Chapter XIV: Introduction: The Council on Pharmacy and Chemistry was established (7)

Here, as in the case of “40 per cent. Gluten Flour,” the company’s label attributes to “Dr. Wm. Osler in ‘Practice of Medicine,’” the following quotation: “Of Gluten Foods, many are very unpalatable, others are frauds. A Good Gluten Flour is made by the Battle Creek Sanatarium Co., Mich.” I have no way of knowing to which gluten flour of the company Dr. Osler had reference. The “Pure Gluten Meal” might be called properly a “good gluten flour,” but this “40 per cent. Gluten Flour” is no better, and no worse, than the average gluten flour on the market. The quotation from Osler gives an entirely false impression.

40 PER CENT. GLUTEN FLOUR
Referee Company
Water 8.62 5-10
Ash 0.89 0.5-1
Protein (N × 5.7) 33.63 40-45
Fiber 0.08 1-3
Carbohydrates 55.35 40-45
Fat 1.43 0.2-0.5
Starch 48.04 ...

My analysis shows 6.37 per cent. less protein than the company’s minimum, and 10.35 more carbohydrates than their maximum. In past years I have found the protein in this brand to range from 35.0 to 42.9 per cent. (using the factor 5.7). It is true that the manufacturer does not state what protein factor is used in his reported analysis, but as in four other brands 5.7 is used, it is fair to assume that the same factor applies to this as well. At least such should be the case, as otherwise the manufacturer’s analyses would be meaningless. Even using the factor 6.25 this later sample contains only 36.88 per cent. of protein.

The following statement, in my judgment, as applied to a food containing over 48 per cent. of starch, does not hold water: “This food is of special service in cases of Glycosuria and in the milder forms of Diabetes.” With this brand as with “40 per cent. Gluten Biscuit” the manufacturer again uses the misleading quotation from Osler.

40 PER CENT. GLUTEN MEAL

Referee Company
Water 7.30 5-10
Ash 1.36 1-2
Protein (N × 5.7) 41.55 40-45
Fiber 0.10 1-2
Carbohydrates 48.58 40-45
Fat 1.11 0.2-0.5
Starch 36.59 40-45

The claimed analysis is justified by my findings. I must take exception, however, to the following statement: “Prepared with great care from a good grade of Spring Wheat, by our special process, which preserves the natural food properties of the product.” The company evidently tries to carry water on both shoulders, on the one hand claiming a reduction in the starch content, while on the other claiming the preservation of all “the natural food properties.”

20 PER CENT. GLUTEN MEAL

Referee Company
Water 7.65 5-10
Ash 1.22 1-2
Protein (N × 5.7) 24.68 20-30
Fiber 0.12 1-2
Carbohydrates 65.41 65-70
Fat 0.92 1-2
Starch 51.24 65-70

The company’s analysis is confirmed. As the company claims directly that this is “Not A Diabetic Food,” any criticism of its use for that purpose is disarmed. However, again exception must be taken to the statement that “the natural food properties of the product” are preserved.

PURE GLUTEN MEAL

Referee Company
Water 4.60 5-10
Ash 0.96 1-2
Protein (N × 5.7) 76.78 75-80
Fiber 0.08 1-3
Carbohydrates 16.77 0-5
Fat 0.81 0.25-0.70
Starch 6.77 0-5

The minimum claim as to protein is justified. Again the company confuses carbohydrates and starch, and the food instead of containing from 0 to 5 per cent. of “carbohydrates (starch)” actually contains 16.77 per cent. of carbohydrates, of which 6.77 per cent. is starch. Once more the statement that “the natural food properties” are preserved is untrue as applied to a wheat product deprived of most of its starch.

In justice to the company, it should be noted that on the labels of “Pure Gluten Biscuit” and “Pure Gluten Meal” appears the warning: “Every person suffering from diabetes should be under the care of an experienced physician,” and on the label of “40 per cent. Gluten Meal,” “Persons suffering from diabetes should use this food only on the advice of a physician.” On the other hand, the suggestion on the label of “Pure Gluten Meal,” “Write for a copy of Diabetic Foods and How to Use Them” is a more or less direct invitation to self-treatment. Moreover, a letter dated May 9, 1916, apparently dictated for the Kellogg Food Company by one Ruth French, in reply to an inquiry from a layman, gives direct advice with no reference whatever to a physician.

