 #afa1 #ahd ,salamandra maculosa1 #cci ,salkowski1 #ceb ,salts required for life1 #cjf ff4 ,sansum1 ,w4 ,d41 #fd ,schizophyce1 #ba ,schleip1 ,w41 #bac ,schoenbein1 #ceh ,schottelius1 #ccd1 #ccg ,schroeder1 #ad1 #cc ,schultze1 ,o41 #ada ,schtze1 #ee ,schwann1 #cc ,schwarzschild1 #cd ,secretions1 internal1 #ade1 #aee1 #aeg ,self-digestion1 #cej ff4 ,self-sterility1 #hi ff4 ,senescence1 #cfg ,sequoia1 #ca1 #cfh ,setchell1 ,w4 ,a41 #afe1 #bhg ,sex1 of parthenogenetic frogs1 #abe2 of twins1 #baa ,sex chromosome1 #aii ff4 ,sex determination1 cytological basis of1 #aih ff42 physiological basis of1 #bad ff4 ,sexual characters1 #aih ff4 ,shibata1 #ic ,shull1 ,a4 ,f41 #bad1 #bbd ,sicyonia1 #aic ,side-chain theory1 #hh1 #ahh ,smith1 ,geoffrey1 #aei1 #bag ,smith1 ,graham1 #eh ,spain1 ,k4 ,c41 #ahh ,spallanzani1 #cc ,species1 chemical basis of1 #dj ff42 specificity of1 #da ff42 incompatibility of1 not closely related1 #dd ff4 ,species specificity1 determined by proteins1 #fc1 #fh1 #cdh2 apparently not by nucleins1 #fi ,specificity1 of grafted tissues1 #dg2 of spermatozoa1 #dh2 of blood sera1 #ec ff42 in fertilization1 #ga ff42 of activation of sperm by eggs1 #hj ff4 ,spelerpes1 #cbj ,spermatozoa1 fertilization of eggs by1 #gb ff42 activation by eggs of1 #hj ff42 agglutination of1 #hb ff42 cluster formation of1 #hc2 chemotropism of1 #ib ff42 cultivating of1 #abf ff42 chromosomes of1 #aih ff4 ,spirographis1 #bfj ,spondylomorum1 #bgg ,spontaneous generation1 #cc1 #ch ,spooner1 ,g4 ,b41 #acd ,standfuss1 #cjc ,staphylococcus pyogenes aureus1 #cf ,steffenhagen1 ,k41 #ee ,steinach1 ,e41 #bbe ff41 #bed1 #cdc ,stereotropism1 #agh1 #ahg1 #bhc ,stevens1 ,miss1 #fh1 #aii ,stimulus1 #aif ,stockard1 #cbb1 #cdj ,strassburger1 #bfj ,streaming as means of egg differentiation1 #ade1 #adf ,strongylocentrotus franciscanus1 #ej1 #eb1 #ge1 #ha ff41 #ajc1 #bdg ,strongylocentrotus lividus1 #abi ,strongylocentrotus purpuratus1 #eb1 #gc ff41 #ha ff41 #id1 #ih ff41 #ajc1 #ajh1 #aji1 #aaa ff41 #acg1 #aia1 #bdf ff41 #bic ff41 #cfd2 larv of1 #di ff4 ,sturtevant1 ,a4 ,h41 #bbi ff4 ,styela1 #adf ,sulphur bacteria1 #ai ff4 ,supergenes1 #e1 #i1 #acf1 #cai ,sutton1 ,w4 ,s41 #fh1 #bcc ff4 ,synthesis of living matter1 by micro-organisms1 #ae ff42 by enzymes1 #bd ff4 ,synthetic action of enzymes1 #bc ff41 #ch ,tnia1 #bab ,talbot1 #bfb ,tammann1 #bia ,tanaka1 #bdc ,taylor1 ,a4 ,e41 #bg1 #fi ff4 ,tchistowitch1 #ed ff4 ,teleost fish1 crosses of1 #f ff41 #cde ,temperature1 effect on heliotropism1 #bhj2 upper limit for organisms1 #bhg ff42 effect on life1 #bhh ff42 on butterflies1 #cjc ff42 adaptation to1 #ccd ff4 ,temperature coefficient1 #bij ff41 #cje2 for enzyme1 #bia2 for development1 #bib ff42 for oxidations1 #bie2 and fluctuating variation1 #bif ff42 for heart-beat1 #cjj ff42 for duration of life1 #cff ,thatcher1 ,miss1 #aha ,thyroid inducing metamorphosis in tadpoles1 #aee1 #aef ,tichomiroff1 #ie ,tissue culture of spermatozoa1 #abg ,tissues1 transplantation of1 #cj ff41 #dd ff42 cultivation of1 #ca ff42 specificity of1 #dd ff4 ,torrey1 ,h4 ,b41 #bfd1 #bfi ,tower1 #cdh ,transfusion of blood1 #ec ,transplantation1 of tissues1 #cj ff41 #dd ff42 of cancers1 #de2 of anlagen1 #adh2 of eye of salamander1 #aeg2 of testes1 #bbf2 of ovaries1 #bbg ,traube1 #bh ,treub1 #ba ,trial and error1 #bfh1 #bgj ,trifolium arvense1 #cg ,tropisms1 #aa ff41 #ib ff41 #adg1 #agh1 #ahg1 #bec ff42 and instincts1 #bec2 theory of1 #beg ff4 ,tropisms1 in embryonic development1 #adg2 of cave animals1 #cbd ,trypanosomes1 #ccb ff4 ,trypsin1 synthetic action of1 #bg ,tuber brumale1 #fj ,tubularia crocea1 #aga ,tubularia mesembryanthemum1 #afg1 #afi1 #aib ,twins1 origin of1 #acf ff42 sex of1 #baa ,tyndall1 #cc ,typhlogobius1 #cbj ,typhlomolge1 #cbj ,typhlotriton1 #cbj1 #cbc ,tyrosinase1 #bdi1 #bej ,tyrosine1 #bdi1 #bej v4 ,uexkll1 ,j41 #d ff41 #abh1 #aci ,uhlenhuth1 ,e41 #aeg1 #ahc1 #ahg ,uhlenhuth1 ,p41 #ee1 #eh1 #ff1 #cbb ,underhill1 ,f4 ,p41 #bc ,vanessa1 prorsa1 #cjc2 levana1 #cjc ,vaney1 #bag ,van ,slyke1 ,d4 ,d41 #bb1 #bd1 #bia van't ,hoff1 #bd ff41 #bij1 #bib1 #bif ,variation1 #f1 #big ff41 #cdf-cdh ,vitzou1 #aei ,volvox1 #bhj ,walcott1 #db1 #fa ,warburg1 ,o41 #aag ff4 ,warming1 #da ,wasps1 polymorphism in1 #bbb-bbd2 sex determination1 #bee ff4 ,wassermann1 #ee ,wasteneys1 ,h41 #bi1 #hb1 #hg1 #aab1 #aac1 #aag1 #aia1 #bgg1 #bic1 #bie1 #cce1 #cfd ,weiggert1 #ahh ,weismann1 #g1 #cj1 #cjc ,wells1 ,h4 ,g41 #fb1 #fi ,welsh1 ,d4 ,a41 #fj ,werner1 ,f41 #cdj ,wheeler1 ,w4 ,m41 #dc ,white1 ,j41 #cf ,whitney1 ,d4 ,d41 #bbd ,wilson1 ,e4 ,b41 #fh1 #adc1 #aii ff4 ,winkler1 #dg ,winogradsky1 ,s41 #af ff41 #db ,wolf1 ,g41 #ahb1 #ahg ,yeast cells1 cultivation of1 #ae ff4 ,young1 #af1 #ceh ,a ,selection from the ,catalogue of ,g4 ,p4 ,,putnam',s ,,sons ,complete ,catalogues sent on application ,putnam's ,science ,series #a4--,the ,study of ,man4 ,by ,professor ,a4 ,c4 ,,haddon1 ,m4,a41 ,d4,sc41 ,m4,r4,i4,a4 ,fully illustrated4 #ho4 8,a timely and useful volume4444 ,the author wields a pleasing pen and knows how to make the subject attractive4444 ,the work is calculated to spread among its readers an attraction to the science of anthropology4 ,the author's observations are exceedingly genuine and his descriptions are vivid40--,london ,athenum4 #b4--,the ,groundwork of ,science4 ,a ,study of ,epistemology4 ,by ,,st4 ,,george ,,mivart1 ,f4,r4,s4 #ho4 8,the book is cleverly written and is one of the best works of its kind ever put before the public4 ,it will be interesting to all readers1 and especially to those interested in the study of science40--,new ,haven ,leader4 #c4--,rivers of ,north ,america4 ,a ,reading ,lesson for ,students of ,geography and ,geology4 ,by ,,israel ,c4 ,,russell1 ,professor of ,geology1 ,university of ,michigan1 author of 8,lakes of ,north ,america10 8,glaciers of ,north ,america10 8,volcanoes of ,north ,america10 etc4 ,fully illustrated4 #ho4 8,there has not been in the last few years until the present book any authoritative1 broad rsum on the subject1 modified and deepened as it has been by modern research and reflection1 which is couched in language suitable for the multitude4444 ,the text is as entertaining as it is instructive40--,boston ,transcript4 #d4--;,earth ,sculpture2 or1 ,the ,origin of ,land-,forms4 ,by ,,james ,,geikie1 ,,ll4,d41 ,d4,c4,l41 ,f4,r4,s41 etc41 ,murchison ,professor of ,geology and ,mineralogy in the ,university of ,edinburgh2 author of 8,the ,great ,ice ,age10 etc4 ,fully illustrated4 #ho4 8,this volume is the best popular and yet scientific treatment we know of of the origin and development of land-forms1 and we immediately adopted it as the best available text-book for a college course in physiography4444 ,the book is full of life and vigor1 and shows the sympathetic touch of a man deeply in love with nature40--,science4 #e4--,volcanoes3 ,their ,structure and ,significance4 ,by ,t4 ,g4 ,,bonney1 ,f4,r4,s41 ,university ,college1 ,london4 ,fully illustrated4 #ho4 ,revised and ,enlarged ,edition4 ,illustrated4 8,it is not only a fine piece of work from a scientific point of view1 but it is uncommonly attractive to the general reader1 and is likely to have a larger sale than most books of its class40--,springfield ,republican4 #f4--;,bacteria3 ,especially as they are