NEED FOR PATENT LAW REVISION

“For the source of secretin I preferably use that part of the alimentary tract of any lower animal—such as a hog or sheep—including the gastric pylorus, the duodenum and the jejunum. This part is split open and washed with a normal saline solution to clean the mucosa or mucous membrane of any detritus which may be present. The mucosa with the epithelial cells is then removed or separated from the muscular wall by scraping with a blunt knife or in any other suitable way. The scrapings or cuttings, which contain the secretin, are then macerated or broken up.”“The macerated mass is placed in a suitable vessel and subjected to the action of an acid solution until digested. The time for the digestion of the mass will, of course, depend upon the strength and temperature of the acid solution employed. The stronger the solution and the higher the temperature, the shorter the time necessary for complete digestion. This period may vary from several minutes to several hours. In my experiments I found that the best results were obtained with hydrochloric acid solution of one-tenth to five-tenths of one per cent. in strength, although as high as eight-tenths per cent. might be used. The mixture is brought to a temperature of approximately 210 F., and it may even for a few moments exceed that temperature, but it should be kept below the boiling point, forexcessive heat injures or breaks down the secretin molecule and impairs or destroys its activity. Although I prefer to use hydrochloric acid, I would have it understood that other acids—both organic or inorganic—may be employed, provided that the percentage of acidity is regulated to prevent a chemical change in the secretin, and further provided, of course, that the acid has no injurious effect on the human system.”“After the mass has been digested in the heated solution, the decoction is decanted, and after being allowed to cool is passed through a suitable filter until the filtrate is clear. I found that by filtering the decoction from four to six times through a carbon filter, I obtained a clear colorless filtrate. This is a solution of secretin and the acid which was used, and the clearness of the solution shows that it is practically free from albumoses, gelatin and other impurities (such as cell tissues, etc.) present in the raw material under treatment.”

“The macerated mass is placed in a suitable vessel and subjected to the action of an acid solution until digested. The time for the digestion of the mass will, of course, depend upon the strength and temperature of the acid solution employed. The stronger the solution and the higher the temperature, the shorter the time necessary for complete digestion. This period may vary from several minutes to several hours. In my experiments I found that the best results were obtained with hydrochloric acid solution of one-tenth to five-tenths of one per cent. in strength, although as high as eight-tenths per cent. might be used. The mixture is brought to a temperature of approximately 210 F., and it may even for a few moments exceed that temperature, but it should be kept below the boiling point, forexcessive heat injures or breaks down the secretin molecule and impairs or destroys its activity. Although I prefer to use hydrochloric acid, I would have it understood that other acids—both organic or inorganic—may be employed, provided that the percentage of acidity is regulated to prevent a chemical change in the secretin, and further provided, of course, that the acid has no injurious effect on the human system.”

“After the mass has been digested in the heated solution, the decoction is decanted, and after being allowed to cool is passed through a suitable filter until the filtrate is clear. I found that by filtering the decoction from four to six times through a carbon filter, I obtained a clear colorless filtrate. This is a solution of secretin and the acid which was used, and the clearness of the solution shows that it is practically free from albumoses, gelatin and other impurities (such as cell tissues, etc.) present in the raw material under treatment.”

“To the solution of pure and active secretin prepared as above explained, there is added a suitable quantity of blood serum—say from one-fifth to two per cent. or any equivalent medium—such as albumin solution or a peptone solution—which will aid and sustain the activating power of secretin as provided by the blood. That is to say, any medium having the same power, similar quality or chemical composition that the blood-stream possesses in combining with secretin to stimulate the pancreas. The addition of such a medium to the active secretin solution increases the potency of the secretin and its degreeof stability by preventing oxidation or deterioration thereof. If this strengthening or fortifying medium, as it may be properly termed, is alkaline, it performs the additional function of lowering the acidity of the secretin filtrate. It is preferable that the final product be just faintly acid. If desired, the final product may be made into an elixir by the addition of aromatics.”“Any desired strength of secretin solution may be obtained according to the quantity of acid solution. In my experiments I used from ten to fourteen duodena to a pint of acid solution.”“The solution of secretin prepared as above described is characterized by its ability to resist oxidation or deterioration for a sufficient period of time to render the solution available as a commercial article, and is furthermore characterized by freedom from poisonous and irritable chemical substances, whereby the secretin is chemically adapted to the human system to stimulate the pancreas to increased secretion.”“As previously stated, the secretin prepared according to my method may be administered orally to produce the desired physiological action. Of course, if desired, the secretin might be injected intravenously, but this more or less dangerous procedure is not at all necessary, and I merely mention it here to point out that when I refer to the oral administration of my new secretin preparation, I do not mean to exclude its administration by injection.”“As to the commercial stability of the secretin prepared according to my method, I may say that I have found by actual tests that the preparation maintains its stability for as long a period as five or six months. When I refer to my product as being “commercially stable,” I mean that it resists oxidation or deterioration for a sufficient period to render the same available as a commercial article. This period may vary from several weeks to several months, depending upon certain commercial factors well understood by the manufacturer. So, roughly speaking, I should say that secretin is commercially stable when it retains its activity from one to six months. I do not wish to be understood, however, as limiting myself to these exact figures.”

“Any desired strength of secretin solution may be obtained according to the quantity of acid solution. In my experiments I used from ten to fourteen duodena to a pint of acid solution.”