CLAIMS MADE IN A LETTER TO A LAYMAN

In addition to this inconsistent attitude the letter makes certain clear misstatements, as follows:

“40 per cent. Gluten Flour actually contains 40 per cent. of pure Gluten, making it a perfectly safe article of diet in all but the gravest cases of diabetes. From our Gluten Flour excellent bread, gems and puffs are made that perfectly satisfy the craving for bread with no harmful results.” This flour contains 33.63 per cent. of gluten, not 40 per cent.; it is not “a perfectly safe article of diet in all but the gravest cases of diabetes,” for if one reads the literature correctly, starch restriction is more necessary in mild than in severe cases of diabetes. Furthermore, the bread, gems and puffs made from such a flour do not “satisfy the craving for bread with no harmful results.”

In the next paragraph of the letter, undue emphasis is laid on the “objectionable properties” of flesh foods, a statement only in accord with the tenets of extreme vegetarians. I also doubt very much whether the statement is true that “under a diet of our diabetic foods the thirst to which diabetics are so often subject is usually very much relieved.”

In the next paragraph the assertion is made that “The diet indicated ... is in keeping with the ideas of the highest medical authorities.... Meat is entirely excluded from the dietary.” My reading of the literature does not show that the leading authorities take any such position. Later on reference is made to von Noorden’s claim as to the superiority of vegetable over animal proteins, which I have already discussed under “Pure Gluten Biscuit.” (Certain detached sentences of von Noorden might justify such a statement, but a reading of all he says on the subject leads to a very different conclusion.)

CLAIMS MADE IN AN ADVERTISING BOOKLET

The whole booklet is written from the standpoint of an extreme vegetarian, and therefore is often misleading in its conclusions.

Page 5. “The researches of Ogata and others have shown that cane sugar is a less wholesome food than the natural sugars found in fruits and produced in the body by the digestion of starch, that is, fruit sugars and malt sugars.” In opposition to this I quote from von Noorden, their own authority, “Die Zuckerkrankheit und ihre Behandlung,” Berlin, 1910, page 270:

“That levulose, milk sugar and inulin are more useful than the other carbohydrates is a common opinion, but the importance of their use in practice does not correspond with the theory. In light cases the form of carbohydrates makes little difference; in severe cases the advantage from using levulose, milk sugar, etc., is only slightly greater than from using bread and flour.... Only in certain cases does it appear to me that the special form of carbohydrates possesses any particular significance.”

On page 92 of the same work von Noorden tells us that of the carbohydrates dextrose is the worst, with maltose almost as bad (in spite of the fact that Kellogg exploits his “Meltose,” the “new carbohydrate,” as of special value for diabetics). He also says that levulose increases glycosuria only about half as much as dextrose, when used occasionally, but with long use it is as bad as dextrose and starch.

Page 5. The company refers to sugar as “possibly also causing diabetes.” Sugar or any other carbohydrate may under diabetic conditions cause an increase of glucose in the urine, but I do not believe that any food or any diet can cause diabetes.

Page 7. “That the large use of meat and eggs is not only detrimental but positively dangerous in many cases of diabetes is now a well known and recognized fact.” The dietaries of well known authorities on diabetes are not in harmony with this statement.

Page 13. “It has been discovered that the complete suppression of carbohydrates from the dietary is not only unnecessary but is highly detrimental and even dangerous.” “The complete suppression of carbohydrates from the dietary” is the only means the physician has to determine the diabetic’s carbohydrate tolerance. If carbohydrate-poor foods are so “highly detrimental and even dangerous,” why does the company exploit foods like “Pure Gluten Flour” and “Pure Gluten Biscuit,” whose chief claim to excellence is their comparative freedom from carbohydrates?

Page 17. “Cream is an emulsion, and, with the exception of egg yolk, is the only form in which animal fat is found in an emulsified state.” Milk, Nature’s most wonderful emulsion, is apparently overlooked.

Page 19. “... these foods ... will be found of great value ... especially as substitutes for the breads and meats which are the most objectionable features of the ordinary diet, and which should, as far as possible, be interdicted in this class of cases.” This is simply special pleading for the Kellogg vegetarian diet.

