Each of the three samples of secretin sent us by Dr. Beveridge was tested in the above manner on five dogs. The first tests were made June 27, 28 and 29, respectively, that is, within nine days of the preparation of these samples of secretin. None of the samples was active (Fig. 1), even when injected intravenously in quantities up to 50 c.c.: 40–50 c.c. of Beveridge’s secretin mixture may kill a dog by too great lowering of the blood pressure. A good secretin preparation yields a copious secretion of pancreatic juice on intravenous injection of a few cubic centimeters.

It is not difficult to prepare a secretin, by the original Bayliss or Starling method or by the Beveridge method, that retains some activity for a longer period than nine days. Hence we cannot account for the absolute inactivity of these preparations except on the assumption that they did not contain any secretin to start with; that is, faulty preparation and absence of physiologic standard­ization.

The sample kept intact in its original container for six months became gradually cloudy, a large mass of amorphous precipitate settled to the bottom and the odor showed bacterial decomposition. It is reprehensible, to say the least, to state concerning such a mixture: “Of course, if desired, it may be injected intravenously.” The fact that Beveridge’s secretin may be rendered clear by filtering through carbon is not sufficient evidence that it is “pure secretin,” free from bacteria and other injurious substances.

II. Beveridge Secretin Mixture Is Rapidly Rendered Inactive by Human Gastric Juice.—We prepared active secretin solutions by the Beveridge method, using 0.2 per cent. serum as the protein “stabilizer” (?). The addition of the serum does not appear to affect the activity of the fresh secretin preparation. If Beveridge’s secretin is able to act on the pancreas when given by mouth, it is obvious that it must run the gamut of gastric digestion, except in cases of complete achlorhydria. It has been repeatedly demonstrated that all other secretin preparations are rapidly destroyed by pepsin-hydrochloric acid digestion. Is Beveridge’s secretin an exception? What is there in a little serum, native albumin, or peptones to protect secretin against gastric digestion?

The pure human gastric juice used in these tests was secured from the fistula case (Mr. F. V.) that has been under observation in our laboratory for years.[123]

BEVERIDGE’S SECRETIN AND BAYLISS-STARLING SECRETIN PREPARED
Sept. 29, 1916

Date of TestQuantity of
Secretin
Injected, C.c.
Response of Pancreas
(No. of Drops of Secretin)
Bayliss-Starling
Secretin
Beveridge
Secretin

Sept. 29

107578

Oct.   2

106161

Oct.   6

102817

Oct.  13

102531

Oct.  27

10 5 6

Nov.  3

10 7 6

Nov. 17

10 4 5

Nov. 30

10 3 4

Dec.   4

10 2 2

Dec.  20

10 0 0

Two cubic centimeters of fresh gastric juice added to 8–10 c.c. Beveridge secretin, the mixture being kept at body temperature (38 C.), renders the secretin completely inactive in from 5 to 8 minutes (Fig. 2). There is no exception to this rule, as we have repeated the test on many different secretin preparations and using different samples of human gastric juice. The secretin of Beveridge is just as vulnerable as the secretin of Bayliss and Starling to pepsin-hydrochloric acid digestion. On what kind of tests does Beveridge base his claim that his secretin mixture acts on the pancreas when given by mouth?

III. The Relative Rate of Deterioration of the Secretin Solutions Prepared According to Bayliss and Starling and According to Beveridge.—Six different preparations of the two kinds of secretin were made, kept in dark stoppered bottles in the ice box, and tested by intravenous injection in dogs under ether anesthesia from time to time until all influence on the pancreas had been lost. One typical series of these tests is given by the way of illustration. (See Table on page [126].)