“The solution of secretin prepared as above described is characterized by its ability to resist oxidation or deterioration for a sufficient period of time to render the solution available as a commercial article, and is furthermore characterized by freedom from poisonous and irritable chemical substances, whereby the secretin is chemically adapted to the human system to stimulate the pancreas to increased secretion.”

“As previously stated, the secretin prepared according to my method may be administered orally to produce the desired physiological action. Of course, if desired, the secretin might be injected intravenously, but this more or less dangerous procedure is not at all necessary, and I merely mention it here to point out that when I refer to the oral administration of my new secretin preparation, I do not mean to exclude its administration by injection.”

“As to the commercial stability of the secretin prepared according to my method, I may say that I have found by actual tests that the preparation maintains its stability for as long a period as five or six months. When I refer to my product as being “commercially stable,” I mean that it resists oxidation or deterioration for a sufficient period to render the same available as a commercial article. This period may vary from several weeks to several months, depending upon certain commercial factors well understood by the manufacturer. So, roughly speaking, I should say that secretin is commercially stable when it retains its activity from one to six months. I do not wish to be understood, however, as limiting myself to these exact figures.”

That active secretin may be extracted from macerated intestinal mucosa by weak acids below the temperature of boiling is well known. In fact, weak acids at body temperature in contact with the duodenal mucosa lead to the formation of secretin. The claims that secretin given by mouth reaches the blood and acts on the pancreas has been made for other preparations of secretin. It has also been shown that these claims are erroneous.122Thus it would appear that the only novel element in Dr. Beveridge’s patented secretin is the addition of serum, soluble proteins or peptones. What reason is there for believing that this will render the secretin stable for months, and physiologically active when taken by mouth? We do not believe Dr. Beveridge ever injected his secretin—protein mixture—intravenously in man or animals not under anesthesia, otherwise he would not have stated: “Of course, if desired, the secretin may be injected intravenously.”

I.The Samples of Secretin Sent Us by Dr. Beveridge.—Physiological tests were made on four quart bottles of the secretin kindly sent us by Dr. Beveridge June 26, 1916. According to a letter from Dr. Beveridge of July 20, 1916, those samples of secretin were prepared June 20, that is, only six days before received by us. The material came in dark colored bottles. It was kept in the original bottles and placed in the ice box immediately on receipt. Dr. Beveridge stated the secretin “should remain active until the month of November, 1916, at least.”

Tests were made on three out of the four bottles. The fourth bottle was not opened, as we desired to learn what change it might undergo in the way of protein precipitation and bacterial decomposition. There is nothing in the Beveridge method of preparation that insures a sterile secretin unless it is passed through a Berkefeld filter. In all our crucial experiments the animals (dogs) were kept under light ether anesthesia, a cannula inserted into the pancreatic duct, the blood pressure recorded from the carotid artery and the various secretin preparations injected intravenously. When inactive secretin preparations were encountered, control tests were always made with activesolutions of secretin to eliminate possible individual peculiarities of the animal. Thus when the pancreas of a dog reacts to the injection of preparationA, but not to preparationB, it is evident that absence of response toBis due to this preparation and not to the animal or to the experimental conditions.

Fig. 1.—Records of carotid blood pressure and secretion of pancreatic juice on intravenous injection of Beveridge’s secretin in dogs.X, injection of 10 c.c. secretin;b, record of flow of pancreatic juice in drops. TracingA, injection of 10 c.c. of one sample secretin (ten days old) furnished by Dr. Beveridge. TracingB, injection of 10 c.c. of second sample of secretin (ten days old) furnished by Dr. Beveridge. TracingC, injection of 10 c.c. of secretin (twenty hours old) made by us according to the Beveridge method. Showing that the secretin preparations sent us by Dr. Beveridge contained no secretin.

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 PREPAREDSept. 29, 1916

Date of TestQuantity ofSecretinInjected, C.c.Response of Pancreas(No. of Drops of Secretin)Bayliss-StarlingSecretinBeveridgeSecretinSept. 29107578Oct. 2106161Oct. 6102817Oct. 13102531Oct. 271056Nov. 31076Nov. 171045Nov. 301034Dec. 41022Dec. 201000

Sept. 29

Oct. 2

Oct. 6

Oct. 13

Oct. 27

Nov. 3

Nov. 17

Nov. 30

Dec. 4

Dec. 20

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 page126.)

Fig. 2.—Records of carotid blood pressure and flow of pancreatic juice on intravenous injection of secretin prepared by us according to the Beveridge method.X, injection of 10 c.c. of the secretin;b, record of flow of pancreatic juice in drops. TracingA, the 10 c.c. of Beveridge’s secretin injected had been digested for five minutes with 3 c.c. of human gastric juice. TracingB, injection of 10 c.c. of the same secretin preparation not subjected to gastric digestion. Showing rapid and complete destruction of Beveridge’s secretin by human gastric juice.

It will be seen that the rate of deterioration (oxidation or decomposition) of the secretin is practically the same whether prepared according to Bayliss and Starling or according to Beveridge (Figure 3). In both preparations the rate of deterioration is most rapid the first few days after preparation. It is scarcely necessary to point out that secretin preparations not kept constantly at low temperature and in the dark, as in the above experiments, will deteriorate more rapidly.