Page 19. “Our glutens ... are all thoroughly standardized, so that in their use the physician and the patient know just the amount of starch eaten.” This standardization is largely mythical. For instance, “Pure Gluten Biscuit” claims 0 to 5 per cent. “carbohydrates (starch),” whereas I find 14.84 per cent. carbohydrates with 4.02 per cent. starch. “40 per cent. Gluten Flour” claims 40 per cent. gluten and 40 to 45 per cent. carbohydrates, whereas I find 33.63 and 55.35 per cent., respectively. “Pure Gluten Meal” claims 0 to 5 per cent. “carbohydrates (starch)” whereas I find 16.77 per cent. carbohydrates and 6.77 per cent. starch. I have a record of six analyses each of “40 per cent. Gluten Flour” and “40 per cent. Gluten Biscuit,” which show the hollowness of this claim of “standardization.” The flour showed 33.6, 35.0, 42.9, 36.8, 35.6, and 40.9 per cent. of protein, with from 40.8 to 55.4 per cent. of carbohydrates; the biscuits 32.7, 33.2, 39.5, 43.3, 33.9, and 41.2 per cent. of protein, with from 41.1 to 54.0 per cent. of carbohydrates. In fact, my experience shows that the Kellogg products are more poorly “standardized” than most of the diabetic foods on the market.

Page 20. “May be made to carry a large amount of fat in the form of butter, a most desirable thing in the treatment of diabetes,” while on page 16 the company claims that in an experiment of Minkowski on a dog, butter “passed through the body without change, none being absorbed”; these are certainly contradictory statements. The explanation is that on the one page the company is exploiting its biscuits, and on the other its nut preparations.

Page 20. Again the incorrect claim is made for “40 per cent. Gluten Flour” that “we believe this to be the only standardized gluten flour made.”

Page 21. The claim is made that flesh foods are “objectionable on account of the large amounts of ptomains and toxins which they contain.” I was not aware that fresh meats contained any ptomains whatever. On the same page the claim is again made that by the use of the Kellogg nut foods “diabetics lose their thirst,” a claim which I think is more than doubtful.

Page 22. “Nuts are a whole food, containing all the elements required for the perfect nutrition of the body.” A marked characteristic of nuts is that they are not “a whole food,” as with the exception of a few varieties, such as the chestnut, they are extremely poor in carbohydrates, which fact gives them their value in the diabetic diet.

Page 23. “With the exception of the potato, the beet and the carrot, vegetables contain little sugar or starch.” Corn, beans and peas are all vegetables which are relatively high in carbohydrates, and for this reason are specifically excluded from the diabetic’s dietary.

From the foregoing considerations I would recommend that the company’s analyses of “40 per cent. Gluten Biscuit,” “40 per cent. Gluten Meal,” and “20 per cent. Gluten Meal” be accepted as correct. Before the Council can accept any of these products, the following steps should be taken:

The company on all its labels should correct the impression that “carbohydrates” and “starch” are synonymous terms.

The labels of all the preparations examined should be changed in accordance with the criticisms given above.

In all cases in which analytic data are given, it would be preferable to state only the minimum of protein and the maximum of carbohydrates.

The booklet, “Practical Suggestions About Diet in Diabetes,” should be radically changed along the lines noted above.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 56._)

IODO-MANGAN OMITTED FROM N. N. R.

Report of the Council on Pharmacy and Chemistry

Iodo-Mangan, made by the Chemische Fabrik Helfenberg A. G., near Dresden, Germany, and sold in the United States by the Reinschild Chemical Company, New York, is a solution said to contain iron, manganese and iodin in combination with peptone. It is claimed to be a reconstructive tonic and blood-making adjuvant, with favorable action in affections of the glandular system. It was admitted to New and Nonofficial Remedies in 1907, before the Council had adopted the present Rule 10, which provides that no article shall be admitted to New and Nonofficial Remedies which, because of its unscientific composition, is useless or inimical to the best interests of the public or of the medical profession. In 1911 the Council considered the question whether or not this product was still eligible and decided in the end to retain it as probably having some merit. To determine if Iodo-Mangan was eligible for New and Nonofficial Remedies, 1917, the Reinschild Chemical Company was requested to send in the current advertising matter. As this advertising was not sent in and as apparently the product was not marketed at the present time, the Council on Pharmacy and Chemistry voted to omit Iodo-Mangan from New and Nonofficial Remedies. At the same time the Reinschild Chemical Company was informed that the preparation might be submitted for reconsideration at any time.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 64._)

LIQUID ALBOLENE

Report of the Council on Pharmacy and Chemistry

As now marketed, Liquid Albolene (McKesson and Robbins, New York), is claimed to be made only from genuine Russian oil and hence to possess distinct advantages over

“... Oils purporting to be Russian, most of which are imperfectly
purified and many of which are positively dangerous for continued
use.”