related to the economy of nature1 to industrial processes1 and to the public health4 ,by ,,george ,,newman1 ,m4,d41 ,f4,r4,s4 7,edin471 ,d4,p4,h4 7,camb471 etc41 ,demonstrator of ,bacteriology in ,king's ,college1 ,london4 ,with #bd micro-photographs of actual organisms and over #gj other illustrations4 #ho4 8,dr4 ,newman's discussions of bacteria and disease1 of immunity1 of antitoxins1 and of methods of disinfection1 are illuminating1 and are to be commended to all seeking information on these points4 ,any discussion of bacteria will seem technical to the uninitiated1 but all such will find in this book popular treatment and scientific accuracy happily combined40--,the ,dial4 _/ #g4--;,a ,book of ,whales4 ,by ,f4 ,e4 ,,beddard1 ,m4,a41 ,f4,r4,s4 ,illustrated4 #ho4 8,mr4 ,beddard has done well to devote a whole volume to whales4 ,they are worthy of the biographer who has now well grouped and described these creatures4 ,the general reader will not find the volume too technical1 nor has the author failed in his attempt to produce a book that shall be acceptable to the zologist and the naturalist40--,n4 ,y4 ,times4 #h4--;,comparative ,physiology of the ,brain and ,comparative ,psychology4 ,with special reference to the ,invertebrates4 ,by ,,jacques ,,loeb1 ,m4,d41 ,professor of ,physiology in the ,university of ,chicago4 ,illustrated4 #ho4 8,no student of this most interesting phase of the problems of life can afford to remain in ignorance of the wide range of facts and the suggestive series of interpretations which ,professor ,loeb has brought together in this volume40--,,joseph ,,jastrow1 in the ,chicago ,dial4 #i4--,the ,stars4 ,by ,professor ,,simon ,,newcomb1 ,u4,s4,n41 ,nautical ,almanac ,office1 and ,johns ,hopkins ,university4 #ho4 ,illustrated4 8,the work is a thoroughly scientific treatise on stars4 ,the name of the author is sufficient guarantee of scholarly and accurate work40--,scientific ,american4 #aj4--,the ,basis of ,social ,relations4 ,a ,study in ,ethnic ,psychology4 ,by ,,daniel ,g4 ,,brinton1 ,a4,m41 ,m4,d41 ,,ll4,d41 ,sc4,d41 ,late ,professor of ,american ,archaeology and ,linguistics in the ,university of ,pennsylvania2 ,author of 8,history of ,primitive ,religions10 8,races and ,peoples10 8,the ,american ,race10 etc4 ,edited by ,,livingston ,,farrand1 ,columbia ,university4 #ho4 8,professor ,brinton his shown in this volume an intimate and appreciative knowledge of all the important anthropological theories4 ,no one seems to have been better acquainted with the very great body of facts represented by these sciences40--,am4 ,journal of ,sociology4 #aa4--;,experiments on ,animals4 ,by ,,stephen ,,paget4 ,with an ,introduction by ,lord ,lister4 ,illustrated4 #ho4 8,to a large class of readers this presentation will be attractive1 since it gives to them in a nut-shell the meat of a hundred scientific dissertations in current periodical literature4 ,the volume has the authoritative sanction of ,lord ,lister40--,boston ,transcript4 #ab4--;,infection and ,immunity4 ,with ,special ,reference to the ,prevention of ,infectious ,diseases4 ,by ,,george ,m4 ,,sternberg1 ,m4,d41 ,,ll4,d41 ,surgeon-,general ,u4 ,s4 ,army 7,retired74 ,illustrated4 #ho4 8,a distinct public service by an eminent authority4 ,this admirable little work should be a part of the prescribed reading of the head of every institution in which children of youths are gathered4 ,conspicuously useful40--,n4 ,y4 ,times4 #ac4--;,fatigue4 ,by ,a4 ,,mosso1 ,professor of ,physiology in the ,university of ,turin4 ,translated by ,,margaret ,,drummond1 ,m4,a41 and ,w4 ,b4 ,,drummond1 ,m4,b41 ,c4,m41 ,f4,r4,c4,p4,e42 extra ,physician1 ,royal ,hospital for ,sick ,children1 ,edinburgh2 ,author of 8,the ,child1 ,his ,nature and ,nurture40 ,illustrated4 #ho4 8,a book for the student and for the instructor1 full of interest1 also for the intelligent general reader4 ,the subject constitutes one of the most fascinating chapters in the history of medical science and of philosophical research40--,yorkshire ,post4 _/ #ad4--;,earthquakes4 ,in the ,light of the ,new ,seismology4 ,by ,,clarence ,e4 ,,dutton1 ,major1 ,u4 ,s4 ,a4 ,illustrated4 #ho4 8,the book summarizes the results of the men who have accomplished the great things in their pursuit of seismological knowledge4 ,it is abundantly illustrated and it fills a place unique in the literature of modern science40--,chicago ,tribune4 #ae4--,the ,nature of ,man4 ,studies in ,optimistic ,philosophy4 ,by ,,lie ,,metchnikoff1 ,professor at the ,pasteur ,institute4 ,translation and introduction by ,p4 ,,chambers ,,mitchell1 ,m4,a41 ,d4,sc4 ,oxon4 ,illustrated4 #ho4 8,a book to be set side by side with ,huxley's ,essays1 whose spirit it carries a step further on the long road towards its goal40--,mail and ,express4 #af4--,the ,hygiene of ,nerves and ,mind in ,health and ,disease4 ,by ,,august ,,forel1 ,m4,d41 formerly ,professor of ,psychiatry in the ,university of ,zurich4 ,authorized ,translation4 #ho4 ,a comprehensive and concise summary of the results of science in its chosen field4 ,its authorship is a guarantee that the statements made are authoritative as far as the statement of an individual can be so regarded4 #ag4--,the ,prolongation of ,life4 ,optimistic ,essays4 ,by ,,lie ,,metchnikoff1 ,sub-,director of the ,pasteur ,institute4 ,author of 8,the ,nature of ,man10 etc4 #ho4 ,illustrated4 ,net1 #b4ej4 ,popular ,edition4 ,with an introduction by ,prof4 ,,charles ,s4 ,,minot4 ,in his new work ,professor ,metchnikoff expounds at greater length1 in the light of additional knowledge gained in the last few years1 his main thesis that human life is not only unnaturally short but unnaturally burdened with physical and mental disabilities4 ,he analyzes the causes of these disharmonies and explains his reasons for hoping that they may be counteracted by a rational hygiene4 #ah4--,the ,solar ,system4 ,a ,study of ,recent ,observations4 ,by ,prof4 ,,charles ,,lane ,,poor1 ,professor of ,astronomy in ,columbia ,university4 #ho4 ,illustrated4 ,the subject is presented in untechnical language and without the use of mathematics4 ,professor ,poor shows by what steps the precise knowledge of to-day has been reached and explains the marvellous results of modern methods and modern observations4 #ai4--;,heredity4 ,by ,j4 ,,arthur ,,thomson1 ,m4,a41 ,professor of ,natural ,history in the ,university of ,aberdeen2 ,author of 8,the ,science of ,life10 etc4 #ho4 ,illustrated4 ,the aim of this work is to expound1 in a simple manner1 the facts of heredity and inheritance as at present known1 the general conclusions which have been securely established1 and the more important theories which have been formulated4 #bj4--;,climate--,considered ,especially in ,relation to ,man4 ,by ,,robert ,,decourcy ,,ward1 ,assistant ,professor of ,climatology in ,harvard ,university4 #ho4 ,illustrated4 ,this volume is intended for persons who have not had special training in the technicalities of climatology4 ,climate covers a wholly different field from that included in the meteorological text-books4 ,it handles broad questions of climate in a way which has not been attempted in a single volume4 ,the needs of the teacher and student have been kept constantly in