,transcriber's notes3    ,in this       
transcription1 paired underscores denote
 italicised text4 ,a  single underscore 
preceding curly brackets indicates that 
the bracketed  character is subscripted 
7mostly in chemical formulae1 e4g4      
,,co#b74  ,footnotes have been          
positioned below the relevant           
paragraphs4    ,punctuation             
inconsistencies have been corrected     
silently1 except for  those occurring in
 footnote reference sources1 which      
remain as in the  original4             
,inconsistencies of hyphenation1 use of 
italics1 and spacing of  abbreviations  
7such as i4e4 and c4c47 have not been   
changed4    ,in a large table following 
page #ca1 apparent inconsistencies of   
the  authors of referenced sources are  
as in the original4 ,some of the        
figures in this table are indistinct4   
,passages of ,german text contain       
possible typographic errors that have   
been left as in the original4           
,spelling inconsistencies have not been 

altered1 e4g4 albumin_/                 
albumen_/albumine_/albumid1 but the     
following overt spelling errors  were   
corrected3      synonomous -- synonymous
    an ,medndel -- and ,mendel          
akaline -- alkaline    ,wochenscrift -- 
,wochenschrift    by -- bei             
transferrence -- transference           
quantitity -- quantity    recticulin -- 
reticulin    sythetical -- synthetical  
,elaatin -- ,elastin    hiaton -- histon
          ,illustration3 ,cover         
,,cartwright ,,lectures                 
#ahid                                   
,,on                                    
,,digestive ,,proteolysis               
,,being ,,the ,,cartwright ,,lectures   
,,for #ahid              ,,delivered    
,,before ,,the ,,alumni ,,association   
,,of ,,the ,,college                    
,,of ,,physicians ,,and ,,surgeons ,,of 
,,new ,,york4                           
,,by                            ,r4 ,h4 
,,chittenden1 ,ph4,d4                   
,professor of ,physiological ,chemistry 

in ,yale ,university                    
,,new ,,haven1 ,,conn43                 
,,tuttle1 ,,morehouse  ,,taylor1        
,,publishers4                           
#ahie                  ,,the ,,tuttle1  
,,morehouse  ,,taylor ,,press1 ,,new    
,,haven1 ,,conn4          ,,preface     
,the present volume1 as explained by the
 title1 consists mainly of  a reprint of
 the ,cartwright ,lectures for #ahid4   
,these lectures were  originally printed
 in the current numbers of the ,medical 
,record1 but so  many requests have been
 made for their publication in a more   
convenient  and accessible form that    
they are now re-issued1 through the     
courtesy  of the publishers of the      
,record1 in book-form4    ,it is hoped  
that these lectures may prove of value  
not only in  calling attention to some  
of the fundamental chemico-physiological
  facts of digestion1 but in stimulating
 closer investigation of the  many      
questions which are so intimately       
associated with a proper  understanding 

of the processes concerned in the       
digestion and  utilization of the       
proteid food-stuffs4        ,r4 ,h4     
,,chittenden4          ,,contents4      
,,lecture ,i4      ,the general nature  
of ,proteolytic ,enzymes and of         
,proteids4      ,introductory           
observations1                           
#a        ,early history of gastric     
digestion1                              
#c        ,the proteolytic power of the 
pancreatic juice1                     #g
      ,the general nature of proteolytic
 enzymes1                           #h  
,origin of proteolytic enzymes1         
#h        ,preparation of pepsin1       
#aj        ,reactions and composition of
 proteolytic enzymes1                   
#ac        ,the proteid nature of       
enzymes1                                
#ae        ,conditions modifying the    
action of enzymes1                      
#ag        ,the influence of temperature
 on proteolytic action1                 
#ah        ,the influence of acids1     

alkalies1 and other substances on the   
activity of enzymes1                    
#bj        ,action of chloroform on     
pepsin1                                 
#ba        ,theories of enzyme action   
with special reference to catalysis1    
#bb      ,the general nature of         
,proteids1                              
#bg        ,classification of proteids1 
#bi        ,chemical composition of some
 of the more prominent proteids         
occurring in nature1                    
#ca        ,chemical constitution of    
proteids1                               
#cc        ,the presence of hemi- and   
anti-groups in all typical proteids1    
#cd        ,cleavage of the             
albumin-molecule with dilute sulphuric  
acid1      #cd        ,hydration and    
cleavage of albumin by the action of    
superheated        water1 with formation
 of atmid-albumoses1 etc41              
#cg        ,action of powerful          
hydrolytic agents on proteid matter1    
#ci        ,initial action of           

pepsin-acid on proteids1                
#dj        ,scheme of the general line  
of proteolysis as it occurs in          
pepsin-digestion1 with a view to the    
structure of the                        
albumin-molecule1                       
#da        ,,lecture ,,ii4              
,proteolysis by pepsin-hydrochloric     
acid1 with a consideration    of the    
general nature of proteoses and         
peptones4      ,proteolysis by          
pepsin-acid1                            
#dd        ,formation of hydrochloric   
acid in the gastric glands1             
#de        ,liebermann's theory         
regarding the formation of the acid of  
the        gastric juice1               
#df        ,differences in the action of
 free and combined acid1                
#dg        ,proteolysis in the presence 
of combined acid1                       
#di        ,the combining power of      
various forms of proteid matter with    
hydrochloric acid1                      
#ea        ,quantitative estimation of  

the affinity of the products of         
digestion for acid1                     
#ec        ,richet's theory regarding   
the conjugate character of the acid     
of the gastric juice1                   
#ed        ,proteolysis in the presence 
of amido-acids1                         
#ee        ,necessity for knowing the   
amount of combined acid in the          
stomach-contents1                       
#eg        ,antiseptic action of the    
hydrochloric acid of the gastric juice1 
#eh        ,the maximum action of pepsin
 exerted only in the presence of        
free hydrochloric acid1                 
#ei        ,division of the products of 
pepsin-proteolysis into three main      
groups1                                 
#fj        ,detection of the products of
 digestion1                             
#fa        ,separation of proteoses and 
peptones from a digestive mixture or    
from the stomach-contents1              
#fb        ,some of the chemical        
properties of peptones1                 

#fd        ,the so-called propeptone a  
mixture of proteoses1                   
#fe        ,pepsin-proteolysis          
synonymous with a series of progressive 
hydrolytic changes1                     
#ff        ,chemical composition of     
proteoses and peptones1                 
#fg        ,pepsin-proteolysis a true   
hydrolytic and cleavage process1        
#ga        ,schtzenberger's results on  
the formation of fibrin-peptone1        
#gb        ,amphopeptones the final     
products of gastric digestion1 but      
proteolysis never results in complete   
peptonization1            #gc           
,solution of a proteid by pepsin-acid   
not synonymous with                     
peptonization1                          
#ge        ,influence of the removal of 
the products of digestion on the        
activity of the ferment1                
#ge        ,lack of complete            
peptonization by pepsin-acid not due to 
accumulation of the products of         
digestion1                      #gf     

,the diffusibility of proteoses and     
peptones1                      #gg      
,absorption of peptones from the living 
stomach1                   #gi          
,differences between natural digestion  
in the stomach and        artificial    
proteolysis1                            
#hj        ,relative formation of       
proteoses and peptones in the living    
stomach1                                
#ha        ,gastric digestion merely a  
preliminary step in proteolysis1        
#ha        ,intestinal digestion alone  
capable of accomplishing all that is    
necessary for the complete nourishment  
of an animal1            #hb      ,some 
physiological properties of proteoses   
and peptones1            #hc        ,the
 experiments of ,schmidt-,mlheim and    
,fano on the action of        peptones  
when injected into the blood1           
#hd        ,physiological action of     
albumoses1                              
#he        ,introduction of albumoses   
into the blood1                         

#hg        ,proteose-like nature of the 
poisons produced by bacteria1           
#hi        ,the acrooalbumoses formed by
 the tubercle-bacillus1                 
#ij        ,toxic nature of proteoses   
and peptones1                           
#ia        ,,lecture ,,iii4             
,proteolysis by trypsin--,absorption of 
the main products    of proteolysis4    
,proteolysis by trypsin1                
#ic        ,comparison of pepsin and    
trypsin1                                
#id        ,trypsin especially a        
peptone-forming ferment1                
#ie        ,the primary products of     
trypsin-proteolysis1                    
#ie        ,scheme of trypsin-digestion1
 showing the relationship of        the 
products formed1                        
#if        ,the fate of hemi-groups in  
trypsin-proteolysis1                    
#ig        ,the primary products of     
trypsin-digestion mainly antibodies1    
#ih        ,character and composition of
 antipeptones1                          

#ii        ,antialbumid as a product of 
pancreatic digestion1                   
#ajj        ,the peculiar action of     
trypsin in the formation of amido-acids1
        etc41                           
#aja        ,formation of lysin and     
lysatin in pancreatic digestion1        
#ajc        ,the relationship of lysatin
 to urea1                               
#aje        ,formation of tryptophan or 
proteinochromogen by trypsin1           
#aje        ,appearance of ammonia in   
trypsin-proteolysis1                    
#ajg        ,relationship between       
artificial pancreatic digestion and     
proteolysis in the living intestine1    
#aji        ,leucin and tyrosin products
 of the natural pancreatic digestion    
in the intestine1                       
#aab        ,the physiological          
significance of leucin and tyrosin1     
#aac      ,absorption of the main       
products of proteolysis1                
#aaf        ,absorption of acid-albumin1
 alkali-albuminate1 etc4                

#aag        ,absorption limited mainly  
to the intestine1 very little           
absorption from the stomach1            
#aai        ,the change which the       
primary products of proteolysis undergo 
in the process of absorption1           
#abj        ,peptones not present in the
 circulating blood1                     
#aba        ,the change which peptones  
and proteoses undergo by contact with   
the living mucous membrane of the small 
intestine1             #abb             
,retrogression of peptones by contact   
with other living cells1        etc41   
#abe        ,functional activity of     
leucocytes in absorption1               
#abh        ,digestive leucocytosis     
incited by nuclein1                     
#aca        ,shore's experiments on the 
ability of lymph-cells to assimilate    
either proteoses or peptones1           
#acc        ,lymph a true secretion from
 the blood-vessels1                     
#acd        ,direct excitatory effect of
 peptones when present in the blood     

on the endothelial cells1               
#acf        ,selective activity of      
endothelial cells1                      
#acg          ,,digestive ,,proteolysis 
,,lecture ,i4    ,,the ,,general        
,,nature ,,of ,,proteolytic ,,enzymes   
,,and ,,of ,,proteids4                  
,,introductory4    ,in digestive        
proteolysis we have a branch of         
physiological study which  of late years
 has made much progress4 ,chemistry has 
come to the aid  of physiology and by   
the combined efforts of the two our     
knowledge of  the digestive processes of
 the alimentary tract has been gradually
  broadened and deepened4 ,that which at
 one time appeared simple  has become   
complex1 but increasing knowledge has   
brought not only  recognition of        
existing complexity1 but has enabled us1
 in part at  least1 to unravel it4      
,by digestive proteolysis is to be      
understood the transformation of the    
proteid food-stuffs into more or less   
soluble and diffusible products  through

 the agency of the digestive juices1 or 
more especially through  the activity of
 the so-called proteolytic ferments or  
enzymes contained  therein2 changes     
which plainly have for their object a   
readier and more  complete utilization  
of the proteid foods by the system4     
,in selecting this topic as the subject 
for this series of ,cartwright          
,lectures ,i have been influenced       
especially by the opinion that both for 
the physiologist and the physician there
 are few processes going on in  the     
animal body of greater importance than  
those classed under the head  of        
digestion4 ,further1 few processes are  
less understood than those  concerned in
 this broad question of digestive       
proteolysis1 especially  those which    
relate specifically to the digestion of 
the various classes  of proteid         
food-stuffs1 and to the absorption and  
utilization of the  several products    
formed4 ,moreover1 the subject has ever 
had for me a  strong attraction as      

presenting a field of investigation     
where chemical  work can advantageously 
aid in the advance of sound             
physiological  knowledge2 and certainly 
every line of advance in our            
understanding of  the normal processes  
of the body paves the way for a better  
and clearer  comprehension of the       
pathological or abnormal processes to   
which the  human body is subject4       
,you will pardon me if ,i specially     
emphasize in this connection  the fact  
that advance along the present lines was
 not rapid until  physiologists began to
 appreciate the importance of           
investigating  the chemico-physiological
 problems of digestion by accurate      
chemical  methods4 ,something more than 
simple test-tube study1 or even         
experimental work on animals1 is        
required in dealing with the changes    
which complex proteids undergo in       
gastric and pancreatic digestion4 ,the  
nature and chemical composition of the  
proteids undergoing digestion1  as well 

as of the resultant products1 are       
necessary preliminaries to  any rightful
 interpretation of the changes          
accompanying digestive  proteolysis2 but
 physiology has been slow to appreciate 
the  significance of this fact1 and1    
until recently1 has done very little  to
 remedy the noticeable lack of accurate 
knowledge regarding the  composition and
 nature of the proteid and albuminoid   
substances which  play such an important
 part in the life-history of the human  
organism1  either as food or as vital   
constituents of the physiologically     
active  and inactive tissues4 ,this is  
to be greatly deprecated1 since our     
understanding of the nature of          
proteolysis1 of the mode of action of   
the enzymes or ferments involved1 and of
 the relationships of the  products     
formed1 is dependent mainly upon an     
accurate determination of  the exact    
changes in chemical composition which   
accompany each step in  the proteolytic 
process4 ,how otherwise can we hope to  

attain a proper  appreciation of the    
real points of difference between bodies
 so closely  related as those composing 
the large group of proteids and         
albuminoids8  ,surely1 in no other way  
can we measure the nature or extent of  
the  changes involved in the various    
phases of proteolysis than by a         
thorough study of chemical composition  
and constitution1 as well as of         
chemical reactions and general          
properties4    ,in the early history of 
physiology there was1 quite naturally1  
little or no thought given to the nature
 of proteolytic changes4 ,the  gastric  
juice1 as one of the first digestive    
fluids to be studied1  was recognized as
 a kind of universal solvent for all    
varieties of  food-stuffs1 and this even
 long before anything was known         
regarding  its composition1 but beyond  
this point knowledge did not extend4    
,active study of the gastric juice1 as  
you well know1 dates from #aghc1  when  
the brilliant ,italian investigator     

,spallanzani commenced his  work on     
digestion4 ,the names of ,carminati1    
,werner and ,montgre#a are  also        
associated with various phases of work  
and speculation in this  early history  
of the subject1 especially those which  
pertained to the  possible presence of  
acid in the stomach juices4 ,in #ahbd1  
however1  ,prout showed conclusively    
that gastric juice was truly acid1 and1 
moreover1 that the acidity was due to   
the presence of free hydrochloric  acid1
 and not to an organic acid4 ,still1    
many observations failed to  show the   
presence of an acid fluid in the        
stomach1 and it was not until           
,tiedemann and ,gmelin's#b masterly     
researches were published that the      
cause of this discrepancy was made      
clear4 ,it was then seen that the       
secretion of an acid gastric juice was  
dependent upon stimulation or           
irritation of the mucous membrane of the
 stomach1 and that so long as  the      
stomach was free from food or other     

matter capable of stimulating  the      
mucosa1 it contained very little fluid1 
and that neutral or very  slightly acid 
in reaction4 ,these early observers also
 recorded the fact  that the amount or  
strength of acid increased with the     
outpouring of  the secretion1 incidental
 to natural or artificial stimulation1  
thus  giving a hint of the now          
well-known fact that any and every      
secretion  may show variations in       
composition incidental to the character 
and  extent of the stimulation which    
calls it forth4    #a ,see ,berzelius's 
,lehrbuch der ,chemie1 ,band #i1 p4     
#bje1 #dte ,auflage1  for an account of 
these early discoveries4    #b          
,tiedemann und ,gmelin3 ,die ,verdauung 
nach ,versuchen4 ,heidelberg und        
,leipzig4 #ahbf4    ,the period between 
#ahbe and #ahcc was characterized       
especially by the  presentation of the  
many results bearing on gastric         
digestion obtained  by ,dr4 ,beaumont on
 ,alexis ,st4 ,martin1 followed a little

 later1 in  #ahdb1 by a long period of  
experimentation by many physiologists1  
as ,blondlot1#c ,bassow1#d              
,bardeleben1#e ,bernard1#f ,bidder and  
,schmidt1#g and many others on methods  
of establishing gastric fistul  on      
animals1 by which many interesting      
results were accumulated  regarding the 
physiology of gastric digestion4 ,up to 
#ahcd1 however1  there was no adequate  
explanation offered of the solvent power
 of  the stomach juice2 aside from the  
presence of hydrochloric acid1  nothing 
could be discovered by the earlier      
chemists to account for the  remarkable 
digestive action4 ,eberle1#h however1   
attributed to the  mucous membrane of   
the stomach a catalytic action1 and     
claimed that it  only needed the        
presence of a small piece of the stomach
 mucosa with  weak hydrochloric acid for
 the manifestation of solvent or        
digestive  power4 ,it remained for      
,schwann1#i to show the true explanation
 of this  phenomenon1 and although he   

was unable to make a complete separation
  of the active principle which he      
plainly believed existed1 he gave to  it
 the name of pepsin4 ,wassmann1         
,pappenheim1#aj ,valentin1 and later    
,elssser1#aa all endeavored to obtain   
the substance in a pure form1  and      
,wassmann1#ab in #ahci1 surely succeeded
 in obtaining a very active  preparation
 of the ferment--one capable of exerting
 marked digestive  action when mixed    
with a little dilute acid4 ,thus1 a true
 understanding  of the general nature of
 gastric juice was finally arrived at1  
and the  cause of its digestive power   
was rightfully attributed to the        
presence  of the ferment pepsin and the 
dilute acid4 ,further1 the analysis of  
human gastric juice made by             
,berzelius1#ac in #ahcd1 showed that the
  secretion contains very little solid  
matter 7#a4bf per cent471 thus  calling 
attention to the fact that the digestive
 power of this fluid is  out of all     
proportion to the amount of pepsin1 or  

even to the amount  of total solid      
matter present1 and consequently paving 
the way for  a general appreciation of  
the peculiar nature of the dominant     
body1  i4e41 the pepsin4    #c ,trait   
analytique de la ,digestion4 ,paris1    
#ahdb4    #d ,bulletin de la ,socit des 
,naturalistes de ,moscou1 vol4 #af4     
#ahdb4    #e ,archiv fr physiol4        
,heilkunde1 vol4 #h4 #ahdi4    #f       
,lecons de ,physiologie de la           
,digestion4 ,paris1 #ahfg4    #g ,die   
,verdauungssfte4    #h ,physiologie der 
,verdauung4 ,wrzburg1 #ahcd4    #i      
,ueber das ,wesen der                   
,verdauungsprocesse4 ,mller's ,archiv1  
#ahcf1 p4  #ij4    #aj ,zur ,kenntniss  
d4 ,verdanuung4 ,breslau1 #ahci4    #aa 
,magenerweichung der ,suglinge4         
,stuttgart und ,tbingen1 #ahdf4    #ab  
,lehmann's ,lehrbuch d4 physiol4 ,chem41
 ,band #b1 p4 #da1 #bte ,auflage4    #ac
 ,lehrbuch der ,chemie1 ,band #i1 p4    
#bji4    ,the original conception       
regarding the manner in which gastric   

juice  exerts its solvent power on      
proteid foods was apparently limited to 
simple solution2 chemical solution if   
you choose1 brought about by  catalytic 
action1 but without any hint as to the  
possible nature of  the soluble products
 formed4 ,mialhe1#ad however1 recognized
 the fact  that this transformation1 by 
which insoluble and non-diffusible      
proteid  matter was converted into a    
soluble and diffusible product1 was a   
form  of hydration1 comparable to the   
change of insoluble starch into soluble 
sugar1 and he named the hypothetical    
product albuminose4 ,mialhe's study  of 
the matter in #ahdf was followed by     
,lehmann's#ae investigation of  the     
subject1 and the coining of the word    
peptones as an appropriate  name for the
 soluble products of gastric digestion4 
,the peptones  isolated by ,lehmann were
 described as amorphous1 tasteless      
substances1  soluble in water in all    
proportions and insoluble in alcohol4   
,they  were likewise precipitated by    

tannic acid1 mercuric chloride1 and lead
  acetate1 and were considered as weak  
acid bodies1 having the power  of       
combining with bases to form salts of a 
more or less indefinite  character4     
,twelve years later1 in #aheh1          
,mulder#af gave a more complete         
description of peptones1 but his study  
of the subject failed to advance        
materially our knowledge of the broader 
questions regarding the nature  of the  
process1 or processes1 by which the     
so-called peptones were  formed4 ,a year
 later1 in #ahei1 ,meissner#ag brought  
forward the first  of his contributions1
 and during the following three or four 
years  several communications were made 
representing the work of himself and    
pupils upon the question of gastric     
digestion1 or more especially upon  the 
character of the products resulting from
 the digestive action of                
pepsin-hydrochloric acid4    #ad        
,canstatt's ,jahresbericht d4 ,pharm41  
#ahdf1 p4 #afc4    #ae ,lehmann's       

,physiologische ,chemie1 ,band #b1 p4   
#cah4    #af ,archiv f4 d4 ,hollnd4     
,beitr41 #b1 #aheh4    #ag ,zeitschr4 f4
 rat4 ,med41 ,band #g1 #h1 #aj und #ad4 
,the general tenor of ,meissner's       
results is shown in the description  of 
a row of products as characteristic of  
the proteolytic action of  pepsin-acid  
on proteid matter4 ,in other words1     
there was a clear  recognition of the   
fact that proteid digestion in the      
stomach1 through  the agency of the     
ferment pepsin1 is something more than a
 simple  conversion of the proteid into 
one or two soluble products4 ,the       
several  bodies then isolated were named
 parapeptone1 metapeptone1 dyspeptone1  
1 1 and  peptone2 names now seldom used1
 but significant as showing  that at    
this early date there was a full        
appreciation of the fact  that digestive
 proteolysis as accomplished by the     
ferment pepsin is an  intricate process1
 accompanied by the formation of a      
series of products  which vary more or  

less with the conditions under which the
 digestion  is conducted4    ,this was  
the commencement of our more modern     
ideas regarding digestive  proteolysis1 
but only the commencement1 for it       
ushered in an era of  unparalleled      
activity1 in which ,brcke1              
,schtzenberger1 and ,khne each          
contributed a large share toward the    
successful interpretation of the        
results obtained4 ,further1 knowledge   
regarding the proteid-digesting  power  
of the pancreatic juice was rapidly     
accumulating1 thus  broadening our ideas
 regarding digestive proteolysis in     
general4  ,corvisart#ah had called      
attention to the proteolytic power of   
the  pancreatic juice in #aheg1 and     
although his observations were more or  
less generally discredited for a time1  
they were eventually confirmed  by      
,meissner1#ai ,schiff1 ,danilewsky1#bj  
and ,khne1#ba the latter  particularly  
contributing greatly to the development 
of our knowledge  concerning this phase 

of digestive proteolysis4 ,the          
proteolytic power  was proved to be due 
to a specific ferment or enzyme1 now    
universally  called trypsin1 which      
digests proteid foods to the best       
advantage in  the presence of sodium    
carbonate4 ,digestive proteolysis in the
 human  body was thus shown to be due   
mainly to the presence of two distinct  
enzymes1 the one active in an acid      
fluid1 the gastric juice1 the other  in 
an alkaline-reacting fluid1 the         
pancreatic juice1 but both endowed  with
 the power of digesting all varieties of
 proteid foods1 with the  formation of a
 large number of more or less closely   
related products4    #ah ,sur une       
,fonction peu connue du ,pancras3 ,la   
digestion des aliments  azots4 ,paris1  
#aheg-eh4    #ai ,verdauung der         
,eiweisskrper durch den pankreatischen  
,saft4  ,zeitschr4 f4 rat4 ,med41 #c;d  
ser41 ,band #g1 p4 #ag4 #ahei4    #bj   
,virchow's ,archiv1 ,band #be1 p4 #bfg4 
#ahfb4    #ba ,ibid41 ,band #ci1 p4     

#acj4 #ahfg4    ,so much for the early  
history of our subject1 and now1 without
  attempting any exhaustive sketch of   
its gradual development during  the last
 decade and a half1 allow me to present 
to you digestive  proteolysis as it     
stands to-day1 developed somewhat1 ,i   
trust1 by the  results ,i have been able
 to contribute to it during the last    
twelve  years4      ,,the ,,general     
,,nature ,,of ,,proteolytic ,,enzymes4  
,these peculiar bodies owe their origin 
to the constructive power of  the       
gland-cells from which the respective   
secretions are derived4  ,during        
fasting1 the epithelial cells of the    
gastric glands and of  the pancreas     
manufacture from the cell-protoplasm a  
specific zymogen  or ferment-antecedent1
 which is stored up in the cell in the  
form  of granules4 ,these granules of   
either pepsinogen or trypsinogen1  as   
the case may be1 are during secretion   
apparently drawn upon for  the          
production of the ferment1 and it is an 

easy matter to verify  ,langley's#bb    
observation that the amount of pepsin1  
for example1  obtainable from a definite
 weight of the gland-bearing mucous     
membrane is proportionate to the number 
of granules contained in  the           
gland-cells4 ,during ordinary secretion1
 however1 these granules  of zymogen do 
not entirely disappear from the cell4   
,when secretion  commences and the      
granules are drawn upon for the         
production of  ferment1 fresh granules  
are formed1 and inasmuch as these latter
 are  produced through the katabolism of
 the cell-protoplasm it follows  that   
anabolic processes must be              
simultaneously going on in the cell1  by
 which new cell-protoplasm is           
constructed4 ,hence1 as ,heidenhain1    
,langley1 and others have pointed out1  
during digestion there are  at least    
three distinct processes going on side  
by side in the  gland-cell1 viz41 the   
conversion of the zymogen stored up in  
the cell  into the active ferment1 or   

other secretory products1 the growth of 
new cell-protoplasm1 and the attendant  
formation of fresh zymogen to  replace1 
or partially replace1 that used up in   
the production of the  ferment4         
,consequently1 we are to understand that
 in the living mucous  membrane of the  
stomach there is little or no preformed 
pepsin present4  ,similarly1 the cells  
of the pancreatic gland are practically 
free  from the ferment trypsin4 ,in both
 cases the cell-protoplasm stores up    
zymogen and not the active ferment1 but 
at the moment of secretion  the zymogen 
is transformed into ferment and possibly
 other organic  substances              
characteristic of the fluid secreted4   
,absorption of the  products of         
digestion tends to increase the activity
 of the secreting  cells1 but we have no
 tangible proof that any particular     
kinds of food  are directly peptogenous1
 i4e41 that they lead to a storing up in
  the gastric cells1 for example1 of    
pepsinogen1 although it may be that  the

 so-called peptogenous foods give rise  
to a more active conversion  of         
pepsinogen into pepsin4#bc ,as already  
stated1 the zymogen is  manufactured    
directly from the cell-protoplasm1 and  
the constructive  power is certainly not
 directly controlled by the character of
 the food  ingested4    #bb ,proceedings
 of the ,royal ,society1 vol4 #cb1 p4   
#bj2 ,on the ,histology  and ,physiology
 of the ,pepsin-forming ,glands4    #bc 
,langley and ,edkins3 ,pepsinogen and   
,pepsin4 ,journal of ,physiology1  vol4 
#g1 p4 #cid4    ,all this in one sense  
is to-day ancient history1 but ,i recall
 it to  your minds in order to emphasize
 the fact that these two energetic      
ferments or enzymes stand in close      
relation to the protoplasm of  the cell 
from which they originate4 ,so far as we
 can measure the  transformations       
involved1 there are only two distinct   
steps in the  process1 viz41 the        
formation of the inactive zymogen stored
 up in the  cell1 and the conversion of 

the antecedent body into the soluble and
  active ferment4 ,in this connection   
,pod-wyssozki#bd has reported that  the 
mucous membrane of the stomach exposed  
to the action of oxygen gas  shows a    
marked increase in the amount of pepsin1
 from which he infers  that the natural 
conversion of pepsinogen into pepsin is 
an oxidation  process4 ,further1 he     
claims the existence of at least two    
forms of  pepsinogen in the stomach     
mucosa1 one closely akin to the ferment 
itself and very easily soluble in       
glycerin1 while the other is more       
insoluble in this menstruum4 ,langley   
and ,edkins1#be however1 find  that     
oxygen has no effect whatever on the    
pepsinogen of the frog's  mucous        
membrane1 thus throwing doubt on the    
above conclusion4 ,still1               
,podolinski#bf claims that trypsin      
originates from its particular  zymogen 
through a process of oxidation1 and     
,herzen#bg has proved  that the ferment 
can be reconverted into trypsinogen     

under the  influence of carbon-monoxide 
and again transformed into the ferment  
by  contact with oxygen gas4 ,this      
latter observer#bh has also noticed a   
connection between the amount of trypsin
 obtainable from the pancreas  and the  
dilatation of the spleen1 from which he 
was eventually led  to conclude that the
 spleen during its dilatation gives     
birth to a  zymogen-transforming ferment
 which thus leads to the production of  
trypsin1 presumably from the already    
manufactured zymogen4 ,in any  event1   
their peculiar origin lends favor to the
 view that these two  enzymes are       
closely allied to proteid bodies1 and   
that they are  directly derived from the
 albuminous portion of the              
cell-protoplasm4  ,analysis shows that  
they always contain nitrogen in fairly  
large  amount1 although the percentage  
is sometimes less than that found in a  
typical proteid body4    #bd ,pflger's  
,archiv f4 ,physiol41 ,band #ci1 p4 #fh4
    #be ,journal of ,physiol41 vol4 #g1 

p4 #djj4    #bf ,pflger's ,archiv f4    
,physiol41 ,band #ac1 p4 #dbb4    #bg   
,ueber den ,rckschlag des ,trypsins zu  
,zymogen unter dem ,einfluss  der       
,kohlenoxydvergiftungen4 ,pflger's      
,archiv f4 ,physiol41 ,band #cj1 p4     
#cjh4    #bh ,ueber den ,einfluss der   
,milz auf die ,bildung des ,trypsins4   
,pflger's ,archiv f4 ,physiol41 ,band   
#cj1 p4 #bie4    ,it must be remembered1
 however1 that in spite of oft-repeated 
attempts  to obtain more definite       
knowledge regarding the composition of  
these  proteolytic enzymes our efforts  
have been more or less baffled4 ,we  are
 confronted at the outset with the fact 
that no criterion of  chemical purity   
exists1 either in the way of chemical   
composition  or of chemical reactions4  
,the only standard of purity available  
is  the intensity of proteolytic action1
 but this is so dependent upon          
attendant circumstances that it is only 
partially helpful in forming an         
estimate of chemical purity4 ,my own    

experiments in this direction1 and  they
 have been quite numerous1 have         
convinced me that it is practically     
impossible to obtain a preparation of   
either pepsin or trypsin at  all active 
which does not show at least some       
proteid reactions4  ,furthermore1 such  
samples of these two enzymes as ,i have 
analyzed have  shown a composition      
closely akin to that of proteid bodies4 
,i will not  take time to go into all   
the details of my work in this          
direction1  contenting myself here with 
the statement that the purest specimens 
of  pepsin and trypsin ,i have been able
 to prepare have always shown their     
relationship to the proteid bodies by   
responding to many of the typical       
proteid reactions1 and their            
composition1 though somewhat variable1  
has  in the main substantiated this     
evident relationship4    ,the most      
satisfactory method ,i have found for   
obtaining a comparatively  pure         
preparation of pepsin1 and one at the   

same time strongly active1  is a        
modification of the method published    
some years ago by ,khne and  myself4#bi 
,the mucous membrane from the cardiac   
portion of a pig's  stomach is dissected
 off and washed with water4 ,the upper  
surface of  the mucosa is then scraped  
with a knife until at least half of the 
membrane is removed4 ,these scrapings1  
containing the fragments of the  peptic 
glands1 are warmed at #dj ,c4 with an   
abundance of #j4b per cent4             
hydrochloric acid for ten to twelve days
 in order to transform all of  the      
convertible albuminous matter into      
peptone4 ,the solution is then  freed   
from insoluble matter by filtration and 
immediately saturated  with ammonium    
sulphate1 by which the pepsin1 with some
 albumose1 is  precipitated in the form 
of a more or less gummy1 or             
semi-adherent  mass4 ,this is filtered  
off1 washed with a saturated solution of
  ammonium sulphate and then dissolved  
in #j4b per cent4 hydrochloric  acid4   

,the resultant solution is next dialyzed
 in running water until  the ammonium   
salt is entirely removed1 thymol being  
added to prevent  putrefaction1 after   
which the fluid is mixed with an equal  
volume of  #j4d per cent4 hydrochloric  
acid and again warmed at #dj ,c4 for    
several  days4 ,the ferment is then once
 more precipitated by saturation of the 
fluid with ammonium sulphate1 the       
precipitate strained off1 dissolved  in 
#j4b per cent4 acid and again dialyzed  
in running water until the  solution is 
entirely free from sulphate4 ,the clear 
solution of the  ferment obtained in    
this manner can then be concentrated at 
#dj ,c4 in  shallow dishes1 and if      
desired the ferment obtained as a scaly 
residue4  ,so prepared1 the pepsin is   
certainly quite pure1 that is           
comparatively1  and although it may     
contain some albumose1 the latter must  
be very  resistant to the action of the 
ferment2 indeed1 pepsin is in many      
respects an albumose-like body itself4  

#bi ,zeitschr4 f4 ,biol41 ,band #bb1 p4 
#dbh4    ,in any event1 the enzyme      
prepared in this manner shows decided   
proteid  reactions1 and contains        
nitrogen corresponding more or less     
closely to  the recognized composition  
of an albumose4 ,my own belief1         
therefore1  is that these enzymes1 both 
pepsin and trypsin1 are proteid bodies  
closely related to the albumoses4 ,they 
are soluble in water and more  or less  
soluble in glycerin2 at least glycerin  
will dissolve them from  moist tissues1 
or from moist precipitates containing   
them4 ,langley1#cj  however1 states1 and
 perhaps justly1 that we have no        
positive proof  that either ferments or 
zymogens are soluble in pure strong     
glycerin1  and that if they are soluble1
 it is extremely slowly4 ,in dilute     
glycerin1 however1 these ferments       
dissolve readily1 as we very well  know4
 ,furthermore1 they are practically     
non-diffusible1 and1 like many          
albumoses1 are precipitated in part by  

saturation with sodium chloride  and    
completely on saturation with ammonium  
sulphate4    #cj ,gamgee's              
,physiological ,chemistry of the ,animal
 ,body1 vol4 #b1 p4 #d4  #ahic4    ,when
 dissolved in water and heated above #hj
 ,c41 these enzymes are  decomposed to  
such an extent that their proteolytic   
power is totally  destroyed4 ,the amount
 of coagulum produced by heat1 however1 
is  comparatively small1 though variable
 with different preparations4 ,thus     
with trypsin1 ,khne originally          
considered that boiling an aqueous      
solution of the ferment would give rise 
to about twenty per cent4  of coagulated
 proteid and eighty per cent4 of        
peptone-like matter4  ,with the purer   
preparations now obtainable there is    
apparently less  coagulable matter      
present1 and ,loew#ca has succeeded in  
preparing  from the pancreas of the ox a
 sample of trypsin containing #eb4ge per
  cent4 of carbon and #af4ee per cent4  
of nitrogen1 and yielding only  a small 

coagulum by heat4 ,loew considered the  
ferment to be a true  peptone1 but in   
view of our present knowledge regarding 
the albumoses1  ,i think we are         
justified in assuming it to be an       
albumose-like body  rather than a true  
peptone4 ,at the same time it may be    
well to again  emphasize the fact that  
our only 8means of determining the      
presence  of an enzyme is that of       
ascertaining the change which it is able
  to bring about in other substances1   
and since the activity of the  enzymes  
is extraordinarily great1 a minute trace
 suffices to produce  a marked effect4  
,from this it follows that the purified 
enzymes  which give distinct proteid    
reactions might merely consist of very  
small quantities of a true non-proteid  
enzyme1 adherent to or mixed  with a    
residue of inert proteid material40#cb  
,this quotation gives  expression to a  
possibility which we certainly cannot   
ignore1 but my  own experiments lead me 
to believe firmly in the proteid nature 

of  these two enzymes4 ,further1 we find
 partial substantiation of this view  in
 the results obtained by ,wurtz#cc in   
his study of the vegetable  proteolytic 
ferment papain1 and in my own results   
from the study of the  proteolytic      
ferment of pineapple juice4#cd ,thus1   
,wurtz prepared from  the juice of      
,carica papaya an active sample of      
papain1 and found it to  contain on     
analysis about #af4g per cent4 of       
nitrogen and #eb4e per cent4  of carbon1
 while the reactions of the product     
likewise testified to the  proteid      
nature of the enzyme4 ,martin1 too1 has 
concluded from his study  of papain that
 the ferment is at least associated with
 an albumose4#ce    #ca ,ueber die      
chemische ,natur der ungeformten        
,fermente4 ,pflger's  ,archiv f4        
,physiol41 ,band #bg1 p4 #bjc4    #cb   
,sheridan ,lea3 ,chemical ,basis of the 
,animal ,body1 p4 #ee4    #cc ,sur la   
papaine3 ,contribution  l'histoire des  
ferments solubles1  ,comptes ,rendus1   