On the other hand, a short time ago, McKesson and Robbins claimed that Liquid Albolene was then available.

“... Of as high a quality as we had supplied before the European
War. Thanks to the research and scientific achievement of Our
Chemists, we are now able to offer LIQUID ALBOLENE, using as a base
a specially refined Domestic Oil that is in every way suitable for
medicinal purposes, and having the same viscosity as Russian Oil.”

The advertising matter suggests the promiscuous, thoughtless and irrational use of Liquid Albolene and of a number of Albolene preparations by extravagant claims, such, for example, as the following:

“Albolene will never fail to bring a free, easy stool, no matter
what condition may be present, from obstinate atony of the bowel to
fissure, fistula, or even malignant disease, and in spite of the
failure of ordinary purgatives to which the patient may have become
habituated....

“Aromatic Liquid Albolene is actually the first laxative presented
to the medical profession that seems to have no drawback....

“It will not have been lost upon the physician who has read the
remarks on the use of Aromatic Liquid Albolene to regulate the
bowels in surgical cases, that there are many instances where
it would prove equally valuable during the treatment of acute
diseases. In the exanthemata, in pneumonia, for example, to cite
only a few of the conditions where it may be used to advantage, an
absolutely reliable laxative that will not in any way weaken or
distress the patient, presents obvious superiority to any of the
agents heretofore in common use.”

The Council held Liquid Albolene ineligible because the product is marketed in a way to encourage its indiscriminate and irrational use by the public (Rule 4) and because unwarranted therapeutic claims are made for it (Rule 6).--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 65._)

NAPHEY’S MEDICATED UTERINE WAFERS

Report of the Council on Pharmacy and Chemistry

Naphey’s Medicated Uterine Wafers were submitted to the Council by the manufacturers, Naphey & Co., some years ago and were rejected. Naphey & Co. has recently requested reconsideration of the preparation, and has submitted advertising matter, trade packages and sample packages. The label of the trade package contains the following:

“Naphey’s Wafers. For the local treatment of diseases of women,
indicated in catarrhal conditions of the vagina, and of the uterine
cervix. As a [_sic!_] adjuvant for the physician to use in carrying
out treatment of disease of the uterus.”

“Zinc Sulphate, 3-3/4 gr., Sodium Sulphate, 3-1/2 gr., Sodium
Borate, 4 gr., Boric Acid, 3/4 gr.”

“Naphey & Co., Warren, Pa., U. S. A.”

“Each box contains 25 wafers, sufficient for three months’
treatment. Price per box, 25c.”

In name, composition, and general appearance of the package, Naphey’s Medicated Uterine Wafers bear a strong resemblance to Micajah’s Medicated Uterine Wafers (The Journal, A. M. A., March 26, 1910, p. 1070). An advertising pamphlet reads:

“In every form of leucorrhea Naphey’s Medicated Uterine Wafers are
indicated ...”

“What is true of leucorrhea is also true of all other functional
troubles affecting the female genital canal; they are all treated
best by astringents and antiseptics. And these, to be effective,
must be applied in prolonged contact.”

The implication that all “functional troubles affecting the female genital canal” are best treated by astringent tablets like Naphey’s Medicated Uterine Wafers is an absurdity. The naming of disease conditions on the label, the manifestly unwarranted and exaggerated therapeutic claims, the name, which is non-descriptive of composition but suggestive of use, and the fixed formula, which cannot rationally be expected to give uniformly satisfactory results in the wide range of conditions for which the product is recommended, render Naphey’s Medicated Uterine Wafers ineligible for New and Nonofficial Remedies under Rules 4, 6, 8 and 10.