Fig. 3.—Records of carotid blood pressure and flow of pancreatic juice on intravenous injection of secretin preparations.X, injection of 10 c.c. secretin;b, record of flow of pancreatic juice in drops. TracingA, secretin prepared according to the Beveridge method September 30.I, injection of 10 c.c. October 2.II, injection of 10 c.c. November 30. TracingB, secretin prepared by the Bayliss-Starling method September 30.III, injection of 10 c.c. October 2;IV, injection of 10 c.c. November 30. Showing no greater stability of Beveridge’s secretion over that of Bayliss and Starling.

Why can we hope that the addition of serum or any solution of protein will render secretin more stable? In the intact man or animal under normal conditions of digestion, secretin reaches the pancreas by way of the blood, that is, it is in solution in blood. Does that fact render the secretin stable? By no means. The reader is familiar with the fact that the response of the pancreas to a single intravenous administration of secretin is very transitory (5–15 min.). The cessation of activity is due, not to fatigue of the pancreas, as a second injection of secretin gives a prompt response of pancreatic secretion, but to the disappearance of active secretin from the blood. In fact, secretin left in the test tube or in the bottle remains active over a much longer period of time than when introduced into the blood stream.

IV.Beveridge’s Secretin Given by Mouth to the Intact Animal Has No Specific Action on the Pancreas.—Active secretin prepared according to the method of Beveridge was fed on an empty stomach to a small dog (5 kilo) with permanent fistula of one of the pancreatic ducts. On control days we gave the dog (a) equal quantities of n/10 HCl, and (b) bread and milk. The Beveridge secretin was prepared with 0.3 per cent. HCl and the addition of 0.2 per cent. serum. The results may be stated by the following summary:

GIVING BEVERIDGE’S SECRETIN BY MOUTH

Material FedNumberof TestsSecretin of thePancreas for ThreeHours Followingthe Feeding150 c.c. Beveridge Secretin610.2 c.c.150 c.c. n/10 HCl522.7 c.c.Bread soaked in milk46.6 c.c.

150 c.c. Beveridge Secretin

150 c.c. n/10 HCl

Bread soaked in milk

The Control experiments with pure hydrochloric acid show that the secretion of pancreatic juice following the introduction of Beveridge’s secretin into the stomach is due to the acid factor and the protein content.

The patented secretin of Beveridge is rendered inactive by gastric juice, is without effect when given by mouth, and exhibits no greater stability or keeping qualities than the secretin prepared according to Bayliss and Starling. It has no merit as a therapeutic agent. It should under no conditions be administered intravenously in man, as it contains deleterious protein split products and living bacteria.—(From The Journal A. M. A., Jan. 12, 1918.)

At the present critical time when the efficiency of this nation must be raised to the highest point, it is essential that the United States government should lead in the efforts tending to such increased efficiency. To bring this about the government must protect and stimulate science, art and industry and at the same time curb or prevent waste of the country’s resources. In this field the United States Patent Office has unlimited power for good and evil—good, in the issuance of patent grants for novel devices and substances which go to increase national efficiency; evil, in the granting of patent protection where such protection is not in the interest of national efficiency, conservation of energy and material resources.

For years the American Medical Association, in common with the national pharmaceutical bodies, has been urging amendment of the law which governs the issuance of patents on medicinal preparations and more particularly revision of the procedure under which such patents are issued. At the Chicago (1908) meeting of the American Medical Association a special committee of five was appointed by the House of Delegates to study the questions involved, and to cooperate with the Association’s committee on medical legislation in preparing and securing the enactment of a bill which would correct the abuses connected with the enforcement of our patent laws (The JournalA. M. A., June 13, 1908, p. 2003). This committee presented a comprehensive report at the Atlantic City (1909) meeting of the American Medical Association (The JournalA. M. A., June 19, 1909, p. 2063). A further report was presented at the St. Louis (1910) meeting of the American Medical Association (The JournalA. M. A., June 18, p. 2079). In 1911 (The JournalA. M. A., Nov. 25, 1911, p. 1780) the Council on Pharmacy and Chemistry of the American Medical Association issued a report which set forth the inadequacy of our patent laws as they are administered in relation to medical products particularly.

Since that time the Council has continued its study of the U. S. Patent law as it applies to medicine and has become convinced that in many instances the patent law or its enforcement is contrary to the best interest of the public, both as concerns health and prosperity. The Council feels it a duty at this time to protest against the provisions of our patent law, or the methods of its enforcement, which permit the granting of patents without thorough and scientific investigation of the claims advanced in such letters patent. As one means of improving conditions the Council urges that the U. S. Public Health Service, the Bureau of Chemistry, U. S. Department of Agriculture and other scientific departments of the United States government conversant with medicines and related subjects be consulted before the issuance of patents on medicinal preparations.

In support of the Council’s contention that the patent law procedure requires revision, the following is offered: In 1912 a U. S. Patent (No. 1,031,971) was granted on a cresol derivative, metacresyl acetate, a product described in chemical literature in 1903. When the Council inquired as to the grounds for the issuance of a patent for a substance known to science, the Patent Office replied that it was not familiar with the publication in which metacresyl acetate had been described. It seems evident that this patent would not have been issued had the application first been submitted to a government department familiar with chemical literature.

An illustration of the granting of a patent on the use of well-known chemical bodies which present no discovery or originality, is the patent issued for the use of peroxids, perborates and percarbonates as ingredients of tooth powders (U. S. Patents Nos. 760,397 and 802,099). Regarding these patentsThe Journalof the American Medical Association (Sept. 20, 1913, p. 978) commented:

“The patents held by McKesson and Robbins give this firm the exclusive right of manufacturing tooth powders containing peroxids, perborates and percarbonates. It is another illustration of the unfair monopolies that may be secured under our present patent laws.”