,tome #ij1 p4 #acgi4 ,ibid41 ,tome #ia1 
p4 #ghg4    #cd ,on the ,proteolytic    
,action of ,bromelin1 the ,ferment of   
,pineapple  ,juice4 ,journal of         
,physiol41 vol4 #ae1 p4 #bdi4    #ce    
,the ,nature of ,papain1 etc4 ,journal  
of ,physiol41 vol4 #f1 p4 #ccf4    ,with
 the proteolytic ferment of pineapple   
juice my observations have  led me to   
the following conclusions1 viz41 that   
the ferment is at least  associated with
 a proteid body1 more or less completely
 precipitable  from a neutral solution  
by saturation with ammonium sulphate1   
sodium  chloride1 and magnesium         
sulphate4 ,this body is soluble in      
water1  and consequently is not         
precipitated by dialysis4 ,it is further
  non-coagulable by long contact with   
strong alcohol1 and its aqueous         
solution is very incompletely           
precipitated by heat4 ,placing it in    
line  with the known forms of albuminous
 bodies it is not far removed from      
protoalbumose or heteroalbumose1        

differing1 however1 from the latter in  
that it is soluble in water without the 
addition of sodium chloride4 ,at  the   
same time1 it fails to show some of the 
typical albumose reactions1  and verges 
toward the group of globulins4 ,in any  
event1 it shows many  characteristic    
proteid reactions1 and contains         
considerable nitrogen1  viz41 #aj4df per
 cent41 with #ej4g per cent1 of carbon4 
,consequently1 we  may conclude that the
 chemical reactions and composition of  
the more  typical proteolytic enzymes1  
both of animal and vegetable origin1 all
  favor the view that they are proteid  
bodies not far removed from the         
albuminous matter of the                
cell-protoplasm4    ,further1 the very  
nature of these substances and their    
mode of action  strengthen the idea that
 they are not only derived from the     
albumin  of the cell-protoplasm1 but    
that they are closely related to it4    
,one  cannot fail to be impressed with  
the resemblance in functional power     

between the unformed ferments as a class
 and cell-protoplasm4 ,to what  can we  
ascribe the particular functional power 
of each individual  ferment8 ,why1 for  
example1 does pepsin act on proteid     
matter only in  the presence of acid1   
and trypsin to advantage only in the    
presence  of alkalies8 ,why does pepsin 
act only on proteid matter1 and ptyalin 
only on starch and dextrins8 ,why does  
trypsin produce a different set  of     
soluble products in the digestion of    
albumin than pepsin does8  ,similarly1  
why is it that the cell-protoplasm of   
one class of cells  gives rise to one   
variety of katabolic products1 while the
 protoplasm  of another class of cells1 
as in a different tissue or organ1      
manifests  its activity along totally   
different lines8 ,the answer to both    
sets of  questions is1 ,i think1 to be  
found in the chemical constitution of   
the cell-protoplasm on the one hand1 and
 in the constitution of the  individual 
enzymes on the other4 ,the varied       

functional power of the  ferment is a   
heritage from the cell-protoplasm1 and1 
as ,i have said1 is  suggestive of a    
close relationship between the enzymes  
and the living  protoplasm from which   
they originate4 ,we might1 on purely    
theoretical  grounds1 consider that     
these unformed ferments are isomeric    
bodies  all derived from different      
modifications of albumin and with a     
common  general structure1 but with     
individual differences due to the extent
 of  the hypothetical polymerization    
which attends their formation4          
,whenever1 owing to any cause1 the      
activity of the ferment is  destroyed1  
as when it is altered by heat1 strong   
acids1 or alkalies1  then the death of  
the ferment is to be attributed to a    
change in its  constitution2 the atoms  
in the molecule are rearranged1 and as a
 result  the peculiar ferment power is  
lost forever4 ,the proteolytic power of 
these enzymes is therefore bound up in  
the chemical constitution of  the       

bodies1 and anything which tends to     
alter the latter immediately  interferes
 with their proteolytic action4 ,but how
 shall we explain  the normal action of 
these peculiar bodies8 ,intensely       
active1 capable  in themselves of       
producing changes in large quantities of
 material  without being destroyed1     
their mere presence under suitable      
conditions  being all powerful to       
produce profound alterations1 these     
enzymes play  a peculiar part4 ,present 
in mere traces1 they are able to        
transform  many thousand times their    
weight of proteid matter into soluble   
and  diffusible products4 ,all that is  
essential is their mere presence under  
suitable conditions1 and strangely      
enough the causative agent itself       
appears to suffer no marked change from 
the reactions set up between  the other 
substances4    ,there are many theories 
extant to explain this peculiar method  
of  chemical change1 but few of them    
help us to any real understanding of    

the matter4 ,these enzymes are typical  
catalytic or contact agents1  and by    
their presence render possible marked   
changes in the character  of the proteid
 or albuminoid matter with which they   
happen to be  in contact4 ,but the      
conditions under which the contact takes
 place  exercise an important control   
over the activity of the ferment4       
,temperature1 reaction1 concentration of
 the fluid1 presence or absence  of     
various foreign substances1 etc41 all   
play a very important part  in          
regulating and controlling the activity 
of these two proteolytic  enzymes4 ,in  
fact1 as one looks over the large number
 of data which  have gradually          
accumulated bearing upon this point1 one
 is impressed  with the great           
sensitiveness of these ferments toward  
even so-called  indifferent substances4 
,their specific activity appears to     
hinge  primarily upon the existence of a
 certain special environment1           
alterations of which may be attended    

with an utter loss of proteolytic       
power1 or1 in some less common cases1   
with a decided increase in the  rate of 
digestive action4 ,this constitutes one 
of the peculiar features  of these      
proteolytic enzymes2 powerful to produce
 great changes1 they  are nevertheless  
subject to the influence of their       
surroundings in a  way which testifies  
to their utter lack of stability4       
,furthermore1 as  you well know1        
conditions favorable for the action of  
the one ferment  are absolutely         
unfavorable for the activity of the     
other1 and indeed  may even lead to its 
destruction4 ,thus1 while pepsin        
requires for its  activity the presence 
of an acid1 as #j4b per cent4 ,h,cl1    
trypsin is  completely destroyed in such
 a medium4 ,again1 trypsin exhibits its 
peculiar proteolytic power in the       
presence of sodium carbonate1 a salt    
which has an immediate destructive      
action upon pepsin4 ,hence1 a medium    
which is favorable for the action of the

 one ferment may be directly            
antagonistic to the action of the other4
    ,another factor of great moment in  
determining the activity of these  two  
enzymes is temperature4 ,that which is  
most favorable for their  action is #ch 
to #dj ,c41 and any marked deviation    
from this temperature  is attended by an
 immediate effect upon the proteolysis4 
,exposure to  a low temperature simply  
retards proteolytic action1 doubtless in
  the same manner that cold checks or   
retards other chemical changes4  ,there 
is no destruction of the ferment1 even  
on exposure to extreme  cold1 the enzyme
 being simply inactive for the time     
being4 ,exposure  of either pepsin or   
trypsin to a high temperature1 say #hj  
,c41 is  quickly followed by a complete 
loss of proteolytic power1 i4e41  the   
ferment is destroyed4 ,it is to be      
noticed1 however1 that the  destructive 
action of heat is greatly modified by   
the attendant  circumstances4 ,thus1    
fairly pure trypsin1 dissolved in #j4c  

per cent4  sodium carbonate1 is         
completely destroyed on exposure to a   
temperature  of #ej ,c4 for five to six 
minutes1 while a neutral or slightly    
acid  solution of the pure enzyme is    
destroyed in five minutes by exposure   
to a temperature of #de ,c4 ,on the     
other hand1 the presence of inorganic   
salts and the products of digestion1    
such as albumoses1 amphopeptone1  and   
antipeptone1 all tend to protect the    
trypsin somewhat from the  destructive  
effects of high temperatures1 so that in
 their presence  the enzyme may be      
warmed to #fj ,c4 before it shows any   
diminution in  proteolytic power4       
,alkaline reaction1 combined with the   
presence of  salts and proteid1 viz41   
just the conditions existent in the     
natural  pancreatic secretion1          
constitute the best safeguard against   
the  destructive action of heat1 and    
under such conditions trypsin may be    
warmed to about #fj ,c4 before it begins
 to suffer harm4 ,but all this          

testifies in no uncertain way to the    
extreme sensitiveness of the  ferment to
 changes in temperature2 a sensitiveness
 which manifests  itself not only in    
diminished or retarded proteolytic      
action1 but  terminates in destruction  
of the ferment when the temperature     
rises  beyond a certain point4          
,similarly1 pepsin dissolved in #j4b per
 cent4 hydrochloric acid feels  the     
destructive effect of heat when a       
temperature of #fj ,c4 is reached4  ,in 
a neutral solution1 on the other hand1  
destruction of the ferment  may be      
complete at #ee ,c4 ,here1 too1 peptone 
retards very noticeably the  destructive
 action of heat1 especially in an acid  
solution of pepsin1  so that under such 
circumstances the ferment may not be    
affected until  the temperature reaches 
#gj ,c4 ,i have tried many experiments  
along  this line1 not only with pepsin  
and trypsin1 but also with many other   
ferments4 ,we may briefly summarize1    
however1 all that is necessary for  us  

to consider here in the statement that  
the pure isolated ferments  are far more
 sensitive to the destructive action of 
heat than when  they are present in     
their natural secretions4 ,this1 as     
stated1 is due  not only to the reaction
 of the respective fluids but also to   
the  protective or inhibitory action of 
the inorganic salts and various         
proteids naturally present4 ,we may thus
 say with ,biernacki#cf that the  purer 
the ferment the less resistant it is to 
the effects of heat4    #cf ,das        
,verhalten der ,verdauungsenzyme bei    
,temperaturerhhungen4  ,zeitschr4 f4    
,biol41 ,band #bh1 p4 #di4    ,it is    
thus plain that these enzymes1 capable  
though they are of  accomplishing great 
tasks1 are nevertheless exceedingly     
unstable and  prone to lose their       
proteolytic power under the slightest   
provocation4  ,when1 however1 they are  
surrounded by their natural environment1
  the acid or alkali of the respective  
secretion1 together with salts  and     

proteids1 they then appear more stable2 
their natural lability  becomes for the 
time being transformed into             
semi-stability1 and the  temperature1   
for example1 at which they lose their   
peculiar power1 is  raised ten degrees  
or more4 ,i have also found the same to 
be true of  the vegetable proteolytic   
ferments1 and also of the amylolytic    
ferment  of saliva4    ,the above facts 
furnish us1 ,i think1 a good            
illustration of how  dependent these    
proteolytic enzymes are upon the proper 
conditions of  temperature1 to say      
nothing of other conditions1 for the    
full exercise  of their peculiar power4 
,toward acids1 alkalies1 metallic salts1
 and  many other compounds they are even
 more sensitive than toward heat1  and  
much might be said regarding the        
effects1 inhibitory or otherwise1       
produced by a large number of common    
drugs or medicinal agents on  these two 
ferments4 ,any lengthy discussion of    
this matter1 however1  would be foreign 

to our subject1 and ,i will only call   
your attention  in passing to one or two
 points which have a special bearing    
upon the  general nature of the enzymes4
 ,take1 for example1 the influence of   
such substances as urethan1 paraldehyde1
 and thallin sulphate on the            
proteolytic action of                   
pepsin-hydrochloric acid#cg and we find 
that  small quantities1 #j4a to #j4c per
 cent4 tend to increase the rate of     
proteolysis1 while larger amounts1 say  
one per cent41 decidedly check          
proteolysis4 ,similarly1 among inorganic
 compounds1 arsenious oxide1  arsenic   
oxide1 boracic acid1 and potassium      
bromide#ch in small amounts  increase   
the proteolytic power of pepsin in      
hydrochloric acid solution1  while      
larger quantities check the action of   
the ferment in proportion  to the       
amounts added4 ,again1 with the enzyme  
trypsin1 similar results  with such     
salts as potassium cyanide1 sodium      
tetraborate1 potassium  bromide and     

iodide#ci may be quoted as showing not  
only the  sensitiveness of the ferment  
toward foreign substances1 but likewise 
its peculiar behavior1 viz41 stimulation
 in the presence of small  amounts and  
inhibition in the presence of larger    
quantities4    #cg ,chittenden and      
,stewart3 ,studies in ,physiol4 ,chem41 
,yale  ,university4 ,vol4 #c1 p4 #fd4   
#ch ,chittenden and ,allen1 ,ibid41 vol4
 #a1 p4 #gf4    #ci ,chittenden and     
,cummins1 ,ibid41 vol4 #a1 p4 #aab4     
,furthermore1 we have found that even   
gases1 as carbonic acid and  hydrogen   
sulphide1 exert a marked retarding      
influence on the  proteid-digesting     
power of trypsin4 ,moreover1 while it is
 generally  stated that proteolytic and 
other enzymes are practically           
indifferent  to the presence of         
chloroform1 thymol1 and other like      
substances  that quickly interfere with 
the processes of the so-called organized
  ferments1 pepsin and trypsin certainly
 do show a certain degree of            

sensitiveness to chloroform1 and indeed 
even to a current of air  passed through
 their solutions4 ,thus1 very recently1 
,bertels#dj and  ,dubs#da1 working under
 ,salkowski's direction1 have called    
attention  to the peculiar behavior of  
pepsin to chloroform2 their results     
showing1 first1 that small amounts of   
this agent tend to increase the         
proteolytic power of the enzyme1 while  
larger amounts decrease its  digestive  
power4 ,another interesting point       
brought out especially  by ,dub's       
experiments is the fact that an impure  
solution of the  ferment1 viz41 an acid 
extract1 for example1 of the mucous     
membrane  of the stomach containing more
 or less albuminous matter1 is far less 
sensitive to chloroform than an acid    
solution of the purified ferment1  thus 
showing again the protective influence  
of proteids and other  extraneous       
matters2 the latter guarding the enzyme 
to a certain extent  from both the      
stimulating and inhibitory action of    

various agents4    #dj ,ueber den       
,einfluss des ,chloroforms auf die      
,pepsinverdauung1  ,virchow's ,archiv1  
,band #acj1 p4 #dig4    #da ,der        
,einfluss des ,chloroforms auf die      
knstliche ,pepsinverdauung1  ,ibid41    
,band #acd1 p4 #eai4    ,another point  
to be emphasized just here is that any  
chemical  substance1 such as a metallic 
salt1 having a specific action upon     
proteid matter1 will almost invariably  
interfere more or less with  the        
proteolytic action of these enzymes1    
both through a direct  action upon the  
soluble ferment itself1 and also through
 an indirect  action in modifying or    
inhibiting the digestibility of the     
proteid  exposed to proteolysis4 ,all of
 these facts emphasize more or less the 
proteid-like nature of the enzymes1 or  
at least the carriers of the  ferments4 
,it is further very suggestive that the 
destruction of these  enzymes by heat   
happens to occur at approximately those 
temperatures  which are generally       

recognized as the coagulation points of 
ordinary  proteids4 ,moreover1 the      
apparent lack of stability so           
characteristic of  these ferments1 their
 inherent proneness to alteration1 their
 marked  susceptibility to every change 
in environment1 all point to large      
complex molecules1 such as we have in   
proteids and are familiar with in       
living protoplasm4    ,whatever the     
exact nature of these proteolytic       
enzymes1 they are  certainly endowed    
with the power of transforming          
relatively large  amounts of proteid    
matter into soluble products1 even      
though they  themselves are present in  
very small quantity4 ,they are derived1 
as  we have seen1 from living           
protoplasmic cells1 and we might        
perhaps1  with v4 ,ngeli#db and         
,mayer1#dc consider them as retaining a 
portion  of that molecular motion so    
characteristic of living protoplasm1 by 
which the equilibrium of the dead       
food-proteid may be disturbed and  thus 

changes started which result in what we 
call proteolysis4 ,however  this may be1
 we must look to some phase of catalytic
 or contact  action as the true         
explanation of this power of            
proteolysis4 ,at first  glance1 any     
explanation or theory involving the use 
of catalysis seems  exceedingly vague   
and indefinite1 and yet many            
illustrations can be  given of chemical 
reactions where the dominating agent    
evidently acts  in this manner4 8,we    
call a force catalytic10 says the       
philosopher of  ,heilbron1 8when it     
holds no communicable proportion to the 
assumed  results of its action4 ,an     
avalanche is hurled into the valley4444 
,a puff of wind or the fluttering of a  
bird's wing is the catalytic  force     
which has given the signal for1 and     
which is the cause of the  wide-spread  
disaster40#dd ,in the older theories of 
catalytic action1  the catalytic agent  
was supposed to remain passive1 but not 
so in the  more modern conception of    

catalysis4 ,the ferment by its presence 
makes  possible certain changes and     
combinations which could not occur in   
its  absence1 at least under the        
existing circumstances1 although all the
  other conditions might be favorable4  
,the proteids1 for example1 have  a     
natural tendency to undergo hydration2  
thus1 simple boiling with  dilute acid  
or exposure to the action of superheated
 water alone1#de  will produce many if  
not all of the products formed in       
natural  digestive proteolysis4 ,to be  
sure1 they are not formed as readily as 
in artificial or natural digestion1 and 
there may be some minor points  of      
difference1 but still proteolysis can be
 imitated in this manner4  ,the         
proteolytic enzymes simply help on this 
natural tendency of proteid  bodies to  
undergo hydration1 and by their presence
 and action enable  it to occur at lower
 temperatures than it otherwise could1  
and at the  same time render it more    
rapid and complete4 ,this is not        

accomplished1  however1 by simple       
contact4 ,the enzymes1 we may assume1   
combine in  some manner with the proteid
 undergoing digestion1 starting thereby 
a  train of reactions in which the      
proteid and the water present are the   
main actors1 they being1 however1       
perfectly passive in the absence of  the
 inciting agent1 the enzyme4 ,as        
expressed by ,ganger1 8the ferment      
phenomena resemble those in which there 
is apparently a periodic  synthesis and 
dissociation of the catalyzing agent1   
which acts in a  similar manner to the  
agent which explodes a train of         
gunpowder40    #db ,theorie der ,ghrung4
 ,mnchen1 #ahgi4    #dc ,die ,lehre von 
den chem4 ,fermenten4 ,heidelberg1      
#ahhb4    #dd ,quoted from ,gamgee's    
,physiological ,chemistry of the ,animal
 ,body1  vol4 #b1 p4 #g4    #de         
,chittenden and ,meara4 ,a study of the 
primary products resulting  from the    
action of superheated water on          
coagulated egg-albumin4 ,journal  of    

,physiol41 vol4 #ae1 p4 #eja4    ,we can
 find many illustrations among chemical 
phenomena where one  body1 even though  
present in small quantity1 acts as a    
go-between and  makes possible an almost
 indefinite exchange of matter and      
energy4  ,take as an illustration1 the  
part played by water in determining the 
explosion of oxygen and carbon-monoxide 
gas4 ,some years ago1 ,dixon#df  called 
attention to the fact that a mixture of 
these two gases when  perfectly dry     
would not explode even by contact with  
red hot platinum  wire4 ,the presence1  
however1 of a small amount of aqueous   
vapor  would at once cause an explosion 
to occur4 ,in confirmation of this      
observation1 ,traube#dg has reported    
that a flame of carbon-monoxide  gas    
introduced into a perfectly dry         
atmosphere is at once extinguished4  ,in
 a moist atmosphere1 on the other hand1 
the flame will continue to  burn        
indefinitely1 that is as long as the    
,,co gas is supplied4 ,in these  cases1 

the water1 which is so necessary for the
 appearance of the  reaction1 and which 
furnishes a striking illustration of the
 action of  a contact or catalytic      
substance is not purely passive4 ,to be 
sure1  only a minimal amount is         
necessary for the combustion of an      
indefinite  amount of carbonic oxide1   
but the water enters into the reaction  
itself4 ,it is to be noticed that       
carbonic oxide and water alone1 even  at
 high temperatures1 will not react1 but 
in the presence of oxygen  the water is 
decomposed with formation of            
hydrogen-peroxide1 thus3        ,,co  #b
 ,h#b,o  ,o#b  ,,co7,,oh7#b  ,h#b,o#b4  
#df ,chemical ,news1 vol4 #df1 p4 #aea4 
#dg ,bericht4 d4 ,deutsch4 chem4        
,gesellsch41 ,band #ah1 p4 #ahij4       
,the hydrogen-peroxide thus formed      
combines with carbonic oxide to form    
carbonic acid1 which in turn is         
decomposed into the anhydride ,,co#b1   
with regeneration of water1 the latter  
being available for further  action of  

the same order3        ,h#b,o#b  ,,co   
,,co7,,oh7#b        #b ,,co7,,oh7#b  #b 
,,co#b  #b ,h#b,o4    ,indeed1 as can be
 readily seen from the equations1 this  
may be kept  up indefinitely1 a small   
amount of water1 i4e41 the go-between1  
the catalytic agent1 sufficing to       
accomplish the transformation of  almost
 any amount of carbon-monoxide4 ,this1  
,i think1 furnishes an  excellent       
illustration of the way in which        
catalytic agents1 such as  the          
proteolytic enzymes1 may be supposed to 
act4 ,it is truly contact  action1 but  
the agent is not purely passive2 the    
enzyme combines with  the substance     
undergoing proteolysis1 and the         
resultant compound thus  formed is      
enabled now to combine with water and   
undergo hydrolysis1  something which    
could not be accomplished by the proteid
 and water  alone1 that is at body      
temperature4 ,this new and more complex 
compound  is naturally less stable and  
soon undergoes dissociation or cleavage 

with a splitting off of the original    
enzyme for one product1 which is  thus  
available for further action of the same
 order2 while1 as other  products1 we   
find the hydrated and otherwise altered 
substances coming  from the proteid1 and
 whose formation is the ultimate object 
of the  whole process4    ,the          
parallelism between this hypothetical   
action of the proteolytic  enzymes and  
the known reactions in the above        
combustion of carbonic  oxide is        
certainly very close1 and leaves little 
doubt that this  explanation of enzyme  
action is1 in a general way at least1   
correct4  ,thus the carbonic oxide1     
,,co1 brought in contact with pure1 dry 
oxygen  gas 7apparently all that is     
necessary for its direct oxidation into 
carbonic acid1 ,,co#b71 undergoes no    
change2 the burning ,,co gas is at  once
 extinguished4 ,evidently1 something    
more is necessary in order to  start the
 process of oxidation4 ,so1 too1 in     
proteolysis2 the process1  as we shall  

see later on1 is essentially one of     
hydration1 but bring  the proteid and   
the water1 or acid-water1 together and  
although all  the conditions are        
apparently favorable for hydration there
 is1 as  you know1 little or no change4 
,but introduce the catalytic agent and  
immediately the reaction commences4 ,in 
the case of the burning ,,co  gas in    
contact with oxygen1 the water acting as
 contact agent makes  oxidation         
possible1 enabling the main actors in   
the transformation  to react upon each  
other4 ,but1 as we have seen1 the       
contact agent is  something more than a 
mere looker-on1 it becomes for the time 
being an  integral part of the molecule1
 undergoing change1 combining with it   
and  thus making possible the subsequent
 alterations characteristic of the      
specific transformation1 in which1      
however1 the regeneration of the        
contact agent is a prominent feature4   
,so1 too1 with the proteolytic  enzymes1
 pepsin and trypsin1 they are the       

go-betweens1 making possible  the union 
of the proteids with water by combining 
with the proteid  molecule and thus     
paving the way for both hydration and   
cleavage4 ,in  the cleavage of the      
complex molecule1 we have the           
regeneration of the  ferment as a       
prominent feature1 and in proteolysis we
 understand that  the regenerated       
ferment may act not only upon more of   
the original  proteid1 but likewise upon
 the primary products of its action1    
thus  giving rise eventually to a row of
 more or less closely related  cleavage 
products4 ,finally1 we can conceive that
 the enzyme may  gradually be affected  
by the process1 that its regeneration   
may become  less complete1 and thus     
digestive power be eventually           
diminished4    ,much more might be said 
in support of the above hypothesis4 ,on 
the  other hand1 some objections might  
be raised against it1 but ,i know  of no
 more reasonable explanation of enzyme  
action than that here  presented1 or one

 which so well accords with all of the  
known facts  concerning the conditions  
which modify proteolytic action4#dh     
,thus1  the influence of heat1 of the   
products of proteolysis1 of acids1      
alkalies1 and various organic and       
inorganic salts on the action of  these 
digestive enzymes is such as lends favor
 to the above view rather  than opposes 
it4    #dh ,compare ,l4 de ,jager1      
,erklrungsversuch ber die ,wirkungsart  
der ungeformten ,fermente1 ,virchow's   
,archiv1 ,band #aba1 p4 #ahb4 ,also     
,chandelon3 ,bulletin de l',academie    
,royale de ,md4 de ,belgique1 #ahhg1 #a1
  p4 #bhi4      ,,the ,,general ,,nature
 ,,of ,,proteids4    ,proteids are      
confessedly among the most complex      
bodies the physiologist  has to deal    
with1 while at the same time they are   
perhaps the most  important1 not only in
 view of their wide-spread distribution 
through  animal and vegetable tissues1  
but because of the prominent part they  
take in the nutrition of the body4 ,the 

more our knowledge is broadened         
concerning these varied substances1 the 
more we are impressed with  their       
complexity1 and at the same time with   
the necessity for a more  accurate study
 of both their composition and          
constitution4 ,concerning  the latter1  
full fruition of our hopes is probably  
in the distant  future1 but every step  
of advance in this direction adds       
greatly  to our resources in the        
interpretation of the varied and complex
  changes characteristic of proteid     
metabolism4 ,every study of proteid     
decomposition adds something to our     
store of knowledge1 and gives  perhaps  
an added fact available for broadening  
our deductions4#di  ,moreover1 the      
composition and general reactions of the
 proteids  may be investigated with full
 confidence of obtaining many useful    
results1 which must necessarily be an   
aid in interpreting the changes         
accompanying digestive proteolysis4     
#di ,see ,drechsel3 ,der ,abbau der     

,eiweisstoffe4 ,du ,bois ,reymond's     
,archiv  f4 ,physiol41 #ahia1 p4 #bdh4  
,take1 for example1 the single question 
of peptonization by gastric  digestion4 
,what is the nature of the process8 ,is 
the proteid  transformed into a soluble 
and diffusible peptone as a result of   
hydration and cleavage1 or is it a      
transformation which results from  a    
simple depolymerization of the proteid  
molecule1 i4e41 are we to  consider     
albumin and peptone as isomeric bodies8 
,these questions1 on  which             
physiologists seem loath to agree1 can  
certainly be answered  definitely2 not1 
however1 by arguments but by careful    
experimentation1  in which the          
composition of the proteid undergoing   
digestion must be  a necessary          
preliminary factor1 and the composition 
of the resultant  product1 or products1 
a secondary factor of equal importance4 
,further1  the question needs to be     
answered not with reference to one      
proteid  merely1 but with reference to  

every proteid capable of digestion by   
either gastric or pancreatic juice4     
,when these questions have been  fully  
answered in this manner1 we shall have  
positive data to deal  with1 and our    
conclusions will rest upon a foundation 
of fact not  easily set aside4 ,this is 
one of the problems upon which ,i have  
been at  work for some years1 and       
although progress may in one sense be   
slow1  yet it is sure and gives results 
of no uncertain character4    ,first1   
then1 let us consider briefly the nature
 of the proteids whose  proteolysis we  
may be interested in2 remembering1      
however1 that in so  doing we can merely
 touch upon the points essential for our
 purpose4  ,allow me to say in          
parenthesis that there is being         
published in ,moscow  a work on proteids
 alone of five volumes1 #ijj pages each1
 which it is  supposed will constitute  
an exhaustive treatise of the           
subject4#ej    #ej ,die ,einheit der    
,proteinstoffe4 ,historische u4         

experimentelle  ,untersuchungen1 by ,l4 
,morokhowetz4    ,if we attempt to      
classify all of the proteid bodies      
hitherto discovered  and studied we are 
at once confronted with a problem of no 
small  proportions4 ,so varied are they 
in their reactions1 solubilities1 and   
behavior toward general reagents1 so    
inclined to merge into each other  by   
almost insensible gradations that it    
becomes an extremely difficult  matter  
to make an arrangement that will satisfy
 all the requirements  of the case4 ,i  
have to suggest1 however1 the following 
classification1  which is merely a      
modification of several existing ones1  
based  primarily upon chemical          
composition1 and solubility in the more 
common  menstruums4    ,proteids may    
first be divided into three main groups 
as follows3    ,i4 ,simple              
,proteids4--,composed of carbon1        
hydrogen1 nitrogen1 sulphur1  and       
oxygen1 and yielding by decomposition   
aromatic bodies such as  tyrosin1       

phenol1 indol1 etc4    ,,ii4 ,compound  
,proteids4--,composed of a simple       
proteid united to some  non-proteid     
body4    ,,iii4 ,albuminoids4--,a class 
of nitrogenous bodies related to and    
derived from proteids1 but differing    
especially from the latter by  great    
resistance to the ordinary solvents of  
true proteids4    ,the individual       
members of these three groups may be    
arranged as follows  on the basis of    
solubility1 coagulability1 etc43    ,i4 
,,simple ,,proteids4--,a4 ,soluble in   
water4--a4 ,coagulable by heat1  and by 
long contact with alcohol4 ,albumins3   
serum-albumin1 egg-albumin1             
lacto-albumin1 myo-albumin1 vegetable   
albumins4 b4 ,non-coagulable by  heat   
and by long contact with alcohol4       
,proteoses3#ea protoproteoses1          
deuteroproteoses4 ,peptones3#ea         
amphopeptones1 antipeptones1            
hemipeptones4    #ea ,used in the       
generic sense2 the proteoses including  
albumoses1  globuloses1 myosinoses1     

elastoses1 etc41 and the peptones the   
peptone-products formed in the digestion
 of any or all proteids4    ,b4         
,insoluble in water1 but soluble in salt
 solutions4--a4 ,more or  less          
coagulable by heat4 ,globulins4 #a4     
,soluble in dilute and saturated  ,na,cl
 solutions4 ,vitellins4 #b4 ,soluble in 
dilute ,na,cl solutions1 but            
precipitated by saturation with ,na,cl4 
,myosins1 paraglobulin#eb  or           
serum-globulin1 fibrinogen1             
myo-globulin1 paramyosinogen1           
cell-globulins4 b4 ,non-coagulable by   
heat1 soluble in dilute ,na,cl  solution
 and precipitated by saturation with    
,na,cl4 ,heteroproteoses4    #eb ,not   
completely insoluble in saturated ,na,cl
 solution4    ,c4 ,insoluble in water   
and salt solutions1 soluble in dilute   
alcohol--,zein1 gliadins4    ,d4        
,insoluble in water1 salt solutions and 
alcohol2 soluble in  dilute acids or    
alkalies4--a4 ,coagulable by heat when  
suspended in  a neutral fluid4          

,acid-albumins1 alkali-albumins or      
albuminates4 b4  ,non-coagulable by heat
 when suspended in a neutral fluid4     
,antialbumids1  dysproteoses1 glutenins4
    ,e4 ,insoluble in water1 salt       
solutions1 alcohol1 dilute acids and    
alkalies2 soluble in strong acids1      
alkalies1 and in pepsin-hydrochloric    
acid and alkaline solutions of          
trypsin4--,coagulated proteids1         
fibrin4#ec    #ec ,in blood-fibrin we   
have a good illustration of the fact    
that these  divisions are not absolutely
 exact1 since this form of proteid      
matter1  for example1 is somewhat       
soluble in dilute acids and in salt     
solutions1  although requiring a long   
time for marked solution4    ,,ii4      
,,compound ,,proteids4--,a4 ,compounds  
of a proteid 7globulin7 with an         
iron-containing pigment1 soluble in     
water and coagulable by heat and        
alcohol4 ,hmoglobin1 oxyhmoglobin1      
methmoglobin1 etc4    ,b4 ,compounds of 
proteids with members of the            

carbohydrate group4  ,insoluble in      
water2 soluble in very weak             
alkalies4--a4 ,true mucins4  b4 ,mucoids
 or mucinoids4    ,c4 ,compounds of     
proteids with nucleic acid4             
,phosphorized bodies  yielding by       
decomposition metaphosphoric acid4      
,insoluble in water  and in             
pepsin-hydrochloric acid1 but more or   
less soluble in  alkalies4--,nucleins4  
,d4 ,compounds of proteids with         
nucleins4 ,very soluble in dilute       
alkalies4--,nucleoalbumins1 as casein of
 milk1 and nucleoalbumins of            
cell-protoplasm and cell-nuclei1 etc4   
,,iii4 ,,albuminoids4--,a4 ,soluble in  
boiling water with formation of  gelatin
 and yielding by decomposition leucin   
and glycocoll4--,collagen  7gelatin74   
,b4 ,insoluble in boiling water1 and    
yielding by decomposition  much leucin  
and some tyrosin1 together with         
glycocoll and lysatin4  ,slowly hydrated
 by boiling dilute acids and by         
treatment with  pepsin-hydrochloric     

acid4--,elastin4    ,c4 ,insoluble in   
water1 dilute acids and alkalies1 also  
in  gastric and pancreatic juice4 ,yield
 leucin and tyrosin by                  
decomposition4--,keratin1 neurokeratin4 
,we may now advantageously consider the 
composition of a few of the  more       
prominent representatives of the        
individual groups1 taking  for          
illustration those bodies which have    
been most thoroughly  studied1 and which
 we may have occasion to refer to in our
  discussion of proteolysis4 ,i have not
 included in the table any of  the      
alteration-products of the proteids     
formed by the action of  pepsin-acid1   
trypsin1 or boiling dilute acids1       
confining myself here  simply to those  
bodies which occur ready-formed in      
nature4    ,,composition ,,of ,,some    
,,of ,,the ,,more ,,prominent ,,proteids
 ,,occurring ,,in  ,,nature4,a          
,substance4   ,c    ,h   ,n    ,s   ,o  
,p  ,ash4  ,origin4    ,author4         
----------------------------------------

------------------------------          
,serum-      #ec4jef4heaf4jda4ggbb4bi   
#j4eg,serum from ,hammarsten4#ed        
albumin                               --
  horse blood    ,serum-                
#eb4bef4feae4hhb4bgbb4ie                
#a4hd,pleural    ,hammarsten4#ed        
albumin                                 
exudation      ,egg-albumin             
#eb4bef4ijae4bea4icbc4fg         ,non-  
,hammarsten4#ed                         
coagulated     ,egg-albumin             
#eb4ccf4ihae4hia4hcbb4ig     #a4aa,non- 
,chittenden and                         
coagulated ,bolton4#ee    ,lacto-       
#eb4aig4ahae4gga4gcbc4ac         ,cow's 
milk ,sebelien4#ef     albumin          
,vegetable-  #eb4bef4gfaf4jga4dhbc4dd   
#j4gj;,corn       ,chittenden and       
albumin                                 
or maize   ,osborne4#eg    ,vegetable-  
#ec4jbf4hdaf4hja4bhbb4jf     #j4hb,wheat
      ,osborne and     albumin          
,voorhees4#eh    ,proteose1             
#eb4acf4hcaf4eea4jibc4dj                

