SECRETOGEN

Report of the Council on Pharmacy and Chemistry

About a year ago the Council declared Secretogen,[103] a product the active ingredient of which was stated to be “pancreatic secretin” and advertised as a remedy for certain conditions of defective digestion and assimilation, to be ineligible for New and Non­official Remedies. The reasons for this decision were stated at the time as follows:

“1. No evidence has been presented that the absence of secretin is a cause of gastro-intestinal diseases. It is usually present, and if not present, as in achylia gastrica, there is evidently some compensating arrangement by which the pancreas is stimulated to perform its regular functions.

“2. There is no evidence that secretin in any form is physiologically active when administered by mouth.”

Since Secretogen was not the only so-called secretin preparation on the market, and since the use of secretin preparations was recommended by certain writers, notwithstanding the lack of evidence of its value, the Council caused an experimental investigation of the question to be made. This was carried out by Prof. A. J. Carlson of the University of Chicago.

No secretin was found in the commercial products examined, namely, Secretogen Tablets, Secretogen Elixir and Duodenin. Furthermore, Carlson’s results[104] confirmed the Council’s previous conclusion as to the inertness of secretin administered by mouth. The Council endorsed Professor Carlson’s findings.[105]

The G. W. Carnrick Company has replied to the publication of this report in the letter printed below. (A portion of this letter, which consists of a communication from an unnamed correspondent of the G. W. Carnrick Company and the company’s comment thereon, has been omitted.) The Council offered to publish this if the Carnrick Company would furnish the name of the writer. This it has not done. As will be seen, the company now shifts ground, abandoning entirely the claim that Secretogen contains secretin. The Council has authorized publication of the letter (omitting the part just mentioned), together with the comment that follows.

W. A. Puckner, Secretary.

“The Council on Pharmacy and Chemistry of the American Medical Association.

“Gentlemen:—The opinion of the Council and the contribution by Professor Carlson which appeared in The Journal of the American Medical Association for Jan. 15, 1916, have been read by us with interest. The column of Current Comment dealing with ‘Tiger-Bone Therapy and Clinical Experience’ has appealed to our good nature and, under the circumstances, our sense of humor.

“Professor Carlson seems to have quite well established that the so-called secretin preparations do not contain secretin to any appreciable extent, and that they are inert in laboratory experiments on normal animals. At the same time, to do away with an apparent discrimination on the part of the management of the Council, it would have been well if Professor Carlson had included the so-called secretin preparations belonging to another well-known firm which markets such a product. This discrimination has already been referred to by us.

“Had Professor Carlson stopped at the determination of the therapeutic availability of secretin given by mouth, his work might have been accepted without comment, even if we should have thought it advisable to object to the matter published by the Council. But the professor went beyond his province entirely when, in commenting on the findings obtained by using Secretogen clinically, he said: ‘It is, perhaps, impertinent for laboratory men to comment on these clinical results.’ It is. His point was well taken and it is a profound pity that Professor Carlson did not observe his own ruling.

“In the words of a correspondent of The Journal of the American Medical Association, in discussing Professor Carlson’s criticism of Dr. Crile’s ‘Kinetic Drive,’ ‘it behooves the laboratory man to be circumspect in his criticism of clinical theories, since going beyond the bounds of well-established things weakens his position, not merely with reference to the particular subject under discussion, but with reference to clinical phenomena in general.’ Clinical results have definitely established the value of Secretogen. As the matter now stands this statement is beyond criticism.

“When Secretogen was first introduced we assumed that it depended on secretin for results produced. In this assumption we were in good company, as witnessed by the testimony of Moore, Edie and Abram when, in the course of their investigations as to the value in diabetes of a secretin-bearing extract given by mouth,[106] they said: ‘In the majority of these cases ... there has been no appreciable fall in the output of sugar ... in some of these negative cases there has been noted, however, improvement in the digestion and, in certain cases, the patient’s weight has increased.’ They also state that the secretin-bearing product ‘appears to stimulate the functional activity of the duodenum.’[106] They give a most significant report.[107] We quote from the paper as follows:

“ ‘The patient had been under observation for six months before treatment and the sugar was not reducible by diet. Almost at once the dyspepsia from which he was suffering was relieved and his general nutrition improved to such an extent that he regained over eighteen pounds in weight, which he had previously lost, and this improvement was accompanied by complete recovery of his physical and mental energies.’[106]

“Inasmuch as this improvement could not have been due to the contained secretin it must have been due to some other principle contained in the extract. Our experience and that of the physicians who have used Secretogen establish the fact that Moore, Edie and Abram made no mistake when they came to the conclusion that what they termed a secretin-bearing extract stimulates the functional activity of the duodenum and improves the digestion.