Again in 1913 U. S. Patent No. 1,081,069 was granted to a citizen of Switzerland (a country which does not grant patents on medicinal preparations) for a “composition which is intended to be used internally and which confers to the organisms immunity against the following microbial infectious illnesses:diphtheria, pneumonia, typhus, scarlet fever, influenza, septic infections, cerebral-spinal meningitis, syphilis, pest, cholera and tuberculosis; it is also effective in another kind of disease, viz., goiter.” (Italics not in original). The patent specification states that “The principal of these substances is creatinin…,” but offers no evidence whatever that this well-known chemical body has the extensive and miraculous powers claimed for it. In publishing a notice of this patentThe Journalof the American Medical Association (Jan. 3, 1914, p. 54) explained:

“It appears that the inventor is dead, and that his estate took out the patent. Since this great benefactor should have been, by the use of his preparation, immune to practically all diseases, he must have died of senility, although this seems hardly to have been the case.”

and held:

“Assuredly granting patents on such claims ought to be sufficient to show the need of a change in the methods of granting patents—at least of the methods governing the issuance of patents for medicinal products.”

We submit, that had the department of the government entrusted with the enforcement of the federal Food and Drugs Act been consulted as to the claims of this patent, it would probably have advised that, if the absurd and palpably fraudulent claims set forth in this application for a patent were made on the label of a preparation of creatinin offered for sale in interstate commerce or in the District of Columbia, the vendor would be prosecuted.

In 1914 there was issued U. S. Patent No. 1,086,339. Here the “inventor” declared:

“It is the object of my invention to destroy parasitic micro-organisms, particularly on living tissue without injuring the latter, by progressively evolving sodium hydroxid contiguous to said tissue, from and in a moist mixture of calcium hydroxid, sodium carbonate, aluminum sulfate and boric acid...”

In a word, this patent apparently was granted for the production of sodium hydroxid by a chemical reaction which had been in use for several centuries. Because the patentee had twisted the granting of this patent into a quasi-endorsement of his nostrum, the Council’s consideration of this preparation was sent the Patent Office as a protest against the present law which authorizes the granting of patents on unproved and improbable medical claims. At that time the Council was informed by the Patent Office that reforms in the issuance of patents for medicinal substances had been instituted, and that “the trouble will not be so pronounced in the future as it has been in the past.”

There was issued early in 1917 U. S. Patent No. 1,212,888 for a method of flavoring Epsom salt—yet this “discovery” is a procedure which has been practiced ever since the cathartic action of this bitter salt has been known. Not only does the patent describe a process long known to physicians and pharmacists, but it sets forth claims that the flavored cathartic salt produced by the process cures flatulency, indigestion, sick and sour stomach, colic and destroys worms. In commenting on this patentThe Journalof the American Medical Association (June 23, 1917, p. 1914) was constrained to remark:

“The splendid conception of the framers of our constitution in providing a plan for promoting progress in science and useful arts by granting to inventors for a limited time the exclusive use of their inventions, in exchange for the publication of full knowledge thereof, is being debased. No branch of our government is of greater importance to the progress of the country than the patent office, provided that office is intelligently administered. When the patent office is used, however, for an extension of the nostrum business, founded on the abuse of patent and trade-mark laws, it becomes a menace to the public health. The objects of the patent law are being defeated by the practices of the patent office.”

Still further, attention is called to U. S. Patent No. 1,226,394 for a process of making hexamethylenamin tetraiodid and on the product so produced. This patent was issued after the Council had notified the Patent Office that hexamethylenamin tetraiodid had been discovered in 1888 and that a process identical in principle with that for which patent application appeared to have been made was published in 1916. On the basis of claims for which no evidence is produced this patent is issued for a well-known substance on the ground that as previously produced it contained a little free iodin or that the known processes were less economical. This patent appears to be an illustration of our patent procedure which obliged American users of acetylsalicylic acid to pay an exorbitant price because this country granted a patent which gave to the patentee, a foreigner, the exclusive right to the manufacture of the substance, whereas no such patent was issued in the patentee’s own country nor, so far as we can learn, in any other country. It forcibly illustrates the need for a revision either of our patent laws or of their methods of enforcement or both.

In further justification of the Council’s protest against the provisions of our present law, or the methods of its enforcement, which permit the granting of patents without thorough and scientific investigation of the claims advanced in such letters patent, the Council calls attention to the report, appearing above, of an investigation made by A. J. Carlson, A. E. Kanter and I. Tumpowski, “The Question of the Stability of Secretin,” which relates to U. S. Patent No. 1,181,424, issued to James Wallace Beveridge.

Whereas the regulations governing the issuance of patents demand that the processes shall be described in such detail that one versed in the sciences can confirm the claims made by the patentee, no pretense whatever of fulfilling this requirement is made in the patent specifications of this patent. The substance of the first three paragraphs of this patent has long been general knowledge. Nearly every sophomore medical student has himself performed, or seen performed such “experiments” as are therein described. The claims of novelty evidently are confined to the assertion that the preparation is able to “resist oxidation or deterioration”; that it is free from “poisonous and irritable chemical substances”; that it “may be administered orally to produce the desired physiological action.” etc., etc. Not the slightest hint is given as to how any person can substantiate these claims. As a matter of fact, the investigation of Professor Carlson and his co-workers has shown that a preparation having the properties claimed cannot be made by the process described in this patent. Any one familiar with the subject could have demonstrated readily that the applicant was withholding information concerning essential features of his process, assuming that he had any information on the subject (which he probably did not have) and would have advised against the issuance of the Beveridge patent.—(From The Journal A. M. A., Jan. 12, 1918.)