#j4gi;,hemialbu-  ,khne and     animal  
mose1 urine,chittenden4#ei    ,proteose1
   #ej4fjf4fhaf4cca4fbbd4gg             
#b4ii;,corn       ,chittenden and       
vegetable                               
or maize   ,osborne4#eg    ,proteose1   
#ea4hff4hbag4cb              #j4be,wheat
      ,osborne and     vegetable        
,voorhees4#eh    ,proteose1             
#di4ihf4ieah4gh                         
#a4hj;,flax-seed  ,osborne4#fj          
vegetable                               
,proteose1   #df4ebf4djah4be            
#b4bj;,cocoanut   ,chittenden and       
vegetable                               
meat       ,setchell4#fa    ,vitellin1  
#ea4gaf4hdah4abj4hebb4dh     #a4bj;,corn
       ,chittenden and     spheroidal   
or maize   ,osborne4#eg    ,vitellin1   
#ea4fjf4igah4hja4jaba4fb                
#j4cj,squash-seed,chittenden and        
crystalline                             
,hartwell4#fb    ,vitellin1             
#ea4haf4idah4gaa4jaba4ec      #j        
,squash-seed,chittenden and             

amorphous                               
,hartwell4#fa    ,vitellin1             
#ea4dhf4idah4fjj4habb4ag                
#j4ed;,flax-seed  ,osborne4#fj          
crystalline                             
,vitellin1   #ea4jcf4heah4cij4fibc4jd   
#j4di,wheat      ,osborne and           
spheroids                               
,voorhees4#eh    ,vitellin1             
#ea4fcf4ijah4ghj4ijba4gi                
#j4ef;,hemp-seed  ,chittenden and       
crystalline                             
,mendel4#fa    ,vitellin1               
#ea4caf4igah4gej4gfbb4ba                
#j4jc;,castor bean,osborne4#fc          
crystalline                             
,vitellin1   #eb4ahf4ibah4cja4jfba4ed   
#j4bj;,brazil nut ,osborne4#fc          
crystalline                             
,vitellin1   #ea4bcf4ijah4dja4jfbb4da   
#j4be;,cocoanut   ,chittenden and       
semi-                                   
meat       ,setchell4#fb     crystalline
                                        
,myosin1 #ac  #eb4hbg4aaaf4gga4bgba4ij  

#a4de,muscle-    ,chittenden and        
different                               
tissue     ,cummins4#fd     samples     
,myosin1     #eb4fhg4jbaf4gha4cjbb4bb   
#j4fc;,corn or    ,chittenden and       
vegetable                               
maize      ,osborne4#eg    ,myosin1     
#eb4ahg4jeag4ijj4ecbb4cd     #j4aj,oats 
,osborne4#fe     vegetable1             
crystalline                             
,paraglobulin#eb4gag4jaae4hea4aabc4bd   
#j4cj;,blood      ,hammarsten4#ff       
of horse      ,fibrinogen               
#eb4icf4ijaf4ffa4bebb4bf                
#a4ge;,blood      ,hammarsten4#fg       
of horse      ,zein                     
#ee4bcg4bfaf4acj4fjbj4gh     #j4dc;,corn
 or    ,chittenden and                  
maize      ,osborne4#eg    ,gliadin     
#eb4gbf4hfag4ffa4adba4fb     #j4ea,wheat
      ,osborne and                      
,voorhees4#eh    ,gliadin               
#ec4jaf4iaaf4dcb4bfba4ci         ,oats  
,osborne4#fc                            
,glutenin    #eb4cdf4hcag4dia4jhbb4be   

,wheat      ,osborne and                
,voorhees4#eh    ,coagulated            
#eb4ccf4ihae4hda4habc4jd                
#j4bg;,egg-albumin,chittenden           
proteid                                 
and ,bolton4#ee    ,coagulated          
#ea4ehf4hhah4hja4jiba4fe                
#j4be,vitellin1  ,chittenden            
proteid                                 
hemp-seed  and ,mendel4#fa    ,fibrin   
#eb4fhf4hcaf4iaa4ajbb4dh                
#j4ef;,blood      ,hammarsten4#fg       
of horse       ,oxyhmo-                 
#ec4heg4cbaf4agj4ciba4hd                
#j4dc;,blood of   ,hoppe-     globin    
,fe4dog         ,seyler4#fh    ,oxyhmo- 
#ed4gag4chag4dcj4dhai4fj                
#j4ci;,blood of   ,htner4#fi     globin 
,fe4pig            ,mucin               
#ej4cjf4hdac4fba4gabg4ec     #j4cc;,from
 snail ,hammarsten4#gj                  
,mucin       #dh4hdf4hjab4cbj4hdca4bj   
#j4ce,submaxil-  ,hammarsten4#ga        
liary gland    ,chondro-                
#dg4cjf4dbab4ehb4dbca4bh                

,cartilage  ,mrner4#gb     mucoid       
,nuclein     #ej4fjg4fjac4ah            
#a4hi     ,human brain,v4 ,jaksch4#gc   
,nuclein     #di4ehg4ajae4jb            
#b4bh     ,pus        ,hoppe-           
,seyler4#gd    ,casein                  
#eb4ifg4jeae4fej4gabb4ghj4hd     ,cow's 
milk ,hammarsten4#ge                    
,casein                                 
#ec4cjg4jgae4iaj4hbbb4jcj4hg            
#j4ih;,cow's milk ,chittenden and       
,painter4#gf    ,nucleo-                
#dh4dag4baaf4hej4gjbd4dab4db            
,leucocytes ,lilienfeld4#gg     histon  
or                                      
leuco-                                  
nuclein                                 
,gelatin     #di4chf4haag4igj4gabe4ac   
#a4bf;,connective ,chittenden and       
tissue     ,solley4#gh    ,elastin      
#ed4bdg4bgaf4gjj4cjba4gi                
#j4ij,neck-band  ,chittenden            
and ,hart4#gi    ,elastin               
#ec4ieg4jcaf4fgj4chba4ig                
#j4gb;,aorta      ,schwarz4#hj          

,keratin     #di4def4ebaf4had4jbbc4bj   
#a4ja,white      ,khne and              
rabbit's   ,chittenden4#ha              
hair                                    
,neurokeratin#ef4iig4ecac4aea4hgbj4df   
#a4ce;,human brain,khne and             
,chittenden4#hb    ,reticulin           
#eb4hhf4igae4fca4hhbb4cjj4cd            
#b4bg,reticular  ,siegfried4#hc         
tissue                                  
----------------------------------------
------------------------------    ,a    
,many of these results represent the    
average of a large number of  individual
 analyses4    #ed ,jahresbericht f4     
,thierchemie1 ,band #aa1 p4 #ai4    #ee 
,studies in ,physiol4 ,chemistry1 ,yale 
,univer41 vol4 #b1 p4 #abf4    #ef      
,zeitschr4 physiol4 ,chem41 ,band #i1 p4
 #dfc4    #eg ,amer4 ,chemical ,journal1
 vols4 #ac and #ad4    #eh ,ibid41 vol4 
#ae1 p4 #cgi4    #ei ,zeitschr4 f4      
,biol41 ,band #ai1 p4 #aih4    #fj      
,amer4 ,chemical ,journal1 vol4 #ad1 p4 
#fbi4    #fa ,not hitherto published4   

#fb ,journal of ,physiology1 vol4 #aa1  
p4 #dce4    #fc ,amer4 ,chemical        
,journal1 vol4 #ad1 p4 #ffb4    #fd     
,studies in ,physiol4 ,chemistry1 ,yale 
,university1 vol4 #c1 p4 #aae4    #fe   
,fourteenth ,annual ,report ,conn4 ,ag4 
,exp4 ,sta41 #ahij2 #b;d paper1  ,amer4 
,chemical ,journal1 vol4 #ad1 p4 #bab4  
#ff ,pflger's ,archiv f4 ,physiol41     
,band #bb1 p4 #dhi4    #fg ,ibid41 ,band
 #bb1 p4 #dgi4    #fh ,hoppe-,seyler's  
,med4 ,chem4 ,untersuch1 p4 #ahi4    #fi
 ,hoppe-,seyler's ,chem4 ,analyse1 #fth 
auflage1 p4 #bge4    #gj ,pflger's      
,archiv f4 ,physiol41 ,band #cf4 p4     
#cib4    #ga ,zeitschr4 f4 physiol4     
,chem41 ,band #ab4 p4 #ahe4    #gb      
,jahresbericht f4 ,thierchemie1 ,band   
#ah1 p4 #bai4    #gc ,pflger's ,archiv  
f4 ,physiol41 ,band #ac1 p4 #dfi4    #gd
 ,hoppe-,seyler's ,med4 ,chem4          
,untersuch1 p4 #dhi4    #ge ,zeitschr4  
f4 physiol4 ,chem41 ,band #g1 p4 #bfi4  
#gf ,studies in ,physiol4 ,chemistry1   
,yale ,university1 vol4 #b1 p4 #agb4    

#gg ,du ,bois ,reymond's ,archiv f4     
,physiol41 #ahib1 p4 #agj4    #gh       
,journal of ,physiology1 vol4 #ab4 p4   
#bc4    #gi ,studies in ,physiol4       
,chemistry1 ,yale ,university1 vol4 #c1 
p4 #ai2  also ,zeitschr4 f4 ,biol41     
,band #be1 p4 #cfh4    #hj ,zeitschr4 f4
 physiol4 ,chem41 ,band #ah1 p4 #dia4   
#ha ,zeitschr4 f4 ,biol41 ,band #bf1 p4 
#cjd4    #hb ,ibid41 p4 #cja4    #hc    
,jahresbericht f4 ,thierchemie1 ,band   
#bb1 p4 #ae4    ,in considering the     
results tabulated above1 it is to be    
remembered  that all of these bodies1   
with the exception of keratin1          
neurokeratin1  and reticulin1 are more  
or less digestible in either gastric or 
pancreatic juice1 or indeed in both     
fluids4 ,i will not take time here  to  
point out the obvious genetic           
relationships and differences in        
composition shown by the above data1 but
 will immediately call your  attention  
to the fact that there are other and    
more important points  of difference    

between many of these proteids which are
 hidden beneath  the surface1 and which 
a simple determination of composition   
will not  bring to light4 ,i refer to   
the chemical constitution of the bodies1
 to  the way in which the individual    
atoms are arranged in the molecule1  on 
which hinges more or less the general   
properties of the bodies and  which in  
part determines their behavior toward   
the digestive enzymes1  as well as      
toward other hydrolytic agents4 ,these  
differences in inner  structure can only
 be ascertained by a study of the       
decomposition  products of the proteids1
 and of the way in which the complex    
molecules  break down into simpler4 ,the
 nature of the fragments resulting from 
the  decomposition of a complex proteid 
molecule1 gives at once something  of an
 insight into the character of the      
molecule4 ,thus1 egg-albumin  exposed to
 the action of boiling dilute sulphuric 
acid yields1 among  other fragments1    
large quantities of leucin and tyrosin1 

the latter  belonging to the aromatic   
group and containing the phenyl radical4
  ,collagen1 or gelatin1 on the other   
hand1 by similar treatment fails  to    
yield any tyrosin or related aromatic   
body1 but gives instead  glycocoll or   
amido-acetic acid1 in addition to       
leucin1 lysin1 and other  products      
common to albumin4 ,its constitution1   
therefore1 is evidently  quite different
 from that of albumin1 but the          
composition of the body  reveals no sign
 of it4 ,further1 we have physiological 
evidence of this  difference in         
constitution in that gelatin1 though    
containing even  more nitrogen than     
albumin1 is not able to take the place  
of the latter  in supplying the         
physiological needs of the body2 its    
food-value is of  quite a different     
order from that of albumin4    ,but     
while all of the individual proteids    
show many points of  difference1 either 
in composition1 constitution1 reactions1
 or  otherwise1 they are nearly all     

alike in their tendency to undergo      
hydrolytic decomposition under proper   
conditions2 the extent of the           
hydrolysis and accompanying cleavage    
being dependent simply upon the  vigor  
or duration of the hydrolytic process4  
,furthermore1 all of the simple         
proteids1 at least1 give evidence of    
the presence of two distinct groups or  
radicals1 which give rise by            
decomposition or cleavage to two        
distinct classes of products4 ,these    
two groups1 which we may assume to be   
characteristic of every typical         
proteid1 ,khne has named the anti- and  
hemi-group respectively4 ,this          
conception of the proteid molecule is   
one of the foundation-stones  on which  
rest some of our present theories       
regarding the hydrolytic  decomposition 
of proteids1 especially by the          
proteolytic enzymes4  ,moreover1 it is  
not a mere conception1 for it has been  
tested so  many times by experiment that
 it has seemingly become a fact4 ,the   

two groups1 or their representatives1   
can be separated1 in part1 at  least1 by
 the action of dilute sulphuric acid    
7three per cent47 at  #ajj ,c4 ,thus1   
after a few hours' treatment of         
coagulated egg-albumin1  about fifty per
 cent4 of the proteid passes into       
solution1 while there  remains a        
homogeneous mass1 something like silica 
in appearance1  insoluble in dilute     
acid1 but readily soluble in dilute     
solutions of  sodium carbonate4 ,this   
latter is the representative of the     
anti-group1  originally named by        
,schtzenberger#hd hemiprotein1 but now  
called  antialbumid4#he ,it is only     
slightly digestible in gastric juice1   
but  is readily attacked by alkaline    
solutions of trypsin1 being converted   
thereby into a soluble peptone known as 
antipeptone4 ,in the sulphuric  acid    
solution1 on the other hand1 are found  
the representatives  of the hemi-group2 
viz41 albumoses1 originally known as one
 body1  hemialbumose1#hf together with  

more or less hemipeptone1 leucin1       
tyrosin1 etc4    #hd ,recherches sur    
l'albumine et les matires albuminoides4 
,bulletin  de la ,socit chimique de     
,paris1 vols4 #bc and #bd4    #he ,khne3
 ,weitere ,mittheilungen ber            
,verdauungsenzyme und die  ,verdauung   
der ,albumine4 ,verhandl4 d4 ,naturhist4
 ,med4 ,ver4 zu  ,heidelberg1 ,band #a1 
p4 #bcf4    #hf ,khne und ,chittenden3  
,ueber die nchsten ,spaltungsproducte   
der  ,eiweisskrper4 ,zeitschr4 f4       
,biol41 ,band #ai1 p4 #aei4    ,the fact
 that we have so many representatives of
 the hemi-group in  this decomposition  
is significant of the readiness with    
which the  so-called hemi-group         
undergoes change4 ,all of its members   
are prone  to suffer hydration and      
cleavage1 passing through successive    
stages  until leucin1 tyrosin1 and other
 simple bodies are reached4 ,these1  and
 other similar crystalline bodies1 are  
likewise the typical  end-products of   
proteolysis by trypsin1 and presumably  

come directly  from the breaking-down of
 hemipeptone4 ,antipeptone1 on the other
  hand1 is incapable of further change  
by the proteolytic ferment  trypsin4    
,hence1 the hemi-group can be identified
 by the behavior of  the body containing
 it toward trypsin2 i4e41 it will       
ultimately  yield leucin1 tyrosin1 and  
other bodies of simple constitution to  
be  spoken of later on4 ,the anti-group1
 however1 will show its presence by  a  
certain degree of resistance to the     
action of trypsin1 antipeptone  being   
the final product of its transformation 
by this agent2 i4e41  leucin1 tyrosin1  
etc41 will not result4 ,in this         
hydrolytic cleavage  of proteids the    
anti-group does not always appear as    
antialbumid4 ,it  may make its          
appearance in the form of some related  
body1 the exact  character of the       
product being dependent in great part   
upon the nature  of the hydrolytic      
agent1 but in every case the            
characteristics of the  anti-group will 

come to the surface when the body is    
subjected to the  action of trypsin4    
,the above-described treatment of a     
coagulated proteid with water           
containing sulphuric acid evidently     
induces profound changes in the  proteid
 molecule4 ,the conditions are certainly
 such as favor hydration1  and in the   
case of complex molecules1 like the     
proteids1 cleavage might  naturally be  
expected to follow4 ,analysis of        
antialbumid from various  sources       
plainly shows that its formation is     
accompanied by marked  chemical changes4
 ,thus1 the following data1 showing the 
composition of  antialbumid formed from 
egg-albumin and serum-albumin by the    
action  of dilute sulphuric acid at #ajj
 ,c41 gives tangible expression to the  
extent of this change3                  
,antialbumid#hg         ,antialbumid#hg 
,egg-       from       ,serum-          
from            albumin4 egg-albumin4   
albumin4  serum-albumin4                
----------------------------------------

---------------    ,c4444444 #eb4cc     
#ec4gi      #ec4je        #ed4ea        
,h4444444  #f4ih        #g4jh           
#f4he         #g4bg    ,n4444444 #ae4hd 
#ad4ee      #af4jd        #ad4ca        
----------------------------------------
---------------    #hg ,khne und        
,chittenden3 ,zeitschr4 f4 ,biol41 ,band
 #ai1 pp4 #afg and #agh4    ,in both    
cases there is a noticeable decrease in 
nitrogen1 and a  corresponding increase 
in the content of carbon4 ,evidently1   
then1  this cleavage of the             
albumin-molecule into the anti-group on 
the one  hand1 and into bodies of the   
hemi-group on the other1 is accompanied 
by chemical changes of such magnitude   
that their imprint is plainly  visible  
upon the resultant products2 changes    
which certainly are far  removed from   
those common to polymerization4    ,this
 proneness of proteid matter to undergo 
hydration and subsequent  cleavage is   
further testified to by the readiness   
with which even such  a resistant body  

as coagulated egg-albumin breaks down   
under the simple  influence of          
superheated water at #acj to #aej ,c4   
,many observations are  recorded bearing
 on this tendency of proteid matter1 but
 few observers  have carried their      
experiments to a satisfactory           
conclusion4 ,a recent  study of this    
question in my own laboratory1 has given
 some very  interesting results4#hh     
,thus1 coagulated egg-albumin placed in 
sealed  tubes with a little distilled   
water and exposed to a temperature of   
#aej ,c4 for three to four hours1       
rapidly dissolves1 leaving1 however1  an
 appreciable residue4 ,the solution     
reacts alkaline1 there is a  separation 
of sulphur1 and in the fluid is to be   
found not albumin1 but  two distinct    
albumose-like bodies1 together with some
 true peptone1 and  a small amount of   
leucin1 tyrosin1 and presumably other   
bodies4#hi ,the  albumose-like bodies   
are in many ways quite peculiar4 ,in    
some respects  they resemble the        

albumoses formed in ordinary digestion2 
but in others  they show peculiarities  
which render them quite unique1 so that 
they  merit the specific name of        
atmidalbumoses1 as suggested by         
,neumeister4  ,what1 however1 ,i wish to
 call attention to here is the          
composition of  these albumoses4        
,prepared from coagulated egg-albumin by
 the simple  action of heat and water1  
they show a deviation from the          
composition of  the mother-proteid1     
which plainly implies changes of no     
slight degree4  ,this is clearly        
apparent from the following table3      
,coagulated,atmidalbumose ,atmidalbumose
 ,deutero-          egg-                
precipitatedprecipitated by atmid-      
,antialbumid4       albumin4    by      
,na,cl4   ,na,cl  acid4  albumose4      
----------------------------------------
---------------------    ,c   #eb4cc    
#ee4ac         #ee4jd       #ea4ii      
#ec4gi    ,h    #f4ih        #f4ic      
#f4hi        #f4fj      #g4jh    ,n     

#ae4hd       #ad4bh         #ad4ag      
#ac4be     #ad4ee    ,s    #a4ha        
#a4ff          ---         #j4ih        
---    ,o   #bc4jd       #bb4jj         
---        #bg4ah      ---              
----------------------------------------
---------------------    #hh ,chittenden
 and ,meara3 ,a ,study of the ,primary  
,products ,resulting  from the ,action  
of ,superheated ,water on ,coagulated   
,egg-albumin4 ,journal  of ,physiology1 
vol4 #ae1 p4 #eja4    #hi ,compare      
,neumeister's experiments on            
blood-fibrin4 ,ueber die  nchste        
,einwirkung gespannte ,wasserdmpfe auf  
,proteine und ber eine  ,gruppe         
eigenthmlicher ,eiweisskrper und        
,albumosen4 ,zeitschr4 f4 ,biol41  ,band
 #bf1 p4 #eg4    ,here we see that two  
of these primary albumoses formed by the
 action  of superheated water1 like the 
previously described antialbumid1 show  
a loss of nitrogen with a marked        
increase in the content of carbon4      
,evidently1 they are related to the     

antialbumid formed by the action  of    
dilute acid4 ,they are1 however1 soluble
 in water1 and in many  ways differ from
 true antialbumid1 but there is         
evidently an inner  relationship4 ,the  
so-called deuteroatmidalbumose shows a  
still more  noticeable falling off in   
nitrogen and sulphur1 while the content 
of carbon is more closely allied to that
 of the mother-proteid4 ,the  albumose  
precipitable by sodium chloride1        
although different from an  albumid1    
evidently comes from the anti-group and 
is a cleavage product  which in turn may
 undergo further hydration and splitting
 by continued  treatment4 ,the so-called
 deutero-body1 on the other hand1 may   
well be a  representative of the        
hemi-group4#ij    #ij ,compare          
,krukenberg1 ,sitzungsberichte der      
,jenaischen ,gesellschaft  fr ,medicin1 
etc4 #ahhf4    ,it is not my purpose    
here to enter into details connected    
with the  action of superheated water on
 proteids4 ,such a course would take  us

 too far from our present subject1 but  
,i do wish to emphasize the  fact that  
even the most resistant of proteids has 
an innate tendency  to undergo hydration
 and cleavage1 and that even simple     
heating with  water alone1 at a         
temperature slightly above #ajj ,c41 is 
sufficient to  induce at least partial  
solution of the proteid4 ,further1 this 
solvent  action in the case of water and
 dilute acids1 at least1 is certainly   
associated with marked chemical changes4
 ,it is not mere solution1 it  is not   
simply the formation of one soluble     
body1 but solution of the  proteid is   
accompanied by the appearance of a row  
of new products1  in which the terminal 
bodies are crystalline substances of    
simple  composition4 ,further1 this     
conclusion does not rest upon the       
results  obtained from a single proteid1
 for ,i have at various times studied   
also the primary products formed in the 
cleavage of casein1 elastin1  zein1 and 
other proteids by the action of hot     

dilute acid1 and in all  cases have     
obtained evidence of the formation of   
several proteose-like  bodies1 as well  
as of true peptones4    ,by the action  
of more powerful hydrolytic agents1 such
 as boiling  hydrochloric acid to which 
a little stannous chloride has been     
added  to prevent oxidation1 the proteid
 molecule may be completely broken  down
 into simple decomposition products1 of 
which leucin1 tyrosin1  aspartic acid1  
glutamic acid1 glucoprotein1 lysin1 and 
lysatinin are  typical examples4#ia ,in 
other words1 by this and other methods  
of  treatment1 which we cannot take time
 to consider1 we can easily break  down 
the albumin-molecule completely into    
bodies which1 as we shall see  later on1
 are typical end-products of            
trypsin-proteolysis1 and which  are far 
removed from the original proteid4 ,but1
 as we have seen1 even  the primary     
bodies formed in the less profound      
hydrolysis induced by  superheated      
water1 do not show the composition of   

the mother-proteid4  ,hydration and     
cleavage leave their marks upon the     
products1 and thereby  we know that     
solution of the proteid is the result of
 something more  than a mere            
rearrangement of the atoms in the       
molecule4    #ia ,hlasiwetz und         
,habermann1 ,ann4 ,chem4 u4 ,pharm41    
,band #afi1 p4 #aej4  ,also ,drechsel1  
,du ,bois-,reymond's ,archiv f4         
,physiol41 #ahia1 p4 #bee4    ,further1 
we are to remember that boiling dilute  
acid and superheated  water tend to     
produce a cleavage along specific lines2
 viz41 a cleavage  into the anti- and   
hemi-groups of the molecule1 and as     
representatives  of these groups we may1
 in the hydration of every native       
proteid1 look  for two distinct rows of 
closely related substances4    ,in      
digestive proteolysis it will be our    
purpose to show that cleavage  of much  
the same order occurs1 not necessarily  
resulting1 however1  in the formation of
 identically the same products1 but     

certainly  accompanied with the         
production of bodies belonging to the   
hemi- and  anti-groups1 although they   
may be less sharply separated from each 
other than in the cleavage with dilute  
sulphuric acid4    ,the body originally 
described as hemialbumose1 and          
identified as a  product of every       
gastric digestion1 is now known to be a 
mixture of  closely related substances  
ordinarily spoken of as albumoses1#ib   
or generically as proteoses4 ,these are 
primary products in the  digestion of   
every form of proteid matter1           
intermediate between the  mother-proteid
 and the peptone which results from the 
further action  of the proteolytic      
enzymes4 ,associated with the           
hemialbumoses are  corresponding        
antialbumoses1 coming from the anti-half
 of the proteid  molecule1 and differing
 from their neighbors1 the hemi-bodies1 
mainly in their behavior toward the     
ferment trypsin4 ,thus1 we have  the    
counterpart of the many bodies described

 by ,meissner1 although  now arranged   
systematically and on the basis of      
structural and other  differences not   
thought of in his day4    #ib ,khne und 
,chittenden3 ,ueber ,albumosen1         
,zeitschr4 f4 ,biol41 ,band  #bj1 p4    
#aa4    ,by the initial action of       
pepsin-acid1 proteids are first         
transformed  into acid-albumin or       
syntonin1 then1 by the further action of
 the  ferment1 this body is changed into
 the primary proteoses1 proto and       
heteroproteose1 of each of which there  
must be two varieties1 a hemi  and an   
anti4 ,these may then undergo further   
transformation into what  is known as a 
secondary proteose1 viz41               
deuteroproteose1 of which  there must   
likewise be two varieties1 corresponding
 to the hemi- and  anti-groups          
respectively4 ,by continued proteolytic 
action there results  as the final      
product of gastric digestion peptones2  
approximately1 an  equal mixture of     
so-called hemipeptone and antipeptone1  

generally known  as amphopeptone4 ,such 
a peptone exposed to the proteolytic    
action of  trypsin should obviously     
break down in part into simple          
crystalline  bodies1 leaving a residue  
of true antipeptone4 ,in truth1 this is 
exactly what does happen when the       
peptone resulting from gastric          
digestion is warmed with an alkaline    
solution of trypsin4 ,the so-called     
hemipeptone quickly responds to the     
action of the pancreatic ferment1  and  
is converted into other products1 while 
the so-called antipeptone  resists its  
action completely1 thus giving results  
in harmony with our  general conception 
of the proteid molecule4    ,,albumin   
,,molecule4        7,hemi-groups4       
,anti-groups47                          
,protoalbumose    ,heteroalbumose       
,antialbumid          7amphoalbumose7   
7amphoalbumose7                         
,deuteroalbumose  ,deuteroalbumose      
,deuteroalbumose                        
7amphoalbumose7  7amphoalbumose7        

7antialbumose7                          
,amphopeptone    ,amphopeptone          
,antipeptone    ,on the basis of these  
facts1 and others not yet mentioned1 we 
may  accept provisionally1 at least1 the
 above schematic view1 suggested  in    
part by ,neumeister1#ic of the general  
line of proteolysis as  it occurs in    
pepsin-digestion2 a view which clearly  
expresses the  significant relationship 
of the hemi- and anti-groups in the     
proteid  molecule4    #ic ,zur ,kentniss
 der ,albumosen1 ,zeitschr4 f4 ,biol41  
,band #bc1 p4 #cia4    ,the dark and    
light lines in this scheme are intended 
to represent the  relative share which  
the hemi- and anti-groups take in the   
formation  of the individual bodies4    
,thus1 we see that protoproteoses have  
their  origin mainly in the hemi-groups 
of the molecule1 although1 as the  fine 
line indicates1 anti-groups are somewhat
 concerned in their  construction4      
,heteroproteoses1 on the other hand1    
come mainly from  the anti-groups1 but  

still some hemi-groups have a part in   
their  structure4 ,as previously stated1
 these two primary proteoses by further 
hydrolytic action may be transformed    
into secondary products2 viz41  into    
deuteroproteoses1 but1 as the above     
scheme indicates1 the two  deutero      
bodies will be more or less unlike in   
their inner nature4 ,in  one sense1 they
 are both amphodeuteroproteoses1 but    
they necessarily  differ in the         
proportion of hemi- and anti-groups they
 contain4 ,by  the still further action 
of pepsin-acid1 the deutero bodies may  
be  changed1 in part at least1 into     
peptone1 i4 e41 into amphopeptone1      
although1 as ,neumeister has pointed    
out1 protoproteose tends to yield  an   
amphopeptone in which the hemi-groups   
predominate1 while the peptone  coming  
from heteroproteose contains an excess  
of anti-groups4 ,moreover1  in the      
gastric digestion of any simple proteid 
a certain number of  anti-groups are    
split off in the form of antialbumid1 a 

body which is  only slowly digestible in
 pepsin-acid4 ,by the very powerful     
proteolytic  action of a strong gastric 
juice1 however1 antialbumid may be      
somewhat  digested1 and is then         
transformed into antideuteroalbumose1   
which in  turn may be eventually changed
 into antipeptone4    ,from these       
statements it is evident that a given   
proteid exposed to  pepsin-proteolysis  
may give rise to a large number of      
products2 in  fact1 to a far larger     
number than is implied by the names in  
the above  scheme4 ,thus1 at first      
glance you would be inclined to say     
there can  be only three                
deuteroalbumoses1 for example2 one1 a   
pure antibody1 the  other two1          
amphoalbumoses1 differing from each     
other simply in their  content of hemi- 
and anti-groups4 ,it must be remembered1
 however1 that  the inner constitution  
of these bodies1 as implied by the      
relative  proportion of the above       
groups1 may vary to almost any extent4  

,thus1  every variation in the number of
 anti-groups split off from the         
original albumin molecule to form       
antialbumid means just so much of  a    
change in the relative proportion of    
hemi- and anti-groups entering  into the
 structure of both primary and secondary
 albumoses4 ,hence1 as  you can see1    
digestive proteolysis1 even in gastric  
digestion1 is a  somewhat complex       
process4 ,we have to deal not only with 
a number of  bodies superficially       
unlike1 as the primary and secondary    
proteoses  and peptones1 but these      
bodies may show marked variations in    
structure  dependent upon the exact     
conditions attending their formation4   
,evidently1 the complexities attending  
digestive proteolysis are  connected    
primarily with the complex nature of the
 proteids themselves1  while            
proteolysis1 as a process1 is made      
possible through the natural  tendency  
of the proteids to undergo hydration and
 cleavage4          ,,lecture ,,ii4     

,,proteolysis ,,by                      
,,pepsin-,,hydrochloric ,,acid1 ,,with  
,a ,,consideration ,,of ,,the  ,,general
 ,,nature ,,of ,,proteoses ,,and        
,,peptones4      ,,proteolysis ,,by     
,,pepsin-,,acid4    ,gastric digestion  
is essentially an acid digestion4 ,as a 
proteolytic  agent1 pepsin can act only 
in the presence of acid1 and we have    
every  reason for believing that the    
enzyme and the acid form a compound1    
which in turn combines with the proteid 
undergoing digestion2 or1 what  amounts 
to much the same thing1 that the acid   
perhaps forms first a  compound with the
 proteid1 to which the pepsin can then  
unite to form  a still more complex     
compound capable of undergoing hydration
 and  cleavage4 ,pepsin-proteolysis1    
therefore1 is strictly the proteolysis  
produced by pepsin-acid4 ,in view of    
this fact1 we may well give a  moment's 
thought to the nature and origin of this
 acid4    ,without attempting any       
statement of the gradual development of 

our  knowledge regarding the acid of the
 gastric juice1 we may accept the  now  
well-established fact that the acid is  
hydrochloric acid1 and  that it has its 
origin in the parietal1 or so-called    
border-cells of  the gastric glands4    
,that the acid is derived from the      
decomposition  of chlorides is          
practically self-evident1 but ,cahn#id  
has added  experimental proof which     
removes all shadow of doubt1 through his
 study  of the gastric secretion in     
animals deprived for many days of salt2 
the  gastric juice in such cases being  
perfectly neutral in reaction1 but      
normal as regards its content of pepsin4
    #id ,die ,magenverdauung im         
chlorhunger4 ,zeitschr4 f4 physiol4     
,chem41  ,band #aj1 p4 #ebb4    ,the way
 in which the specific gland-cells      
manufacture free hydrochloric  acid out 
of material contained in an alkaline    
medium is somewhat  doubtful4 ,there    
are1 however1 at the present day two    
theories worthy of  special notice4 ,the

 first is based upon observations made  
by ,maly#ie  many years ago1 which tend 
to show that certain mineral salts      
present  in the blood are capable of    
reacting upon each other with formation 
of hydrochloric acid4 ,thus1 while the  
blood is an alkaline fluid1  it really  
owes its alkalinity to the presence of  
two acid salts1  viz41 sodium           
bicarbonate 7,h,na,c,o#c7 and disodium  
hydrogen phosphate  7,h,na#b,,po#d74    
,this latter compound1 acted upon by the
 carbonic  acid of the blood1 is        
transformed into a dihydrogen sodium    
phosphate  with simultaneous formation  
of acid sodium carbonate1 as shown in   
the  following equation3                
,na#b;,,hpo#d  ,,co#b  ,h#b,o           
,na,h#b,,po#d  ,h,na,c,o#c4    #ie      
,untersuchungen ber die ,quelle der     
,magensaftsure4 ,annalen d4  ,chem4 u4  
,pharm41 ,band #agc1 p4 #bbg4    ,this  
acid sodium phosphate dissolved in a    
fluid containing sodium  chloride1 gives
 rise to free hydrochloric acid by a    

very simple  reaction3                  
,na,h#b,,po#d  ,na,cl  ,na#b;,,hpo#d    
,h,cl4    ,it is also to be noted that  
the disodium hydrogen phosphate1 may1   
likewise1 give rise to hydrochloric acid
 through its action on calcium          
chloride1 as indicated by the following 
equation3        #b,na#b;,,hpo#d        
#c;,ca,cl#b  ,ca#c7,,po#d7b  #d,na,cl   
#b;,h,cl4    ,it is thus evident that   
hydrochloric acid may originate in the  
inter-reaction of these several salts   
which are known to be present  in the   
blood2 but obviously1 the above         
reactions cannot take place  in the     
blood itself1 and we must look to the   
selective power of the  epithelial cells
 of the gastric glands1 as suggested by 
,gamgee1#if for  the withdrawal of the  
needed salts from the blood4 ,once      
present in the  acid-forming cells1 and 
perhaps aided by the inherent qualities 
of the  protoplasm1 the necessary       
chemical reactions may be assumed to    
take  place1 after which the newly      

formed acid may pass from the           
gland-cells  into the secretion of the  
gland4    #if ,physiological ,chemistry 
of the ,animal ,body1 vol4 #b1 p4 #aac4 
,a later theory regarding the formation 
of the acid of the gastric juice        
emanates from ,liebermann4#ig ,this     
investigator claims the existence in    
the mucous membrane of the stomach of an
 acid-reacting1 nuclein-like  body1     
which is apparently a combination of the
 phosphorized substance  lecithin with a
 proteid4 ,to this compound body        
,liebermann gives  the name of          
lecithalbumin4 ,it is apparently located
 in the nuclei  of the gastric cells1 is
 strongly acid in reaction1 and1        
according  to ,liebermann1 is an        
important agent in the production of the
 free  hydrochloric acid of the gastric 
juice1 although its action is somewhat  
indirect4 ,according to this theory1 the
 free acid is formed in the  mucous     
membrane of the stomach from sodium     
chloride1 through the  dissociating     

action of the carbonic acid coming from 
normal oxidation4  ,the thus-formed acid
 then diffuses in both directions1 viz41
 through  the lumen of the gland into   
the stomach-cavity1 and in part in the  
opposite direction into the veins and   
lymphatics4 ,it is the assumed  function
 of the lecithalbumin to react with the 
alkaline sodium  carbonate1 produced    
simultaneously with the hydrochloric    
acid4 ,this  naturally gives rise to the
 liberation of carbonic acid and to the 
formation of a non-diffusible           
sodium-lecithalbumin compound1 which  is
 retained for the time being in the body
 of the cell4 ,when the  circulation of 
the blood1 accelerated by the digestive 
process1 returns  to its ordinary pace1 
this latter compound is slowly          
decomposed by  the carbonic acid with   
formation of the readily diffusible     
sodium  carbonate1 which passes into the
 blood-current4 ,the rate of this       
latter reaction is impeded1 or1 perhaps 
regulated1 by the swelling up  of the   

lecithalbumin-containing cells1 thus    
rendering the imbibition  of the        
carbonic acid a slow process4 ,the rate 
of production of the  hydrochloric acid 
by this hypothetical process depends    
primarily upon  the blood supply1 and   
the oxidative changes by which carbonic 
acid is  formed4    #ig ,studien ber    
chemische ,processe in der              
,magenschleimhaut4 ,pflger's  ,archiv f4
 ,physiol41 ,band #ej1 p4 #be4 ,neue    
,untersuchungen ber das  ,lecithalbumin4
 ,liebermann1 ,ibid41 ,band #ed1 p4     
#egc4    ,there is much that might be   
said for and against this theory1#ih but
  we cannot stop to discuss it here4    
,like the previous theory1 it implies   
the production of hydrochloric acid from
 a chloride or chlorides1  through      
chemical processes taking place in the  
stomach-mucosa1 and  presumably in the  
large border-cells of the peptic glands4
 ,this  hydrochloric acid1 as you know1 
in the act of secretion1 reacts upon    
the pepsinogen with which it may come in

 contact1 transforming it into  pepsin4 
,it also has the power of combining with
 all forms of proteid  matter1 not      
excepting the products of proteolytic   
action1 to form acid  compounds in which
 the so-combined acid1 although equal   
quantitatively  to the original amount  
of free acid1 is less active in many    
ways4  ,thus1 it does not possess in the
 same degree a destructive action on    
the amylolytic ferments2#ii it does not 
play the same part in aiding  the       
proteolytic action of pepsin1 and its   
antiseptic power is far from  equal to  
that of a like amount of free acid4#ajj 
#ih ,see discussion by ,plsz and        
,liebermann in ,jahresbericht fr        
,thierchemie1 ,band #bb1 p4 #bfj4    #ii
 ,chittenden and ,h4 ,e4 ,smith3        
,studies in ,physiol4 ,chem41 ,yale     
,univer41 vol4 i41 p4 #ah4    #ajj      
,compare ,f4 ,o4 ,cohn3 ,ueber die      
,einwirkung des knstlichen  ,magensaftes
 auf ,essigsure-und ,milchsureghrung4   
,zeitschr4 f4 physiol4  ,chem41 ,band   

