15 



the addition of 0-4 per cent, hydrochloric acid, and then to boil the mix- 

 ture over a free flame, the liquid when boiled being neutralised with 

 caustic potash. All the proteids of the decoction are" precipitated and, :f 

 the mixture be thrown on a filter, a clear fluid filters through. This fluid 

 contains the secretin. In order further to free it from traces of gelatin 

 and proteid, it may be precipitated by absolute alcohol and ether ; the 

 secretin is not thrown down, and can be recovered from the alcohol-ether 

 solution by evaporation of the latter. A few cubic centimetres of the 

 original filtrate from the boiled mucous membrane or of a watery extract 

 of the residue left on evaporating the alcohol-ether solution, on injection 

 into the veins of an animal, evoke a plentiful secretion of clear pancreatic 

 juice which can be collected by means of a cannula placed in the duct of 

 the gland. The secretin can be obtained in this way from the upper part 

 of the intestine of any member of the vertebrata, and a solution of secretin 

 obtained from any animal will, on injection into any other animal, evoke a 

 secretion in the latter of pancreatic juice. We have, therefore, in secretin 

 a substance of the same general distribution as adrenalin, which, like this 

 latter, is unaltered by boiling, is soluble in alcohol, and, as we have 

 determined by direct experiments, is more or less diffusible. Although 

 secretin has not been further isolated and we have therefore no clue as to 

 its chemical characters, there can be little doubt that it belongs, like 

 adrenalin, to the drug class of substances which exercise an influence on 

 the physiological workings of the body. The limited seat of production 

 of secretin and the definite response evoked by its injection determine a 

 chemical reflex, which is as adapted to the needs of the organism as are 

 the muscular reflexes carried out by the central nervous system. The 

 acid chyme entering the duodenum excites the formation of secretin in the 

 mucous membrane, which in its turn causes a flow of alkaline pancreatic 

 juice. The formation and absorption of secretin will proceed until 

 the chyme is exactly neutralised by the alkaline juice. As soon as 

 this neutralisation occurs, the pyloric sphincter, which remains firmly 

 closed so long as the duodenal contents are acid, opens and allows 

 the entry of a fresh portion of acid gastric contents which, in their 

 turn, will, through the secretin mechanism, call forth a secretion of an 

 exactly corresponding amount of pancreatic juice. It is thus contrived 

 that the further digestion of the foodstuffs in the small intestine will pro- 

 ceed in a medium which is approximately neutral, and is at any rate free 

 from any trace of mineral acid. 



We may next inquire into the manner in which the contact of acid 

 can give rise to the production of secretin in the mucous membrane. It 

 seems most probable that the action of acid is one of hydrolysis, since, 

 although various acids can be used for the preparation of secretin, their 

 efficacy is more or less proportional to their strength or rather to their 

 acidity, a weak acid such as boracic having no influence on the produc- 

 tion of secretin. Bayliss and I have suggested therefore that the 

 epithelial cells lining the upper part of the small intestine contain a sub- 

 stance, pro-secretin, from which by hydrolytic agents secretin can be 

 split off. This precursor of secretin is quite insoluble, since we have been 