The following report submitted by a referee was adopted by the Council and authorized for publication.

W. A. Puckner, Secretary.

Surgodine (Sharp and Dohme, Baltimore, Md.), according to an advertising pamphlet, is a solution of 21⁄4per cent. of iodin in alcohol, containing no alkaline iodid, but miscible with water in all proportions. The A. M. A.Chemical Laboratory reports that Surgodine is an alcoholic liquid (containing 91.8 per cent. alcohol by volume) containing free iodin, combined iodin and free acid, probably hydrogen iodid (hydriodic acid). Quantitative estimations gave 2.51 gm. free iodin per 100 c.c. and 1.78 gm. combined iodin (the greater part apparently was present as hydrogen iodid).

It is therefore similar to several other iodin preparations already considered by the Council. Like these, it is essentially similar to the official tincture of iodin, except that it is considerably weaker, and instead of potassium iodid it presumably contains hydrogen iodid and probably ethyl iodid to render the iodin water-soluble. Its composition, however, is secret.

There would be no objection to the use of ethyl iodid or hydrogen iodid, except perhaps the acidity of the latter, as a solvent agent rather than of potassium iodid. But neither is there any important advantage, and these preparations would have to be considered as unessential modifications of official preparations, and therefore ineligible for New and Nonofficial Remedies.

The attempt to make these modifications commercially profitable, however, seems inevitably to lead to exaggerations and misstatements. In an advertising pamphlet the following claims for Surgodine are unsupported by any evidence:

“But from the surgical viewpoint the addition of this potassium salt is most objectionable because when such solutions as the official tincture are used locally in the antiseptic treatment of open and often infected wounds the Potassium Iodide acts as an irritant to the wound and therefore produces a localized irritation which is not only objectionable from the surgical standpoint but also materially lessens the antiseptic power of the Iodine itself.”“It has been demonstrated repeatedly that Iodine without the admixture of any alkaline iodide is much more efficient as a surgical antiseptic than any iodine solution that contains such an addition.”“Iodine does not produce ‘iodism’ as quickly as the alkaline iodides do because it is eliminated more quickly and more perfectly than the alkaline iodides.”

“It has been demonstrated repeatedly that Iodine without the admixture of any alkaline iodide is much more efficient as a surgical antiseptic than any iodine solution that contains such an addition.”

“Iodine does not produce ‘iodism’ as quickly as the alkaline iodides do because it is eliminated more quickly and more perfectly than the alkaline iodides.”

The next statement intimates that iodin taken by mouth enters the intestinal tract unchanged and is there free to combine with various gases:

“Iodine in the presence of phosphorated or sulphurated gases in the gastro-intestinal tract unites with their hydrogen and thus breaks up these noxious compounds.”

This is certainly untrue at least for ordinary doses.

It is recommended that Surgodine be held inadmissible to New and Nonofficial Remedies because its composition is secret (Rule 1); because the therapeutic claims made for it are exaggerated and unwarranted (Rule 6); and because it is an unessential modification of the official tincture of iodin (Rule 10).

[Editorial Comment.—Surgodine is a good illustration of the economic waste inseparable from most proprietary medicines. A hospital pharmacist writes that whereas his hospital obtains tincture of iodin at less than 82 cents a pint, Surgodine costs $2.13 a pint. This means that while the free-iodin strength of Surgodine is only about one-third that of the official tincture, its price is between two and three times as high.]—(From The Journal A. M. A., Jan. 26, 1918)

The following report on Medeol Suppositories has been adopted by the Council, and its publication authorized.

W. A. Puckner, Secretary.

“Medeol Suppositories” (Medeol Company, Inc., New York) appear to be an imitation of “Anusol Suppositories” which, in 1907, were found to be inadmissible to New and Nonofficial Remedies. A comparison of the composition and of the claims made for the two preparations will be of interest in the present consideration of Medeol Suppositories:

Anusol Suppositories(1909)Medeol Suppositories(1917)Anusoli7.5Medeol0.25Zinc oxid6.0Zinc oxid0.5Balsam Peru1.5Acid. tannic0.15Ol. theobrom.19.0Bals. Peru0.16Ungt. cerat.2.5Cocoa butter and waxq. s.for 1 suppository.for 12 suppositories.

Anusoli

Medeol

Zinc oxid

Balsam Peru

Acid. tannic

Ol. theobrom.

Bals. Peru

Ungt. cerat.

“Anusol” was formerly said to be bismuth iodoresorcinsulphonate. The A. M. A. Chemical Laboratory published a report in 1909 showing that the suppositories contained only 1 per cent. of the iodin declared in the “formula,” and were greatly deficient in bismuth and sulphur. After the publication of the report the American agents for the product disclaimed that “Anusol” was a definite chemical compound. Today Anusol Suppositories are said to contain unstated amounts of the indefinite “bismuth oxyiodid and resorcinsulphonate.”

