May 19, 1904] 



NATURE 



67 



fore impossible to say what proportion of the trypsinogen 

 of the juice secreted in these experiments had been converted 

 into trypsin by the small amount of intestinal mucous mem- 

 brane at the mouth of the duct. While, therefore, we are 

 unable to ascribe much importance to the results as regards 

 the proteolytic power of the juice, there seems no reason to 

 doubt the results obtained by these workers as regards the 

 starch-digesting power of the juice. In 1899 Walther {ihid., 

 1899, vol. vii. p. i) made a series of observations on a dog 

 with pancreatic fistula in order to determine whether the 

 amounts of ferments secreted were determined by the nature 

 of the food at any given meal. He was satisfied that his 

 results showed that, even without prolonged adherence to 

 one diet, the composition of pancreatic juice was adapted 

 to the nature of the meal taken. His results do not entirely 

 bear out his contentions, as is seen by the following table, 

 in which it will be noticed that although milk contains no 

 starch, it evokes the secretion of a large amount of amyl- 

 opsin, and that meat causes a secretion of more steapsin 

 than does milk, although this latter contains much more 

 fat than the meat diet. 



Table I. — Results of Walther's Experiments. 



Of course Walther, as well as the other observers men- 

 tioned, regard the adaptation as determined by the stimu- 

 lation of special nerve endings in the mucous membrane by 

 each constituent of the food, a conclusion hardly borne out 

 by the results just quoted. Another disturbing factor in 

 these experiments is the large variation in total quantity of 

 juice secreted with different food-stuffs. 



Table II. — Amount of Pancreatic Juice Secreted for 

 different Food-stuffs (Walther). 



8-2 6-0 23-0 



600 c.c. milk 

 250 grams 



bread 

 100 grams III 



meat ... 45-0 52-0 35-0 975' 



6-2 j 175 



355470 20-5 16-5 100 



67 8 9 j 



! 



— 1 ', 45 c.c. 



I206-530— 151 „ 



- I 142 ., 



The quantity of juice secreted will depend on the amount 

 of secretin turned into the circulation, and this, in its turn, 

 on the amount of acid entering the duodenum from the 

 stomach. The amount of juice will, therefore, be measured 

 by the stay and resistance to digestion of the substance in 

 the stomach rather than to any direct nervous or other 

 influence of the duodenal contents on the pancreas. A 

 repetition of Walther's experiments by Popielski (Central- 

 blatl f. Physiologic , vol. xvii., 1903), working independently, 

 has in fact led the latter to deny altogether the adaptation 

 of the pancreatic juice to the nature of the food. Popielski 

 concludes from his experiments that variations in the juice 

 depend only on the intensity and duration of the stimulus, 

 the intensity of the stimulus determining the amount of 

 enzymes, whilst its duration determines the total quantity 

 of juice. 



In the meantime the question had been attacked from 

 another side. It had been shown by Fischer and Niebel 

 (Sitzungsberichte der K. Preuss. Akad. d. Il^'iss., 1895, p. 

 7;,). as well as by Portier (C. R. Soc. de Biologic, 1898, p. 

 ,87), that watery extracts of the pancreas of the cow, horse, 

 .md dog had no influence on lactose. Weinland in 1899 



confirmed these results so far as concerns the pancreas of 

 dogs on an ordinary diet free from milk. On the other 

 hand, he found that extracts of the pancreas of dogs, which 

 had been fed for several days on milk, sometimes with the 

 addition of lactose, invariably contained lactase in consider- 

 able amount, and these results have been confirmed lately 

 by Bainbridge working in our laboratory. Here then we 

 have a definite instance of adaptation of the pancreas, the 

 pancreatic juice or pancreatic extracts of dogs on normal 

 diet containing no lactase, while the administration of 

 lactose to these animals causes the appearance of lactase 

 in both cases. Since in this case we have to determine, not 

 simply an increase or diminution in the amounts of ferments 

 always present in the juice, but the presence or absence of 

 a definite substance, this was evidently the best starting 

 point for an investigation of the mechanism by which the 

 pancreas can adapt itself to the nature of the food, an in- 

 vestigation which has been carried out and completed by 

 Dr. Bainbridge. 



What are the limiting conditions? In the first place the 

 reaction is absolutely specific. Unless the animal is taking 

 lactose in its diet no lactase is ever found in the pancreas 

 or in its secretion. The pancreas of new-born animals, for 

 instance, is quite free from lactase, which, however, makes 

 its appearance two or three days after birth as the result 

 of the milk diet. The production of lactase is not a direct 

 reaction of the pancreas to the presence of lactose in the 

 blood, since subcutaneous or intravenous injection of lactose" 

 does not cause the appearance of lactase in the pancreas. 

 The intestinal mucous membrane of all animals, whether 

 on a milk diet or not, contains lactase and has an inverting 

 action on lactose. It might be thought therefore that the 

 production of lactase by the pancreas was a reaction to the 

 presence of the products of inversion of lactose in the blood. 

 This was found not to be the case. Subcutaneous injection 

 of galactose for several days was not followed by any appear- 

 ance of lactase in the pancreas or its juice. Nor was the 

 appearance of lactase due to the increased production of 

 this ferment in the mucous membrane, and its escape into 

 the blood. Injection of an extract of mucous membrane 

 rich in lactase, repeated several days in succession, was not 

 followed by any appearance of lactase in the pancreas. In- 

 jection of lactose into the duodenum, and the subsequent 

 injection of secretin after an interval of one hour, was in- 

 efficacious in causing the appearance of lactase in the pan- 

 creatic juice. For the production of lactase in the pancreas, 

 or its juice, it is therefore necessary that lactose should act 

 on the intestinal mucous membrane for some time. The 

 reaction is a slow one, like the adaptation in Vasilieff's ex- 

 periments, and is certainly not due to the stimulation of 

 certain nerve endings in the mucous membrane by the 

 lactose. 



The problem was somewhat similar to that presented by 

 I the action of acid in the duodenum, since this introduced 

 i into the duodenum produces secretion of juice, whereas, 

 I when introduced into the blood stream, it has no effect 

 whatever on the pancreas. The question suggested itself 

 whether, under the influence of lactose, a special secretin 

 j was formed in the intestinal mucous membrane which, on 

 I access to general circulation, evoked the formation and 

 I secretion of lactase by the pancreas. Secretin was there- 

 fore made in the usual way {i.e. acidification, boiling, 

 neutralisation, and filtering) from the mucous membrane 

 of milk-fed dogs. The secretion evoked by the injection of 

 this liquid resembled that obtained from the injection of 

 ordinary secretin, and contained no lactase. 



Yet it was evident from the results already obtained that 

 lactose must act on the pancreas through the mucous mem- 

 I brane of the intestine. An extract was therefore made from 

 the mucous membrane of the whole small intestine of a 

 milk-fed dog. This was filtered through muslin, and about 

 10 c.c. injected subcutaneously into a biscuit-fed dog once 

 a day for three days. The dog was then anaesthetised, a 

 cannula placed in its pancreatic duct, and ordinary secretin 

 i injected. A flow of pancreatic juice was obtained, and this 

 juice was found to contain lactase. This experiment was 

 performed eight times, and in each case the juice obtained 

 from a biscuit-fed dog which had been injected with an 

 extract of the mucous membrane of a milk-fed dog con- 

 tained lactase. 



NO. 1803, 'VOL. 70] 