mind4 #ba4--;,age1 ,growth1 and ,death4 ,by ,,charles ,s4 ,,minot1 ,james ,stillman ,professor of ,comparative ,anatomy in ,harvard ,university1 ,president of the ,boston ,society of ,natural ,history1 and ,author of 8,human ,embryology10 8,a ,laboratory ,text-book of ,embryology10 etc4 #ho4 ,illustrated4 ,this volume deals with some of the fundamental problems of biology1 and presents a series of views 7the results of nearly thirty years of study71 which the author has correlated for the first time in systematic form4 _/ #bb4--,the ,interpretation of ,nature4 ,by ,c4 ,,lloyd ,,morgan1 ,,ll4,d41 ,f4,r4,s4 ,crown #hvo4 ,dr4 ,morgan seeks to prove that a belief in purpose as the causal reality of which nature is an expression is not inconsistent with a full and whole-hearted acceptance of the explanations of naturalism4 #bc4--,mosquito ,life4 ,the ,habits and ,life ,cycles of the ,known ,mosquitoes of the ,united ,states2 ,methods for their ,control2 and ,keys for ,easy ,identification of the ,species in their ,various ,stages4 ,an account based on the investigation of the late ,james ,william ,dupree1 ,surgeon-,general of ,louisiana1 and upon the original observations by the ,writer4 ,by ,,evelyn ,,groesbeeck ,,mitchell1 ,a4,b41 ,m4,s4 ,with #fd ,illustrations4 #ho4 ,this volume has been designed to meet the demand of the constantly increasing number of students for a work presenting in compact form the essential facts so far made known by scientific investigation in regard to the different phases of this1 as is now conceded1 important and highly interesting subject4 ,while aiming to keep within reasonable bounds1 that it may be used for work in the field and in the laboratory1 no portion of the work has been slighted1 or fundamental information omitted1 in the endeavor to carry this plan into effect4 #bd4--,thinking1 ,feeling1 ,doing4 ,an ,introduction to ,mental ,science4 ,by ,e4 ,w4 ,,scripture1 ,ph4,d41 ,m4,d41 ,assistant ,neurologist ,columbia ,university1 formerly ,director of the ,psychological ,laboratory at ,yale ,university4 #ahi ,illustrations4 #b;d ,edition1 ,revised and ,enlarged4 #ho4 8,the chapters on ,time and ,action1 ,reaction ,time1 ,thinking ,time1 ,rhythmic ,action1 and ,power and ,will are most interesting4 ,this book should be carefully read by every one who desires to be familiar with the advances made in the study of the mind1 which advances1 in the last twenty-five years1 have been quite as striking and epoch-making as the strides made in the more material lines of knowledge40--,jour4 ,amer4 ,med4 ,ass'n41 ,feb4 #bb1 #aijh4 #be4--,the ,world's ,gold4 ,by ,l4 ,,de ,,launay1 ,professor at the cole ,suprieure des ,mines4 ,translated by ,orlando ,cyprian ,williams4 ,with an ,introduction by ,charles ,a4 ,conant1 author of 8,history of ,modern ,banks of ,issue10 etc4 #ho4 ,m4 de ,launay is a professor of considerable repute not only in ,france1 but among scientists throughout the world4 ,in this work he traces the various uses and phases of gold2 first its geology2 secondly1 its extraction2 thirdly1 its economic value4 #bf4--,the ,interpretation of ,radium4 ,by ,,frederick ,,soddy1 ,lecturer in ,physical ,chemistry in the ,university of ,glasgow4 ,third ,edition1 rewritten1 with data brought down to #aiab4 #ho ,with #cc ,diagrams and ,illustrations4 ,as the application of the present-day interpretation of ,radium 7that it is an element undergoing spontaneous disintegration7 is not confined to the physical sciences1 but has a wide and general bearing upon our whole outlook on ,nature1 ,mr4 ,soddy has presented the subject in non-technical language1 