The report having been sent to Naphey & Co., the manufacturer offered, on condition that the preparation be accepted, to revise the advertising matter in minor particulars, to remove disease names from the trade package and to adopt the name Naphey’s Wafers or Naphey’s Tablets. The Council advised Naphey & Co. that the proposed names do not conform to the requirements for acceptance in New and Nonofficial Remedies because they do not indicate the composition of this pharmaceutical mixture, and moreover, that the routine use of a complex formula such as that of these tablets is irrational.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 66._)

NUJOL

Report of the Council on Pharmacy and Chemistry

Nujol, a liquid petrolatum (Standard Oil Company of New Jersey, Bayonne, N. J.), was submitted to the Council by the manufacturers. The Council advised the company that, before Nujol could be made eligible for New and Nonofficial Remedies, the advertising claims made for it must be revised to conform to the rules of the Council and the term “liquid petrolatum” must be used in connection with the brand designation and given equal prominence on the labels, advertisements and all circulars. The company thereupon submitted a label on which the name “Nujol” appeared in large red letters and under it in small letters the words “Liquid Petrolatum.” This did not meet the Council’s requirement with regard to the name. Moreover, Nujol continued to be advertised to the public under exaggerated and unwarranted claims.

The foregoing report was sent to the Standard Oil Company of New Jersey, which thereupon submitted revised advertising copy. This copy was decidedly less objectionable than the previous advertising but still contained exaggerated statements. The copy for use in lay journals particularly evidenced exaggeration. Observation on many occasions of a similar fact has convinced the Council of the inexpediency of admitting to New and Nonofficial Remedies any article which is advertised to the public.[101]

[101] Since publication of this report the Council on Pharmacy and Chemistry has revised its rule against recognition of articles advertised to the public so that this shall not apply (_a_) to disinfectants, germicides and antiseptics, provided the advertising be limited to conservative recommendations for their use as prophylactic applications to superficial cuts and abrasions of the skin and to the mucous surfaces of the mouth, pharynx and nose, and provided they are not advertised as curative agents, and (_b_) to non-medicinal food preparations, except when advertised in an objectionable manner.

The Council held that conflict with Rules 3, 6 and 8 prevented the acceptance of Nujol and authorized the publication of this report.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 68._)

PULVOIDS NATRIUM COMPOUND

Report of the Council on Pharmacy and Chemistry

Pulvoids Natrium Compound was submitted to the Council by the Drug Products Company, Inc., New York, with the statement that each pulvoid (coated tablet, said to be made to dissolve in the intestinal tract) represents the equivalent of:

Potassium Nitrate 2-1/2 grs.
Sodium Nitrite 1/2 gr.
Sodium Bicarbonate 2 grs.
Fl. Ext. Crataegus Oxycantha 1 min.
Nitroglycerin 1/250 gr.

According to the advertisements the tablets are “indicated in the treatment of high blood pressure and all forms of hypertension of the cardio-vascular system.” It is claimed that the tablets “will not irritate the kidneys.”

The Council, having submitted its objections to the manufacturer and considered the firm’s reply, held that Pulvoids Natrium Compound was inadmissible to New and Nonofficial Remedies for the following reasons:

1. The claim is made that the tablets disintegrate in the intestines; experiments conducted by the Council indicated that in most cases they would be broken up in the stomach. It was found that the tablets were visibly changed immediately after being put into gastric juice or even into distilled water; they disintegrated within from three to four hours, not only in gastric juice (obtained from a dog) at 37 C., but also in distilled water. It is quite usual for solids to remain in the stomach for more than three hours. If they make their way out of the stomach in less than that time the gastric movements must be so vigorous as further to hasten the disintegration of the tablets.

2. The rules of the Council require that the name of a pharmaceutical mixture shall indicate the potent ingredients. The name of this mixture does not indicate the presence of the nitrites, the potassium nitrate, the bicarbonate or the extract of hawthorne and the nondescriptive name is likely to lead physicians to use the tablets without fully realizing what they are giving.

3. No evidence was submitted that the tablets, as found on the market, contained the amount of sodium nitrite and nitroglycerin claimed. That is, it does not appear that the manufacturer checks the sodium nitrite and nitroglycerin content by analysis. The Council did not determine the nitrite content of the tablets. It maintains that when a manufacturer places a product on the market the burden of proof is on that manufacturer to show that the facts are in accordance with his claims for his product. Further, the examination by the Council of one or several specimens of any commercial product (particularly in the case of nitroglycerin preparations) would not be a guarantee of the constancy of its composition so long as the manufacturer does not himself control the composition by analysis. The necessity of such control of tablets containing nitroglycerin is evident from the report[102] of L. F. Kebler of the U. S. Bureau of Chemistry. Dr. Kebler said:

[102] J. A. M. A., Nov. 2, 1912, p. 1604.