“When Professor Carlson was investigating Secretogen he must have realized that he was dealing essentially with an extract of the duodenal mucosa. It is, therefore, all the more surprising, considering his extensive researches into the literature, that he should have ignored the testimony of some of his own authorities, particularly Hallion, as to the value of extracts of the duodenal mucosa in duodenal insufficiencies. The meticulous carefulness with which this evidence was avoided is hardly worthy of the best traditions of physiology, a science which has truth for its first and last aim.

“Hallion in his ‘La Pratique de l’Opothérapie’ says that the ‘aims of duodenal opotherapy are: 1, To supply deficient duodenal juice. 2, Above all to stimulate and to relieve this organ—notably to aid the production of secretin[106]—and so profit by the stimulating action which duodenal extract exercises on the duodenal mucosa which action we, Enriquez and myself, believe and have experimentally proved, conforms to the general principles of opotherapy. 3, By means of the production of secretin, to reinforce the biliary, pancreatic and intestinal secretions. 4, To stimulate intestinal peristalsis.

“ ‘Principal indications: Intestinal dyspepsias, intestinal autointoxications, certain forms of constipation and duodenal insufficiency.’

“At the International Congress of Medicine, Madrid, 1903, Hallion said that he felt justified in stating that duodenal opotherapy correctly carried out must be classed under the very best methods of treating dyspepsia.[106] The results had been satisfactory and, in many cases, remarkable. It had been nil in a few cases but it had never been harmful in any degree. He pointed out that Marfan was the first to employ this substance clinically. Marfan had had particularly excellent results in children of 15 months to 4 years suffering with marked malnutrition, anorexia and constipation. Marfan prescribed the duodenal extract given in milk.[106] Hallion further remarks that, as he is not a practitioner, he had had only one opportunity to test duodenal opotherapy clinically. The case was that of a man of 26 years with obstinate intestinal dyspepsia and severe constipation which had persisted from childhood. This patient had been treated by enemas, laxatives, diet, etc. Treatment with duodenal extract resulted in a complete cure.[106] Hallion points out that the most satisfactory aspect of duodenal opotherapy is the permanent effect produced,[106] which bears out his statement that these extracts have the power to aid in the restoration of function and structure of an organ.

“This has been so well established that the principle is now embodied in a law which is frequently referred to as ‘Hallion’s Law’: ‘Extracts of an organ exert on the same organ an exciting influence which lasts for a longer or shorter time. When the organ is insufficient it is conceivable that this influence augments its action and, when it is injured, that it favors its restoration.’

“In ‘La Pratique de l’Opothérapie’ Hallion points out that ‘the opotherapeutic product which corresponds to the affected organ represents in some way the stimulating and elective food for that organ, and if we supply the organ with a food which is more complete than it necessarily needs, the affected organ can exercise its elective action and take up only those substances of which it is in need.’

“Hallion’s observations on this point are beautifully borne out by the classic work of J. W. Draper, as reported in The Journal of the American Medical Association, Sept. 26, 1914. This report gives results in both laboratory and clinical experiments.

“In order to show that fed jejunal and ileac epithelium exercise some special detoxicating power, not yet understood but definitely recognizable, Draper fed a control series of dogs with intestinal obstruction, experimentally produced, on emulsified cells of liver, spleen, pancreas and muscle tissue. These animals lived a few hours longer than not-fed controls, but Draper says that it is evident that these cells had either no detoxicating action, or a very feeble one compared with intestinal epithelium. He used jejunal and ileac epithelium clinically in two instances: 1st, In a female dog which had had ‘chronic stomach trouble’ for six months. When Draper saw her she had had complete intestinal obstruction for five days, with symptoms of tachycardia, extreme nervousness and great weakness in the hind legs. Draper removed a pebble from her intestine but her condition was still grave.

“She was immediately put on small-intestine epithelium derived from two dogs of different breed. Draper says that from a long experience with duodenally obstructed dogs, he should not have expected her to recover, but the symptoms gradually subsided and she lived. The second instance in which he used the epithelium thera­peutically was in the case of a man who suffered from an annular cancer of the intestine with definite symptoms of obstruction. After the operation, and realizing that the patient was in a desperate condition, he fed him an emulsion of intestinal epithelium from a dog. The pulse improved and the patient lived.