#ad1 p4 #gd4    ,with relatively large  
amounts of proteid1 we may have half or 
even  quarter saturated proteid         
molecules1 in which the weakness of the 
combined acid is far more pronounced    
than in the case of the fully  saturated
 molecule4 ,such a condition of things  
must obviously exist  in the early      
stages of gastric digestion4 ,with an   
excess of proteid  matter in the        
stomach1 some time must elapse before   
the secretion  of hydrochloric acid will
 be sufficient to furnish acid for all  
of  the proteid matter present1 yet     
pepsin-proteolysis does not wait the    
appearance of free acid4 ,indeed1 the   
proteid matter may not have  combined   
with more than half its complement of   
hydrochloric acid before  digestive     
proteolysis is well under way4 ,i have  
made many analyses of  the              
stomach-contents after test meals1 and  
under other conditions1  where no free  
acid could be detected by the tropaeolin
 test1 or better1  by ,gnzburg's reagent

 7phloroglucin-vanillin71 although      
phenolphthalein  as well as litmus      
showed strong acid reaction1 and yet not
 only could  acid-albumin be detected in
 the filtered fluid1 but likewise       
proteoses  and peptones4 ,in other      
words1 pepsin-proteolysis can proceed in
 the  absence of free hydrochloric acid1
 although not at the same pace4  ,hence1
 proteoses and even peptones may make   
their appearance in the                 
stomach-contents at a very early period 
of digestion1 i4 e41 the  final products
 of proteolysis may be found in a       
mixture containing even  a large        
proportion of wholly unaltered proteid1 
and obviously at an  early stage in the 
process4 ,expressed in other language1 a
 portion of  the first formed           
acid-albumin or syntonin may be carried 
forward by the  digestive process to the
 secondary proteose and peptone stage1  
before  the larger portion of the       
ingested proteid food has even combined 
with  sufficient acid to insure the     

complete formation of acid-albumin4     
,this introduces another factor1 to be  
referred to later on1 viz41  the        
relative combining power of different   
forms of proteid matter1  especially the
 proteoses and peptones1 as contrasted  
with native  proteids4    ,in proof of  
the statement that pepsin-proteolysis   
can proceed in the  absence of free     
hydrochloric acid1 provided combined    
acid be present1  allow me to cite one  
or two experiments bearing on this      
point4 ,a  perfectly neutral solution of
 egg-albumen1 containing #j4hafi gramme 
of ash-free albumin per #aj c4c4 of     
fluid1 was employed as the proteid      
material4 ,in order to completely       
saturate the proteid contained in  #bj  
c4c4 of this neutral albumen solution1  
#ej c4c4 of #j4b per cent4 ,h,cl  were  
required4 ,two mixtures were then       
prepared as follows3    ,a4 ,twenty c4c4
 of the neutral albumen solution  #ej   
c4c4 #j4b per  cent4 ,h,cl  #cj c4c4 of 
a weak aqueous solution of pepsin1      

perfectly  neutral to litmus4 ,this     
mixture gave only the faintest tinge of 
a  reaction for free acid when tested by
 ,gnzburg's reagent4    ,b4 ,twenty c4c4
 of the neutral albumen solution  #be   
c4c4 #j4b per  cent4 ,h,cl  #cj c4c4 of 
the neutral pepsin solution4 ,in this   
mixture1  the proteid matter was        
obviously only half saturated with acid4
    ,the two solutions were placed in a 
bath at #dj ,c41 where they were        
allowed to remain for forty-four hours1 
a little thymol being added to  guard   
against any possible putrefactive       
changes4 ,at the end of this  time the  
amount of undigested albumin was        
accurately determined4 ,the  #bj c4c4 of
 original albumen solution contained    
#a4fcch grammes of dry  coagulable      
albumin4 ,at the end of the forty-four  
hours1 ,a contained  only #j4edcj gramme
 of unaltered albumin1 or acid-albumin1 
while ,b  contained #a4bbbe grammes4    
,that is to say1 in the mixture ,a1     
where the  acid existed wholly in the   

form of combined acid1 but with the     
albumin  completely saturated1 #a4jijh  
grammes of the proteid were converted   
into soluble albumoses and peptones4 ,in
 ,b1 on the other hand1 where  the      
albumin was only half saturated with    
acid1 #j4daac gramme of the  proteid was
 converted into soluble products4 ,this 
difference in action  is made more      
striking by the statement that where the
 proteid was only  half saturated with  
acid1 #be4a per cent4 of the albumin was
 digested2  while with a complete       
saturation of the proteid1 #ff4g per    
cent4 of the  albumin was digested4     
,to give emphasis to this matter1 a     
second experiment may be quoted as      
follows3 ,the proteid used was the same 
neutral solution of egg-albumen         
containing #j4hafi gramme of albumin per
 #aj c4c4 ,two mixtures were  prepared  
as follows3    ,a4 ,ten c4c4 of the     
neutral albumen solution  #ba4g c4c4    
#j4b per cent4  ,h,cl1 the amount needed
 to completely saturate the proteid1    

#dj c4c4 of  a weak solution of pepsin1 
perfectly neutral4    ,b4 ,ten c4c4 of  
the albumen solution  #aj4i c4c4 #j4b   
per cent4 ,h,cl   #dj c4c4 of the pepsin
 solution1 making a mixture half        
saturated with  acid4    ,these two     
solutions were warmed at #dj ,c4 for    
seventeen hours4 ,the  extent of        
digestive action was then determined1   
when it was found that  in ,a only      
#j4afch gramme of the proteid was       
undigested1 while in ,b1  #j4fjhh gramme
 remained unaltered4 ,in other words1   
where the proteid was  completely       
saturated with acid1 but with an utter  
lack of free acid1  #gi4i per cent4 of  
the albumin was converted into albumoses
 and peptone1  while in the mixture half
 saturated with acid only #be4d per     
cent4 was  digested4    ,these two      
experiments thus give striking proof    
that free acid is not  absolutely       
essential for pepsin-proteolysis4       
,digestion is1 to be sure1  more rapid  
and complete when free hydrochloric acid

 is present1 but  proteolysis is still  
possible1 and even vigorous1 when there 
is a  marked deficiency of free acid4   
,further1 as we have seen1 proteolysis  
may proceed to a certain extent even    
though the amount of acid  available is 
not sufficient to combine with more than
 half the proteid  matter present4      
,these facts at once raise the question 
whether the products of  proteolysis may
 not have a stronger affinity for acid  
than the native  proteids2 an affinity  
so strong that they may be able to      
withdraw acid  from the acid-albumin    
first formed4 ,one of our conceptions   
regarding  pepsin-proteolysis is that   
acid is necessary for every step in the 
proteolytic process4 ,a primary         
albumose1 for example1 cannot be further
  changed by pepsin1 unless there is    
acid present for it to combine  with4   
,this being true1 it is clear1 in view  
of the fact that even  peptones may     
appear in a digestive mixture containing
 an amount of  acid insufficient to     

combine even with the albumin present1  
that the  products of proteolysis must  
withdraw acid from the acid-albumin     
first  formed4 ,in regard to the first  
point1 my own experiments certainly     
tend to show that the products of       
gastric digestion do combine with       
larger amounts of hydrochloric acid than
 undigested proteids2 and  further1 that
 of the several products of proteolysis1
 the secondary  proteoses combine with a
 larger percentage of acid than the     
primary  proteoses1 while true peptones 
combine with still larger amounts4 ,in  
other words1 the simpler and more       
soluble the proteid1 the larger the     
amount of acid it is capable of         
combining with2 a statement which       
accords with results obtained by other  
workers#aja in this direction4          
,further1 another factor of considerable
 importance in connection  with the     
natural digestive process is that a     
dissolved proteid1 such  as             
protoalbumose for example1 will combine 

more readily with free  acid than an    
insoluble proteid2 from which           
,gillespie#ajb is led to  infer that in 
pepsin-proteolysis where there is no    
free acid present1  only acid-albumin1  
proteoses may be formed to a limited    
extent at  the expense of some of the   
acid of the acid-albumin1 a portion of  
the latter being perhaps reconverted    
into albumin4 ,the ability of  the      
proteoses1 however1 to withdraw acid    
from its combination with a  native     
proteid is perhaps best indicated by    
,kossler's#ajc experiments1  which show 
that a solution of acid-albumin         
containing only enough  hydrochloric    
acid to hold the albumin dissolved1 on  
being warmed at  #dj ,c4 for some hours 
with addition of a neutral solution of  
pepsin1  may undergo partial conversion 
into albumose or peptone4    #aja ,see  
especially ,gillespie3 ,gastric         
,digestion of ,proteids4 ,journal  of   
,anat4 and ,physiol41 vol4 #bg1 p4 #bjg4
    #ajb ,loc4 cit4    #ajc ,beitrge zur

 ,methodik der quantitativen            
,salzsurebestimmung im  ,mageninhalt4   
,zeitschr4 f4 physiol4 ,chem41 ,band    
#ag1 p4 #ic4    ,in spite of these      
facts1 there is some evidence that while
 proteoses  and peptones have the power 
of combining with more acid than a like 
weight of native proteid1 the latter1   
leaving out all action of the  pepsin1  
has a stronger affinity for the acid2 in
 fact1 the firmness  or strength of the 
union appears to diminish as the        
products become  simpler4#ajd ,hence1 a 
peptone separated from a digestive      
mixture1 will  part with its combined   
acid somewhat more readily than         
acid-albumin  for example1 although on  
this point there is not complete        
unanimity  of opinion4#aje ,in digestive
 proteolysis1 however1 where the pepsin 
is accompanied by a minimal amount of   
hydrochloric acid1 insufficient  perhaps
 to even half saturate the proteid      
present1 the formation of  proteoses and
 peptones must be accompanied by a      

withdrawal of acid from  its combination
 with the native proteid4    #ajd       
,compare ,blum3 ,ueber die              
,salzsurebindung bei knstlicher         
,verdauung4 ,zeitschr4 f4 klin4         
,medicin1 ,band #ba1 p4 #eeh4    #aje   
,see ,sansoni3 ,beitrag zur kenntniss   
des ,verhaltens der ,salzsure  zu den   
,eiweisskrpern in ,bezug auf die        
,chemische ,untersuchung des            
,magensaftes4 ,berliner klin4           
,wochenschrift1 #ahic1 ,nos4 #db and    
#dc4    ,in illustration of some of     
these points1 and especially of the     
statement that the products of gastric  
digestion have the power of  combining  
with more hydrochloric acid than the    
original proteid1 allow  me to cite the 
following experiment3 #aj c4c4 of a     
neutral solution of  egg-albumen        
containing about #j4hb gramme of pure   
dry albumin1 free  from mineral salts1  
required #bc4h c4c4 of #j4b per cent4   
hydrochloric  acid to completely        
saturate the proteid matter4 ,a mixture 

was then  prepared as follows3 #aj c4c4 
of the albumen  #bd c4c4 #j4b per cent4 
,h,cl   #cj c4c4 of a neutral pepsin    
solution1 the mixture showing a faint   
trace of free acid when tested by       
,gnzburg's reagent4 ,this solution  was 
placed in a thermostat at #ch ,c41 and  
from time to time a drop of  the fluid  
was removed and tested for free acid4   
,if no reaction could  be obtained1 #j4b
 per cent4 hydrochloric acid was added  
to the mixture1  until ,gnzburg's       
reagent showed free acid to be again    
present4 ,the  following table shows the
 rate of disappearance of free acid1 and
 the  amounts of #j4b per cent4 ,h,cl   
required to make good the deficiency4   
,the mixture was placed at #ch ,c4 on   
,february #fth1 at #aa4cj ,a4,m41 and1  
as stated1 contained a trace of free    
acid1 #bd c4c4 #j4b per cent4 ,h,cl     
having been added to accomplish this    
result4                 ,time4          
,acid added to show trace of free acid4 
,february  #f1 #aa4cj ,a4,m4            

#b4ae ,p4,m4    #d4e c4c41 #j4b per     
cent4 ,h,cl4                   #e4jj    
,p4,m4    #a4j                          
,february  #g1  #h4de ,a4,m4    #c4j    
#b4jj ,p4,m4    #a4j                    
#e4jj ,p4,m4    #a4e                    
,february  #h1  #h4cj ,a4,m4    #a4j    
#b4cj ,p4,m4    #j4j                    
,february  #i1  #h4cj ,a4,m4    #c4j    
,february #aj1  #i4cj ,a4,m4    #b4j    
----                                    
#ag4j    ,from these results several    
interesting conclusions may be drawn1   
in conformity with the statements       
already made4 ,thus1 as soon as         
proteolysis commences1 the products     
formed begin to show their greater      
affinity for acid by withdrawing acid   
from its combination with the  native   
proteid1 a supposition which is         
necessary to account for even  the      
starting of the proteolytic process4    
,further1 it is evident that  proteoses 
and peptones combine with a far larger  
equivalent of acid  than the native     

albumin is capable of2 #ag c4c4 of #j4b 
per cent4 ,h,cl  being required in the  
above experiment to satisfy the greater 
combining  power of the newly formed    
products4 ,this doubtless depends upon  
the  cleavage of the large proteid      
molecule into a number of smaller or    
simpler molecules1 each of the latter1  
perhaps1 combining with a  like number  
of ,h,cl molecules4 ,this view of the   
relationship of the  individual         
proteoses and peptones is one more or   
less generally held1  and is supported  
by many facts4#ajf ,however this may be1
 it is evident  that the products of    
pepsin-proteolysis combine with a larger
 amount of  hydrochloric acid than the  
mother-proteid1 and that the            
transformation  of the latter1 at least 
under the conditions of this experiment1
  is a slow and gradual process4 ,in the
 living stomach1 on the other  hand1    
where the secretion of acid is          
progressing with ever-increasing        
rapidity1 it is easy to see that the    

process of proteolysis would  naturally 
be much more rapid4    #ajf ,see        
,gillespie3 ,on the ,gastric ,digestion 
of ,proteids4 ,journal of  ,anatomy and 
,physiology1 vol4 #bg1 p4 #bji4    ,just
 here we may recall the theory advanced 
by ,richet#ajg quite a  number of years 
ago that the acid of the gastric juice  
is a conjugate  acid1 composed of leucin
 and hydrochloric acid1 a theory which  
has  found little acceptance4           
,klemperer1#ajh however1 assumed that   
solutions of leucin hydrochloride with  
pepsin would not digest albumin1  but   
,salkowski and ,kumagawa#aji have shown 
by experiments that leucin  and other   
amido-acids1 as glycocoll1 may be       
dissolved in hydrochloric  acid in such 
proportion that the solution is         
practically composed of  leucin         
hydrochloride1 without interfering with 
the digestive action  of pepsin-acid on 
blood-fibrin2 the solution being        
physiologically  active1 although       
,gnzburg's reagent shows an entirely    

negative result  for free acid4 ,if the 
matter is studied quantitatively1       
however1 it  will be found that the     
amido-acids combining in this manner    
with the  hydrochloric acid of the      
gastric juice do give rise to some      
disturbance  of proteolytic action2#aaj 
i4 e41 digestion may be less rapid1     
especially on egg-albumin1 a conclusion 
which ,salkowski#aaa has lately         
confirmed4 ,still1 under such           
circumstances1 digestion does go on and 
at a fairly rapid rate2 hence1 if there 
is a combination between the  acid and  
these organic bodies1 as is indicated by
 ,gnzburg's reagent1  the acid is still 
active physiologically1 even more so    
than in the  compound formed by the     
interaction of proteid and acid4 ,in    
other  words1 many of these neutral     
organic bodies that may originate in    
the stomach through fermentative        
processes1 or otherwise1 and which  tend
 to combine with the acid of the gastric
 juice1 do not1 as a  rule1 impede      

pepsin-proteolysis to the same extent   
that an excess of  proteid matter may4  
,in fact1 in artificial digestions long 
continued1  pepsin-acid solutions       
containing considerable leucin1 for     
example1 may  accomplish as much in the 
way of digesting proteid matter as the  
same  amount of pepsin-acid without     
leucin2 but the inhibitory action of the
  amido-acid is there1 and may be shown 
during the first few hours of the       
experiment1 when less proteoses and     
peptones are formed than in the  control
 experiment without leucin4    #ajg ,le 
suc gastrique chez l'homme et les       
animaux1 ses proprits  chimiques et     
biologiques4 ,paris1 #ahgh4    #ajh     
,zeitschr4 f4 klin4 ,medicin1 ,band #ad1
 ,heft #a and #b4    #aji ,ueber den    
,begriff der freien und gebundenen      
,salzsure im  ,magensaft4 ,virchow's    
,archiv1 ,band #abb1 p4 #bce4    #aaj   
,rosenheim3 ,centralbl4 f4 klin4        
,medicin1 #ahia1 ,no4 #ci4 ,f4 ,a4      
,hofman1 ibid41 ,no4 #db4    #aaa ,ueber

 die ,bindung der ,salzsure durch       
,amidosuren4 ,virchow's  ,archiv1 ,band 
#abg1 p4 #eja4    ,it is foreign to our 
subject to discuss here methods for the 
detection of so-called free and combined
 hydrochloric acid in the               
stomach-contents1 or the special        
significance of such findings in  health
 and disease4 ,i cannot refrain1        
however1 in connection with what  has   
been said above concerning the          
proteolytic action of pepsin in the     
presence of combined acid1 from saying a
 word concerning the usual  deductions  
drawn from the absence of free acid in  
the stomach-contents4  ,as              
,langermann#aab has recently expressed  
it1 we have methods for  discriminating 
between free and combined acid2 we can1 
moreover1  determine the amount of free 
acid1 but is it not equally important to
  be able to say something definite     
concerning the amount of combined  acid 
in the stomach-contents8 ,even in the   
absence of free hydrochloric  acid there

 may be a sufficient amount of ,h,cl    
secreted to answer all the  purposes of 
digestion1 and yet at no time may there 
be any free acid  present to be detected
 by the various color-tests ordinarily  
made use  of4 ,i am aware that in       
ordinary examinations of the            
stomach-contents  after a test meal the 
results are essentially comparative1 and
 possibly  all that are necessary for   
clinical purposes4 ,what ,i wish to     
emphasize1  however1 is that in order to
 pass conclusively upon tsufficiency or 
insufficiency of the gastric secretion1 
it is wise to know not only the  total  
acidity of the stomach contents and     
whether there is free acid  or not1 but 
to know more about the amount of        
combined acid present4  ,thus1 there is 
a natural tendency to divide the fluids 
withdrawn from  the stomach into three  
groups1 viz41 those which contain free  
acid in  moderate amount1 those which   
contain free acid in excess1 and those  
in which free acid is entirely absent2  

but in the latter group1 there  may be  
very marked differences in the amount of
 acid combined with  the proteid and    
other material present4 ,it appears to  
me that one of  the questions to be     
answered is whether there is sufficient 
combined  ,h,cl present to meet all the 
requirements for digestion4 ,if there   
is1 that gastric juice may be just as   
normal as the one containing  free      
mineral acid1 and yet1 according to our 
present tendencies1  we should be       
inclined to call the juice containing no
 free acid  abnormal1 although there may
 be sufficient combined acid present to 
meet all the requirements for digestion4
 ,hence1 in examination of the          
stomach-contents1 it is well to consider
 the use of those methods  which tend to
 throw light upon the amount of combined
 acid present1  for in my opinion it is 
only by a determination of the total    
amount of  combined acid that we can    
arrive at a true estimate of the extent 
of  the ,h,cl deficiency4 ,obviously1 in

 simple clinical examinations of the    
stomach-contents after a test meal1     
where proteid matter is not present  in 
large amount1 free acid may reasonably  
be expected to appear after  a definite 
period2 but in any event1 it is well to 
remember that free  hydrochloric acid is
 not absolutely indispensable for fairly
 vigorous  proteolytic action1 and that 
in the presence of moderate amounts of  
proteid matter a large quantity of acid 
is required to even saturate  the       
albuminous material4    #aab ,virchow's 
,archiv1 ,band #abh1 p4 #djh4           
,consider for a moment the amount of    
acid a given weight of proteid  will    
combine with1 before a reaction for free
 acid can be obtained4  ,thus1 ,blum#aac
 has stated that #ajj grammes of dry    
fibrin will require  #i4a litres of #j4a
 per cent4 hydrochloric acid to         
completely saturate  it4 ,hence1 with a 
daily consumption of #ajj grammes of    
proteid1 there  would be needed for     
gastric digestion #d4e litres of #j4b   

per cent4  hydrochloric acid daily1 and 
even this would not suffice to give any 
free acid1 assuming that none of the    
acid is used over again4 ,the  results  
,i have already given for egg-albumin   
tend to show that #a  gramme of pure    
albumin1 free from inorganic salts1 when
 dissolved in  a moderate amount of     
water will combine with about #cj c4c4  
of #j4b per  cent4 hydrochloric acid4   
,consequently1 on this basis1 #ajj      
grammes of  dry egg-albumin will combine
 with #c litres of #j4b per cent4 ,h,cl1
 and  not until this amount of acid has 
been added to such a mixture will       
reaction for free acid be obtained with 
,gnzburg's reagent4 ,hence  we can      
easily see1 in view of these figures1   
that the production of  hydrochloric    
acid by the gastric glands may at times 
be very extensive1  without the         
stomach-contents necessarily containing 
free acid4    #aac ,zeitschr4 f4 klin4  
,medicin1 ,band #ba1 p4 #eeh4    ,while 
,i am by no means willing to agree with 

,bunge#aad that the  chief importance of
 the acid of the gastric juice is its   
action as  an antiseptic1 ,i am         
decidedly of the opinion that the lack  
of free  hydrochloric acid in the       
stomach-contents is more liable to cause
  disturbance through the consequent    
unchecked development of bacteria  than 
through lack of proteolytic action1     
assuming1 of course1 the  presence of a 
reasonable amount of combined ,h,cl4    
,the hydrochloric  acid of the gastric  
juice unquestionably plays a very       
important part  in checking the growth  
and development of many pathogenic      
bacteria1  as well as of less poisonous 
organisms1 which are taken into the     
mouth with the food4 ,on all1 or at     
least on nearly all of these  organisms1
 hydrochloric acid exerts a far greater 
destructive action  when free than when 
combined with proteid matter4 ,as       
,cohn#aae has  plainly shown1 both      
hydrochloric acid and                   
pepsin-hydrochloric acid  quickly hinder

 acetic- and lactic-acid fermentation1  
but when the  acid is combined with     
peptone1 for example1 it is no longer   
able to  exercise the same inhibitory   
influence4 ,it is also important to note
  that the lactic-acid ferment is not so
 sensitive to hydrochloric  acid as the 
acetic-acid ferment4 ,consequently1 when
 lactic-acid  fermentation is once      
developed a comparatively large amount  
of ,h,cl is  required to arrest it4     
,hence1 as we all know1 a diminished    
secretion  of hydrochloric acid renders 
possible acid fermentation of the       
stomach-contents1 as well as            
putrefactive changes which would not    
occur  in the presence of free ,h,cl1   
and which are very incompletely checked 
when the acid is over-saturated with    
proteid matter4    #aad ,physiologische 
und ,pathologische ,chemie1 p4 #aec4    
#aae ,ueber die ,einwirkung des         
knstlichen ,magensaftes auf             
,essigsure-und ,milchsure ghrung4       
,zeitschr4 f4 physiol4 ,chemie1 ,band   

#ad1 p4 #ge4 ,see also ,hirschfeld3     
,pflger's ,archiv f4 ,physiol41 ,band   
#dg1  p4 #eaj4    ,pepsin-proteolysis1  
however1 may proceed1 to some extent1 at
 least1  even though a small amount only
 of combined acid is present4 ,the      
combined acid1 however1 must be         
hydrochloric acid1 if proteolysis is to 
be at all marked4 ,to be sure1 pepsin   
will act in the presence of lactic      
acid1 as well as in the presence of     
other organic acids1 and inorganic      
acids1 likewise1 but such action at the 
best is considerably weaker  than the   
action of pepsin-hydrochloric acid4#aaf 
#aaf ,chittenden and ,allen3 ,influence 
of ,various ,inorganic and  ,alkaloidal 
,salts on the ,proteolytic ,action of   
,pepsin-,hydrochloric ,acid4  ,studies  
in ,physiol4 ,chem41 ,yale ,university1 
vol4 #a1 pp4 #ia1 #id4    ,the ferment  
pepsin can exert its maximum action only
 in the  presence of free hydrochloric  
acid4 ,there must be sufficient ,h,cl to
  combine with all of the proteid matter

 present1 and the products of           
proteolysis as fast as they are formed1 
if digestion is to be rapid  and        
attended with the formation of a large  
proportion of the final  products of    
proteolysis4 ,it is under such          
conditions that our study  of           
pepsin-proteolysis is usually conducted4
 ,further1 it is to be  remembered that 
our knowledge of the products of such   
proteolytic  action depends almost      
entirely upon data accumulated by       
artificial  digestive experiments4 ,in  
no other way can we be absolutely       
certain  of the conditions under which  
the proteolysis is accomplished1 for it 
is a significant fact1 perhaps plainly  
evident from what has already  been said
 in the preceding lecture1 that the     
character of the products  resulting    
from ordinary proteolysis is dependent  
in great part upon  the attendant       
circumstances4 ,thus1 with a relatively 
small amount of  acid1 and perhaps also 
of pepsin1 the initial products of      

proteolysis  are especially prominent1  
while with an abundance of both pepsin  
and  free acid1 coupled with            
long-continued action1 the final        
products  predominate4 ,between these   
two extremes there are many possible    
variations1 as was1 ,i think1 made clear
 in the previous lecture4 ,at  the same 
time1 it is to be noticed that these    
differences are mainly  differences in  
the proportion of the several products1 
rather than in  the nature of the       
resultant bodies4    ,in a general way1 
the products of pepsin-proteolysis may  
be divided  into three main groups1     
viz41 bodies precipitated by            
neutralization and  represented mainly  
by the so-called syntonin or            
acid-albumin2 bodies  precipitated by   
saturation of the neutralized fluid with
 ammonium  sulphate and represented by  
proteoses2 bodies non-precipitable by   
saturation with ammonium sulphate and   
represented by amphopeptones4 ,the      
relationship of the individual products 

may be clearly seen from the  following 
scheme1 arranged after the plan         
suggested by ,neumeister4               
,,native ,,proteid4                     
,syntonin4                              
,protoproteose4   ,heteroproteose4      
7dysproteose74                          
,deuteroproteose4  ,deuteroproteose4    
,peptone4          ,peptone4    ,it is1 
of course1 to be understood that this is
 not intended to  represent anything    
more than the order of formation of the 
several  bodies1 no attention being paid
 here to the hemi- or anti-character  of
 the several products1 or classes of    
products4 ,thus1 proto and              
heteroproteose are primary bodies formed
 directly from the initial  product     
syntonin by the further action of the   
ferment4 ,in the same  sense1           
deuteroproteose is a secondary proteose1
 being formed by the  further hydration 
of the primary body4 ,lastly1 peptones1 
the final  products of                  
pepsin-proteolysis1 are the result of   

the hydration and  possible cleavage of 
deuteroproteoses4 ,further1 in almost   
every gastric  digestion there is also  
formed a small amount of antialbumid1 a 
product  insoluble in dilute            
hydrochloric acid and which consequently
 appears  as an insoluble residue4 ,this
 body is very resistant to the action of
  pepsin-acid when once formed1 but may 
be slowly converted1 in part at  least1 
into a soluble antialbumose and thence  
into antipeptone4    ,all of these      
bodies can be readily identified in any 
digestive  mixture containing them by a 
few simple reactions4 ,thus1 after      
having  removed any acid-albumin or     
syntonin present by neutralization1 the 
concentrated fluid can be tested at     
once4 ,if primary proteoses are         
present1 the neutral fluid will yield a 
more or less heavy precipitate  on      
addition of crystals of rock-salt1      
precipitation being complete  only when 
the fluid is saturated with the salt4   
,further1 if the  proteoses are present 

in not too small quantity1 nitric acid  
added drop  by drop to the neutralized  
fluid will produce a white precipitate1 
readily soluble on application of heat  
but reappearing as the solution  cools4 
,if primary proteoses are wholly        
wanting1 then no precipitate  will be   
obtained by acid unless the fluid is    
saturated with salt1 in  which case a   
portion of the deuteroproteose will be  
precipitated4  ,the two primary         
proteoses differ from each other        
especially in  solubility2 protoproteose
 being readily soluble in water alone1  
while  heteroproteose is soluble only in
 salt solutions1 dilute acids1 and      
alkalies4 ,hence1 when these two bodies 
are precipitated together by  saturation
 with salt1 they may be readily         
separated by dissolving them  in a      
little dilute salt solution1 and        
dialyzing the fluid in running  water   
until the salt is entirely removed2     
heteroproteose will then be             
precipitated1 while the proto-body      

remains in solution4    ,by long contact
 with water1 and even with concentrated 
salt solutions1  heteroproteose tends to
 undergo change into a semi-coagulated  
form1  named dysproteose1 insoluble in  
dilute sodium-chloride solutions4  ,this
 body can be reconverted into           
heteroproteose1 in part at least1  by   
solution in dilute acid1 or alkali1 and 
reprecipitation by  neutralization4     
,as a class1 the proteoses are          
characterized by far readier  solubility
 in water than native proteids1 by a far
 greater degree of  diffusibility1 by   
non-coagulability by heat and by        
alcohol1 although  precipitable by the  
latter agent4 ,further1 nearly all      
proteose  precipitates are exceedingly  
sensitive toward heat1 tending to       
dissolve  as the fluid is warmed and    
reappearing as the solution cools4 ,in  
fact1 this peculiarity often serves as a
 means of identification4  ,potassium   
ferrocyanide and acetic acid1 picric    
acid in excess1 and  likewise cupric    

sulphate1 all precipitate the primary   
proteoses1 while  deuteroproteose is    
only slightly affected by these         
reagents1 or indeed  not at all4    ,in 
order to separate the secondary proteose
 from the primary bodies  in the absence
 of peptones1 the fluid is neutralized  
as nearly as  possible1 and then1 after 
suitable concentration1 is saturated    
with  sodium chloride for the partial   
precipitation of the primary proteoses4 
,to the clear filtrate1 acetic acid#aag 
is added drop by drop as long  as a     
precipitate results1 the latter being   
composed of a mixture of  protoproteose 
and deuteroproteose4 ,that is to say1   
protoproteoses  are not completely      
precipitated from neutral solutions by  
saturation  with salt alone2 a little   
acid is required to complete it1 but    
this  tends to bring down a certain     
amount of deuteroproteose4 ,from this   
filtrate1 however1 the deutero-body can 
be separated in a pure form by          
dialyzing away the salt and acid1 and   

then concentrating the fluid and        
precipitating with alcohol4 ,when the   
proteoses are mixed with peptones1  the 
former must first be separated          
collectively by saturation of the  fluid
 with ammonium sulphate4    #aag        
,saturated with sodium chloride4        
,peptones are especially characterized  
by non-precipitation with the  ordinary 
precipitants for proteid bodies1 and    
especially by the  fact that they are   
wholly indifferent to saturation with   
ammonium  sulphate either in neutral1   
acid1 or alkaline fluids4 ,this         
reaction1  which constitutes the main1  
and perhaps the only absolute method  of
 separating peptones from proteoses must
 be carried out with  great thoroughness
 in order to insure a complete          
precipitation of  deuteroproteose4 ,the 
latter stands midway between primary    
proteoses and  peptones in many         
respects1 and seems to share with       
peptones something  of a tendency to    
resist precipitation by the ammonium    

salt4 ,indeed1 as  ,khne#aah has        
recently pointed out1 the last traces of
 deuteroproteose  can be precipitated   
from the fluid only by long continued   
boiling of  the ammonium                
sulphate-saturated fluid1 and even then 
it is seldom  complete unless the       
reaction of the fluid is alternately    
made neutral1  acid1 and alkaline1 and  
the heating continued for some time     
after each  change in reaction4 ,under  
such circumstances1 the last portions of
  deuteroproteose separate from the     
salt-saturated fluid and float on the   
surface in the form of an oily or gummy 
mass1 while the true peptone  remains in
 the fluid absolutely non-precipitable  
by the salt4    #aah ,erfahrungen ber   
,albumosen und ,peptone4 ,zeitschr4 f4  
,biol41 ,band  #bi1 p4 #b4    ,in this  
filtrate1 peptone can be detected by    
adding to a small portion  of the fluid 
a very large excess of a strong solution
 of potassium  hydroxide1 followed by   
the addition of a few drops of a very   

dilute  solution of cupric sulphate4 ,if
 peptone is present a bright red color  
will appear1 the intensity of which1    
with the proper amount of cupric        
sulphate1 will be proportional to the   
amount of peptone present4 ,if it  is   
desired to separate the peptone from the
 ammonium-sulphate-saturated  fluid1    
there are several methods available1 of 
which the following is  perhaps the most
 satisfactory3 ,the fluid is            
concentrated somewhat1  and set aside in
 a cool place for crystallization of a  
portion of the  ammonium salt4 ,the     
fluid is then mixed with about one-fifth
 its volume  of alcohol1 and allowed to 
stand for some time1 when it separates  
into two layers--an upper one1 rich in  
alcohol1 and a lower one1 rich  in      
salts4 ,the latter is again treated with
 alcohol1 by which another  separation  
of the same order is accomplished4      
,finally1 the lighter  alcoholic layers 
containing the peptone are united1 and  
exposed to a  low temperature until     

considerable of the contained salt      
crystallizes  out4 ,the fluid is then   
concentrated1 and after addition of a   
little  water is boiled with barium     
carbonate until the fluid is entirely   
free from ammonium sulphate4 ,any excess
 of baryta in the filtrate is  removed  
by cautious addition of dilute sulphuric
 acid1 after which the  concentrated    
fluid1 reduced almost to a sirupy mass1 
is poured into  absolute alcohol for    
precipitation of the peptone4    ,so    
separated1 the peptone formed in gastric
 digestion is exceedingly  gummy1 but   
can be transformed into a yellowish     
powder1 very  hygroscopic1 of more or   
less bitter taste1 and1 when thoroughly 
dry1  dissolving in water with a hissing
 sound and with considerable            
development of heat1 like phosphoric    
anhydride4#aai    #aai ,khne and        
,chittenden3 ,peptones4 ,studies in     
,physiol4 ,chem41 ,yale  ,university1   
vol4 #b1 p4 #ad4    ,i have introduced  
these dry chemical facts1 none of which 

are  especially new1 because ,i deem    
them of considerable importance and     
because they are not very generally     
known4 ,in fact1 there seems to be  a   
tendency on the part of some who are    
more or less familiar with the  advances
 made in our knowledge of the products  
of pepsin-proteolysis  to question the  
existence of these different bodies1 or 
to show at  least a spirit of           
indifference toward these recent facts  
which have  been gradually accumulated1 
and ,i may say accumulated at the       
expense  of considerable labor4 ,the    
time is past for calling the products of
  gastric digestion peptones2 it is time
 for a full recognition of the  fact    
that pepsin-proteolysis is synonymous   
with the production of a row  of bodies1
 chemically and physiologically distinct
 from each other1  each endowed with    
individuality enough to admit of certain
 detection1  and all bearing a certain  
specific and harmonious relationship to 
their  neighbors1 the other members of  

the series4    ,further1 it is not      
enough to admit the formation of a      
single  intermediate body1 midway       
between syntonin and peptone4 ,the      
so-called  propeptone of the past is    
simply a mixture of proteoses1 of ever  
changing composition1 varying with each 
change in the proportion of the         
component proteoses4 ,each of these     
proteoses can be detected1 under        
suitable conditions1 in the products of 
every artificial digestion  as well as  
in the stomach-contents1 and no better  
measure of the  proteolytic power of the
 natural stomach-secretion can be       
devised  than a study of the character  
of the individual bodies present in the 
stomach-contents after a suitable test  
meal4 ,the proper tests and  separations
 can be made with a small amount of the 
filtered fluid1 and  much light thrown  
upon the digestive power of the         
secretion by even a  rough estimate of  
the proportion of primary and secondary 
proteoses  and peptones formed in a     

given time1 after the ingestion of a    
certain  amount of proteid food4    ,in 
pepsin-proteolysis we have to deal1 in  
my opinion1 with a series of            
progressive hydrolytic changes in which 
peptones are the final products  of the 
transformation4 ,commencing with the    
formation of acid-albumin  or syntonin1 
hydrolysis and cleavage proceed hand in 
hand1 under the  guiding influence of   
the proteolytic enzyme1 and each onward 
step in  the process is marked by the   
appearance of a new body corresponding  
to  the extent of the hydrolysis2 each  
body1 perhaps1 being represented  by a  
row or series of isomers1 all externally
 alike1 but different  in their inner   
structure1 according to the proportion  
of hemi- and  anti-groups contained in  
the molecule4 ,as opposed to this       
theory1 we  have the older views of     
,maly1#abj ,herth1#aba ,henninger#abb   
and  others1 based upon observations    
which tend to show that peptones do  not
 differ in chemical composition from the

 proteids which yield them4  ,as a      
matter of fact1 the products then       
analyzed were not peptones at  all2 they
 were merely the primary products of    
pepsin-proteolysis1  i4 e41 what we now 
term primary proteoses1 and it is time  
we stopped  using such data to enforce  
the theory that peptones are polymers of
 the  proteids from which they are      
derived4    #abj ,ueber die chemische   
,zusammensetzung und physiologische     
,bedeutung  der ,peptone4 ,pflger's     
,archiv f4 ,physiol41 ,band #i1 p4 #ehe4
    #aba ,ueber die chemische ,natur des
 ,peptones und sein ,verhltniss zum     
,eiweiss4 ,zeitschr4 f4 physiol4 chem41 
,band #a1 p4 #bgg4    #abb ,de la       
,nature et du rle physiologique des     
peptones4 ,paris1 #ahgh4    ,in #ahhf1  
the writer1 in conjunction with         
,professor ,khne1 commenced  a study of 
the various cleavage products#abc formed
 by the action  of pepsin-hydrochloric  
acid from the better characterized and  
purer proteids1 this being a            

continuation of our earlier work on  the
 proteoses and peptones formed from     
blood-fibrin1 serum-albumin1  etc4 ,this
 work ,i have continued in my laboratory
 up to the present  time1 with many     
co-workers1 and as a result we have     
to-day a series  of observations        
gradually accumulated during these last 
seven years1  some the results of work  
carried on this last year1 which speak  
in  no uncertain way of the character of
 both the primary and secondary         
products of pepsin-proteolysis4         
,furthermore1 in attempting to settle   
this question once for all1 ,i have     
selected for study examples from  the   
various classes of both animal and      
vegetable proteids2 and as              
representatives of the latter have had  
carried out two lengthy series  of      
experiments on the crystallized proteids
 which occur so abundantly  in some     
seeds1 on the assumption that these     
crystalline bodies would  furnish a     
certain guarantee of purity which might 

naturally be lacking  in the amorphous  
proteids of animal origin4 ,some of     
these results are  now placed together  
in the following tables1 a study of     
which reveals  some very interesting    
facts3    #abc ,globulin and            
,globuloses4 ,studies in ,physiol4      
,chem4 ,yale  ,university1 vol4 ii41 p4 
#a4      ,,composition ,,of             
,,proteolytic ,,products ,,formed ,,by  
,,pepsin-,,hydrochloric ,,acid4         
,proteolysis of ,blood-fibrin4          
,mother   ,proto-    ,hetero-  ,deutero-
  ,ampho-                               
,proteid4fibrinose4fibrinose4fibrinose4p
eptone4                  #abd     #abd  
#abd    #abe                            
----------------------------------------
--------      ,c  #eb4fh    #ea4ej      
#ej4gd     #ej4dg    #dh4ge      ,h     
#f4hc     #f4hj      #f4gb      #f4ha   
#g4ba      ,n  #af4ia    #ag4ac         
#ag4ad     #ag4bj    #af4bf      ,s     
#a4aj     #j4id      #a4af      #j4hg   
#j4gg      ,o  #bb4dh    #bc4fc         