“Medeol” is said to be “resorcinated iodo bismuth,” but no information is vouchsafed as to the character or composition of the ingredient. The therapeutic claims made for the two preparations are similar, as the following, taken from circulars, show:

Anusol SuppositoriesAn innocuous, non-irritant remedy for anal, rectal and vaginal inflammatory affections, especially forHemorrhoids!The local medicinal treatment of hemorrhoidal and other inflammatory ano-rectal conditions has always been unsatisfactory. The usual media cannot be applied in effective concentration without producing intense inflammatory reactions; they are either ineffective or intolerable....Anusol suppositories are absolutely free from narcotic, caustic or other injurious ingredients and may unhesitatingly be used by both sexes, at any age and under all conditions.Medeol SuppositoriesAn innocuous, Non-irritant, Efficient Antiphlogistic for use in inflammatory diseases of the rectum, anus and vagina especially inHemorrhoids.Hitherto most of the local remedies used in these conditions have either been too irritating to be employed in sufficient concentration to be efficient or they have lacked efficiency per se....Medeol suppositories do not contain any narcotic or any caustic or other constituent having violent action; their blandness permits of their use in either sex and at all ages.

Anusol Suppositories

An innocuous, non-irritant remedy for anal, rectal and vaginal inflammatory affections, especially forHemorrhoids!

The local medicinal treatment of hemorrhoidal and other inflammatory ano-rectal conditions has always been unsatisfactory. The usual media cannot be applied in effective concentration without producing intense inflammatory reactions; they are either ineffective or intolerable....

Anusol suppositories are absolutely free from narcotic, caustic or other injurious ingredients and may unhesitatingly be used by both sexes, at any age and under all conditions.

Medeol SuppositoriesAn innocuous, Non-irritant, Efficient Antiphlogistic for use in inflammatory diseases of the rectum, anus and vagina especially inHemorrhoids.Hitherto most of the local remedies used in these conditions have either been too irritating to be employed in sufficient concentration to be efficient or they have lacked efficiency per se....Medeol suppositories do not contain any narcotic or any caustic or other constituent having violent action; their blandness permits of their use in either sex and at all ages.

Medeol Suppositories

An innocuous, Non-irritant, Efficient Antiphlogistic for use in inflammatory diseases of the rectum, anus and vagina especially inHemorrhoids.

Hitherto most of the local remedies used in these conditions have either been too irritating to be employed in sufficient concentration to be efficient or they have lacked efficiency per se....

Medeol suppositories do not contain any narcotic or any caustic or other constituent having violent action; their blandness permits of their use in either sex and at all ages.

The claims made for these preparations—as for instance “that surgical treatment... should rarely be undertaken until Medeol Suppositories have been given a thorough trial”—are misleading in that they create the inference that the limitations in the palliative treatment of piles have been overcome. It is altogether untrue that these mixtures can be expected to “relieve the most obstinate cases,” as stated in a Medeol circular. This, from an Anusol circular, is equally misleading:

“If dietetic and other requirements are complied with, even the most obstinate chronic cases will frequently readily yield to treatment with Anusol Suppositories.”

The Council declared Medeol Suppositories inadmissible to New and Nonofficial Remedies because their composition is secret (Rules 1 and 2); because unwarranted therapeutic claims are made for these (Rule 6); because the name is objectionable (Rule 8), and because the combination is unscientific (Rule 10).

In those cases of hemorrhoids in which palliative measures may be expected to enable the patient to avoid surgical interference and afford relief from attacks, the object should be to secure cleanliness, to avoid irritation, whether it beby friction or irritating fecal matter, to reduce inflammation by astringents and, when necessary, to relieve pain by analgesics. If an antiseptic dusting powder is desired, boracic acid in impalpable powder with talc may be employed; if an astringent, finely powdered oxid of zinc may be added; if a local analgesic is necessary, a little extract of belladonna may be incorporated with petrolatum or other ointment base. The main reliance, in any event, should be to effect normal bowel movements by regulating the diet rather than by the use of purgatives; the use of warm water to insure cleanliness; the avoidance of irritation, especially that caused by friction and secretions; a mild astringent to reduce inflammation.—(From The Journal A. M. A., March 9, 1918)

The following report on Guaiodine, marketed by the Intravenous Products Company, Denver, has been adopted by the Council and its publication authorized.

W. A. Puckner, Secretary.

A referee of the Committee on Pharmacology, in submitting to the Council a report from the A. M. A. Chemical Laboratory on Guaiodine, advises that the Laboratory’s examination shows that instead of containing free “colloidal” iodin as claimed, the preparation is essentially an iodated fatty oil, containing only combined iodin. Equally misleading, in view of the Laboratory’s findings, are the implied claims that the antiseptic action of Guaiodine corresponds to that of free iodin.

Guaiodine is advertised mainly for the treatment of gonorrhea. While it may be true that the guaiacol contained in Guaiodine has some beneficial effect, especially when preceded by potassium permanganate irrigation as advised, the advertised claim that “Guaiodine acts as a specific for gonorrhea in a majority of cases” is utterly false.

The “case records” offered to establish the therapeutic value of Guaiodine are in themselves sufficient to condemn the “evidence.” The following are fair samples:

“The second boy came a day or so later with a slight discharge with the characteristic burning and itching, and with symptoms of a beginning gonorrhea, and judging from the source of the infection, it was believed to be so. Two injections of Guaiodine were given when the discharge ceased.”“I have several cases that were completely cured in a very short time. I note this, that the first dose causes a cessation of the discharge and the second seems to increase the flow, but the color is changed. I give three doses, and then use a mild wash, and in ten days they are well. I am very pleased with this preparation and very truly believe that it is the best there is to date for the positive cure of gonorrhea.”