“Some of Draper’s conclusions are as follows:

“ ‘Autotoxemia in intestinal obstruction undoubtedly arises from an interference with cellular reactions of the intestinal epithelium.... When small-intestine epithelial cells of healthy animals are placed in the stomach[106] of duodenally obstructed animals, such animals have lived nearly twice as long as not-fed controlled animals. This evidence is strongly opposed to the bacterial theory of origin of toxins.’

“The point to be emphasized is this: If this emulsion of intestinal epithelium had been fed to a normal dog and a normal man, what would have happened? Absolutely nothing. On the other hand, given as it was to a dog and a man in desperate need it exercised a potent effect.

“Abundant clinical testimony can be cited in support of the opinions of Moore, Edie and Abram, Hallion, Marfan and Draper as to the value of extracts of the intestinal mucosa given by mouth in pathological conditions. We have previously cited the published favorable opinions of such gastro­enter­olo­gists as Anthony Bassler, Lewis Brinton, G. R. Lockwood, and R. C. Kemp, so there is no need to recapitulate their experiences with what they honestly believed to be secretin-bearing extracts, but which were essentially extracts of the duodenal mucosa.

“Supplementing the evidence of these men as to the value of these extracts we submit an excerpt from a letter from one of the best known physicians of Edinburgh:

“ ‘I can speak in very high praise of Secretogen, which I have used in both tablet form and as the elixir. There is no doubt about its value in a certain class of intractable indigestion which refuses to be benefited by any other remedy. On several occasions I have been much gratified by the definite relief obtained in this class of cases. It hits the mark also in some types of obstinate constipation—I think those cases where the trouble is wrapped up in impaired enervation of the intestine, and where stasis occurs at certain segments of the canal.’

“Hallion very pertinently points out[108] that it is now accepted that opotherapy is not substitutive, but homostimulative and he remarks further that it is well to bear in mind that the so-called active substances which make the extract efficacious need not necessarily be the hormones. ‘It may be the elements of tissue structure which may come to the aid of the injured organ. The hormone should not therefore be looked on as the only active agent of opotherapy and, while its action is important, it need not necessarily be preponderant. The chemical isolation of the hormones is, of course, of interest but may not be as vital to organotherapy as we have thought.’ ...”

COMMENT BY THE COUNCIL ON PHARMACY AND CHEMISTRY

The G. W. Carnrick Company, which formerly claimed that Secretogen was efficacious because it contained secretin, now admits this claim to be unfounded. Notwithstanding, the manufacturers still call their product Secretogen and make for it practically the same therapeutic claims as before. They now base these claims on vague “principles of opotherapy” and on so-called “clinical testimony.” The burden of proof rests on them to show that these old claims, already discredited but put forth again on new grounds, are justified. Have they done so?

The “clinical testimony” is not convincing. So much of it as is definite enough to permit of criticism has already been dealt with. The remainder consists of mere assertions; it is not through reliance on such evidence that the Council can discharge its trust. On this side of the question there is nothing new to be said—reassertion of a refuted argument does not constitute fresh proof.

Nor is the case better on the experimental side. The statements of Hallion, Enriquez, Zuelzer and others[109] as to the existence of a “peristaltic hormone” not only have failed of confirmation, but also have been positively discredited. With regard to Draper’s work, which dealt with acute intestinal obstruction, it is difficult to see what is its relevance to the present issue, particularly since Draper’s results were obtained with a product derived from the mucosa of the jejunum and ileum and not with an extract of the duodenum such as Secretogen purports to be.

The innuendo that the Council discriminates in favor of certain manufacturers, is itself a confession of weakness.

In publishing this correspondence the Council’s sole object is to put the medical profession in possession of the exact facts of the case. These may fairly be summed up as follows:

1. Secretogen was originally marketed as a preparation containing secretin. None was found in it.

2. Notwithstanding proof of this fact, the G. W. Carnrick Company retain the original name of the product, knowing that, by its association with their former erroneous assertions concerning Secretogen, this name must inevitably convey to a physician using the product the impression that he is administering secretin. In the advertising literature no hint is given that this original statement was erroneous.

3. The product called “Secretogen” has not been shown, either experimentally and by sound clinical evidence, to possess useful therapeutic properties.

Under these circumstances the Council reaffirms its decision.—(From Reports of Council on Pharmacy and Chemistry, 1916, p. 72.)