#bd4bd     #bd4fe    #bg4ja             
----------------------------------------
--------    #abd ,khne and ,chittenden3 
,zeitschr4 f4 ,biol41 ,band #bj1 p4 #dj4
    #abe ,khne and ,chittenden3 ,studies
 in ,physiol4 ,chem41 ,yale ,univer41   
vol4 ii41 p4 #dj4      ,proteolysis of  
,paraglobulin4#abf                      
,mother   ,proto-   ,hetero-   ,deutero-
                                        
,proteid4globulose4globulose4globulose4 
----------------------------------------
      ,c  #eb4ga    #ea4eg     #eb4aj   
#ea4eb      ,h   #g4ja     #f4ih        
#f4ih      #f4ie      ,n  #ae4he        
#af4ji     #af4jh     #ae4id      ,s    
#a4aa                           ,o      
#bc4bd   #be4cf     #bd4hd     #be4ei   
----------------------------------------
    #abf ,khne and ,chittenden3 ,studies
 in ,physiol4 ,chem41 ,yale ,univer41   
vol4 ii1 p4 #ab4      ,proteolysis of   
,coagulated ,egg-albumin4               
,mother   ,proto-  ,hetero- ,deutero-   
,hemi-                                  

,proteid4albumose4albumose4albumose4pept
one4                  #abg    #abg      
#abg   #abh                             
----------------------------------------
-----      ,c  #eb4cc    #ea4dd         
#eb4jf    #ea4ai   #di4ch      ,h       
#f4ih     #g4aj     #f4ie     #f4id     
#f4ha      ,n  #ae4hd    #af4ah         
#ae4ee    #ae4gg   #ae4jg      ,s       
#a4ha     #b4jj     #a4fc     #b4jb     
#a4aj      ,o  #bc4jd    #bc4bh         
#bc4ha    #bd4jh   #bg4fd               
----------------------------------------
-----    #abg ,chittenden and ,bolton3  
,ibid41 vol4 ii1 p4 #aec4    #abh ,khne 
and ,chittenden3 ,zeitschr4 f4 ,biol41  
,band #ai1 p4 #bja4      ,proteolysis of
 ,casein from ,milk4                    
,mother  ,proto- ,hetero-  ,deutero-    
,deutero-                               
,proteid4caseose4caseose4 caseose4      
caseose4                 #abi   #acj    
#abi     #abi                           
----------------------------------------
------      ,c  #ec4cj   #ed4eh   #ec4hh

    #eb4aj     #dg4gb      ,h   #g4jg   
#g4aj    #g4bg     #f4ic      #f4gc     
,n  #ae4ia   #ae4hj   #ae4fg    #ae4ea  
#ae4ig      ,s   #j4hb                  
,o  #bb4jc  #bb4eb   #bc4ah    #be4df   
#bi4eh                                  
----------------------------------------
------    #abi ,chittenden3 ,studies in 
,physiol4 ,chem41 ,yale ,univer41 vol4  
iii41  p4 #hj4    #acj ,chittenden and  
,painter3 ,ibid41 vol4 ii41 p4 #aie4    
,proteolysis of ,myosin from            
,muscle4#aca                ,mother     
,proteid4,protomyosinose4,deuteromyosino
se4                                     
----------------------------------------
---------      ,c      #eb4hb           
#eb4dc          #ej4ig      ,h          
#g4aa           #g4ag           #g4db   
,n      #af4gg          #af4ib          
#ag4jj      ,s       #a4bg              
#a4cb           #a4bb      ,o           
#ba4ij          #bb4af          #bc4ci  
----------------------------------------
---------    #aca ,khne and ,chittenden3

 ,ibid41 vol4 iii1 p4 #adg4             
,proteolysis of ,elastin4#acb           
,mother                                 
,proteid4,protoelastose4,deuteroelastose
4                                       
----------------------------------------
-------      ,c     #ed4bd              
#ed4eb          #ec4aa      ,h          
#g4bg           #g4ja           #g4jh   
,n     #af4gj          #af4if           
#af4he      ,s                          
,o    #ba4gi          #ba4ea            
#bb4if                                  
----------------------------------------
-------    #acb ,chittenden and ,hart3  
,studies in ,physiol4 ,chem41 ,yale     
,univer41  vol4 iii1 p4 #cg4            
,proteolysis of ,gelatin4#acc           
,mother                                 
,proteid4,protogelatose4,deuterogelatose
4                                       
----------------------------------------
-------      ,c     #di4ch              
#di4ih          #di4bc      ,h          
#f4ha           #f4gh           #f4hd   

,n     #ag4ig          #ag4hf           
#ag4dj      ,s      #j4ga               
#j4eb           #j4ea      ,o     #be4ac
          #bd4hf          #bf4jb        
----------------------------------------
-------    #acc ,chittenden and ,solley3
 ,journal of ,physiol41 vol4 xii1 p4    
#cc4      ,proteolysis of               
,phytovitellin#acd 7,crystallized7 from 
,squash ,seed4                ,mother   
,proteid4,protovitellose4,deuterovitello
se4                                     
----------------------------------------
---------      ,c     #ea4fj            
#ea4eb          #di4bg      ,h          
#f4ig            #f4ih           #f4gj  
,n     #ah4hj           #ah4fg          
#ah4gh      ,s      #a4ja               
,o     #ba4fb          #bb4hc           
#be4be                                  
----------------------------------------
---------    #acd ,chittenden and       
,hartwell3 ,ibid41 vol4 xi1 p4 #dda4    
,proteolysis of ,phytovitellin#ace      
7,crystallized7 from ,hemp ,seed4       

,mother                                 
,proteid4,protovitellose4,deuterovitello
se4,peptone4                            
----------------------------------------
-----------------      ,c      #ea4fc   
#ea4ee           #di4gh        #di4dj   
,h       #f4ij          #f4gc           
#f4gc         #f4gg      ,n      #ah4gh 
#ah4ij           #ag4ig        #ah4dj   
,s       #j4ij          #a4ji           
#a4jh         #j4di      ,o      #ba4gi 
#ba4gc           #bd4dd        #bd4id   
----------------------------------------
-----------------    #ace ,chittenden   
and ,mendel3 ,ibid41 vol4 xvii1 p4 #dh4 
,proteolysis of ,glutenin#acf from      
,wheat4                 ,mother         
,proto-   ,hetero-   ,deutero-          
,proteid4glutenose4glutenose4glutenose4 
----------------------------------------
      ,c  #eb4cd    #ea4db     #ea4hb   
#di4he      ,h   #f4hc     #f4gj        
#f4gi      #f4fi      ,n  #ag4di        
#ag4ef     #ag4dc     #ag4eg      ,s    
#a4jh     #a4cd      #a4ei      #j4hj   

,o  #bb4bf    #bb4ih     #bb4cg         
#be4ji                                  
----------------------------------------
    #acf ,formerly called gluten-casein1
 and the products gluten-caseoses4      
,chittenden and ,e4 ,e4 ,smith3 ,journal
 of ,physiol41 vol4 xi1 p4 #dbj4        
,proteolysis of ,zein4#acg              
,mother                                 
,proteid4,protozeose4,deuterozeose4     
----------------------------------------
-      ,c      #ee4bc        #ec4bi     
#ea4ca      ,h       #g4bf         #f4hg
        #f4hh      ,n      #af4ac       
#af4aj       #af4bg      ,s       #j4fj 
#a4ed        #a4jh      ,o      #bj4gh  
#bb4bj       #bd4df                     
----------------------------------------
-    #acg ,chittenden and ,williams3    
,not heretofore published4    ,in       
considering these results1 it is to be  
noticed that there is a  general        
unanimity of agreement except in the    
case of the albuminoid  gelatin4 ,in the
 proteolysis of this body1 for some     

reason not  explainable1 the digestive  
products show no marked deviation from  
the  composition of the mother-proteid1 
but in every other instance there  is to
 be traced a distinct tendency toward   
diminution in the content  of carbon1   
proportional to the extent of           
proteolysis4 ,in the primary  bodies1   
proto and heteroproteoses1 the          
percentage of carbon is only  slightly  
lowered2 indeed1 in some few cases1     
notably in elastin and  casein1 the     
primary products show a slight increase 
in their content  of carbon1 but in most
 instances there is a slight falling off
 in the  percentage of this element4 ,in
 the deuteroproteoses1 however1 the loss
  of carbon is very marked4 ,the        
percentage loss1 to be sure1 varies with
  the different proteids1 doubtless     
dependent in part upon the nature  of   
the proteid itself1 and also1 ,i think1 
upon the strength of the  proteolytic   
agent employed and the duration of the  
proteolysis4 ,it is  to be further      

noticed that peptones1 whenever         
analyzed1 show a still  further loss of 
carbon and also a marked loss of        
sulphur4 ,in nitrogen  there is no      
constant difference4    ,on the         
assumption that these various products  
of proteolysis are  formed by a series  
of hydrolytic changes1 accompanied by   
cleavage of  the molecule1 we might at  
first glance look for a marked increase 
in  the content of hydrogen4 ,but when  
we consider the size of the proteid     
molecule1 with the small proportion of  
hydrogen contained therein  and the     
large amount of carbon1 it is plain that
 hydrolytic cleavage  might naturally   
leave its mark on the percentage of     
carbon1 rather  than on the percentage  
of hydrogen of the resultant products4  
,in view  of these facts1 the above     
results show nothing inconsistent with  
the  theory that pepsin-proteolysis1 as 
a rule1 is accompanied by a series  of  
progressive hydrolytic cleavages in     
which the primary proteoses are  the    

result of a slight hydration1 these     
bodies by continued proteolysis  being  
further hydrated with formation of      
secondary proteoses1 which in  turn     
undergo final hydration and cleavage    
into true peptones4 ,in accord  with    
this theory1 true peptones always show a
 marked difference in  composition from 
that of the mother-proteid1 the most    
striking feature  being the greatly     
diminished content of carbon1 which may 
be taken as  a measure1 in part at      
least1 of the extent of the hydrolytic  
change4  ,and it is to be noticed that  
the crystallized phytovitellins are no  
exception to the general rule2 the      
secondary vitelloses and peptones       
resulting from proteolysis bear         
essentially the same relationship to    
the mother-proteids that the albumoses  
from egg-albumin do4 ,moreover1  the    
alcohol-soluble proteids1 of which the  
zein of cornmeal is a good  example1    
show the same general tendency1 and it  
is an interesting  fact that the        

proteoses1 or more specifically the     
zeoses1 formed from  this peculiar      
proteid1 are readily soluble in water   
and show the  general proteose          
reactions4 ,it may also be mentioned    
that these zeoses1  as well as the      
elastoses1 are very resistant to further
 hydrolysis  by pepsin-acid1 and yield  
only comparatively small amounts of true
  peptones4    ,in connection with this 
question of the composition of proteoses
  and peptones as formed by             
pepsin-proteolysis1 it is interesting to
  note a recent observation recorded by 
,schtzenberger4#ach ,this  experimenter 
took #cej grammes of moist blood-fibrin1
 corresponding to  #ge4e grammes of dry 
substance1 and subjected it to          
proteolysis with  #b4e litres of a very 
strong pepsin-hydrochloric acid solution
 for five  days4 ,the resultant fluid   
was then freed from acid by treatment   
with  silver oxide1 after which the     
solution was evaporated to dryness on  a
 water-bath and the residue dried in    

vacuo4 ,this residue1 termed  by        
,schtzenberger fibrin-peptone1 was found
 on analysis to contain  #di4ah per     
cent4 of carbon1 #g4ji per cent4 of     
hydrogen1 and #af4cc per  cent4 of      
nitrogen1 thus agreeing very closely    
with true fibrin-peptone  as analyzed by
 ,khne and myself4 ,further1            
,schtzenberger showed that  the fibrin  
in undergoing this transformation had   
taken on #c4ig per  cent4 of water4 ,but
 to my mind1 the most significant fact  
connected  with this experiment is the  
positive evidence it affords1 not only  
of  hydration as a feature of           
peptonization by pepsin-acid1 but that  
this  greatly diminished content of     
carbon1 so characteristic of peptones1  
and to a less extent of                 
deuteroproteoses1 is wholly independent 
of the  methods of separation and       
purification ordinarily made use of4    
,thus1  ,schtzenberger1 in the above    
experiment1 did not attempt any         
separation  of individual bodies4       

,proteolysis was carried out under      
conditions  favoring maximum conversion 
into peptone1 and the resultant product1
  or products1 was analyzed directly    
without recourse to any methods  of     
precipitation or purification4 ,to be   
sure1 the substance analyzed  could not 
have been peptone entirely free from    
proteose1 but in any  event it          
represented the terminal products of    
pepsin-proteolysis1 and  like true      
amphopeptone contained #c4e per cent4   
less carbon than the  original fibrin4  
,hence1 we may conclude1 without further
 argument1 that  peptonization in       
gastric digestion is the result of      
distinct hydrolytic  action1 in which   
the original proteid molecule is        
gradually broken  down1 or split apart1 
into a number of simpler molecules1 the 
proteoses  and peptones4    #ach        
,recherches sur la constitution chimique
 des peptones4 ,comptes  ,rendus1 vol4  
#aae1 p4 #bjh4    ,peptones1 i4 e41     
amphopeptones1 are the final products of

 gastric  digestion2 but to how great an
 extent is actual peptonization carried 
on in pepsin-proteolysis8 ,as we have   
seen1 syntonin1 primary proteoses1      
secondary proteoses1 and peptones are   
all products of pepsin-digestion1  and  
it might perhaps be assumed that        
ultimately all of a given proteid       
undergoing pepsin-proteolysis would be  
converted into amphopeptone4            
,examination1 however1 shows that such  
is not the case1 at least in  artificial
 digestive experiments4 ,peptones are   
truly formed1 and  many times in large  
amount1 but never under any             
circumstances have  ,i been able to     
effect a complete transformation of any 
proteid into  true peptone by           
pepsin-proteolysis2 there is always     
found a certain  amount of proteoses    
more or less resistant to the further   
action of  the ferment4 ,obviously1 the 
nature and proportion of the individual 
products formed in any digestive        
experiment are dependent greatly  upon  

the attendant conditions2 but even with 
a large amount of active  ferment1 an   
abundance of free hydrochloric acid1 a  
proper temperature1  and a              
long-continued period of digestion1 even
 five and six days1  there is never     
found a complete conversion into        
peptone4 ,indeed1  the largest yield of 
peptone ,i have ever obtained in an     
artificial  digestion is sixty per      
cent41 while the average of a large     
number of  results under most favorable 
circumstances is somewhat less than     
fifty  per cent4#aci    #aci ,chittenden
 and ,hartwell3 ,the ,relative          
,formation of ,proteoses and  ,peptones 
in ,gastric ,digestion4 ,journal of     
,physiol41 vol4 xii1 p4 #ab4    ,we     
understand that peptones are the        
products of the hydration and  cleavage 
of previously formed proteoses4 ,the    
primary proteoses pass  into secondary  
proteoses and these into peptones1 but  
for some reason  this transformation    
after a time becomes a slow and gradual 

process4 ,at  first there is a marked   
and rapid progression2 the proteid      
undergoing  proteolysis is rapidly      
dissolved1 and both proteoses and       
peptones may  be detected in abundance4 
,but if we continue to watch the        
changing  relations of primary and      
secondary proteoses and peptones1 we    
find  that progression soon ceases to be
 rapid1 and eventually travels  onward  
at a snail's pace4 ,thus1 in one        
experiment with coagulated  egg-albumin1
 there was found at the end of          
forty-eight hours' digestion  with      
pepsin-hydrochloric acid1 only          
thirty-seven per cent4 of peptones  with
 fifty-eight per cent4 of proteoses1 and
 yet digestion had been  sufficiently   
vigorous to allow of a complete solution
 of the proteid  in two hours4 ,at the  
end of seventy-two hours the amount of  
peptones  had increased to about        
forty-two per cent41 the proteoses      
having  correspondingly diminished2 but 
even at the end of seventeen days only  

fifty-four per cent4 of peptones were to
 be found1 thus affording  striking     
evidence of the slow conversion of the  
first-formed products  into peptones4   
,naturally1 the individual proteoses    
show marked differences in their  rate  
of conversion into secondary or final   
products4 ,take as an  illustration some
 results#adj obtained with caseoses     
formed in the  digestion of the casein  
of milk4 ,thus1 heterocaseose1 a primary
  product1 yielded only fifteen per     
cent4 of peptone after ninety-four      
hours at #dj ,c4 with a strong          
pepsin-acid solution4 ,protocaseose1    
however1 containing some deuterocaseose1
 under like conditions1 yielded         
thirty-two per cent4 of peptone in one  
hundred and nineteen hours1  while pure 
deuterocaseose gave sixty-six per cent4 
of peptone in one  hundred and          
thirty-seven hours4 ,evidently1 then1   
the first-formed  soluble products of   
gastric digestion1 i4 e41 the primary   
proteoses1  are only slowly converted   

into peptone1 since they must first pass
  through the intermediate stage of     
deuteroproteose1 which is plainly  not a
 rapid process4 ,the deutero-body1 on   
the other hand1 once formed  is more    
rapidly converted into peptone1 but even
 this is in no sense  a rapid process4  
,hence1 in the artificial digestion of  
proteids with  pepsin-hydrochloric acid1
 solubility of the proteids may be quite
  rapid1 and even complete in a very    
short time1 but the resultant  products 
will be mainly proteoses and not        
peptones4 ,the latter are  truly formed 
and in considerable amount1 but         
proteoses1 either as  primary or        
secondary bodies1 are invariably present
 and usually in  excess of the peptones4
    #adj ,chittenden and ,hartwell1 loc4
 cit41 p4 #bb4    ,in this connection   
the question naturally arises how far we
 are  to trust these results in their   
bearing on the natural process of       
digestion as it occurs in the living    
stomach4 ,obviously1 the conditions  are

 quite different in the two cases4 ,in  
artificial digestions1 we  have         
especially the influence of an          
ever-increasing percentage of  soluble  
products on the activity of the ferment1
 a condition of things  generally       
considered as more or less inhibitory to
 enzyme action4  ,we have attempted to  
measure the real value of this influence
 by  experiments#ada conducted in       
parchment dialyzing tubes1 in which  the
 conditions are made favorable for the  
removal of at least some  of the        
products of digestion as fast as they   
are formed4 ,in these  experiments1 the 
dialyzer tubes containing the proteid   
and pepsin-acid  were immersed in a     
large volume of #j4b per cent4          
hydrochloric acid  7about three litres71
 which was gradually changed from time  
to time1  the whole mixture being kept  
at #dj ,c4 during the entire period of  
the experiment4 ,the extent of          
peptonization was then ascertained  by  
analysis of both the contents of the    

dialyzer tubes and of the  surrounding  
acid1 the results being compared with   
those obtained from  control experiments
 carried on in flasks4 ,without         
considering the  results in detail1 it  
may be mentioned that the slow and      
incomplete  peptonization so            
characteristic of artificial gastric    
digestion is not  materially modified by
 this closer approach to the natural    
process4  ,the several digestions       
carried on in the dialyzer tubes were   
certainly  accompanied by a fairly rapid
 withdrawal of the diffusible products  
of  digestion1 yet no noticeable        
increase in the amount of peptone formed
  was observed4 ,the results certainly  
favor the view that the conversion  of  
the primary products of gastric         
digestion into true peptone is a  slow  
and gradual process1 even under the most
 favorable circumstances1  and that this
 lack of complete peptonization is not  
due to accumulation  of the products of 
digestion1 but is rather an inherent    

quality of  pepsin-proteolysis under all
 circumstances4    #ada ,chittenden and 
,amerman3 ,a ,comparison of ,artificial 
and ,natural  ,gastric ,digestion1      
together with a ,study of the           
,diffusibility of  ,proteoses and       
,peptones4 ,journal of ,physiol41 vol4  
xiv1 p4 #dhc4    ,in these dialyzer     
experiments it was observed that not    
only did  peptones diffuse1 but also the
 proteoses4 ,in fact1 it was found that 
six to eight per cent4 of the proteoses 
formed passed through the  parchment    
walls of the dialyzer tubes into the    
surrounding acid in  the nine hours'    
digestion4 ,this led to a study of the  
diffusibility  of proteoses in general1 
from which we were led to conclude that 
these bodies possess this power to a    
greater degree than had hitherto  been  
supposed4 ,as might be expected1 it was 
also found that the  attendant          
conditions modify materially the rate of
 diffusibility2 the  two factors        
especially prominent being temperature  

and the volume of  the surrounding      
fluid4 ,thus1 #a4i grammes of           
protoalbumose dissolved  in #bjj c4c4 of
 water and suspended in #d4e litres of  
water heated to  #ch ,c41 diffused      
through the parchment tube to the-extent
 of #e4ji per  cent41 while at #aj ,c4  
diffusion amounted to only #b4eg per    
cent4 ,under  somewhat similar          
conditions1 pure peptone diffused to the
 extent of  eleven per cent4 in six     
hours at #ch ,c4 ,somewhat singular1    
however1  was the result obtained with  
deuteroalbumose2 this proteose showing a
  diffusibility considerably less than  
that of the proto-body4 ,but as         
,khne#adb has independently obtained    
essentially the same results1  this     
apparent anomaly cannot depend upon any 
errors of work4    #adb ,erfahrungen ber
 ,albumosen und ,peptone4 ,zeitschr4 f4 
,biol41 ,band  #bi1 p4 #bj4    ,it is of
 course to be understood that diffusion 
experiments made with  dead parchment   
membranes cannot necessarily be expected

 to throw much  light upon the rate of  
absorption of these bodies through the  
living  membranes of the stomach and    
intestine1 where1 as ,waymouth ,reid#adc
  has well said1 we have to deal with an
 absorptive force dependent1 no  doubt1 
upon protoplasmic activity1 and         
comparable1 in part at least1  to the   
excretive force of a gland-cell4        
,furthermore1 in considering  absorption
 as it occurs in the living stomach1 we 
must necessarily  give due weight to the
 selective power of the epithelial      
cells1  a power which may be far more   
potent even than we suppose4 ,hence1    
without attempting at this point to draw
 any broad deductions from our          
experiments we may simply lay stress    
upon the facts themselves1 viz41  that  
the primary products of                 
pepsin-proteolysis are diffusible1 and1 
like true peptones1 are capable of      
passing through animal and vegetable    
membranes1 although to a less extent4   
,we may further emphasize the  fact that

 experiments of this character on       
diffusibility can1 at the  most1 only   
indicate general tendencies1 since every
 variation in the  attendant conditions 
will exercise some influence upon the   
final result4    #adc ,osmosis          
,experiments with ,living and ,dead     
,membranes4 ,journal of  ,physiol41 vol4
 xi1 p4 #cab4    ,with reference to the 
bearing digestive experiments made in   
dialyzer  tubes have upon the natural   
process as carried on in the living     
stomach1 we must necessarily grant that 
the conditions approximate  only in the 
crudest way to those existent in the    
alimentary tract4  ,at the same time1 if
 complete peptonization is              
characteristic of  pepsin-proteolysis in
 the stomach1 and failure to obtain such
 results  in an artificial digestion is 
due to lack of withdrawal of the        
diffusible products formed1 then        
certainly the experiments carried on  in
 dialyzer tubes1 with abundant          
opportunity for diffusion1 and with a   

large excess of free hydrochloric acid1 
should show some indications of         
increased peptone-formation4 ,but none  
were obtained4    ,it is more than      
probable that the rate of absorption of 
diffusible  products from the stomach   
has been overestimated4 ,lea1#add for   
example1 assumes that1 8normally the    
products of digestion1 whether  proteid 
or carbohydrate1 are never met with in  
either the stomach  or intestine in     
other than the smallest amounts1        
frequently to be  described as merely   
traces40 ,this certainly implies a far  
more rapid  absorption of proteoses and 
peptones from the stomach than results  
seem to justify4 ,indeed1 recent facts  
obtained by ,brandl1#ade working  under 
,tappeiner's direction1 tend to show    
that absorption from the  stomach is1   
under some circumstances at least1      
comparatively slow4  ,brandl's          
experiments were conducted on large and 
vigorous dogs with  gastric fistul1 the 
stomach being shut off from the         

intestine by the  simple introduction of
 a small rubber balloon into the        
pylorus1 which  when dilated completely 
closed the orifice4 ,by carefully       
conducted  experiments1 it was shown    
that pure peptone1 entirely free from   
proteose1 is absorbed from the empty    
stomach in proportion to the            
concentration of the peptone solution4  
,thus1 #g4e grammes of peptone          
dissolved in water in such proportion as
 to make a five per cent4  solution1 and
 allowed to remain in the stomach for   
two hours1 lost by  absorption only     
#j4bh gramme1 equal to #b4fh per cent4  
of the peptone  introduced4 ,under      
similar conditions1 a ten per cent4     
aqueous solution  of peptone lost only  
#d4e per cent4 by absorption4 ,on the   
other hand1  when peptone was introduced
 in larger quantity1 viz41 in a twenty  
per  cent4 solution1 absorption amounted
 to thirteen per cent4 in two hours4    
#add ,journal of ,physiol41 vol4 xi1 p4 
#bdj4    #ade ,ueber ,resorption und    

,secretion im ,magen1 und deren         
,beeinflussung  durch ,arzneimittel4    
,zeitschr4 f4 ,biol41 ,band #bi1 p4     
#bgg4    ,it is thus evident that pure  
peptones1 even when taken into the      
stomach  in fairly large amounts1 and   
under conditions very favorable for     
rapid  absorption1 pass into the        
circulating blood very slowly4          
,obviously1  however1 one must not lose 
sight of the fact that when digestion is
  under way and the volume of blood     
consequently increased1 there may  be a 
corresponding rise in the rate of       
absorption4 ,there is perhaps a  hint of
 this conclusion in the influence of    
alcohol on the absorption  of peptone as
 brought out by some of ,brandl's       
experiments4 ,thus1 it  was found that  
when alcohol was added in considerable  
quantity to a  ten per cent4 solution of
 peptone1 the stomach-mucosa was greatly
  reddened1 while in two hours the      
absorption of peptone amounted to  #aa4h
 per cent4 ,but in any event1 these     

results certainly do not favor  the view
 that the products of gastric digestion 
are absorbed as soon  as they are       
formed4 ,it is1 no doubt1 quite         
different in the intestine1  but in the 
stomach1 where pepsin-proteolysis       
occurs1 we have1 ,i think1  no grounds  
for assuming that either peptones or    
proteoses are rapidly  absorbed4 ,hence1
 it might perhaps be considered that the
 results of  pepsin-proteolysis in the  
living stomach are much the same as     
those  obtained in artificial digestion 
experiments4    ,still1 there are other 
differences between natural digestion   
and  artificial proteolysis than those  
connected with the possible  absorption 
of the more diffusible products of      
digestion4 ,thus1 in the  living stomach
 there is an ever-increasing secretion  
of hydrochloric  acid1 and perhaps also 
of pepsin1 more or less proportional to 
the  extent of proteolysis4 ,on this    
point ,brandl's experiments again give  
us some light4 ,thus1 it was found that 

the introduction of an aqueous  solution
 of peptone into the empty stomach led  
to the secretion of an  acid fluid      
containing on an average #j4bd per cent4
 ,h,cl1 while1 under  similar           
conditions1 the introduction of sugar or
 potassium iodide  was followed by the  
secretion of a fluid containing on an   
average  only #j4ac per cent4 ,h,cl4    
,further1 the absolute amount of acid   
found  after the introduction of peptone
 was far greater than when sugar or     
iodide was introduced1 since peptone led
 to an increase of at least  fifty per  
cent4 in the volume of fluid secreted4  
,hence1 proteolysis in  the living      
stomach may give rise to such an        
increased production and  secretion of  
hydrochloric acid that formation of the 
terminal products  of gastric digestion 
may be greatly accelerated4 ,that such  
in fact is  the case1 ,i have no manner 
of doubt1 but that it may result in the 
complete conversion of the so-called    
primary and secondary proteoses  into   

peptone ,i very much question4 ,in fact1
 such examinations as ,i have  made of  
the stomach-contents after a suitable   
test-meal have always  resulted in the  
finding of a relatively large amount of 
proteoses4 ,to  be sure1 true peptone   
may be detected and in fairly large     
amounts1  but whenever a quantitative   
determination of the relative proportion
  of the two has been made1 the         
proteoses have always been in excess4 ,i
  have already reported elsewhere the   
results of some experiments in this     
direction made on a healthy young man1  
where the stomach-contents were         
withdrawn at varying periods after the  
ingestion of weighed amounts  of        
coagulated egg-albumin4 ,thus1 in one   
experiment#adf the stomach  was         
thoroughly rinsed with water1 after     
which #ach grammes of finely  divided   
coagulated-albumin1 equal to #af grammes
 of dry albumin1 were  ingested4        
,three-quarters of an hour thereafter1  
the stomach-contents  were withdrawn by 

lavage and analyzed4 ,as a result1 #a4da
 grammes of  albumoses were separated   
and weighed1 and #j4hd gramme of        
peptones1  the relative proportion being
 expressed by sixty-two per cent4 of    
albumoses and thirty-seven per cent4 of 
peptones1 calculated on the  #b4be      
grammes of soluble products recovered4  
,this expresses the general  character  
of the results obtained in experiments  
of this nature1 and in  my opinion adds 
emphasis to the statement already made1 
that complete  peptonization is not a   
feature of pepsin-proteolysis1 either in
 the  artificial or in the natural      
process as it takes place in the living 
stomach4    #adf ,journal of            
,physiology1 vol4 xiv41 p4 #eja4        
,gastric digestion is to be considered  
rather as a preliminary step in         
proteolysis1 preparatory to the more    
profound changes characteristic  of     
pancreatic digestion1 in which the      
ferment trypsin is the important        
factor4 ,we can thus see how1 as in the 

case of ,czerny's dogs1 an  animal may  
be perfectly nourished without a        
stomach1 digestive  proteolysis being   
carried on solely by the pancreatic     
fluid4 ,you will  remember that two of  
the dogs operated on by ,czerny and his 
pupils  lived between four and five     
years after the operation1 with the     
stomach  completely removed1 and yet    
during this period they were well       
nourished  and ate all varieties of food
 with apparently a normal appetite4#adg 
,evidently1 then1 in some cases at      
least1 digestive proteolysis  can be    
carried on without this preliminary     
action of the gastric  juice4 ,ogata#adh
 arrived at essentially the same        
conclusion by the  establishment of a   
duodenal fistula1 shutting off the      
stomach from the  intestine by means of 
a small rubber ball which could be      
inflated with  water4 ,on then          
introducing coagulated egg-albumin and  
other forms of  proteid matter into the 
duodenum1 he found that digestion was at