“... nitroglycerin tablets have in a majority of cases been found
deficient in the nitroglycerin content declared.”

“... these commodities are manufactured largely by rule of thumb.
Little checking obtains in their manufacture and generally no
analyst is employed.”

A further proof that nitroglycerin tablets are likely to be deficient in strength is contained in the convictions under the Food and Drugs Act of manufacturers who sold tablets below the declared strength, recorded from time to time (Notices of Judgments Nos. 3405, 2059, 1843, 1799).

4. There is no good evidence, experimental or clinical, to justify the simultaneous administration in fixed proportion of two vasodilators like sodium nitrite and glyceryl trinitrate (nitroglycerin). Also there is no rational excuse for combining extract of hawthorne, which is said to have a tonic effect on the heart muscle, with nitrites, which cause relaxation of the vascular system, or for the combination with these constituents of potassium nitrate or of sodium bicarbonate.

In the absence of evidence for the combination, Pulvoids Natrium Compound must be considered an irrational mixture, the use of which is a detriment to sound drug therapy and, hence, not admissible to New and Nonofficial Remedies.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 69._)

SALOFORM

Report of the Council on Pharmacy and Chemistry

A referee submitted the following report of the American Medical Association Chemical Laboratory to the Council:

ANALYSIS OF SALOFORM

Saloform (Flexner) is advertised by the Robinson-Pettet Company of Louisville, Ky. In the advertisements for the product it is stated that:

“Saloform is a definite chemical compound the component parts of
which are _Hexamethylene Tetramine_, _Salicylic Acid_ and Lithia.”

“As a Uric Acid Solvent it is indicated in _Rheumatism_, _Gout_, in
_Phosphaturia_, in _Gravel_, and in _Renal Colic_.”

“As a Genito-Urinary Antiseptic it limits suppuration anywhere
along the Urinary Tract, from the Kidneys down to the orifice of
Urethra.”

As, even after diligent search, no description of a compound of hexamethylenamine (hexamethylenetetramine), salicylic acid and lithia was found in chemical literature, it seemed probable that Saloform is merely a mixture of hexamethylenamine and lithium salicylate. Accordingly the separation of Saloform into its component parts by means of selected solvents was attempted. By triturating the powder with chloroform, filtering and evaporating the filtrate, a residue was obtained which gave satisfactory tests for hexamethylenamine but contained only traces of salicylic acid or lithium salicylate. The portion insoluble in chloroform was dissolved in water. The solution gave satisfactory tests for lithium salicylate but not for hexamethylenamine. From these tests it is evident that Saloform is a simple mixture of hexamethylenamine and lithium salicylate. Quantitative examination indicated that the two ingredients, hexamethylenamine and lithium salicylate, are present in approximately equal amounts.

REFEREE’S RECOMMENDATION

The report of our Chemical Laboratory shows that Saloform is not a definite compound as claimed, but a simple mixture of hexamethylenamin and lithium salicylate. It is therefore in conflict with Rule 1. It is also in conflict with Rule 6, for neither hexamethylenamin, lithium, nor salicylate are therapeutically effective “uric acid solvents”; nor would any of these have any effect on “phosphaturia.”

The mixture also conflicts with Rule 10; for it is inadvisable to administer the ingredients in fixed, but unknown proportions.

It is recommended that Saloform be deemed inadmissible to N. N. R.

The Council adopted the recommendation of the referee and authorized publication of this report.--(_From Reports of Council on Pharmacy and Chemistry, 1916, p. 71._)

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:

[103] J. A. M. A., May 1, 1915, p. 1518.

“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]

[104] Carlson. A. J.; Lebensohn, J. E., and Pearlman, S. J.; Has Secretin a Therapeutic Value? J. A. M. A., Jan. 15, 1916, p. 178. Reports Council on Pharm. and Chem., 1915, p. 98.

[105] So-Called Secretin Preparations, J. A. M. A., Jan 15, 1916, p. 208; Reports Council on Pharm. and Chem., 1915, p. 96.

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:

[106] All italics are ours. G. W. Carnrick Company.

[107] Bio-Chem. Jour. =1=:28, 1906.

“‘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_[4]--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.’ ...”

[108] Presse Médicale, 1912, p. 433.

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 te stimony” 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.