“I have several cases that were completely cured in a very short time. I note this, that the first dose causes a cessation of the discharge and the second seems to increase the flow, but the color is changed. I give three doses, and then use a mild wash, and in ten days they are well. I am very pleased with this preparation and very truly believe that it is the best there is to date for the positive cure of gonorrhea.”

Guaiodine is manufactured by the Intravenous Products Company, Denver, Colorado. The “literature” which accompanies the product describes Guaiodine as:

“... an electro-chemically prepared iodin, suspended in oil, containing iodin, the same strength as the U. S. P. tincture of iodin, or 7 per cent., together with a therapeutic dose of guaiacol.”

The Intravenous Products Company claims that Guaiodine is made by an “electro-chemical process of preparing colloidal iodine,” discovered by one E. B. Page, and that by this process the tendency of iodin to produce iodism has been “overcome.” It is said to be “pre-eminently an antiseptic andgermicide.” Guaiodine is a dark brown, oily liquid with a specific gravity of 0.9845 at 15.6 C. and an odor suggestive of guaiacol. Its solubilities were those of a fat. Free iodin was absent in the recently purchased specimen (traces were present in an older one). Steam distillation indicated that the product consisted of volatile and nonvolatile constituents. The volatile matter was concluded to consist, in the main, of guaiacol or some guaiacol-like body, and the nonvolatile matter to be an iodized fatty oil. Quantitative determinations indicated that Guaiodine contained about 7.25 per cent. of iodin in combination, and that it is composed approximately of 3 per cent. volatile matter and 97 per cent. nonvolatile matter. Hence Guaiodine appears to be an iodized fatty oil to which a small amount of guaiacol or some guaiacol-like substance has been added.

On the recommendation of the referee, the Council voted that Guaiodine be declared inadmissible to New and Nonofficial Remedies because of false statements as to composition and action.—(From The Journal A. M. A., April 6, 1918.)

The “mixed” vaccines which are discussed in the reports that follow were considered by the Council during the past year because inquiries had been received in regard to them.

In publishing these reports it is desirable that the attitude of the Council toward “mixed” vaccines again be stated. In view of the rapid development of bacterial therapy, the possibility for harm that attends the use of bacterial vaccines and the skepticism among experienced clinicians as to the value of vaccines representing a combination of organisms, the Council has felt that it should scrutinize the claims for such agents with exceptional care and that there should be admitted to New and Nonofficial Remedies only those vaccine mixtures for which there is acceptable evidence to indicate that the use of the particular mixtures is rational.

In considering the subject the Council has borne in mind the fact that in many institutions in which cases are studied and the results of therapeutic measures carefully observed and controlled, vaccines of any sort are practically never used—certainly here the stock mixed vaccine has no recognition. Experienced clinicians have generally come to the conclusion that mixed vaccines have no specific action and that any effect they may produce is due to a non-specific protein reaction.

As set forth in the reports, in no case was the evidence submitted by the proprietors sufficient to establish the claims made for the preparations. Hence none was accepted for New and Nonofficial Remedies.

The preparations that form the basis for the accompanying reports are only a few of the many that are being made and sold by some biological houses. Doubtless many of those not dealt with in this report are equally irrational and sold under claims equally—or probably even more—unwarranted than those with which the present report deals.

W. A. Puckner, Secretary.

In response to inquiry the Council undertook a consideration of the following “mixed{”} vaccines sold by the Abbott Laboratories:

M. Catarrhalis-Combined-Bacterin, said to contain killed Micrococcus catarrhalis, Bacillus Friedländer, Pneumococci, Streptococci, Staphylococcus aureus and Staphylococcus albus.

B. Coli-Combined-Bacterin, said to contain killed Streptococcus viridans, Streptococcus hemolyticus and Bacillus coli.

Pertussis-Combined-Bacterin, said to contain killed Bacillus pertussis, Pneumococci, Streptococci, Staphylococcus albus, Staphylococcus aureus and Micrococcus catarrhalis.

Streptococcus-Rheumaticus-Combined-Bacterin, said to contain killed “Streptococci (Rheumaticus, Viridans, etc.)” and Pneumococci.

Streptococcus-Viridans-Combined-Bacterin, said to contain killed Streptococcus viridans, Streptococcus hemolyticus, Pneumococcus and Staphylococcus albus.

The Abbott Laboratories were asked to assist in the investigation of these products and to submit evidence to establish their eligibility for admission to New and Nonofficial Remedies. The manufacturer was informed that the Council accepts “mixed” vaccines or bacterins, provided the usefulness of these products is established by acceptable clinical evidence, and references to the literature bearing on the value of the preparations were requested.

The Abbott Laboratories submitted specimens of the products, the advertising matter therefor and a considerable list of references to current literature; all of which was transmitted to the Committee on Serums and Vaccines for consideration. In due time a referee of the committee submitted the following report:

The referee has studied the literature covered by the references submitted. In general the articles are favorable to the use of vaccines, though many of these papers do not consider “mixed” vaccines; indeed, a number of the articles do not discuss treatment at all, but are devoted entirely to the consideration of etiology of the disease. Many of the papers are by those who are obviously overenthusiastic on the subject of the use of biologic preparations. One paper—not included in the references submitted by the Abbott Laboratories—records an alarming reaction following a dose of mixed vaccine; no claim is made that improvement followed.