so that the ideas involved are within reach of the lay reader4 ,no effort has been spared to get to the root of the matter and to secure accuracy1 so that the book should prove serviceable to other fields of science and investigation1 as well as to the general public4 #bg4--,the ,social ,evil4 ,with ,special ,reference to ,conditions ,existing in the ,city of ,new ,york4 ,a ,report ,prepared in #aijb under the ,direction of the ,committee of ,fifteen4 ,second ,edition1 ,revised1 with ,new ,material ,covering the ,years #aijb-aiaa4 ,edited by ,,edwin ,r4 ,a4 ,,seligman1 ,,ll4,d41 ,mc,vickar ,professor of ,political ,economy in ,columbia ,university4 #hvo4 ,a study that is far from being of merely local interest and application4 ,the problem is considered in all its aspects and1 for this purpose1 reference has been made to conditions prevailing in other communities and to the different attempts foreign cities have made to regulate vice4 #bh4--,microbes and ,toxins4 ,by ,,etienne ,,burnet1 of the ,pasteur ,institute1 ,paris4 ,with an ,introduction by lie ,metchnikoff1 ,sub-,director of the ,pasteur ,institute1 ,paris4 ,with about #ga ,illustrations4 ,a well-known ,english authority said in recommending the volume3 8,incomparably the best book there is on this tremendously important subject4 ,in fact1 ,i am assured that nothing exists which gives anything like so full a study of microbiology40 ,in the volume are considered the general functions of microbes1 the microbes of the human system1 the form and structure of microbes1 the physiology of microbes1 the pathogenic protozoa1 toxins1 tuberculin and mallein1 immunity1 applications of bacteriology1 vaccines and serums1 chemical remedies1 etc4 _/ #bi4--,problems of ,life and ,reproduction4 ,by ,,marcus ,,hartog1 ,d4 ,sc41 ,professor of ,zoology in ,university ,college1 ,cork4 #hvo4 ,the author uses all the legitimate arms of scientific controversy in assailing certain views that have been widely pressed on the general public with an assurance that must have given many the impression that they were protected by the universal consensus of biologists4 ,among the subjects considered are3 8,the ,cellular ,pedigree and the ,problem of ,heredity02 8,the ,relation of ,brood-,formation to ,ordinary ,cell-,division02 8,the ,new ,force1 ,mitokinetism02 8,nuclear ,reduction and the ,function of ,chroism02 8,fertilization02 8,the ,transmission of ,acquired ,characters02 8,mechanism and ,life02 8,the ,biological ,writings of ,samuel ,butler02 8,interpolation in ,memory02 8,the ,teaching of ,nature ,study40 #cj4--,problems of the ,sexes4 ,by ,,jean ,,finot1 ,author of 8,the ,science of ,happiness10 etc4 ,translated under authority by ,mary ,j4 ,safford4 #hvo4 ,a masterly presentation of the attitude of the ages toward women and an eloquent plea for her further enfranchisement from imposed and unnatural limitations4 ,the range of scholarship that has been enlisted in the writing may well excite one's wonder1 but the tone of the book is popular and its appeal is not to any small section of the reading public but to all the classes and degrees of an age that1 from present indications1 will go down in history as the century of ,woman4 #ca4--,the ,positive ,evolution of ,religion4 ,its ,moral and ,social ,reaction4 ,by ,,frederic ,,harrison4 #hvo4 ,the author has undertaken to estimate the moral and social reaction of various forms of ,religion--beginning with ,nature ,worship1 ,polytheism1 ,catholicism1 ,protestantism1 and ,deism4 ,the volume may be looked upon as the final word1 the summary of the celebrated author's philosophy--a