[109] Cf. interal. Schagindweit, E.: Experimentelle Versuche mit Hormonal, Arch. Internat. de Pharmacod., 1913, p. 77.

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._)

IRON CITRATE GREEN

Report of the Council on Pharmacy and Chemistry

H. K. Mulford Company and E. R. Squibb and Sons submitted to the Council ampules containing solutions of iron citrate green. It thus became necessary to consider the eligibility of iron citrate green itself for admission to New and Nonofficial Remedies. As the rules of the Council provide that nonessential modifications of official or nonproprietary preparations will not be recognized, the above named firms were asked to state what advantages, if any, the so-called iron citrate green had over the official iron and ammonium citrate. In reply the H. K. Mulford Company wrote that it had come to the conclusion that iron citrate green and ampules thereof would undoubtedly be considered by the Council as a nonessential modification of an official product, adding:

“It seems to differ from the official ferric citrate so far as
essentials go only in color, but custom, which is exceedingly hard
to change in South America, demands that this green variety of
ampules be used in place of the official product.”

In reply to a similar letter of inquiry E. R. Squibb and Sons wrote:

“Iron citrate green (iron and ammonium citrate green) differs from
the U. S. P. iron and ammonium citrate in that it contains less
iron and more citric acid and more ammonium citrate than does the
latter. It is of course a modification of the official salt and is
supplied to meet a real demand. Its reaction is quite decidedly
acid and our present stock contains Fe slightly below the U. S. P.
requirements for iron, assaying 15.74 per cent. instead of 16 per
cent. Fe. The tests used to control its quality are those for the
official product except as before indicated, it is always acid
instead of neutral, as the U. S. P. requires for that salt.”

The smaller iron content (98 per cent. of the U. S. P. requirement) of the green variety referred to by E. R. Squibb and Sons is so small as to be negligible. Further, the low iron content as well as the acidity of the green salt would appear to be detriments rather than advantages. Inasmuch as no evidence has been presented to show that iron citrate green is superior in any way to the well-known iron and ammonium citrate the Council held that iron citrate green, and with it the dosage forms, was ineligible to N. N. R.

The preceding report was submitted to the Mulford Company and to E. R. Squibb and Sons for comment before publication. The former firm replied that in the present case it felt bound to supply the existing demand, the latter replied that, to give the Council its support in this matter, the sale of iron citrate green and ampules thereof would be discontinued.--(_From The Journal A. M. A., Jan. 13, 1917._)

ASPIRIN

Report of the Council on Pharmacy and Chemistry

The referee’s report on Aspirin-Bayer which follows was submitted to the Council and adopted by it and, in accordance with the referee’s recommendation, was sent to the Bayer Company, Inc. The company’s reply contained nothing to warrant the continued recognition of this product by the Council. It was accordingly directed that Aspirin-Bayer be omitted from New and Nonofficial Remedies.

W. A. Puckner, Secretary.

REFEREE’S REPORT

The referee’s attention has been called to the systematic campaign of advertising aspirin to the public. He is informed that tablets have been marketed for some time in “vest-pocket” boxes, bearing the name “Aspirin” permanently affixed, which is in technical conflict with the Council’s rule against indirect advertising to the public. More recently, conspicuous advertisements have appeared in daily papers. These are technically in conflict with the rule against direct advertising to the public.

In addition to the plain technical conflicts with the Council’s rules there is a feature of the case which has not hitherto been raised and which should be fully considered: It may be remarked that the advertisements contain no therapeutic recommendation, and do not, on their face, urge the public to employ aspirin but apparently merely tell the public how it may protect itself against sophistication. In substance, they say: “If you are a user of aspirin, this is how you may obtain the genuine.” It might be said that this is not an attempt to increase the use or sale of aspirin--the ordinary object of advertising--but that the means of protection against adulteration is a “subject on which the public should be instructed.” The principle of such exceptions is stated in the comments to Rule 3 (New and Nonofficial Remedies, 1916, p. 15); and although the present case does not come under the exceptions specified under these comments, it may be urged that the exceptions need to be increased as occasion arises. The notorious adulteration of aspirin may well be urged as establishing a need for a similar exception in its use.

The general principle of protecting the public against fraud, adulteration and substitution is directly in line with the objects of the Council, and deserves commendation and support. It is obvious, however, that the means adopted for this end must be efficient, that they must not open the door to other, perhaps greater evils and that they must be used in good faith. The policy of advertising “Aspirin-Bayer” must be examined in these respects.