The following comments on the submitted references are offered:

M. Catarrhalis-Combined-Bacterin.—Only four of the nine references given deal with the therapeutic use of the vaccine. The reported results in general were favorable, but sometimes in the discussion evoked by certain of the papers, views the reverse of those expressed by the author were brought forward. The enthusiasm of one writer is shown in his statement that following the use of vaccine in cases of carbuncle complicating diabetes the sugar in the urine disappeared or was reduced. One observer, who reports excellent results in nasal pharyngeal catarrh, speaks of certain vaccines as “bulk goods,” while another considers “——’s No. 7” as the proper thing. It is evident that the reports are not based on careful, scientific data, or such unscientific definition of the product employed would not be used.

B. Coli-Combined-Bacterin.—In the references cited in support of this preparation the following general statements are noted: One enthusiastic writer says, “It must be recognized that we have no satisfactory explanation of the action of vaccines, and their use at present is empirical.” One author dwelt on the superiority of autogenous vaccines but admits that occasionally stock vaccines are indicated. One vaccine therapist in concluding an article states, “It is simply impossible to practice modern urology without our modern biologic products.” Yet it is a well-known fact that many successful and capable genito-urinary surgeons avoid the use of vaccines, mixed or simple.

Pertussis-Combined-Bacterin.—These reports are uniformly favorable, but are not controlled and their value is not to be compared with a recent reportfrom the New York City Department of Health which indicates that the vaccine is practically valueless. It is noted, further, that one of the articles cited which dealt rather fully with the treatment of pertussis did not mention vaccines.

Streptococcus-Rheumaticus-Combined-Bacterin.—The references cited in support of the preparations by the manufacturer give no support whatever for the use of mixed stock vaccines. The first reference deals with the relation of Streptococcus viridans to arthritis deformans and endocarditis and reports the following cases:

Case 1.—Vaccine case—improvement after eight months.Case 2.—Slight improvement following use of vaccine.Case 3.—Slight improvement following use of vaccine.Case 4.—Marked improvement.Case 5.—Prompt improvement.Case 6.—Vaccine not mentioned.Case 7.—Vaccine followed by slight improvement.

In each of the cases other methods of treatment were used. The paper shows the etiologic relation of Streptococcus viridans rather than the value of vaccines. There is no indication that stock vaccines were used, though the paper is not clear on this point. The second paper deals with the application of vaccine therapy in the treatment of arthritis. This paper is by a man who is avowedly an enthusiast on vaccine therapy. The indications are that he generally used a mixed autogenous vaccine, but the reports of cases are not always clear. This writer apparently makes no serious attempt at the classification of the joint conditions he treats. The third reference is a purely experimental study and has no bearing on the use of vaccines in treatment. The fourth article was admitted by the manufacturer to be “negative as regards evidence.” The fifth reference specifically states that “the vaccine must be autogenous.” The sixth reference deals with the experimental production of appendicitis by the use of diplococci, and has not the most remote bearing on the use of vaccines in the treatment of rheumatism.

Streptococcus-Viridans-Combined-Bacterin.—The article which bears evidence of more care than the others admits that we are not in position to state the value of vaccines in pyorrhea but the author believes they may have value supplementary to local treatment.

It is not surprising that a large number of favorable reports can be accumulated when we appreciate how promptly men report what they consider to be their successes and how commonly they leave their failures unrecorded. Bearing in mind the fact that these stock mixed vaccines, though before the profession for many years, have not been used, or continued in use, in hospitals where work is rigidly controlled and that they are used practically not at all in the large government hospital service, a candid critic must hold that there is no substantial evidence in favor of the therapeutic use of a mixed vaccine, certainly not for stock “goods” and that probably there is but a limited field for the employment of autogenous vaccines.

The referee calls attention to a shift in the advertising matter on vaccines—the tendency to recommend vaccines to be used in conjunction with drugs. A heading in the Abbott booklet reads, “The Biologics Do Not Replace Drugs”; and the paragraph speaks of serums and bacterins as “new tools, supplemental to those we already have, but not replacing them.”... “We need them both.”

The referee recommends that the several mixed vaccines discussed in this report be not accepted on the grounds that satisfactory evidence of their value is wanting.

Having been endorsed by the Committee on Serums and Vaccines the Council adopted the report and declared M. Catarrhalis-Combined-Bacterin, B. Coli-Combined-Bacterin, Pertussis-Combined-Bacterin, Streptococcus-Rheumaticus-Combined-Bacterin and Streptococcus-Viridans-Combined-Bacterin ineligible for admission to New and Nonofficial Remedies.

Because of inquiry received, the Council requested Eli Lilly and Company to aid in determining the acceptability of the following products for New and Nonofficial Remedies: “Catarrhal Vaccine Combined,” said to contain killed cultures of the Bacillus of Friedländer, Micrococcus catarrhalis, Staphylococcus aureus and albus, Pneumococcus and Streptococcus; “Influenza Mixed Vaccine,” said to contain killed cultures of Staphylococcus albus and aureus, Streptococcus, Pneumococcus, Micrococcus catarrhalis and Bacillus influenzae.

Lilly and Company sent the circulars, etc., used in advertising these products. A circular for “Catarrhal Vaccine Combined” contained the following claim:

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