 least  sufficiently complete to satisfy
 all the demands of the system4 ,the    
only unsatisfactory result was with     
collagenous foods1 which plainly  showed
 the need of a preliminary acid         
digestion4 ,more recently still1        
,cawallo and ,pachon1#adi working in    
,richet's laboratory1 have studied  the 
digestibility of different kinds of     
proteid foods in a dog1 upon  which they
 had performed a gastrectomy2 the entire
 fundus1 as well as  the pyloric        
portion1 of the stomach having been     
removed4 ,in an animal  so operated     
upon1 after recovery was complete1 solid
 food1 as meat1  was completely digested
 when taken in small quantities at a    
time4 ,raw  meat1 however1 was less     
completely utilized1 the fces showing   
portions  of undigested fibres4 ,still1 
it was apparent that intestinal         
digestion  alone was capable of         
accomplishing all that was necessary for
 the  complete nourishment of the       
animal1 when it had once become         

accustomed  to the changed condition of 
its alimentary tract4    #adg ,bunge's  
,physiologische und ,pathologische      
,chemie1 p4 #aeb4    #adh ,ueber die    
,verdauung nach der ,ausschaltung des   
,magens4 ,du  ,bois-,reymond's ,archiv  
f4 ,physiol1 #ahhc1 p4 #hi4    #adi ,une
 observation de chien sans estomac4     
,comptes ,rendus hebd4 de la  ,socit de 
,biologie1 ,december #a1 #ahic4         
,these facts are cited not to belittle  
the importance of gastric  digestion in 
the nutrition of the body1 but rather to
 emphasize the  probability that        
pepsin-proteolysis is simply a          
preliminary step in  digestion2 that its
 function is not in the direction of a  
complete  peptonization of the proteid  
foods ingested1 but that its action is  
especially directed to the production of
 soluble products1 proteoses1  which can
 be further digested in the small       
intestine1 or perhaps  directly absorbed
 after they have passed through the     
pylorus1 or even  from the stomach      

itself to a certain extent4      ,,some 
,,physiological ,,properties ,,of       
,,proteoses ,,and ,,peptones4    ,it is 
very evident from what has been said    
that all forms of proteid  matter1 i4e41
 all the members of the three main      
groups spoken  of in our classification 
of the proteids1 excepting only nuclein1
  reticulin1 and the keratins1 are      
capable of undergoing proteolysis with  
pepsin-hydrochloric acid4 ,further1 in  
every case the main products  of the    
transformation are proteoses2 viz41     
albumoses1 caseoses1  gelatoses1        
vitelloses1 myosinoses1 etc41 according 
to the nature of  the proteid undergoing
 proteolysis2 true peptones being formed
 in  less abundance4 ,corresponding to  
each of these groups are primary and    
secondary proteoses1 all possessed of   
many points in common1 both  chemical   
and physiological1 yet differing from   
each other in many minor  respects4     
,these are the important products of    
gastric digestion1 of                   

pepsin-proteolysis1 and it may be well  
to consider for a moment some  of the   
physiological properties of the         
proteoses and of peptones as  well1 in  
order that we may the better comprehend 
the general nature of  these substances 
with reference to their possible action 
in the economy4    ,as far back as      
#ahhj1 ,schmidt-,mlheim#aej discovered  
that the injection  of aqueous solutions
 of peptone into the blood-vessels of   
living dogs  was attended by a series of
 remarkable phenomena4 ,thus1 the animal
  passed at once into a condition of    
narcosis resembling that produced by    
chloroform1 accompanied by a fall of    
general blood-pressure so great  that   
the animal was liable to die1 as from   
asphyxia4 ,further1 there  was evidence 
of some marked change in the condition  
of the blood1 as  indicated by loss of  
the power of spontaneous coagulation1   
while the  peptone itself evidently     
underwent some alteration1 or else was  
rapidly  eliminated1 since it could not 

be detected in the blood a short time   
after its introduction4 ,these          
experiments1 however1 were not conducted
  with true peptone but with ,witte's   
8peptonum siccum10 which at that  time1 
at least1 was composed in great part of 
proteoses4 ,the general  character of   
these interesting results was confirmed 
by ,fano1#aea who  found that the       
injection of so-called peptone in the   
proportion of #j4c  gramme per kilo4 of 
body-weight was sufficient to bring     
about complete  narcosis1 together with 
loss of coagulability on the part of the
 blood4  ,very suggestive1 however1 was 
the fact that ,fano1 on trying similar  
experiments with the peptone formed by  
pancreatic digestion1 viz41  with       
antipeptone1 which presumably contained 
a far smaller proportion  of proteoses1 
failed to obtain like results2 the      
tryptone1 so-called1  being exceedingly 
irregular in its action1 in many cases  
producing no  effect whatever4    #aej  
,beitrge zur ,kenntniss des ,peptons und

 seiner physiologischen  ,bedeutung4 ,du
 ,bois-,reymond's ,archiv f4 ,physiol41 
#ahhj1 p4 #cc4    #aea ,das ,verhalten  
des ,peptons und ,tryptons gegen ,blut  
und ,lymphe4  ,ibid41 #ahha1 p4 #bgg4   
,the discovery at this date of the      
several albumoses1 and their presence   
in large amounts in all so-called       
peptones1 led to a study of their       
physiological action with special       
reference to the observations  of       
,schmidt-,mlheim and ,fano4             
,politzer1#aeb working under ,khne's    
guidance1 was the first to experiment in
 this direction1 and his  results are   
full of interest as throwing light on   
the action of the  individual albumoses4
 ,thus proto1 hetero1 and               
deuteroalbumose are all  active         
physiologically1 giving rise when       
injected into the veins of  dogs and    
cats to strong narcotic action1 varying 
somewhat in intensity  in different     
individuals4 ,there is also produced a  
marked fall in  blood-pressure1 due     

apparently to vaso-motor paralysis1 the 
action  being manifested chiefly1 if not
 wholly1 on the splanchnic region4      
,thus1 after an injection of one of     
these albumoses1 the mesenteric  vessels
 are always strongly congested1         
accompanied frequently by the           
appearance of a bloody serum in the     
peritoneal cavity4 ,narcotic action  is 
manifested only so long as the          
blood-pressure remains sub-normal1  and 
is due presumably to this marked        
accumulation of blood in the  large     
abdominal veins1 thus leading to anmia  
of the brain4 ,albumoses  and peptones  
injected into the jugular vein likewise 
produce fever1  presumably through some 
action on the nervous system by which   
the  equilibrium of tissue-metamorphosis
 is interfered with4#aec    #aeb ,on the
 ,physiological ,action of ,peptones and
 ,albumoses4 ,journal of  ,physiol41    
vol4 #g1 p4 #bhc4    #aec ,ott and      
,collmar3 ,pyrexial ,agents1 ,albumose1 
,peptone1 and ,neurin4  ,journal of     

,physiol41 vol4 #h1 p4 #bah4            
,further1 ,politzer found that all of   
the albumoses either delayed or         
prevented altogether the coagulation of 
the blood1 in conformity with  the      
observations of ,schmidt-,mlheim and    
,fano4 ,in all of these actions  the    
primary albumoses appeared most         
effective1 deuteroalbumose least  so4   
,heteroalbumose1 however1 was constantly
 most active1 especially in  delaying   
the coagulation of the blood4 ,with     
amphopeptone1 there was  far less       
narcosis and less diminution of         
blood-pressure1 while the  effect on the
 coagulability of the blood was more or 
less variable1  frequently being        
entirely negative4 ,antipeptone1 on the 
other hand1 was  found almost wholly    
wanting in any constant effects1        
although in one  instance deep narcosis 
was produced4 ,thus1 from ,politzer's   
experiments1  it was made clear that the
 albumoses1 when introduced directly    
into  the blood-current1 possess a far  

greater toxic action than either        
amphopeptone or antipeptone4 ,albumoses1
 in sufficiently large doses1  were     
invariably fatal1 while peptones never  
produced fatal results  so long as the  
kidneys of the animal remained intact4  
,the extreme  solubility and            
diffusibility of peptones1 coupled      
perhaps with their  marked diuretic     
action1 lead to rapid elimination       
through the kidneys1  and their         
consequent removal from the system4     
,many of these observations made with   
the albumoses ,i have repeated  with    
several of the proteoses and peptones   
more recently studied1 as  protocaseose1
 protoelastose1 the globuloses1 and     
others4 ,the results  may be taken as   
practically confirmatory of the older   
observations1  and ,i make mention of   
them in this general way simply to      
emphasize  the fact that all of the     
proteoses1 though perhaps showing       
individual  peculiarities1 are possessed
 of marked physiological properties1    

which  plainly testify to their toxic   
nature1 when introduced directly into   
the blood-current4    ,young animals are
 particularly sensitive to the injection
 of  proteoses into the blood1 even when
 the introduction takes place very      
gradually4#aed ,thus1 a young1 healthy  
dog of #b kilos4 body-weight1  eight    
weeks old1 died in one hour after the   
injection into the jugular  vein of #a  
gramme of protoalbumose in #bj c4c4 of  
water1 thus affording  a good           
illustration of the extreme toxicity of 
this albumose when  introduced directly 
into the blood4    #aed ,neumeister3    
,ueber die ,einfhrung der ,albumosen und
 ,peptone in den  ,organismus4          
,zeitschr4 f4 ,biol41 ,band #bd1 p4     
#bhd4    ,of greater interest1          
physiologically1 are the changes the    
individual  proteoses undergo after     
their injection into the blood4 ,as     
already  stated1 peptone so injected may
 appear in the urine wholly unaltered4  
,thus1 ,neumeister#aee has made         

injections of both amphopeptone  and    
antipeptone in the case of dogs1 and was
 able to detect the  peptone very       
quickly in the urine4 ,i have made like 
experiments with  other forms of peptone
 and obtained similar results2 thus1 a  
pure  amphopeptone formed from casein by
 pepsin-proteolysis 7#b grammes in  #ae 
c4c4 water7 was injected into the       
jugular vein of a dog weighing #e       
kilos4 ,the urine collected during      
several hours after the injection  was  
heated to boiling1 and saturated while  
hot with ammonium sulphate4  ,the       
filtrate1 on being tested with cupric   
sulphate and potassium  hydroxide1 gave 
a fairly strong biuret reaction for     
peptone4 ,another  similar experiment   
made with antipeptone1 formed from the  
myosin of  muscle-tissue1 gave like     
results4    #aee ,zeitschr4 f4 ,biol41  
,band #bd1 p4 #bhg4    ,with proteoses1 
however1 different results are obtained1
 as  ,neumeister#aef first pointed out4 
,these bodies introduced into the  blood

 undergo more or less of a change prior 
to their excretion in  the urine1 the   
change partaking of the character of a  
hydrolytic  cleavage in which the       
primary proteoses are transformed into  
secondary  proteoses1 while             
deuteroproteoses are changed into       
peptones4 ,this  is not necessarily to  
be interpreted as meaning that the full 
equivalent of the proteose injected     
appears in the urine1 but that the      
portion which is eliminated through the 
kidneys tends to undergo a              
transformation somewhere en route1 akin 
to the change produced in               
pepsin-proteolysis4 ,as to how common or
 complete this transformation  is under 
the above circumstances1 we have no     
positive knowledge4 ,such  a hydrolytic 
change certainly occurs in the case of  
the dog1 and the  experimental evidence 
is in favor of the view that the        
transformation  is effected in the      
kidneys by the pepsin secreted through  
the urinary  tubules1 where there is    

momentarily a formation of free acid4   
,in the  rabbit1 on the other hand1 no  
such change occurs2 the urine from this 
animal contains practically no pepsin1  
and consequently the proteoses          
eliminated through the kidneys are      
excreted unaltered4 ,as1 however1 the   
experiments of ,stadelmann#aeg and      
others have shown that the urine of  all
 carnivora1 and of man as well1 contains
 a ferment which1 on the  addition of a 
suitable amount of hydrochloric acid1   
will digest fibrin  with formation of   
the ordinary products of                
pepsin-proteolysis1 it is to  be        
presumed that all proteoses passing     
through the kidneys will undergo  at    
least some change prior to their        
excretion in the urine4    #aef ,ibid41 
p4 #bhd4    #aeg ,untersuchungen ber den
 ,pepsin-fermentgehalt des normalen und 
pathologischen ,harnes4 ,zeitschr4 f4   
,biol41 ,band #be1 p4 #bjh4    ,however 
this may be1 it is very evident that the
 proteoses formed  in gastric digestion 

cannot be absorbed as such directly into
 the  blood-current4 ,introduced into   
the blood1 they behave in such a manner 
as to warrant the conclusion that they  
are truly foreign substances1  and the  
system makes a brave endeavor to remove 
them as speedily as  possible4 ,the same
 may be said of amphopeptones1 from     
which we may  conclude that all of these
 products of pepsin-proteolysis undergo 
some transformation during the process  
of absorption1 by which their  toxicity 
is destroyed and their nutritive        
qualities rendered fully  available for 
the needs of the body4 ,discussion of   
this question1  however1 will be left   
until the next lecture4    ,in view of  
these pronounced physiological          
properties of the proteoses1  it is     
interesting to recall the now well-known
 fact that many of  the chemical poisons
 produced by bacteria are proteose-like 
bodies1  chemically1 at least1 closely  
akin to the proteoses resulting from    
pepsin-proteolysis4 ,thus1              

,wooldridge#aeh as early as #ahhh       
pointed out  that an alkaline solution  
of tissue-fibrinogen exposed to the     
action  of anthrax-bacilli suffered some
 change1 so that when introduced into   
the blood it possessed the power of     
producing immunity to anthrax4  ,this   
observation was verified by ,hankin1#aei
 who further showed that  the substance 
formed by the anthrax-bacilli was a     
veritable albumose1  and that it truly  
possessed the power of producing        
immunity4 ,sidney  ,martin#afj carried  
the matter still further1 and by growing
 the  anthrax-bacilli in a pure solution
 of alkali-albuminate prepared  from    
blood-serum1 proved the formation of    
both primary and secondary  albumoses1  
as well as of peptone1 leucin1 tyrosin1 
and a peculiar  alkaloidal substance of 
pronounced toxic properties4 ,martin    
finds that  the albumoses are not as    
poisonous as the alkaloid1 and surmises 
that  the alkaloid is contained in the  
albumose molecule in the nascent  state2

 further1 he suggests that the albumoses
 in small doses may exert  some         
protective influence1 while in larger   
doses they act as vigorous  poisons4    
,how true this may be ,i cannot say1 but
 my own experience  convinces me that   
the anthrax-bacilli grown in a culture  
medium  composed of alkali-albuminate1  
prepared from egg-albumin1 to which  the
 necessary inorganic salts and some     
glycerin have been added1 do  give rise 
to albumoses and peptones which are     
truly endowed with toxic  properties4   
#aeh ,versuche ber ,schutzimpfung auf   
chemischem ,wege4 ,du  ,bois-,reymond's 
,archiv f4 ,physiol41 #ahhh1 p4 #ebg4   
#aei ,british ,med4 ,journal1 ,october1 
#ahhi4    #afj ,proceed4 ,royal         
,society1 #ahij1 vol4 #dh1 p4 #gh4      
,albumose-like bodies have also been    
obtained by ,brieger and  ,frnkel#afa   
with the bacillus of diphtheria4 ,these1
 too1 were endowed  with powerful       
poisonous properties1 and when          
introduced into the  tissues of the body

 gave rise to reactions resembling those
 produced  by the ,lffler bacillus4 ,in 
my own laboratory1 recent experiments   
made with the bacillus of glanders have 
shown that when grown in a  slightly    
acid medium containing                  
alkali-albuminate1 albumoses1 peptones1 
and crystalline bodies such as leucin   
and tyrosin are formed in  considerable 
quantities4 ,kresling#afb has reported  
similar results4  ,with the             
tubercle-bacilli1 many like results have
 been recorded4 ,thus1  among others1   
,crookshank and ,herroun#afc have       
reported the finding of  albumoses1     
peptone1 and a ptomaine when the bacilli
 have been grown in  glycerin agar-agar1
 and also in fluid media4    #afa       
,untersuchungen ber ,bacteriengifte4    
,berlin1 klin4 ,wochenschrift1  #ahij1  
p4 #bda and #bfh4    #afb ,ueber die    
,bereitung des ,malleins und seine      
,bestandtheile4  ,abstract in           
,jahresbericht f4 ,thierchemie1 ,band   
#bb1 p4 #fcd4    #afc ,journal of       

,physiology1 vol4 #ab1 p4 #i4           
,koch#afd has made a special study of   
the albumose which he considers  as the 
specific toxic agent of the so-called   
tuberculin4 ,this albumose  was found by
 ,brieger and ,proskauer#afe to have a  
somewhat peculiar  composition1 inasmuch
 as it contains forty-seven to          
forty-eight per  cent4 of carbon and    
only #ad4gc per cent4 of nitrogen1      
agreeing1  however1 in this respect very
 closely with the peptone formed from   
egg-albumin by the action of            
bromelin4#aff ,still more recently1     
,khne#afg has made a thorough study of  
this albumose1 as well as of  the other 
products elaborated by the growth of the
 tubercle-bacillus4  ,he designates all 
of the peculiar albumoses formed by     
these bacilli  as acrooalbumoses4 ,they 
are endowed with marked chemical and    
physiological properties1 causing a rise
 of temperature when injected  into the 
blood1 as well as other phenomena more  
or less pronounced4  ,it is thus evident

 there is ample ground for the statement
 that all  nutritive media in which     
pathogenic bacteria have been planted   
are  liable to contain1 sooner or later1
 toxic substances1 many of which at     
least are closely related to1 if not    
identical with1 the albumoses4 ,it  is  
not my purpose1 however1 to consider    
these points in detail1 nor to  quote   
the many results obtained by other      
workers in this direction4    #afd      
,deutsche med4 ,wochenschrift1 #ahia1 p4
 #aahj4    #afe ,ibid4    #aff          
,chittenden3 ,on the ,proteolytic       
,action of ,bromelin1 the ,ferment of   
,pineapple ,juice4 ,journal of          
,physiology1 vol4 #ac1 p4 #cjc4    #afg 
,weitere ,untersuchungen ber die        
,proteine des ,tuberculins4  ,zeitschr4 
f4 ,biol41 ,band #cj1 p4 #bba4    ,i    
wish merely to call attention to the    
fact that the proteoses1 and  likewise  
the peptones formed by                  
pepsin-proteolysis1 are more or less    
toxic when introduced directly into the 

blood1 and that they share this         
property with the proteoses formed by   
bacterial organisms1 or by the  enzymes 
which they give rise to4 ,in other      
words1 these primary cleavage  or       
alteration products of the proteid      
molecule1 however produced1  are more or
 less poisonous1 and if introduced into 
the blood-current  without undergoing   
previous change may show marked         
physiological  action4 ,it is1 of       
course1 not to be understood that these 
bodies are  all alike4 ,they are surely 
closely related and possess many points 
in  common1 especially so far as their  
chemical properties are concerned1  but 
their chemical constitution and their   
physiological action must  vary more or 
less with their mode of origin4    ,in  
any event1 it is very evident that the  
proteoses and peptones  formed in the   
alimentary tract by pepsin-proteolysis  
must undergo some  transformation1      
before reaching the blood-current1 by   
which their  peculiar physiological     

properties are modified4 ,this          
modification may  be associated with a  
conversion into the serum-albumin1 or   
globulin of  the blood4 ,however this   
may be1 the fact remains that these     
proteoses  formed so abundantly during  
digestion can be absorbed and serve as  
nutriment for the animal body1 but      
between their formation as a result  of 
proteolysis and their passage into the  
blood they are exposed to  some agency1 
or agencies1 doubtless in the very act  
of absorption1 by  which a further      
transformation is accomplished4 ,with   
this point we  shall be able to deal    
more in detail in the next lecture4     
,,lecture ,,iii4    ,,proteolysis ,,by  
,,trypsin--,,absorption ,,of ,,the      
,,main ,,products ,,of ,,proteolysis4   
,,proteolysis ,,by ,,trypsin4    ,in    
pancreatic digestion1 proteids are      
exposed to the action of an  enzyme of  
much greater power than pepsin1 one     
endowed with a far  greater range of    
activity1 and consequently proteolysis  

as it occurs  in the small intestine    
becomes a broader and more complicated  
process4  ,as you well know1 the ferment
 trypsin manifests its power not only in
  a more rapid transformation of        
insoluble proteids into soluble and     
diffusible products1 but there is a     
diversity in the character of the  many 
products formed which testifies to the  
profound alterations this  ferment is   
capable of producing4 ,the primary and  
secondary products of                   
pepsin-proteolysis1 as well as unaltered
 proteids1 are alike subject  to these  
changes1 and bodies of the simplest     
constitution may result  in both cases  
from the series of hydrolytic changes   
set in motion by  this proteolytic      
enzyme4 ,the power of the ferment as a  
contact agent is  astonishing1 for in   
the case of trypsin no accessory body is
 necessary  to bring out its latent     
power4 ,water1 proteid1 and the enzyme  
at the  body-temperature are all that is
 necessary to call forth prompt and     

energetic hydrolytic action4            
,moreover1 hydrolysis does not stop with
 the mere production of soluble         
proteoses and peptones1 but the         
hemi-portion of the latter is quickly   
broken down into crystalline bodies1    
such as leucin1 tyrosin1 lysin1         
lysatin1 etc4 ,this special             
characteristic of the ferment testifies 
in no uncertain manner to the existence 
of inherent qualities in  the inner     
structure of the enzyme peculiar to the 
body itself4 ,in  general properties and
 reactions1 pepsin and trypsin may be   
closely  related2 both are products of  
the katabolic action of specific        
protoplasmic cells1 but the inner nature
 or structure of the two must  be quite 
different4 ,pepsin1 as we have seen1 is 
powerless to produce  any change in     
proteid bodies unless acids are present 
to lend their  aid4 ,furthermore1 pepsin
 is limited in its action to the        
production  of proteoses and peptones1  
while trypsin gives rise to a series  of

 hydrolytic cleavages which result in   
the ultimate formation of  comparatively
 simple bodies4    ,trypsin1 however1 in
 its natural environment is dissolved in
 an  alkaline medium4 ,its proteolytic  
action is therefore carried on1 under   
normal circumstances1 in an             
alkaline-reacting fluid containing #j4e 
to #a per cent4 sodium carbonate1 and   
the proteolytic power of the  ferment is
 unquestionably manifested to the best  
advantage in such a  medium4 ,at the    
same time1 it will act1 and act         
vigorously1 in a neutral  fluid1 and    
likewise in a fluid having a weak acid  
reaction1 provided  there is little or  
no free acid present4 ,thus1 in         
experiments#afh on  blood-fibrin it was 
found that1 while a solution of trypsin 
containing  #j4e per cent4 sodium       
carbonate1 digested or dissolved #hi per
 cent4  of the proteid in three to four 
hours at #dj ,c41 a perfectly neutral   
solution of the ferment1 otherwise under
 exactly the same conditions1  digested 

#gf per cent41 and a #j4a per cent4     
salicylic acid-solution of  the enzyme  
converted #dc per cent4 of the proteid  
into soluble products4    #afh          
,chittenden and ,cummins3 ,studies in   
,physiol4 ,chem41 ,yale  ,university1   
vol4 i41 p4 #ace4    ,with hydrochloric 
acid1 trypsin is quickly destroyed1     
unless there  is a large excess of      
proteid matter present1#afi which       
obviously  means that the acid in such  
case exists wholly as combined acid4    
,indeed1 experiments made in my         
laboratory have shown that as soon as   
free acid1 especially hydrochloric acid1
 is present in a solution  containing   
trypsin1 then proteolytic action is at  
once stopped4 ,when1  however1 acids1   
especially organic acids1 are present in
 a digestive  mixture containing an     
excess of proteid matter1 so that the   
solution  contains no free acid 7or     
better1 with the proteid matter only    
partially saturated with acid7 then     
trypsin will continue to manifest  its  

peculiar proteolytic power1 although to 
a considerably lessened  extent4 ,hence1
 it is evident that the ferment may     
exert its digestive  power under the    
three possible sets of conditions which1
 under varying  circumstances1          
frequently prevail in the small         
intestine4    #afi ,mays3               
,untersuchungen aus d4 physiol4         
,institute d4 ,universitt  ,heidelberg1 
,band iii41 p4 #cgh2 also ,langley3 ,on 
the ,destruction of  ,ferments in the   
,alimentary ,canal1 ,journal of         
,physiology1 vol4 iii41  p4 #bfc4    ,in
 considering the general phenomena of   
proteolysis by trypsin1 one  is         
especially impressed by the large and   
rapid formation of peptone  which almost
 invariably results from the action of a
 moderately strong  solution of the     
ferment1 on nearly every form of proteid
 matter4 ,to  be sure1 primary products 
are first formed1 but these are quickly 
converted into peptone1 and a little    
experience in studying the  action of   

pepsin and trypsin soon reveals the fact
 that the latter is  especially a       
peptone-forming ferment4 ,in other      
words1 it is peculiarly  adapted to take
 up the work where it has been left by  
pepsin and1 if  necessary1 carry forward
 the hydrolytic change even to the      
extent of a  conversion of the entire   
hemi-moiety into crystalline products4  
,the primary products of                
trypsin-proteolysis1 however1 are not   
exactly  identical with those formed by 
pepsin4 ,thus1 protoproteoses and       
heteroproteoses seldom appear in an     
alkaline trypsin digestion2 the  proteid
 matter being in most cases1 at least1  
directly converted into  soluble        
deuteroproteoses1#agj which are then    
transformed by the  further action of   
the ferment into peptones and other     
products4 ,hence1  we may express the   
order of events in the trypsin digestion
 of a native  proteid as follows3       
,native proteid4                        
,amphodeuteroproteoses4                 

,amphopeptones4                         
,antipeptone4   ,hemipeptone4           
,leucin4  ,tyrosin4  ,aspartic acid1    
etc4    #agj ,r4 ,neumeister3 zur       
,kenntniss der ,albumosen4 ,zeitschr4 f4
 ,biol4  ,band #bc1 p4 #cgh4    ,in the 
digestion of fresh blood-fibrin with    
trypsin1 there is  plainly a preliminary
 solution of the proteid without any    
marked  transformation or cleavage      
occurring1 the soluble product being    
apparently a globulin1 coagulating at   
about #ge ,c41#aga viz41 at             
approximately the same temperature as   
serum-globulin4 ,this body1  however1   
quickly disappears1 giving place to true
 deuteroproteoses as  the ferment-action
 commences2 for it is not probable that 
this globulin  is a product of          
enzyme-action1 but rather represents a  
simple solution  of the fibrin by the   
alkaline fluid and salts4 ,in any event1
 this  globulin-like substance is not   
formed in the pancreatic digestion of   
coagulated-albumin1 serum-albumin1 or   

vitellin1 and hence cannot be           
considered as a true product of         
trypsin-proteolysis4    #aga ,jac4 ,g4  
,otto3 ,beitrge zur ,kenntniss der      
,umwandlung von  ,eiweissstoffen durch  
,pancreas-ferment4 ,zeitschrift f4      
physiol4 ,chem41  ,band #h1 p4 #abi4    
,the fact that deuteroproteoses are the 
primary products of  trypsin-digestion  
again emphasizes the natural            
adaptability of this  ferment to the    
part it has to play in the digestive    
process4 ,its  natural function is to   
take up the work where left by pepsin1  
and  carry it forward to the necessary  
point2 and hence1 when acting  upon a   
native proteid the primary products of  
its action correspond  to the secondary 
products of pepsin-proteolysis4 ,trypsin
 is thus  equally efficient in the      
digestion of all native proteids1 but   
the  products of such action are always 
deuteroproteoses1 peptones1 and         
crystalline amido-acids4 ,it is to be   
remembered1 however1 that in            

trypsin-proteolysis the deuteroproteoses
 and the amphopeptones must  necessarily
 be represented by bodies in which there
 is a preponderance  of anti-groups4 ,in
 pepsin-proteolysis1 as we have seen1   
the hemi- and  anti-groups of the       
proteid molecule remain more or less    
united1 but in  pancreatic digestion1   
the formation of amphopeptone is quickly
 followed  by the breaking down of a    
portion of the hemipeptone into leucin1 
tyrosin1 etc4 thus leaving a larger     
proportion of the anti-moiety in  the   
remaining amphopeptone4                 
,theoretically1 at least1 in the-case of
 a vigorous and long-continued          
pancreatic digestion1 all of the        
hemipeptone formed from any native      
proteid can be converted into           
crystalline and other products1 thus    
leaving a true antipeptone resistant to 
the further action of trypsin4  ,hence1 
we are prone to speak of the peptone of 
pancreatic digestion  as antipeptone1   
although1 as can be readily seen1 the   

exact nature of  the peptone1 i4 e41 the
 relative proportion of hemi- and       
anti-groups  it contains1 will obviously
 depend upon the length of the digestion
  and the strength of the ferment4      
,again1 it is possible1 as certain      
facts seem to suggest1 that the         
amido-acids which are so readily  formed
 from hemipeptone may come in part      
directly from the hydration  of a       
portion of the hemideuteroproteose1     
without passing through the  preliminary
 stage of hemipeptone4 ,if so1 we have  
another source of  variation in the     
relative proportion of hemi- and        
anti-moieties in the  deuteroproteoses  
and peptones of pancreatic digestion4   
,still again1 it  is to be remembered   
that in normal digestive proteolysis1 as
 it occurs  in the living intestinal    
tract1 the proteid matter to be acted   
upon  has already passed through certain
 preliminary stages in1 its transit     
through the stomach1 as a result of     
which still further variations in  the  

proportion of hemi- and anti-groups may 
be possible4    ,it is thus plainly     
evident1 in view of the ready cleavage  
of  the hemi-group into amido-acids1    
that the primary products of            
trypsin-proteolysis1 the proteoses and  
peptones1 must necessarily be  composed 
in great part of those complex and      
semi-resistant atoms which  we include  
under the head of the anti-group4       
,however much one may be  skeptical     
about the real existence of so-called   
hemi- and anti-groups1  there is no     
gainsaying the fact that a given weight 
of native proteid1  like egg-albumin or 
blood-fibrin1 cannot be converted wholly
 into  crystalline or other simple      
products by trypsin2 indeed1 it is quite
  significant that at the end of a      
long-continued treatment with an        
alkaline solution of the pancreatic     
ferment1 there is usually found  about  
fifty per cent1 of peptone1 while the   
other fifty per cent4 of  the proteid is
 represented mainly by more soluble     

products1 such as  the amido-acids4 ,it 
is also significant that the peptone    
obtained from  an artificial pancreatic 
digestion1 where the proteolytic action 
has  been long-continued and vigorous1  
resists the further action of the       
ferment4 ,in other words1 it is the     
so-called antipeptone4 ,in line with    
this result is the fact that the        
peptones formed in pepsin-proteolysis1  
when treated with an alkaline solution  
of trypsin1 are converted into          
amido-acids and other bodies of simple  
constitution to the extent of  about    
fifty per cent4 ,this is easily         
explainable on the ground that  the     
hemi-portions of the above peptones are 
broken down into simple  products1 while
 the anti-portions remain unchanged1    
being resistant to  the ferment and thus
 leading to a separation of the two     
groups1 or at  least to the isolation of
 the anti-molecules4    ,there is much  
that might be cited in further support  
of these views1  but doubtless ,i have  

said enough to make it plainly evident  
that in  the pancreatic digestion of any
 native proteid1 not more than one-half 
can at the most be transformed into     
crystalline products1 while the  other  
half will be represented mainly by a    
peptone incapable of further  change by 
trypsin4 ,similarly1 the products of    
pepsin-proteolysis  exposed to the      
action of trypsin may undergo a like    
separation1 the  hemi-groups only       
breaking down into simple products4     
,hence1 the whole  theory of the hemi-  
and anti-moieties of the proteid        
molecule means  simply that of the many 
complex atoms composing the molecule1   
one-half  are easily decomposable by the
 pancreatic ferment1 while the other    
half  are more resistant and make up the
 so-called anti-group4    ,in any active
 pancreatic digestion of either a native
 proteid1 or of  the products of        
pepsin-proteolysis1 the anti-group is   
represented  mainly by antipeptone1     
although there is often found a small   

amount of  a peculiar antialbumid-like  
body1 insoluble in the weak alkaline    
fluid4  ,antipeptones1 thus far studied1
 when entirely free from proteoses1 are 
characterized by a low content of       
carbon1 like the amphopeptones from     
pepsin-proteolysis4 ,the following table
 shows the composition of a few  typical
 examples3      ,,composition ,,of      
,,antipeptones4             ,from       
,from        ,from           blood-     
blood-      anti-       ,from           
,from          fibrin4    fibrin4       
albumose4    casein4     myosin4        
#agb      #agc       #agd       #age    
#agf        ,c    #dg4cj      #di4ei    
#dh4id       #di4id      #di4bf      ,h 
#f4gc       #f4ib        #f4fe          
#f4ea       #f4hg      ,n    #af4hc     
#ae4gi       #ae4hi       #af4cj        
#af4fb      ,s     #j4gc       ---      
---         #j4fh       #a4af      ,o   
#bh4da       ---         ---            
#bf4eg      #bf4ji    #agb ,khne and    
,chittenden3 ,studies in ,physiol4      

,chem4 ,yale ,univer41  vol4 ii41 p4    
#dj4    #agc ,j4 ,otto3 ,zeitschr4 f4   
physiol4 ,chem41 ,band #h1 p4 #adf4     
#agd ,khne and ,chittenden3 ,zeitschr4  
f4 ,biol41 ,band #ai1 p4 #aif4    #age  
,chittenden3 ,studies in ,physiol4      
,chem4 ,yale ,univer41 vol4 iii41  p4   
#aja4    #agf ,chittenden and ,goodwin3 
,journal of ,physiol41 vol4 xii41 p4    
#cd4    ,from these data it is evident  
that1 while each individual peptone may 
have a composition peculiar to itself1  
they are all alike in possessing  a     
relatively low content of carbon4 ,the  
antialbumid1 however1 split off  in     
these hydrolytic changes1 like the      
antialbumid formed by the action  of    
dilute acids at #ajj ,c41 is            
characterized by a correspondingly high 
content of carbon and a low content of  
nitrogen4 ,as an illustration1  may be  
mentioned the myosin-antialbumid formed 
in the digestion of  myosin from        
muscle-tissue by an alkaline            
trypsin-solution4 ,this body  contains  

#eg4dh per cent4 of carbon1 #g4fg per   
cent4 of hydrogen1 #ac4id  per cent4 of 
nitrogen1 #a4cb per cent4 of sulphur1   
and #ai4ei per  cent4 of oxygen4#agg ,it
 is only necessary to compare these     
figures  with those expressive of the   
composition of myosin-antipeptone1 to   
appreciate how wide a gap there is      
between these two products of           
trypsin-proteolysis1 and both members of
 the anti-group4 ,antialbumid1  however1
 is a peculiar product1 one which is    
liable to crop out  somewhat            
unexpectedly1 and with varying shades of
 resistance toward  the proteolytic     
ferments4 ,as formed in                 
pepsin-proteolysis1 it is more  or less 
readily soluble in sodium carbonate1 and
 in part readily  convertible into      
antipeptone by trypsin4 ,still1 the same
 substance1 or  at least a closely      
related body1 makes its appearance in   
the form of  an insoluble residue       
whenever a native proteid is digested by
 trypsin4  ,at times1 the amount of this

 insoluble product may be quite large1  
even reaching to one-fourth of the total
 proteid matter2#agh but when  so formed
 in the intestine it must entail a heavy
 loss of nutriment1  for whenever the   
anti-group is split off after this      
fashion it becomes  very resistant to   
the further action of the ferment4      
,separating in  this manner from an     
artificial digestive mixture1 it may be 
dissolved  in dilute caustic alkali1    
reprecipitated by neutralization1 and   
then  once again brought into solution  
with dilute sodium carbonate4 ,in this  
form1 it will yield some antipeptone by 
the further action of trypsin1  although
 even then a large amount of the        
antialbumid is prone to  separate out as
 a gelatinous coagulum1 more or less    
resistant to the  further action of the 
ferment4    #agg ,chittenden and        
,goodwin3 ,journal of ,physiol41 vol4   
xii41 p4 #cf4    #agh ,khne und         
,chittenden3 ,ueber die nchsten         
,spaltungsproducte der  ,eiweisskrper4  

