1904.] The Chemical Regulation of the Secretory Process. 313 



ment had, curiously, not been performed by previous workers in the 

 subject. On carrying it out, we found that destruction of all nerve 

 connections made no difference to the result of introducing the acid. 

 The pancreatic secretion occurred as in a normal animal. It was 

 therefore evident that we had to do here with a chemical rather than 

 a nervous mechanism. Previous work had narrowed the question 

 down to such a degree that the further steps were obvious. We 

 knew already that the introduction of acid into the blood-stream had 

 no influence on the pancreas; hence the acid introduced into the 

 intestine must be changed in its passage to the blood-vessels through 

 the epithelial cells, or must produce in these cells some substance 

 which, on access to the blood stream, evoked in the pancreas a 

 secretion. This was found to be the case. On rubbing up the 

 mucous membrane with acid, and injecting the mixture into the 

 blood-stream, a copious secretion of pancreatic juice was produced. 

 It was then found that the active substance, which we call secretin, 

 was produced by the action of acid from a precursor in the mucous 

 membrane, probably in the epithelial cells themselves. Once formed 

 by the action of acid, it could be boiled, neutralised, or made alkaline, 

 without undergoing destruction. The precursor of the substance 

 {prosecretin) cannot be extracted by any means that we have tried 

 from the mucous membrane. Even after coagulation of the mucous 

 membrane by heat or alcohol, however, secretin can still be extracted 

 from the coagulated mass by the action of warm dilute acid. 



The question then arose whether this chemical mechanism repre- 

 sented the normal mode in which secretion of the pancreatic juice was 

 excited by the presence of food in the gut. It had already been 

 shown by Wertheimer that the secretion evoked by the presence of 

 acid diminished as the acid was placed further down in the small 

 intestine, and was absent when the acid was placed in the lowermost 

 section of the ileum or in the large intestine. We found a correspond- 

 ing distribution of pro-secretin. The most active extracts of secretin 

 were to be obtained from the duodenum. The extracts from the 

 jejunum were less powerful, while those from the lower 6 inches of 

 ileum or from the large intestine were practically inert. The proof 

 that secretin is really carried by the blood to the gland has been 

 furnished by Wertheimer,* who has shown that the blood coming 

 from a loop of intestine into which acid has been introduced, when 

 injected into another dog, evokes in the latter a secretion of pancreatic 

 juice. All authors who have investigated the matter since our first 

 publication on the subject have confirmed our results ; but many of 

 them are still loth to give up the idea of a nervous connection 

 between the gut and the pancreas. Pawlow had obtained evidence of 

 the existence of secretory nerves to the pancreas in the vagus as well 

 * 'C. E. Soc. de Biologie,' 1902, p. 475. 



