i6 



unable to obtain secretin by the action of acids on filtered extracts of 

 the mucous membrane. It is not destroyed by the death of the cell, 

 since secretin may be obtained by the action of acids upon boiled mucous 

 membrane or upon mucous membrane which has been repeatedly ex- 

 tracted with absolute alcohol and then dried. On the other hand, if the 

 process by which secretin is formed is hydrolytic this change must be 

 able to be effected by the living cells in the absence of such strong 

 hydrolytic agents as dilute hydrochloric acid. Thus Fleighas shown that 

 a secretin similar in all respects to that described can be obtained by 

 the action of soaps on the mucous membrane ; and there is no doubt that 

 a similar substance is produced in the mucous membrane and absorbed 

 into the blood, when such substances as ether, chloral, or oil of mustard 

 are introduced into the lumen of the gut. It is difficult to imagine that 

 any of these substances can exercise a direct hydrolytic effect ; and it is 

 certainly impossible by their means to extract secretin from a mucous 

 membrane which has been already killed. 



That the secretin formed in the mucous membrane actually reaches 

 the pancreas by way of the blood stream has been shown by Wertheimer. 

 This observer led the blood from the intestinal veins of one dog (A) into 

 the blood stream of a second dog (B) and found that injection of dilute 

 acid into the intestine of dog A evoked a secretion of pancreatic juice in 

 dog B. Although the view given above as to the origin of secretin is most 

 probably correct, our failure up to the present to isolate pro-secretin in 

 any way from the mucous membrane forbids us to accept the theory as 

 definitely established. Delezenne has found that the digestion of a solution 

 of secretin with a fresh extract of intestinal mucous membrane deprives the 

 secretin of its efficacy. He has therefore advanced the suggestion that 

 secretin is really preformed in the wall of the gut, but is accompanied by 

 another body, its physiological antagonist, which he denotes by the name 

 of anti-secretin. He imagines that the action of acid is to destroy the 

 anti-secretin, thus unmasking the action of the secretin. The fact, how- 

 ever, that secretin, which is extremely soluble both in water and fairly 

 strong alcohol, is not extracted in any appreciable quantity by these 

 fluids from the mucous membrane until acid has been added, is difficult 

 to reconcile with Delezenne's suggestion ; moreover, the general characters 

 of secretin, its resistance to proteid-precipitating agents, and so on, point 

 to it as belonging to a class of bodies which would not give rise to anti- 

 bodies when introduced into the organism. 



As to the mechanism by which secretin arouses the activity of the 

 pancreatic cells, the expulsion of its preformed ferment or pro-ferments, 

 together with the building up of new protoplasm and ferments, which 

 always accompanies normal activity, we have little or no conception. 

 Early in our researches the suggestion was made to us by Dr. A. Walker 

 that the secretion of pancreatic juice was of the nature of the formation 

 of an antibody to the secretin. That this explanation will not hold is 

 shown by the fact that secretin is equally efficacious when it is mixed 

 with a large quantity of fresh pancreatic juice. If, however, the pan- 

 creatic juice be activated by the addition of succus entericus so that its 