,zeitschr4 f4 ,biol41 ,band #ai1 p4     
#aif4    ,the peculiar action of        
trypsin1 however1 as a proteolytic      
enzyme is  shown in the production of a 
row of crystalline nitrogenous bodies   
of simple constitution whenever the     
ferment is allowed to continue  its     
action for any length of time1 either on
 native proteids or on  proteolytic     
products containing the hemi-group4     
,this1 to be sure1 is a  fact long      
known1 but it gains added significance  
as year by year new  bodies are         
discovered as products of               
trypsin-proteolysis with various  forms 
of proteid matter4 ,the very character  
of the bodies originating  in this      
manner gives evidence of the            
far-reaching decompositions  involved2  
decompositions which are perhaps        
attributable as much to the  innate     
tendencies of the proteid material as to
 the specific action of  the ferment4   
,as representatives of this peculiar    
line of cleavage1 we  have first the    

well-known bodies1 leucin and tyrosin2  
leucin1 a body  belonging to the fatty  
acid series1 long known as amido-caproic
  acid1 but now generally considered as 
amido-isobutylacetic acid1  7,,ch#c7b   
,,chch#b ,,ch7,,nh#b7 ,,cooh2 and       
tyrosin1 a body  belonging to the       
aromatic group1 having the formula      
,,oh                       ,c#f;,h#d    
,,ch#b ,,ch7,,nh#b7 ,,cooh1    and known
 as oxyphenyl-amido-propionic acid4     
,these two bodies are therefore         
representatives of two distinct groups  
or radicals present in the hemi-portion 
of the proteid molecule2 the  first     
belonging to the fatty acid series1 the 
second to the aromatic  group from which
 come such well-known bodies as indol1  
skatol1 benzoic  acid1 and other        
substances prominent in proteid         
metabolism4 ,moreover1  these two       
hydrolytic products of                  
trypsin-proteolysis are formed in       
considerable quantity1 at least in an   
artificial digestion4 ,thus1  ,khne has 

reported the finding of #i4a per cent4  
of leucin and #c4h per  cent4 of tyrosin
 as the result of a typical digestion1  
and ,i have  tried many similar         
experiments with like results4 ,further1
 we know  from observations made by     
different investigators that both leucin
 and  tyrosin may be formed in          
considerable quantities in              
trypsin-proteolysis  as it occurs in the
 living intestine4 ,but to this point we
 shall return  later on4    ,besides    
leucin and tyrosin1 aspartic acid and   
glutamic acid have long  been known as  
decomposition-products of the vegetable 
proteids4 ,thus1  both acids were       
discovered by ,ritthausen and           
,kreusler#agi in the  cleavage of such  
proteids by boiling dilute acid4        
,hlasiwetz and  ,habermann#ahj likewise 
obtained aspartic acid in large quantity
 by  the breaking down of animal        
proteids under the influence of bromine4
  ,further1 ,siegfried#aha has recently 
obtained glutamic acid as a  product of 

the decomposition of the                
phosphorus-containing proteid1          
reticulin1 from adenoid tissue4 ,as     
products of trypsin-proteolysis1        
,salkowski and ,radziejewski#ahb found  
aspartic acid in the digestion  of      
blood-fibrin2 and v4 ,knieriem#ahc      
likewise obtained it in the  digestion  
of gluten from wheat4 ,both of these    
acids belong to the  fatty acid series1 
the aspartic acid being a dibasic acid1 
,,cooh4 ,,ch#b;,,ch7,,nh#b74 ,,cooh1 or 
amido-succinic acid1 while glutamic     
acid1 ,,cooh4 ,c#c;,h#e7,,nh#b74 ,,cooh1
 is likewise a dibasic acid1  known as  
amido-pyrotartaric acid4    #agi        
,verbreitung der ,asparaginsure und     
,glutaminsure unter den                 
,zersetzungs-producten der              
,proteinstoffe4 ,journal f4 prakt4      
,chemie1 ,band  #c1 p4 #cad4    #ahj    
,ueber die ,proteinstoffe4 ,liebig's    
,annalen1 ,band #aei1 p4 #cjd4    #aha  
,ueber die chemischen ,eigenschaften des
 ,reticulirten ,gewebes4                

,habilitationschrift4 ,leipzig1 #ahib4  
#ahb ,bildung von ,asparaginsure bei der
 ,pancreas-,verdauung4 ,bericht4  d4    
,deutsch4 chem4 ,gesellsch41 ,band #g1  
p4 #ajej4    #ahc ,asparaginsure1 ein   
,product der knstlichen ,verdauung von  
,kleber  durch die ,pancreas-,drse4     
,zeitschr4 f4 ,biol41 ,band #aa1 p4     
#aih4    ,of more interest              
physiologically1 are the recently       
discovered  nitrogenous bases lysin and 
lysatinin1 or lysatin4 ,these two bodies
  were first identified by ,drechsel#ahd
 and his co-workers as products  of the 
decomposition of various proteids1 when 
the latter are boiled  with hydrochloric
 acid and stannous chloride4 ,they were 
first obtained  by ,drechsel as cleavage
 products of casein4#ahe ,later1 ,ernst 
,fischer1#ahf working under ,drechsel's 
direction1 separated them as            
decomposition-products of gelatin2 while
 ,siegfried#ahg obtained them  as       
products of the cleavage of conglutin1  
gluten-fibrin1 hemiprotein1  and        

egg-albumin1 by boiling with            
hydrochloric acid and stannous          
chloride4 ,in all of these cases it is  
obvious1 from the method of  treatment  
pursued1 that the two bodies result from
 a simple hydrolytic  cleavage of the   
proteid molecule4 ,hence1 it might be   
assumed that  these two bases would     
likewise be formed in                   
trypsin-proteolysis4 ,this  assumption1 
,hedin1#ahh working in ,drechsel's      
laboratory1 has proved to  be correct1  
and furthermore he has shown that the   
amount of these bases  formed in        
pancreatic digestion is not             
inconsiderable4 ,thus1 as products  of  
the digestion of three kilos4 of moist  
blood-fibrin with an alkaline  solution 
of trypsin1 #bh grammes of pure         
platino-chloride of lysin were          
obtained1 and sufficient lysatinin to   
establish its identity4    #ahd ,der    
,abbau der ,eiweissstoffe4 ,du          
,bois-,reymond's ,archiv4 f4  ,physiol41
 p4 #bdh4 #ahia4    #ahe ,zur ,kenntniss

 der ,spaltungsproducte des ,caseins4   
,ibid41 p4 #bed4  #ahia4    #ahf ,ueber 
neue ,spaltungsproducte des ,leimes4    
,ibid41 p4 #bfe4 #ahia4    #ahg ,zur    
,kenntniss der ,spaltungsproducte der   
,eiweisskrper4 ,ibid41  p4 #bgj4 #ahia4 
#ahh ,zur ,kenntniss der ,producte der  
tryptischen ,verdauung des ,fibrins4    
,ibid41 p4 #bgc4 #ahia4    ,lysin has   
the composition of ,c#f ,h#ad ,n#b ,o#b1
 being a  diamido-caproic acid1 a       
homologue of diamido-valerianic acid4   
,hence1  this body1 like leucin or      
amido-caproic acid1 is a representative 
of  the fatty acid group1 the chemical  
relationship between the two bodies     
being plainly apparent from their       
constitution4 ,the constitution  of     
lysatinin is less definitely settled1   
but apparently it has the  composition  
of a creatin1 its formula being         
,c#f;,h#ac,n#c,o#b1 in  which case it   
might be more appropriately termed      
lysatin4 ,the special  point of         
interest1 however1 connected with this  

latter body as a  product of            
trypsin-proteolysis is the fact that by 
simple hydrolytic  decomposition1 all   
chance of oxidation being excluded1 it  
can break  down into urea4#ahi ,for     
years1 chemists have been seeking to    
trace  out the line of cleavage or      
decomposition by which urea results in  
proteid metabolism4 ,in the nutritional 
changes of the body1 nearly all  the    
nitrogen of the ingested proteid food is
 excreted in the form of  urea1 but     
chemists working with dead food-albumin 
have been heretofore  unable to break   
down proteid matter directly into urea4 
,this1 however1  ,drechsel has now      
succeeded in doing1 and it is to be     
especially noted  that the line of      
decomposition or cleavage is simply one 
of hydration1  in which the proteid     
molecule1 either through the action of  
boiling  dilute acids1 or through the   
more subtle influence of the hydrolytic 
enzyme1 trypsin1 is gradually broken    
down into cleavage products1 from  one  

or more of which comes lysatin4 ,the    
very resemblance of this body  to       
creatin suggested that1 since the latter
 breaks down into urea and  sarcosin    
when boiled with baryta water1 lysatin  
might possibly behave  in a similar     
manner4 ,this1 as has been previously   
stated1 was found to  be the case1 and  
,drechsel obtained from ten grammes of a
 double salt of  lysatin and silver one 
gramme of urea nitrate1 by simple       
boiling with  baryta water4    #ahi     
,drechsel3 ,ueber die ,bildung von      
,harnstoff aus ,eiweiss4 ,du            
,bois-,reymond's ,archiv f4 ,physiol41  
p4 #bfa4 #ahia4    ,it is thus evident  
that a certain amount of urea may come  
from the more  or less direct hydrolysis
 of proteid matter in the intestinal    
canal1  all but the last steps in the   
process being the result of the ordinary
  cleavage processes incidental to      
trypsin-proteolysis4 ,this fact affords 
additional evidence of the profound     
changes set in motion by this           

proteolytic enzyme4 ,it is not1 of      
course1 to be understood that all the   
urea formed in the body has its origin  
in this manner4 ,such a method of       
decomposition taking place in the       
intestinal tract would be exceedingly   
unphysiological and wasteful1 but we can
 readily see how such a line of         
cleavage might result in inestimable    
gain to the economy in cases where      
excess of proteid food has been         
ingested4 ,under such circumstances1 a  
portion of the surplus might be broken  
down directly in the intestine  into    
this urea-antecedent1 and thus quickly  
removed from the system  with a minimum 
amount of effort on the part of the     
economy4 ,drechsel  estimates that about
 one-ninth of the urea daily excreted   
may come from  the direct decomposition 
of lysatin1 the latter obviously having 
its  origin in trypsin-proteolysis4     
,another product of trypsin-proteolysis 
which has long been recognized1         
although its real nature has not been   

known1 is tryptophan or                 
proteinochromogen4 ,this body is not    
only a product of the pancreatic        
digestion of proteids1 but it is also   
formed whenever native proteids  are    
broken down through any influence       
whatever1 the substance coming          
presumably from the hemi-moiety of the  
molecule4 ,it is especially             
characterized by the bright-colored     
compound it forms with either  chlorine 
or bromine1 so that for a long time it  
went by the mystical  name of the       
8bromine body40 ,when brought in contact
 with either of  these agents1 it       
immediately combines with them to form a
 new compound  of an intense violet     
color1 termed proteinochrome4 ,this     
constitutes  the usual test for its     
presence1 a little bromine water1 for   
example1  quickly bringing out a violet 
color when added to a fluid containing  
the chromogen4 ,the body is readily     
soluble in alcohol1 and hence can  be   
easily separated from the primary       

products of trypsin-proteolysis1  such  
as the proteoses and peptones4          
,krukenberg considered the substance    
not a true proteid1 but rather a body   
belonging to the indigo-group2  but     
,stadelmann1 who has given the matter a 
very thorough investigation1  comes to  
the conclusion that it is truly a       
proteid body1 in part  closely related  
to peptone1 although in many ways quite 
different4    ,the following composition
 of bromine proteinochrome1 as          
determined by  ,stadelmann1#aij shows   
the general nature of the compound      
formed when  bromine combines with the  
chromogen3               ,a      ,d     
,c     #di4jj    #dh4ab      ,h         
#e4bh     #e4ji      ,n     #aj4ii      
#aa4ib      ,s      #c4gg     #c4aj     
,o     #aa4ja    #ab4jj      ,br        
#ai4ie    #ai4gg    #aij ,ueber das beim
 tiefen ,zerfall der ,eiweisskrper      
entstehende  ,proteinochromogen1 den die
 ,bromreaction gebenden ,krper4         
,zeitschr4 f4  ,biol41 ,band #bf1 p4    

#eba4    ,from the average of the       
several results obtained1 it would      
appear  that the proteinochromogen1     
which could not be isolated by itself   
in sufficient purity for analysis1 must 
contain approximately #fa4jb  per cent4 
of carbon1 #f4hi per cent4 of hydrogen1 
#ac4fh per cent4 of  nitrogen1 #d4fi per
 cent4 of sulphur1 and #ac4ga per cent4 
of oxygen4  ,as a proteid-like body1 it 
is thus especially characterized by an  
exceedingly high content of carbon and a
 high content of sulphur4 ,as  a product
 of trypsin-proteolysis1 it must        
presumably come from the  cleavage of   
hemipeptone1 which1 however1 contains   
only #j4ge per cent4  of sulphur4 ,but  
as we have seen1 this latter body breaks
 down by  further cleavage into         
substances such as leucin1 tyrosin1     
lysin1 etc41  which contain no sulphur  
whatever1 and as there is no elimination
  of sulphur in this process through    
formation of hydrogen sulphide  gas or  
otherwise 7putrefaction being excluded  

by the presence of  either chloroform or
 thymol71 it follows that this surplus  
sulphur  must accumulate somewhere4 ,the
 high content of carbon1 however1 in    
proteinochromogen is sufficient evidence
 that the substance cannot  have its    
origin in a simple cleavage of          
hemipeptone4 ,on the other  hand1       
everything points to a synthetical      
process1 in which two or more  cleavage 
products of the proteid molecule combine
 and form a new body1  such as          
proteinochromogen1 containing all the   
sulphur cast off from the  hemipeptone  
in the production of the crystalline    
bodies1 and having in  itself properties
 common to peptone and to a body of the 
indigo-group1  the latter obviously     
coming from some aromatic antecedent4   
,in view of the apparent complexity of  
the processes attending                 
trypsin-proteolysis1 it is not strange  
that even simpler substances  than those
 already described should make their    
appearance4 ,thus1 when  it was         

suggested that ammonia1 ,,nh#c1 might be
 formed under the  influence of trypsin1
 it was not considered at all           
improbable1 for in  the hydrolytic      
decomposition of proteids by boiling    
dilute acid1 as  well as by baryta      
water1 it had long been known as a      
prominent product4  ,obviously1 in      
trypsin-proteolysis1 the one thing to be
 guarded against  in proving the        
formation of ammonia is the             
contaminating influence  of bacteria4   
,hirschler1#aia however1 with a full    
recognition of this  danger1 made       
digestions of blood-fibrin with trypsin 
extending only  through four hours and  
at a temperature of #cb ,c41 and yet he 
obtained  plain evidence of the         
formation of ammonia4 ,stadelmann1#aib  
with  still greater precautions to      
exclude all bacterial agencies1 using   
boiled fibrin as the material to be     
digested and thymol to prevent  any     
possible infection of the digestive     
mixture1 proved conclusively  that      

ammonia was formed as a result of       
trypsin-proteolysis4 ,thus1 in  the     
digestion of #ce grammes of boiled      
blood-fibrin with #fj c4 c4 of  a       
pancreas infusion for three days1 #bj4h 
milligrammes of ,,nh#c were  developed1 
presumably coming from the liberation of
 a certain amount  of nitrogen attendant
 upon the formation of such bodies as   
leucin and  tyrosin1 which contain      
considerably less nitrogen than their   
direct  antecedent hemipeptone1 or the  
original proteid4 ,we thus have striking
  proof of the ability of this peculiar 
proteolytic enzyme to set in  motion    
hydrolytic changes which may extend even
 to the production of  such simple      
substances as ammonia1 thus making still
 more striking  the parallelism between 
trypsin-proteolysis on the one hand1 and
 the  artificial hydrolysis produced by 
boiling dilute acids on the other4      
#aia ,bildung von ,ammoniak bei der     
,pancreasverdauung von ,fibrin4         
,zeitschr4 f4 physiol4 ,chem41 ,band    

#aj1 p4 #cjb4    #aib ,bildung von      
,ammoniak bei ,pancreasverdauung von    
,fibrin4 ,zeitschr4  f4 ,biol41 ,band   
#bd1 p4 #bfa4    ,in view of all these  
facts regarding the nature of the       
products  obtainable by pancreatic      
proteolysis1 it is very evident that    
many  chemical changes may take place   
side by side in a vigorous pancreatic   
digestion of proteid matter4 ,we know   
without a shadow of doubt that all  of  
the bodies enumerated as products of    
pancreatic digestion are the  results of
 trypsin-proteolysis1 and not the       
products of putrefactive  changes4      
,bacteria1 it is true1 are able to      
produce many like products1  and in the 
living intestinal tract exercise an     
important influence1  especially in the 
breaking down of resistant forms of     
proteid matter1  and in the             
decomposition of surplus material which 
has escaped the  pancreatic ferment4    
,but all the bodies described above are 
readily  obtainable by                  

trypsin-proteolysis under conditions    
which exclude all  possibility of       
bacterial action4    ,granting1 then1 as
 we must1 that these various bodies are 
all products  of pancreatic proteolysis 
when the process is carried on in       
beakers  or flasks1 we need to consider 
next how far such bodies appear in  the 
natural process as it takes place in the
 living intestine4 ,we  know indeed that
 the natural and the artificial         
processes are very  much alike so far as
 the qualitative results are concerned1 
but what  differences there may be      
between the quantitative relationships  
in the  two cases is less certain4 ,one 
might naturally reason that1 with the   
facilities for rapid absorption that    
exist in the small intestine1           
trypsin-proteolysis would rarely proceed
 beyond the peptone stage1  yet we have 
ample evidence that1 under some         
circumstances at least1  both leucin and
 tyrosin are formed in considerable     
quantities in the  intestine4    ,it    

obviously makes a very great difference 
to the economy in what  form the proteid
 matter ingested leaves the intestine on
 its way into  the blood-current4 ,it   
has been more or less generally assumed 
that1  under the ordinary circumstances 
existent in the intestinal tract1 the   
crystalline and other bodies coming from
 the more profound changes  incidental  
to trypsin-digestion are rarely formed1 
mainly on the  ground that such         
transformations would entail great loss 
of nutritive  material to the blood4    
,years ago1 ,schmidt-,mlheim#aic made a 
series  of experiments on the changes   
which proteid foods undergo in different
  portions of the alimentary tract1 from
 which he concluded that leucin  and    
tyrosin are formed in such small        
quantities in natural pancreatic        
digestion that they represent only a    
very small part of the nitrogen         
absorbed from the intestine4 ,this      
conclusion has been more or less        
generally accepted1 especially as       

several observers have reported  finding
 only small amounts of these bodies in  
the intestine under what  might be      
assumed to be favorable circumstances   
for their formation4 ,in  artificial    
digestions1 on the other hand1 as we    
have seen1 leucin and  tyrosin1 together
 with the other simple bodies described1
 may appear  in large quantities4       
,obviously1 two suggestions present     
themselves as  explanatory of this      
difference2 either there is such a rapid
 absorption  of these crystalline       
products from the intestine that they   
cannot be  detected other than as mere  
traces1 or else the natural process     
takes  a different course from the      
artificial1 owing to the rapid          
withdrawal  from the intestine of the   
antecedent of the leucin and tyrosin1   
viz41  the hemipeptone4    #aic         
,untersuchungen ber die ,verdauung der  
,eiweisskrper4 ,du  ,bois-,reymond's    
,archiv f4 ,physiol41 #ahgi1 p4 #ci4    
,concerning this point1 ,lea#aid has    

recently reported some experimental     
evidence obtained by a comparative study
 of artificial pancreatic  digestion as 
carried on in a flask1 with similar     
digestions carried on  in parchment     
dialyzer tubes1 the latter so arranged  
that the diffusible  products of        
proteolysis can pass from the tube into 
the surrounding  fluid4 ,as ,lea justly 
says1 this whole question of the        
formation  of leucin by proteolysis is a
 very important one1 since it bears     
closely upon one of the possible methods
 by which urea may be quickly  formed   
from proteid food4 ,thus1 we have       
evidence that when leucin is            
administered to mammals a portion of its
 nitrogen1 at least1 quickly  reappears 
as urea and uric acid in the urine4#aie 
,further1 there is  a certain amount of 
evidence that this transformation takes 
place in  the liver1 viz41 in the organ 
where leucin absorbed from the intestine
  would naturally be first carried4#aif 
#aid ,a ,comparative ,study of          

,artificial and ,natural ,digestions4   
,journal  of ,physiology1 vol4 xi1 p4   
#bbf4    #aie ,e4 ,salkowski3 ,weitere  
,beitrge zur ,theorie der               
,harnstoffbildung4  ,zeitschr4 f4       
,physiol4 ,chem41 ,band #d1 pp4 #ee and 
#ajj4    #aif ,w4 ,salomon3 ,ueber die  
,vertheilung der ,ammoniaksalze im      
thierischen ,organismus und ber den ,ort
 der ,harnstoffbildung4 ,virchow's      
,archiv1 ,band #ig1 p4 #adi4            
,obviously1 the main point to be gained 
in a dialyzer-experiment is  the removal
 of the soluble products of digestion as
 soon as they are  formed2 but peptones 
are not rapidly diffusible1 and the     
process1  as noted under the head of    
gastric digestion1 cannot be considered 
in any sense as yielding the same       
results as might be obtained in  the    
living intestine4 ,still1 the method    
offers a closer approach  to the natural
 process than when carried on in a      
flask1 and the  results are of interest4
 ,thus1 ,lea finds in the first place   

that  in a dialyzer-digestion the       
proteid is more quickly dissolved1 and  
that there is far less tendency for the 
formation of an insoluble  antialbumid  
with its natural resistance to the      
ferment4 ,still1 it is  to be noticed   
that the amount of this                 
antialbumid-residue formed by           
trypsin-proteolysis in a flask is mainly
 dependent upon the strength  of the    
ferment solution1 and the character of  
the proteid undergoing  digestion4 ,if  
the latter is in a fairly digestible    
form1 and the enzyme  solution          
reasonably active1 then even the        
flask-digestion may show  almost no     
residue of antialbumid4 ,yet there is at
 least a shade of  difference in the two
 cases1 which may be expressed by the   
statement  that trypsin-proteolysis1 as 
carried on in a dialyzer-tube1 is prone 
to give less insoluble antialbumid than 
a corresponding digestion  in a flask4  
,further1 the amount of leucin and      
tyrosin formed in a  flask-digestion is 

always greater than in a                
dialyzer-digestion1 other  conditions   
being equal4 ,naturally1 these results  
help us very little  in drawing any     
conclusions regarding the extent to     
which leucin and  tyrosin may be formed 
in the intestine4 ,they merely emphasize
 the  fact that the withdrawal of a     
certain quantity of hemipeptone from    
the digestive mixture tends to reduce by
 so much the yield of leucin  and       
tyrosin4 ,it is hardly to be assumed1   
however1 that the rate of  withdrawal of
 peptone from the intestine can keep    
pace with its  formation1 especially    
when it is remembered that the proteid  
matter  coming into the small intestine1
 owing to its preliminary treatment  in 
the stomach1 is in a comparatively      
digestible condition4 ,further1  the    
pancreatic juice is a remarkably active 
fluid1 and proteolysis  under its       
influence must make rapid strides4 ,i   
can easily conceive  that proteolysis by
 trypsin1 when carried on in a flask1   

may lead to  the formation of much      
larger amounts of leucin and tyrosin1   
and of  other bodies as well1 than      
occurs in the natural process2 but there
 is  certainly no ground for the belief 
that leucin and tyrosin are wholly      
wanting in pancreatic proteolysis as it 
occurs in the intestine4    ,with a view
 to obtaining some positive evidence on 
this point ,i have  tried a few         
experiments on animals1 the results of  
which have convinced  me that1 in the   
case of dogs1 at least1 both leucin and 
tyrosin may  be formed in natural       
pancreatic digestion in considerable    
quantities4  ,thus1 in one experiment a 
good sized dog1 kept without food for   
two  days1 was fed four hundred grammes 
of chopped lean beef at #h ,a4,m4  ,at  
#b ,p4,m4 the animal was killed and the 
intestine ligatured close  to the       
pylorus4 ,the lower end of the small    
intestine was likewise  ligatured4 ,the 
portion inclosed between the two        
ligatures was then  removed from the    

body1 and the contents of the intestine 
pressed and  rinsed out with distilled  
water4 ,in the stomach1 was found a     
small  amount of semi-digested matter   
weighing about fifty grammes4 ,the      
material obtained from the intestine was
 strained through mull1 the  fluid      
rendered faintly acid with acetic acid1 
and heated to boiling4  ,the clear      
filtrate from this precipitate was      
concentrated to a very  small volume1   
and while still hot precipitated with a 
large amount of  ninety-five per cent4  
alcohol4 ,a small gummy precipitate     
resulted1  which was thoroughly         
extracted with boiling alcohol and the  
washings  added to the alcoholic        
filtrate4 ,the precipitate contained    
some  deuteroproteose and a small amount
 of true peptone4    ,the alcoholic     
fluids were evaporated to a small volume
 and set aside  in a cool place4 ,as a  
result1 quite a separation of leucin and
 tyrosin  occurred in the characteristic
 crystalline forms4 ,no attempt was     

made to effect a quantitative separation
 of the two bodies1 but the  mixed      
precipitate finally obtained weighed1   
after recrystallization1  over          
three-fourths of a gramme4 ,leucin was  
plainly in excess1 but  considerable    
tyrosin must have been left in the      
alcoholic precipitate1  owing to its    
greater insolubility in this menstruum4 
,this experiment  is almost a           
counterpart of one reported by ,lea1#aig
 and like  his indicates that both      
leucin and tyrosin may be formed in not 
inconsiderable quantities by pancreatic 
proteolysis as it occurs in  the        
intestine4 ,this being so1 one is       
naturally called on to explain  8the    
physiological significance of a process 
which at first sight  appears to result 
in a degradation of the potential energy
 of proteids1  under conditions such    
that the energy set free can be of      
little use  to the economy40#aih ,but it
 is quite possible1 as ,lea has         
suggested1  that these amido-bodies have

 an important part to play in some of   
the synthetical or other processes of   
the organism1 and that their  formation 
is consequently necessary for the       
well-being of the body4  ,whether this  
is so or not1 we may well consider the  
formation of these  amido-acids in      
pancreatic proteolysis as a means of    
quickly ridding the  body of any excess 
of ingested proteid food1 with the least
 possible  expenditure of energy on the 
part of the system4 ,this has always    
seemed  to me the probable purpose of   
the profound changes which the          
pancreatic  ferment is capable of       
inducing4    #aig ,journal of           
,physiology1 vol4 xi1 p4 #bee4    #aih  
,lea3 loc4 cit4    ,the primary object  
of both gastric and pancreatic          
proteolysis is to  render the proteid   
foods more easily available for the     
needs of the  economy1 viz41 to aid in  
their absorption and consequent         
distribution  to the master tissues and 
organs of the body4 ,this is doubtless  

fully accomplished by the formation of  
the so-called primary and  secondary    
products of proteolysis1 i4 e41 the     
proteoses and peptones  which are1      
comparatively1 not far removed from the 
mother-proteid1  except in solubility   
and other minor points4 ,in the ferment 
trypsin1  however1 we have a special    
agent endowed with the power of carrying
  on the hydrolytic cleavage to a point 
where exceedingly simple bodies  result1
 and through whose agency any excess of 
proteid material in the  intestinal     
canal may be quickly broken down into a 
row of products  easily removed from the
 system4 ,it is to be remembered1       
however1 that  the very nature of the   
proteid molecule precludes the          
possibility  of anything like a complete
 decomposition into crystalline or other
  simple products4 ,full fifty per cent4
 of the peptone formed must  be         
antipeptone1 which cannot be further    
changed by trypsin under  any           
circumstances1 so that1 whether the     

amount of proteid in the  intestine be  
large or small1 or whether it is exposed
 for a longer or  shorter period to     
trypsin-proteolysis1 there will always  
be a fairly  large amount for           
absorption4 ,this may well be considered
 as one of  the reasons for the peculiar
 structure of the proteid molecule1 the 
anti-group being always available for   
the direct nutrition of the body1  while
 the representatives of the hemi-group1 
especially when proteid is  present in  
excess1 can be quickly and readily      
broken down into simple  products4 ,in  
other words1 the direct formation of    
these simple bodies  in the intestine   
furnishes a short path to urea1 thus    
leading to the  rapid elimination of any
 excess of proteid material4    ,we may 
well attribute to the epithelial cells  
of the intestine the  power1 under      
normal circumstances1 of regulating and 
controlling1 even  though indirectly1   
the order of events in the intestine4   
,just as the  so-called secreting cells 

of the tubuli uriniferi may lose for a  
time  their power to pick out from the  
blood material destined for the urine1  
being clogged or exhausted by continued 
effort1 so the epithelial cells  of the 
intestine1 which play such an important 
part in the absorption  of proteid      
matters from the alimentary tract1 may1 
in the presence  of an excess of proteid
 matter1 become temporarily exhausted1  
and1  refusing passage to the proteoses 
and peptone formed by proteolysis1      
render possible further hydrolytic      
cleavage into leucin1 tyrosin1  lysatin1
 etc42 bodies which1 by one method or   
another1 can be readily  transformed    
into urea4 ,at the same time1 as already
 stated1 it seems  more than probable   
that some formation of these amido-acids
 always  occurs in the intestine1 and   
that these bodies have some specific    
part  to play in the normal processes of
 metabolism going on in the body4  ,the 
more one studies the processes of       
nutrition in general1 the more  one is  

impressed with the view that there is a 
purpose in everything1  and that the    
formation of even such bodies as leucin 
and tyrosin may  be connected with      
hidden processes1 the key to which has  
not yet  been found4 ,we see an         
analogous case1 perhaps1 in the action  
of the  inorganic salts in nutrition1   
some of which1 at least1 neither undergo
  change themselves nor induce changes  
in other substances1 and yet we  know   
their presence is indispensable for     
keeping up the normal rhythm  of the    
nutritional processes of the body4      
,,absorption ,,of ,,the ,,main          
,,products ,,of ,,proteolysis4    ,in   
ordinary proteolytic action1 both in the
 stomach and intestine1  it is very     
apparent that the primary products of   
proteolysis1 the  proteoses and         
peptones1 are the chief products formed1
 and that under  normal circumstances   
the greater portion of the proteid food 
finds its  way from the alimentary canal
 into the blood1 after transformation   

into one or more of these two classes of
 products4 ,at the same  time1 it must  
be borne in mind that even the          
acid-albumin formed by                  
pepsin-hydrochloric acid may be absorbed
 without undergoing further  change4    
,the view once held1 that the rate of   
absorption from the  alimentary tract   
stands in close relation to the         
diffusibility of the  products formed1  
and that non-diffusible substances are  
incapable of  absorption1 is no longer  
tenable4 ,absorption from the intestine 
is to  be considered rather as a process
 involving the vital activity of the    
epithelial cells of the intestinal      
mucous membrane1 where chemical         
affinities and other like factors play  
an important part in determining  the   
rate and order of transference through  
the intestinal walls into  the blood and
 lymph4 ,thus1 we have abundant evidence
 that native  proteids which have not   
undergone proteolysis may be absorbed   
from  the intestine1 at least to a      

certain extent1 provided they have been 
dissolved2 i4 e41 converted into        
acid-albumin1 or alkali-albuminate1  by 
the gastric or pancreatic juice4 ,we    
have a practical demonstration  of this 
possibility in the early experiments of 
,voit and ,bauer1#aii as  well as in    
many later ones that need not be        
mentioned here4 ,further1  the recent   
experiments of ,huber#bjj have given us 
quantitative data  on the rate of       
absorption of fluid egg-albumin when    
introduced into  the large intestine in 
the form of a clyster1 showing that even
 fairly  large amounts of a natural     
proteid may be absorbed without         
undergoing  proteolysis if mixed with a 
neutral salt1 like sodium chloride4 ,to 
be  sure1 the rate of absorption is     
greatly increased when the albumin has  
been peptonized1 but still absorption of
 the native proteid is possible  without
 the agency of proteolytic enzymes4     
,when1 however1 large amounts  of       
egg-albumin are introduced into the     

intestine1 albuminuria may  result1 as  
you very well know4    #aii ,ueber die  
,aufsaugung im ,dick und ,dnndarm1      
,zeitschr4 f4 ,biol41  ,band #e1 p4     
#efb4    #bjj ,ueber den ,nhrwerth der  
,eierklystiere1 ,arch4 f4 klin4 ,med41  
,band  #dg1 p4 #die4    ,moreover1 it is
 well known that the proteids of        
muscle-tissue1 in the  form of syntonin1
 may be absorbed from the large         
intestine without  undergoing further   
hydration4 ,when introduced into the    
rectum of a  hungry dog1 the excretion  
of urea may be at once increased and the
  animal brought into a condition of    
nitrogenous equilibrium2 absorption     
taking place from a portion of the large
 intestine1 where proteolysis  is never 
known to occur4#bja    #bja ,eichhorst3 
,ueber die ,resorption der ,albuminate  
im ,dickdarm1  ,pflger's ,archiv f4     
,physiol41 ,band #d1 p4 #egj4    ,again1
 ,neumeister#bjb has shown that the     
direct introduction of  syntonin1       
alkali-albuminate1 crystalline          

phytovitellin1 as well as  pure         
serum-albumin1 into the blood of the    
jugular vein is not attended  with the  
appearance of albumin in the urine4 ,on 
the contrary1 the  proteid matter so    
introduced appears to be assimilated and
 utilized  for the needs of the         
organism4 ,evidently1 then1 these       
substances are  not to be considered as 
foreign bodies1 for if so the kidneys   
would  undoubtedly make some effort to  
remove them from the circulation4 ,it is
  to be noted1 however1 that all native 
proteids are not assimilated in  this   
manner1 as casein1#bjc gelatin1#bjd and 
especially egg-albumin4  ,thus1 ,j4 ,c4 
,lehman1#bje working under ,khne's      
direction1 observed  that the injection 
of a carefully filtered solution of     
egg-albumin into  the veins of a dog was
 always accompanied by albuminuria1     
while similar  injections of            
,lieberkhn's sodium albuminate1 or of   
syntonin from  frog's muscle1 failed to 
show any such result4    #bjb ,zur      

,physiologie der ,eiweissresorption und 
zur ,lehre von den  ,peptonen1          
,zeitschr4 f4 ,biol41 ,band #bg1 p4     
#cji4    #bjc ,neumeister3 ,sitzungsber4
 der ,physik4 med4 ,gesellsch4 zu       
,wrzburg1  #ahhi1 p4 #gc4    #bjd ,f4   
,klug3 ,pflger's ,archiv f4 ,physiol41  
,band #dh1 p4 #abb4    #bje ,virchow's  
,archiv1 ,band #cj1 p4 #eic4    ,while  
these observations tend to show that    
some native proteids may  be absorbed   
from the alimentary tract without       
previously undergoing  proteolysis1 it  
is not to be understood that any        
considerable quantity  is so absorbed   
under normal circumstances4 ,doubtless1 
when small  amounts of proteid food are 
taken1 its denaturalization by the      
primary  action of the gastric or       
pancreatic juice1 viz41 its conversion  
into  syntonin or alkali-albuminate1 may
 be sufficient to insure its partial    
absorption1 but digestive proteolysis is
 unquestionably a necessary  preliminary
 to any general absorption1 and there   

can be no manner of  doubt that the     
greater portion of the proteid food is  
absorbed as  proteoses and peptone4     
,peptones1 as we have seen1 are         
possessed of  a higher endosmotic       
equivalent than the proteoses1 but we   
need to  keep continually in mind the   
possibility that the selective power of 
the epithelial cells of the intestinal  
mucosa may lead to as rapid             
transference of the proteoses as of the 
more diffusible peptones4 ,it  is not to
 be understood by this1 however1 that   
diffusibility is of no  consequence in  
determining the rate of absorption4     
,surely1 everything  else being equal1  
the more diffusible the substance the   
more rapid will  be its passage from the
 intestine into the blood-current4 ,the 
more  the process of absorption is      
studied1 however1 the more clearly do we
  see its dependence upon the functional
 power of the living epithelial  cells1 
a fact which plainly emphasizes the     
physiological nature of the  process4   