systematic study of the entire religious problem4 #cb4--,the ,science of ,happiness4 ,by ,,jean ,,finot1 ,author of 8,problems of the ,sexes10 etc4 ,translated from the ,french by ,mary ,j4 ,safford4 #ho4 ,in this work1 which was crowned by the ,academy1 the author considers a subject1 the solution of which offers more enticement to the well-wisher of the race than the gold of the ,incas did to the treasure-seekers of ,spain1 who themselves doubtless looked upon the coveted yellow metal1 however mistakenly1 as a key to the happiness which all are trying to find4 8,amid the noisy tumult of life1 amid the dissonance that divides man from man10 remarks ,m4 ,finot1 8the ,science of ,happiness tries to discover the divine link which binds humanity to happiness through the soul and through the union of souls40 ,the author considers the nature of happiness and the means of its attainment1 as well as many allied questions4 #cc4--;,genetic ,theory of ,reality4 ,being the ,outcome of ,genetic ,logic as ,issuing in the sthetic ,theory of ,reality ,called ,pancalism4 ,by ,,james ,,mark ,,baldwin1 ,ph4,d41 ,d4,sc41 ,,ll4,d41 ,foreign ,correspondent of the ,institute of ,france1 ,author of 8,history of ,psychology10 etc4 ,the author here states the general results of the extended studies in genetic and social science and anthropology made by him and others1 and gives a critical account of the history of the interpretation of nature and man1 both racial and philosophical4 ,the book offers an ,introduction to ,philosophy from a new point of view4 ,it contains1 also1 a valuable glossary of the terms employed in these and similar discussions4 #cd4--,mosquito ,control in ,panama4 ,the ,eradication of ,malaria and ,yellow ,fever in ,cuba and ,panama4 ,by ,j4 ,a4 ,,le ,,prince1 ,c4,e41 ,a4 ,m41 ,chief ,sanitary ,inspector1 ,isthmian ,canal ,commission1 #aijd-aiad1 and ,a4 ,j4 ,,orenstein1 ,m4,d41 ,assistant ,chief ,sanitary ,inspector1 ,isthmian ,canal ,commission4 ,with an introduction by ,l4 ,o4 ,,howard1 ,ph4,d41 ,entomologist and ,chief1 ,bureau of ,entomology1 ,united ,states ,department of ,agriculture4 #ho4 #ie illustrations4 ,mr4 ,le ,prince's books will be not only of great practical importance as a guide to future work of the same character1 especially in the ,tropics1 but also of permanent historic value4 #ce4--,the ,organism as a ,whole4 ,from a ,physico-,chemical ,viewpoint4 ,by ,,jacques ,,loeb1 ,author of 8,comparative ,physiology of the ,brain40 #ho4 ,the author accounts for the harmonious character of the organism on a purely physico-chemical basis1 without the assumption of design on the one hand1 and without the formulation of too definite a theory of evolution on the other4 ,the book contains1 in addition to the text1 all the necessary illustrations4 99 99 99 99 99 99 ,transcriber's note3 ,footnotes have been repositioned to below the paragraph of reference or below the relevant block quote4 ,a small number of spelling anomalies were noted and these have mostly been corrected1 but a few that possibly represent authentic contemporary alternatives have been left unchanged - see below4 ,corrections3 spermatozoon--spermatozon i4e4--i4 e4 e4g4--e4 g4 nermaphrodite--hermaphrodite suceeded--succeeded f--of tryosinase--tyrosinase in-as-much--inasmuch ultra-violet--ultraviolet view-point--viewpoint ,fredericq--,frdricq ,korsy--,krsy ,sitzngsber--,sitzungsber negaceros--megaceros ,variants3 clew_/clue ,entswcklngsmech_/,entwcklngsmech_/,entw icklngsmech peroxidase_/peroxydase 7latter spelling in quoted text47 #bj;,c_/#bj ,c 7spaced and unspaced temperature specifications7 #hvo_/#ho