In the first place, the acceptance of a product by the Council implies an agreement by the manufacturers or agents that they will adhere strictly to the Council’s rules and will not depart from the letter or spirit of these rules without notice to the Council. This principle has been grossly infringed in the present case. There can be no doubt that the agents were aware that their advertisements conflicted, at least with the letter of Rule 3. Nevertheless, they did not, in any way, inform the Council of the change in policy. In this respect, at least, they have not acted in good faith.

Secondly, the wording of the advertisement implies that only the tablets stamped with “The Bayer Cross” are genuine. This is misleading, since every druggist has the right to make unstamped tablets of aspirin, fully as genuine as those stamped with the cross.

Thirdly, the cross itself cannot be considered an efficient protection; for people who imitate aspirin will not hesitate to imitate the stamp. The remedy, in either case, and as with any other drug, is the examination of trade samples, and the vigorous prosecution of those guilty of violating the law.

Fourthly, the permanent affixing of the name “Aspirin” to the vest-pocket boxes is also inefficient as a protection, and serves mainly as an advertisement.

Fifthly, whatever may have been the motives of the advertisers, and however carefully the advertisements are worded, they will inevitably tend to increase the use of aspirin by the public, and this is directly against the interests of public health. The public does not know, as physicians do, that headaches are merely symptoms of other, sometimes very serious conditions; and that they are often the signal for the need of a thorough physical examination and diagnosis. It is true that they are often also the symptoms of very minor derangements, which will right themselves spontaneously; and that, in such cases, drugs like aspirin may give relief and may do no harm. The patient, however, is not educated to distinguish one class from the other, and therefore anything that tends to promote the indiscriminate use of such remedies as aspirin is detrimental to the public health. Furthermore, aspirin itself is not always harmless. Alarming idiosyncrasies are sufficiently common that the use of the first doses, at least, should require medical supervision. With these considerations in mind, the referee is of the opinion that the direct and indirect advertising of aspirin is to be condemned.--(_From The Journal A. M. A., Jan. 20, 1917._)

PIL. CASCARA COMPOUND-ROBINS

Report of the Council on Pharmacy and Chemistry

A circular issued by the A. H. Robins Company of Richmond, Va., contains the following statement:

“PIL. CASCARA COMPOUND-ROBINS is a rational therapeutic formula,
composed of CASCARA, PODOPHYLLIN, COLOCYNTH and HYOSCYAMUS, which
promotes a natural flow of secretions, which is, in turn, the
physiologic stimulant of peristalsis. Thus, a normal evacuation is
produced without subsequent inhibition.

“They contain no Mercury, Strychnia nor Belladonna.

“An ideal aid to any remedial agent, when a Mild, Medium or Strong
alimentary stimulant is needed [_sic_].

“Made in two strengths, the dosage may be easily regulated so as
to obtain the effects of an Anti-Dyspeptic, Aperient, Laxative or
Cathartic, as desired. They never cause discomfort unless given in
larger dose than needed.”

This preparation is another example of the innumerable mixtures of well-known drugs having nothing in the way of originality or of special therapeutic value to recommend them.

The advertising implies that this particular combination has a special action on the secretions of the gastro-intestinal tract; otherwise it would be hard to explain the claim that the preparation is antidyspeptic, if that means anything more than a laxative or cathartic.

The claim is made that this preparation contains no belladonna--yet it admittedly contains hyoscyamus! This manifests either ignorance on the part of the manufacturers, or an effort to impose on the medical profession. Both belladonna and hyoscyamus contain variable amounts of similar alkaloids, chiefly hyoscyamin. Hyoscyamus is feebler than belladonna in its action, as it contains less alkaloid. The qualitative differences between the two drugs, with reference to their use as laxatives, is so slight as to make the company’s claim for hyoscyamus appear either deliberately misleading or to be the result of crass ignorance. Promoting this mixture of well-known laxatives and cathartics as an “ideal aid to any remedial agent when a mild, medium or strong alimentary stimulant is needed” is a slur on the intelligence of physicians.

Pil. Cascara Compound-Robins is not acceptable for New and Nonofficial Remedies.--(_From The Journal A. M. A., Jan. 27, 1917._)

CASTA-FLORA

Report of the Council on Pharmacy and Chemistry