,further1 as already stated1 absorption 
of proteid food-stuffs1 or their        
products1 from the alimentary tract1 is1
 under ordinary circumstances  at least1
 limited to the intestine2 from the     
stomach there is  comparatively little  
absorbed1 and if necessary we might     
advance this  fact as an important      
argument against the theory of general  
absorption  of proteids in the form of  
acid-albumin4 ,even such indifferent    
fluids  as water1 or physiological salt 
solution1 are absorbed with extreme     
slowness from the stomach2#bjf this     
organ showing very little ability  to   
take up water even when the             
blood-vessels are dilated1 as after the 
ingestion of food4    #bjf ,j4 ,s4      
,edkins3 ,the ,absorption of ,water in  
the ,alimentary ,canal4  ,journal of    
,physiol41 vol4 #ac1 p4 #dde4    ,this  
brings us to a very important point in  
connection with the  utilization by the 
system of the ordinary products of      
proteolysis4  ,the latter1 as we have   

seen1 are mainly proteoses and peptones1
 and  yet all the evidence points       
clearly to the fact that these          
substances  are never present1 at least 
in any quantity1 in the blood or lymph1 
even when digestive proteolysis is at   
its height4 ,further1 the very  nature  
of the proteoses and peptones1 their    
marked physiological action  when they  
are introduced directly into the        
circulating blood1 their  rapid         
excretion1 either as proteoses or       
peptones1 by the kidneys when  so       
introduced1#bjg all indicate that they  
are foreign substances1  totally out of 
their natural environment when          
introduced into the  blood-current4 ,and
 yet we very well know that proteoses   
especially are  possessed of high       
nutritive qualities2 they are abundantly
 able to  support animal life4 ,thus1   
,politzer#bjh found by feeding          
experiments  with heteroalbumose1       
dysalbumose1 and protoalbumose1 that    
these bodies  taken into the stomach    

have the same nutritive value as meat4  
,various  feeding experiments with      
proteoses from different sources1       
carried out  in my laboratory on young  
dogs1 have shown conclusively that for  
short  periods of time1 at least1 these 
hydrolytic cleavage products are fully  
as capable of sustaining the nitrogenous
 equilibrium of the body as the         
proteids from which they are derived4   
,in fact1 the results obtained  favor   
the view that the proteoses1 weight for 
weight1 possess a higher  nutritive     
value than fresh beef4#bji ,it may be   
questionable1 however1  whether such a  
result would follow in experiments      
conducted over longer  periods of time1 
but of this we may be certain1 that the 
proteoses  formed in the alimentary     
tract can be absorbed and utilized by   
the  system without their exerting any  
toxic action whatever4    #bjg ,franz   
,hofmeister3 ,ueber das ,schicksal des  
,peptons im ,blute1  ,zeitschr4 f4      
physiol4 ,chem41 ,band #e1 p4 #abe4     

#bjh ,ueber den ,nhrwerth einiger       
,verdauungsproducte des ,eiweisses1     
,pflger's ,archiv f4 ,physiol41 ,band   
#cg1 p4 #cja4    #bji ,compare          
,hildebrandt1 ,zur ,frage nach dem      
,nhrwerth der ,albumosen1  ,zeitschr4 f4
 physiol4 ,chem41 ,band #ah1 p4 #abj4   
,consequently1 we are forced to the     
conclusion that these primary  products 
of proteolysis1 so important in the     
nutrition of the animal  body1 must     
undergo some change during the process  
of absorption1 by  which they are       
converted into new bodies1 less toxic in
 their nature1  and better adapted for  
the direct nutritional needs of the     
organism4  ,the same statement applies  
likewise to peptones4    ,the fact that 
peptones are not discoverable in the    
blood and lymph1  even during or after  
active digestion1 was practically       
ascertained  years ago by such          
well-known workers as ,maly1            
,adamkiewicz1 and others4  ,the natural 
supposition following this observation  

was that the  products of proteolysis   
underwent some change in the hepatic    
cells2 but  this view was soon shown to 
be untenable by examination of the      
portal  blood1 which was found to be as 
free from peptone as the blood of the   
hepatic vein4 ,neumeister1#baj using the
 more modern methods of work  and with  
the wider knowledge gained during these 
latter years1 has  shown conclusively   
that proteoses and peptones are never   
present in  the blood1 even when these  
substances are contained in the         
intestine  in fairly large amounts4 ,i  
can corroborate these statements from   
the  results of my own experiments in   
this direction4 ,thus1 ,i have taken a  
dog in full digestion1 fed with an      
abundance of meat1 and collecting  the  
blood from the carotid artery have made 
a careful examination  for peptone1 by  
the following method3 ,the blood was    
allowed to flow  directly into a dilute 
solution of ammonium sulphate1          
sufficiently  strong to prevent         

coagulation1 and then shaken with ether 
to rupture  the red blood-corpuscles4   
,the solution1 freed from ether1 was    
next  saturated with crystals of        
ammonium sulphate1 by which the proteid 
matter was completely precipitated4 ,the
 clear filtrate was then  concentrated  
somewhat1 the excess of the ammonium    
salt removed by  filtration1 and the    
filtrate carefully tested for peptone by
 addition  of a large volume of a       
saturated solution of potassium         
hydroxide and  a few drops of a dilute  
solution of cupric sulphate4 ,the test  
was  wholly negative1 although the      
intestine of the animal showed the      
presence of both peptone and proteoses4 
,this result1 as ,i have said1  is      
simply confirmatory of work done by     
others in this direction1  notably      
,neumeister1 and illustrates the        
statement that peptones are  not to be  
found in the circulating blood1 even    
after a full proteid  diet4 ,in this    
connection it is to be remembered that  

we have abundant  proof of the rapid    
disappearance of both proteoses and     
peptones#baa  from the intestine1 either
 by absorption or otherwise4 ,they      
certainly  disappear1 and1 as we have   
seen1 are not to be found in the blood4 
,further1 ,neumeister has confirmed the 
original observation of                 
,schmidt-,mulheim1#bab that both chyle  
and lymph are practically free  from    
proteoses and peptone1 thus again       
forcing us to the conclusion  that the  
primary products of proteolysis must    
undergo change prior to  their passage  
into the blood or lymph4    #baj ,ueber 
die ,einfhrhrung der ,albumosen und     
,peptone in den  ,organismus1 ,zeitschr4
 f4 ,biol41 ,band #bd1 p4 #bgg4    #baa 
,rohmann3 ,ueber ,secretion und         
,resorption im ,dnndarm1 ,pflger's      
,archiv f4 ,physiol41 ,band #da1 p4     
#ddj4    #bab ,du ,bois-,reymond's      
,archiv f4 ,physiol41 p4 #cc1 #ahhj4    
,many observations lend favor to the    
view that a transformation of  some kind

 takes place in the intestine itself1   
not indeed in the  lumen of the tube1   
but somewhere in the walls1 through     
which the  peptones must pass before    
reaching the blood4 ,thus1 peptones     
placed in  contact with pieces of the   
isolated1 though still living1          
intestine1  after a time completely     
disappear from view1#bac so completely  
that  no reaction can be obtained even  
by the most delicate of tests4 ,in      
support of this statement ,i may cite   
the results of several of my  own       
experiments which certainly furnish     
evidence that true peptones  undergo    
profound alteration by simple contact   
with the living mucous  membrane of the 
small intestine4 ,the method employed   
was similar to  that made use of some   
years ago in a study of the influence of
 peptone  on the post-mortem formation  
of sugar in the liver4#bad ,a large1    
well-nourished rabbit was killed by     
severing the carotid artery and the     
blood collected and defibrinated4 ,of   

this1 #ej c4 c4 were mixed with an      
equal volume of #j4e per cent4 salt     
solution containing #a4be grammes of    
pure amphopeptone1 prepared from        
egg-albumin1 the mixture obviously      
containing #a4be per cent4 of peptone4  
,the fluid was transferred to a  large1 
roomy flask1 provided with a stopper    
having two holes1 in one  of which was  
fitted a long glass tube reaching below 
the fluid4 ,the  flask1 with its        
contents1 was then placed in a suitable 
water-bath at a  temperature of #dj ,c4 
#bac ,salvioli3 ,eine neue ,methode fr  
die ,untersuchung der ,functionen  des  
,dnndarms1 ,du ,bois-,reymond's ,archiv 
f4 ,physiol41 #ahhj4 ,supplement  ,band1
 p4 #aab4 ,neumeister3 ,zur ,physiologie
 der ,eiweissresorption und zur  ,lehre 
von den ,peptonen1 ,zeitschr4 f4 ,biol41
 ,band #bg1 p4 #cbd4    #bad ,chittenden
 and ,lambert3 ,studies in ,physiol4    
,chem41 ,yale ,univer41  vol4 i41 p4    
#aga4    ,the small intestine of the    
rabbit was carefully separated from the 

mesentery and from the pancreatic gland1
 and the upper portion cut  open and    
quickly washed free from any contained  
matter or adherent  secretions1 by      
repeated immersion in #j4e per cent4    
salt solution warmed  at #dj ,c4 ,this  
was repeated until the tissue was quite 
free from all  impurities1 after which  
it was cut into small pieces and        
immersed for  a moment in a #j4e per    
cent4 solution of sodium chloride       
containing  #a4be per cent4 of peptone4 
,the tissue was then carefully collected
 on  coarse muslin1 allowed to drain1   
and then quickly transferred to the     
flask containing the warm blood and     
peptone4 ,this mixture was kept at  #dj 
,c4 for two hours1 a slow current of air
 being bubbled through the  fluid during
 the entire period4 ,at the expiration  
of this time the  fluid was separated   
from the pieces of tissue by nitration  
through  muslin1 and then saturated with
 ammonium sulphate after the usual      
method for the separation of albumoses1 

etc4 ,on now testing a portion  of the  
clear filtrate for peptone by the biuret
 test1 not a trace of  a reaction could 
be obtained4 ,the entire amount of      
proteid matter  present was precipitated
 by the ammonium salt1 thus showing that
 the  peptone originally added had been 
completely transformed into something   
precipitable by saturation of the fluid 
with ammonium sulphate4 ,that  this     
transformation of the peptone was       
accomplished mainly through the  action 
of the intestine1 was shown by a        
parallel experiment1 in which  all of   
the above conditions were duplicated1   
omitting only the pieces  of intestine4 
,here1 however1 on testing the filtrate 
from the ammonium  sulphate-precipitate1
 a strong biuret reaction was obtained1 
thus  proving the presence of at least  
some unaltered peptone4    ,this        
experiment is almost a counterpart of   
one reported by ,neumeister1  and like  
his1 testifies to the probability that  
the peptones formed in  the alimentary  

tract1 as a result of proteolysis1      
undergo retrogression  through the      
agency of the epithelial cells of the   
intestinal walls  during their          
absorption4 ,i have tried similar       
experiments with  deuteroproteose1      
notably with deuterocaseose1 and have   
obtained  corresponding results4 ,the   
same method may be employed as that     
already  outlined1 although of course   
the deuterocaseose is in great part     
precipitated by saturation with ammonium
 sulphate4 ,still1 this form  of        
deuteroproteose1  deuterocaseose1 as ,i 
have elsewhere noted1 is  very slowly   
precipitated by the ammonium salt4      
,consequently1 it is an  easy matter to 
demonstrate that this proteose1 on      
treatment with the  intestinal mucosa in
 the presence of blood at the           
body-temperature1  is transformed into  
something completely and readily        
precipitable by  ammonium sulphate2 the 
filtrate from the latter failing to show
 any  biuret reaction1 although the     

corresponding control experiment without
  the intestine gives a bright violet   
color with cupric sulphate and          
potassium hydroxide4    ,hence1 we are  
certainly justified in saying that both 
peptones and  proteoses undergo some    
retrogression when in contact with the  
walls of  the intestine4 ,moreover1     
there is some evidence that the         
proteoses1  before undergoing such a    
transformation1 are first converted into
  peptone by the action of the          
intestinal walls1 a statement which will
  apparently apply to both the primary  
and secondary proteoses4 ,this  primary 
action of the intestinal walls is not   
considered as due to any  adherent      
trypsin1 or to possible traces of succus
 entericus1 but rather  as a part of the
 action of the living epithelial cells1 
or perhaps as  connected with the       
possible presence of lower organisms not
 removable  from the intestinal wall by 
ordinary washing4    ,the transformation
 of peptones by the substance of the    

intestine  is apparently common to the  
intestinal tract of many animals1 and   
perhaps to all1 and indeed can also be  
accomplished by the liver4#bae  ,this   
latter fact is of some importance1 since
 it adds weight to the  supposition that
 this peculiar action of the intestine  
cannot be due  to the possible presence 
of trypsin2 a view which is strengthened
 by  the fact that a glycerin-extract of
 the intestine has no action on         
amphopeptone4 ,certainly1 the latter    
shows no diminution in the strength  of 
the biuret reaction after long contact  
at body temperature with  such an       
extract4 ,further1 it has been shown    
that antipeptone1 which  is not affected
 by the pancreatic enzyme1 suffers the  
same change  as amphopeptone by contact 
with the intestine4 ,far more probable  
is  it that retrogression or            
transformation of peptone by the        
substance  of the intestine1 is due to  
the vital activity of some or all of    
the epithelial cells of the intestinal  

mucosa2 a characteristic  possibly      
shared by some or all of the hepatic    
cells of the liver4 ,the  kidney-cells  
certainly do not possess this power1 but
 we can see a  special fitness in the   
liver-cells being endowed with the      
ability to  quickly break down1 or      
transform1 any peptone or proteose that 
might by  chance escape unaltered from  
the intestinal tract4 ,shore1#baf       
however1  inclines to the view that the 
hepatic cells do not possess this power 
to any great extent1 in opposition to   
the older views of ,plsz and            
,gyergai1#bag as well as of ,seegen#bah 
and of ,neumeister4    #bae ,neumeister3
 ,zeitschr4 f4 ,biol41 ,band #bg1 p4    
#ccb4    #baf ,on the ,fate of ,peptone 
in the ,lymphatic ,system1 ,journal of  
,physiol41 vol4 xi41 p4 #ebh4    #bag   
,ueber ,peptone und ,ernhrung mit       
denselben1 ,pflger's ,archiv f4         
,physiol41 ,band #aj1 p4 #ecf4    #bah  
,zur ,umwandlung des ,peptons durch die 
,leber1 ,ibid41 ,band #cg1  p4 #cbe4    

,with reference to the action of the    
stomach-mucosa on proteoses1 it  has    
been shown#bai that when relatively     
large amounts 7#e grammes7  are         
introduced into the stomach of a rabbit1
 the pylorus being  ligatured1 both     
proteoses and peptones may appear in the
 urine1 thus  indicating that while they
 may be absorbed to some extent under   
the  above conditions1 the proteoses are
 not readily transformed into  native   
proteids without exposure to the        
intestine4 ,smaller amounts  7#b        
grammes71 however1 may1 under the above 
conditions1 be completely  transformed2 
at least ,hildebrandt claims this to be 
the case1 mainly on  the ground that    
after the introduction of albumoses into
 the stomach1  the pylorus being        
ligatured1 no trace of them can be found
 in the  urine4 ,the same observer also 
claims that blood-serum1 in the case of 
dogs1 is able to transform albumoses    
into ordinary serum-globulin4           
,certainly1 after intra-venous          

injection1 proteoses disappear from the 
blood1 but1 as we shall see later on1 a 
certain amount1 at least1 may  be       
transferred to the lymph4 ,it is also   
claimed that when albumoses  are        
injected subcutaneously1 neither        
albumoses nor peptones are to be        
detected in the urine4 ,this1 however1  
seems hardly probable in the  light of  
what has been said1 and especially in   
view of the fact that  ,neumeister's    
experiments tend to show that even #j4a 
gramme of albumoses  introduced         
subcutaneously may give rise to         
temporary albuminuria4    #bai          
,hildebrandt3 ,zur ,frage nach dem      
,nhrwerth der ,albumosen1  ,zeitschr4 f4
 physiol4 ,chem41 ,band #ah1 p4 #ahj4   
,assuming for the moment that the chief 
products of proteolysis1  i4 e41 the    
proteoses and peptones1 are1 during the 
act of absorption1  transformed through 
the vital processes of the epithelial   
cells of the  intestine into            
serum-albumin1 or globulin1 and absorbed

 as such into  the blood1 we may well   
consider whether such transformation1 i4
 e41 a  retrogression into a native     
proteid again1 is inconsistent1 or out  
of  harmony1 with the general character 
of the changes known to occur in  the   
body4 ,in attempting to answer this     
question we need not look far  to find a
 perfectly analogous case4 ,thus1 in the
 digestion of starchy  foods by the     
amylolytic ferments of both the saliva  
and the pancreatic  juice1 the          
carbohydrate material undergoes         
hydration with formation  of dextrins   
and maltose1 the latter1 at least1 being
 quickly absorbed  into the circulating 
blood4 ,but large quantities of sugar in
 the blood  are certainly inimical to   
the well-being of the organism1 and we  
find  in the liver a tendency for the   
sugar to undergo a transformation1  i4  
e41 a retrogression into glycogen1      
either through simple  dehydration or   
otherwise4 ,further1 with reference to  
the possible  conversion of proteoses   

into peptone by the substance of the    
intestine1  we have a perfectly         
analogous case in the behavior of the   
intestinal  mucous membrane toward      
maltose1 the final product of amylolytic
 action4  ,thus1 according to the recent
 work of ,m4 ,c4 ,tebb1#bbj the mucous  
membrane of the intestine has the power 
of transforming maltose into  dextrose2 
simple warming at #dj ,c4 of a solution 
of maltose in #j4e per  cent4 sodium    
carbonate with a few grammes of the     
dried mucous membrane  from the         
intestine1 being sufficient to insure a 
marked conversion of  maltose into the  
higher-reducing sugar1 dextrose4 ,this  
observation1  ,i can confirm from       
experiments just completed in my own    
laboratory4  ,this action is presumably 
due to a ferment1 which1 according to   
,tebb1  is widely distributed throughout
 the body1 being present not only  in   
the intestine1 but also in the liver1   
kidney1 spleen1 striated  muscle-tissue1
 and1 indeed1 in the blood-serum2 so    

that it would appear  that nearly all   
the tissues of the body are endowed with
 the power of  transforming maltose into
 dextrose4 ,these statements being      
correct1 it  would seem that1 while the 
amylolytic ferments of the several      
digestive  juices transform1 by         
hydrolytic action1 starchy foods into   
maltose1  the latter is exposed during  
its passage through the intestinal wall1
  as well as in the blood itself1 to    
another ferment which carries the       
hydration still further1 with formation 
of dextrose2 and yet the latter  product
 is destined1 in part at least1 to      
undergo retrogression into a            
starch-like body1 i4 e41 glycogen1      
before it is completely utilized  by the
 system4 ,thus1 the analogy between     
these carbohydrate bodies and  the      
products of proteolysis is complete1 and
 we may well accept the  statements     
already made regarding the ultimate fate
 of the proteoses  and peptones formed  
during proteolysis1 as in no way        

inconsistent with  the general tenor of 
events going on in the body4    #bbj ,on
 the ,transformation of ,maltose to     
,dextrose1 ,journal of  ,physiol41 vol4 
xv1 p4 #dba4    ,while we are inclined  
to believe that the chemical changes    
attending  the absorption of proteoses  
and peptones occur mainly in the        
epithelial  cells of the intestinal     
mucosa1 and that there is a direct      
transference  of the alteration-products
 to the blood1 there are still other    
views  that cannot be wholly ignored4   
,thus1 the view originally advanced by  
,hofmeister1#bba in which special stress
 is laid upon the functional  activity  
of the leucocytes of the adenoid tissue 
surrounding the  intestine1 demands some
 consideration4 ,the theory supposes    
that these  cells not only have the     
power of taking up peptones1 but also of
  assimilating and transforming them    
into the cell-protoplasm4 ,this view    
being correct1 it is plain that the     
so-absorbed proteid must pass into  the 

circulating blood through the thoracic  
duct1 and ,hofmeister further  considers
 it probable that the lymph-cells of the
 mesenteric glands can  transform any   
absorbed peptone that may escape the    
leucocytes of the  adenoid tissue4      
#bba ,zeitschr4 f4 physiol4 ,chem41     
,band #d4    ,in apparent harmony with  
this view is the fact that the          
leucocytes in  the adenoid tissue of the
 intestine are greatly increased in     
number  during digestion4#bbb           
,furthermore1 it is a well authenticated
 fact  that the proteoses or peptones   
found in pus are contained in the       
pus-cells themselves1 and not in the    
fluid in which the corpuscles           
float4#bbc ,in support of the first     
statement1 ,pohl1#bbd in his recent     
study of the absorption and assimilation
 of food-stuffs1 has emphasized  the    
marked increase in the number of white  
blood-corpuscles in the  circulating    
blood after the ingestion of proteid    
foods1 especially  such as meat1        

,witte's peptone1 and gelatin-peptone4  
,it is to be noted  further that the    
increase is most marked at about the    
third hour after  the taking of food1   
viz41 at a time when digestive          
proteolysis would  naturally be at its  
height4 ,moreover1 the maximal increase1
 according  to ,pohl's data1 is         
astounding1 amounting as it does in many
 cases to  a hundred per cent4 ,thus1 in
 one instance1 in the case of a dog1 the
  number of white blood-corpuscles per  
cubic millimetre of blood was  #h1fhi2  
yet two hours after the feeding of #ajj 
grammes of meat the  number increased to
 #ag1bif per cubic millimetre1 followed 
six hours  after by a return to the     
original figure4    #bbb ,arch4 f4 ,exp4
 ,pathol4 u4 ,pharm41 ,band #bj and     
,band #bb4    #bbc ,zeitschr4 f4        
physiol4 ,chem41 ,band #d1 p4 #bfh4     
#bbd ,arch4 f4 ,exp4 ,pathol4 u4        
,pharm41 ,band #be1 p4 #ca4    ,this    
indicates the general tenor of ,pohl's  
results1 which have been  taken1 by some

 physiologists at least1 as confirmatory
 of ,hofmeister's  views2 the           
interpretation naturally being that     
digestive proteolysis  in the alimentary
 tract is accompanied by a rapid        
production of new  leucocytes in the    
lymph-spaces surrounding the intestine1 
and followed  by a rapid transference of
 the corpuscles from their point of     
origin  to the circulating blood1 from  
which they gradually disappear as  their
 material is made use of in the         
different parts of the body4 ,in        
harmony with this view1 ,pohl finds that
 there is a much larger number  of      
leucocytes in the blood and lymph       
flowing from the intestine of  an animal
 in full digestion1 than in the arterial
 blood coming to  the intestinal tract4 
,further1 when due consideration is     
given to  all the circumstances         
attending the circulation of the blood  
through  the abdominal organs1 in       
connection with the great increase in   
the  number of leucocytes during        

digestive proteolysis1 it seems not     
unreasonable to suppose that some       
proteid matter might be transferred     
from the intestine to the blood during  
the digestive period of six  or eight   
hours4 ,moreover1 if ,pohl's views are  
correct1 we see that  a portion1 at     
least1 of the proteid food-product may  
be transformed  into organized material 
in the body of the lymph-cell prior to  
its  passage into the blood1 thus       
harmonizing with the statement already  
made regarding the utter lack of        
proteoses and peptones in the blood  and
 lymph4 ,this obviously means an        
upbuilding of the ordinary products  of 
digestive proteolysis into the living   
protoplasm of the leucocytes  in the    
intestinal walls1 implying1 however1    
that the transformation  is accomplished
 solely by the leucocytes themselves1   
and not by the  epithelial cells of the 
intestine4    ,i have given this brief  
summary of ,pohl's work because it is so
 closely  in harmony with the original  

views of ,hofmeister1 and because it    
offers an easy explanation of one       
possible way in which some of the       
products of digestion might perhaps pass
 from the intestine into the  blood4 ,i 
am inclined to believe1 however1 that   
the so-called digestive  leucocytosis1  
which unquestionably does exist1 is not 
a direct result  of digestive           
proteolysis in general1 but rather an   
indirect result1  coming from the       
stimulating action of the nuclein1      
contained especially  in animal cells4  
,thus1 it is a significant fact1 as     
,pohl himself  reports1 that            
wheat-bread1 with its fairly large      
amount of proteid  matter1 and which is 
fully capable of nourishing the animal  
body1 fails  to exert any influence on  
the number of leucocytes in the blood4  
,yet we  know that the gluten and other 
proteids of wheat-flour are converted   
by digestive proteolysis into proteoses 
and peptones1 with the same  general    
properties as like products of animal   

origin4    ,in this connection we may   
note the experiments of                 
,horbaczewski1#bbe  which show that     
nuclein administered to a healthy man   
will give rise  to a very marked        
increase in the number of leucocytes in 
the blood4  ,thus1 a few grammes of     
nuclein may produce as striking a       
condition  of leucocytosis as a large   
amount of proteid food1 due no doubt to 
proliferation of the lymphoid elements  
of all the lymphatic tissues  of the    
body4 ,horbaczewski has reported that   
the mere injection of  #j4be gramme of  
nuclein1 in the case of rabbits1 will   
cause marked  enlargement of the spleen1
 with striking karyokinetic changes4    
,hence1 it may be assumed that whenever 
nuclein is set free in the  body1       
leucocytosis may result1 provided the   
nuclein passes into the  circulation and
 is not decomposed immediately after its
 liberation4    #bbe ,monatshefte f4    
,chemie1 ,band #ab1 p4 #bdf4    ,these  
facts1 it appears to me1 offer a more   

consistent line of  explanation of      
digestive leucocytosis than that        
advanced by ,pohl4  ,all animal foods1  
especially meat of various kinds and    
milk1 contain  considerable nuclein or  
nucleo-albumins1 which1 by the action of
 the  gastric juice1 are liberated and  
partially digested1 but the nuclein  is 
certainly not dissolved4 ,nucleins1     
however1 are soluble in weak  alkaline  
fluids1 and when exposed to the action  
of the alkaline  pancreatic juice in the
 intestine1 are in great part dissolved4
 ,thus1  ,popoff#bbf has reported that  
different varieties of nuclein behave   
somewhat differently in the intestine1  
according to their origin4 ,in  young   
and tender tissues1 solution of the     
contained nuclein through the  alkaline 
fluids of the intestinal canal is fairly
 complete1 while the  older products are
 somewhat more resistant both to the    
pancreatic juice  and to the            
putrefactive processes common to the    
intestine4 ,however1  experiments show  

that the greater portion of the nuclein 
of ordinary  proteid foods is dissolved 
in the intestine1 and absorbed as such  
in  a practically unaltered form4       
,consequently1 passing into the adenoid 
tissue surrounding the intestine1 it has
 a marked stimulating action  on the    
lymphoid elements1 accompanied by a     
noticeable increase in the  number of   
leucocytes1 which are perhaps produced  
at the expense of a  portion of the     
proteoses and peptones formed during    
proteolysis4    #bbf ,ueber die         
,einwirkung von ,eiweissverdauenden     
,fermenten auf die  ,nucleinstoffe1     
,zeitschr4 f4 physiol4 ,chem41 ,band    
#ah1 p4 #ecc4    ,thus1 my              
interpretation of these results would   
lead me simply to the  admission that1  
possibly1 a portion of the products of  
proteolysis  might pass from the        
intestine into the blood-current        
indirectly1  through the bodies of the  
leucocytes formed in the adenoid tissue 
of the intestine4 ,but even admitting   

this1 we lack positive proof  of any    
direct transformation of proteoses and  
peptones into the  organized material of
 the white blood-corpuscles1 for it may 
be that  the above products are first   
transformed through other agencies into 
serum-albumin1 or other like proteids4  
,there are1 indeed1 many facts  which   
are plainly opposed to any marked       
absorption and transformation  of       
peptones by the leucocytes of the       
intestinal mucous membrane4 ,thus1      
,heidenhain#bbg has severely criticised 
the theory on the ground that  there is 
very little increase in the flow of     
lymph from the thoracic  duct during    
absorption1 and further that the small  
percentage of  proteid matter in the    
chyle 7about #b4j per cent47 cannot     
account for  the large amount of proteid
 absorbed4 ,further1 the objection is   
made  that the leucocytes present in the
 intestinal mucosa1 though numerous1    
are wholly inadequate to assimilate any 
large proportion of the  ingested       

proteid food4    #bbg ,beitrge zur      
,histologie und ,physiologie des        
,dnndarms1 ,pflger's  ,archiv f4        
,physiol1 ,band #dc1 ,supplement ,heft4 
,still greater stress1 however1 may be  
laid upon the fact that  experimental   
evidence points to the conclusion that  
lymph-cells  cannot assimilate either   
peptones or proteoses4 ,thus1 quite     
recently1  ,shore#bbh has studied the   
results following the introduction of a 
mixture of such products into the       
lymphatic system by secretion1  by      
absorption1 and by direct injection into
 a lymphatic vessel4  ,preliminary      
experiments on dogs showed that when    
peptone is introduced  into the         
bile-duct it gradually appears in the   
lymph of the thoracic  duct1            
consequently this method can be made use
 of as a means of  ascertaining the fate
 of peptone so absorbed into the        
lymphatic system4  ,the results         
obtained1 using the ammonium sulphate   
method for the  isolation of the        

peptone1 showed that when peptone is    
injected into  the bile-duct with       
sufficient force to overcome the low    
pressure under  which bile is secreted1 
there is an increase in the rate of flow
 of  lymph from the thoracic duct4      
,further1 while peptone is somewhat slow
  in appearing in the lymph it          
eventually makes its appearance there1  
in  from sixty to one hundred and forty 
minutes after its injection into  the   
bile-duct4 ,a certain amount of peptone 
naturally passes into the  blood1 but is
 then rapidly excreted through the      
urine4 ,when1 however1  the renal       
vessels are ligatured1 peptone still    
rapidly disappears from  the blood1 but 
then passes into the lymph1 and under   
such circumstances  can be detected in  
the lymph as early as thirty-eight      
minutes after its  injection into the   
bile-duct4 ,these results1 therefore1 do
 not accord  with the view that peptones
 suffer marked transformation by contact
  with lymph-cells1 for when only       

three-fourths of a gramme of peptone  is
 introduced into the bile-duct1         
unaltered peptone can be detected  in   
the lymph of the thoracic duct seventy  
to ninety minutes after its  injection4 
#bbh ,on the ,fate of ,peptone in the   
,lymphatic ,system1 ,journal of         
,physiol41 vol4 xi41 p4 #ebh4    ,with  
reference to the fate of peptone when it
 passes by secretion into  the lymphatic
 system1 it will be remembered that     
,heidenhain#bbi has  shown that the     
injection of peptone into the blood may 
be followed by  a large increase in the 
rate of flow of lymph4 ,further1 the    
amount of  solids in the lymph1         
especially of proteids1 is considerably 
increased4  ,from these and other facts1
 ,heidenhain is led to the view that the
  formation of lymph is a true secretion
 from the blood-vessels4 ,shore  finds  
that when small amounts of peptone are  
slowly injected into the  blood1 there  
is generally only a slight acceleration 
in the flow of  lymph1 but the clotting 

power of the lymph is affected in a     
remarkable  manner4 ,thus1 about twenty 
minutes after the commencement of the   
injection the lymph loses entirely its  
power of coagulating4 ,this  continues  
for about twenty minutes1 and then1 in  
spite of the fact that  the injection is
 being continued1 the lymph rapidly     
regains its power  of clotting1 and     
finally coagulates quicker and firmer   
than before4  ,this peculiar action of  
peptone on the clotting power of lymph  
may  frequently be observed1 even when  
the amount of peptone present is too    
small to be detected with certainty by  
chemical methods4 ,thus1 when  peptone  
in small quantity is injected very      
slowly into the blood1 the  greater part
 of it escapes through the urine1 but a 
small fraction1  sometimes too small to 
actually detect1 passes into the lymph  
and shows  its presence by its peculiar 
influence on the clotting of the fluid4 
#bbi ,versuche und ,fragen zur ,lehre   
von der ,lymphbildung1 ,pflger's        

,archiv f4 ,physiol41 ,band #di1 p4     
#beb4    ,when1 on the other hand1      
peptone is injected rapidly into the    
blood1  #j4c to #j4f gramme per kilo4   
during two to ten minutes1 it may       
disappear  completely from the blood in 
five to ten minutes after the end of the
  injection4 ,in such a case1 the fall  
of blood-pressure induced leads to  more
 or less arrest of the renal secretion1 
peptone appearing in large  amount in   
the lymph2 but there is no indication of
 any alteration of  the peptone by the  
lymph1 or its contained leucocytes4     
,thus1 when there  is no chance for the 
peptone to escape from the body1 as on  
ligation  of the renal vessels1 the     
peptone injected into the blood is      
rapidly  thrown into the lymph1 and from
 the lymph in the tissues of the body it
  is gradually carried to the thoracic  
duct1 and then again passes into  the   
blood2 all of which shows that there is 
little or no transformation  of the     
peptone by the leucocytes of the        

lymphatic system4    ,further1 by direct
 injection of peptone into a lymphatic  
vessel1  ,shore has shown that even so  
small an amount as #j4jdi gramme is not 
assimilated or transformed by the lymph 
in half an hour4 ,consequently1  we seem
 to have strong evidence that peptones  
are not prone to direct  alteration of  
any kind by the leucocytes of the       
lymphatic system4  ,further1 it would   
appear that the lymphoid cells of the   
spleen are  equally unable to assimilate
 small amounts of peptone injected into 
the splenic artery4 ,leucocytes1 then1  
can play no direct part in the          
absorption of the products of           
proteolysis from the intestine2 the     
lymph  is normally free from both       
proteoses and peptones1 and the         
leucocytes  plainly have no power to    
transform these bodies into other forms4
 ,they  can only utilize the proteid    
material elaborated from the products of
  proteolysis by other agencies4        
,plainly1 proteoses and peptones in the 

blood and lymph are foreign  substances4
 ,when present in the circulation they  
give rise1 as we  have seen1 to an      
increased flow of lymph and to a change 
in the  coagulability of the blood4     
,further1 not only is the flow of lymph 
augmented but there is likewise an      
increase in the amount of solid  matter1
 while a corresponding decrease is      
noticed in the solid matter  of the     
blood-plasma4 ,this fact obviously gives
 support to the view  that the increased
 formation of lymph after the injection 
of peptone  is due to an active process 
of secretion by the endothelium cells of
  the capillary walls4#bcj ,further1 as 
we have seen1 peptone disappears  from  
the blood more or less rapidly after its
 injection1 so that it  is quite        
possible that the loss or alteration of 
the coagulability  of the blood may not 
be due to the peptone itself1 but rather
 to an  altered condition of the blood  
induced by the peptone4 ,moreover1 this 
altered condition of the blood may be   

the real cause of the increased         
transudation1 or secretion of lymph so  
conspicuous after the injection  of     
peptone4 ,starling1 however1 by         
carefully conducted experiments  on dogs
 finds1 in conformity with ,heidenhain's
 views1 that peptone  injected into the 
blood exercises a direct excitatory     
effect on the  endothelial cells1       
causing thereby an increased flow of    
lymph2 the  increased flow being in no  
way caused by the change in the blood   
that  is simultaneously produced4       
,further1 it would appear1 according to 
,starling's views1 that the change in   
the coagulability of the blood is  not  
due to the effect of the peptone on the 
endothelial cells of the  blood-vessels1
 or at least on their lymph-producing   
functions4 ,thus1  the injection of     
peptone may result in an action on the  
endothelial  cells of the blood-vessels1
 thereby increasing the flow of lymph1  
or  on the blood itself with a          
destruction or diminution of the        

clotting  power of the blood2 the two   
results being more or less independent4 
,further1 the rapid transferences of    
peptone from the blood to the  lymph is 
effected by the selective activity of   
the endothelial cells  of the           
vessel-wall1 and according to ,starling 
it is probable that a  preponderating   
part is played by the endothelial cells 
of the renal  capillaries4    #bcj      
,starling3 ,contributions to the        
,physiology of ,lymph ,secretion1       
,journal of ,physiol41 vol4 xiv1 p4     
#aca4    ,in view of all these          
statements1 it is very evident that     
proteoses and  peptones once outside the
 limits of the alimentary tract may be  
passed  about from organ to organ and   
from secretion to secretion1 inducing   
changes here and there in their course1 
but suffering very little  change       
themselves4 ,the main efforts of the    
system are directed to the  removal of  
these unwelcome strangers as speedily as
 possible1 for their  marked            

physiological action renders them       
somewhat dangerous visitors4    ,as     
normal products of digestive            
proteolysis1 they are never found       
beyond the limits of the                
gastro-intestinal canal1 but undergo    
retrogression in their passage through  
the epithelial cells of  the intestinal 
wall1 being presumably converted thereby
 into  serum-albumin1#bca which can be  
directly utilized for the nutrition of  
the body2 a conversion which is plainly 
dependent upon certain inherent         
qualities of the living epithelial      
cells1 and is doubtless of the  nature  
of a dehydration4    #bca ,see          
,kronecker and ,popoff3 ,ueber die      
,bildung von ,serumalbumin im           
,darmkanale1 ,du ,bois-,reymond's       
,archiv f4 ,physiol41 #ahhg1 p4 #cde4   
,also  ,nadine ,popoff1 ,zeitschr4 f4   
,biol41 ,band #be1 p4 #dbg4