AMERICAN-MADE SYNTHETIC DRUGS—II

Kind of LiquidPetrolatum UsedDate ofManufactureand FirstAssayWeightPer Cent.IodinUsedPer Cent.IodinFoundPer Cent.IodinNov. 17,1918Per Cent.Iodin†Nov. 19,1919IodinPetrolatumStanolind10/17/182.089188.41.0961.0851.0681.067Squibb10/14/181.9569186.781.03061.02321.0131.009Unknown, bulk*10/28/181.9497158.21.2251.1331.0751.095Parke, Davis & Co10/24/182.0869167.431.2411.24881.1911.180

* Considerable dark sediment formed in this sample during the heating process.† It should be pointed out here that while every sample showed some absorption, the amount, with the exception of the unknown bulk, is so small that it might even be accounted for on the basis of “experimental error.” Every ordinary precaution was taken to insure accuracy, but since about 15 gm. of the solution was used for each determination, it is seen that an error of 0.3 c.c. in the titration would indicate a greater absorption of iodin than that noted.

* Considerable dark sediment formed in this sample during the heating process.

† It should be pointed out here that while every sample showed some absorption, the amount, with the exception of the unknown bulk, is so small that it might even be accounted for on the basis of “experimental error.” Every ordinary precaution was taken to insure accuracy, but since about 15 gm. of the solution was used for each determination, it is seen that an error of 0.3 c.c. in the titration would indicate a greater absorption of iodin than that noted.

Conclusions: These experiments show: A solution of iodin in liquid petrolatum is saturated when it contains about 1.4 per cent. of iodin. The amount of iodin absorbed (disappearing as free iodin) by liquid petrolatum, when in contact at room temperature for as long as seven months, or in contact at 100 C. for four hours, or both, is relatively insignificant. Also all the absorption seems to take place during the heating and in the first month of contact.—(From Reports A. M. A. Chemical Laboratory, 1919, p. 21.)

Paul Nicholas Leech, Ph.D.; William Rabak, Ph.G., Sc.B., and A. H. Clark, Ph.G., Sc.B.

Before European hostilities, the United States was so dependent on Germany for synthetic drugs that the dependence was considered a necessity; this was strikingly manifested by the precipitous rise in prices immediately after the embargo was declared against Germany. Since then the shortage of German-made synthetics has caused two important results: 1. The physician can do without most of the German drugs, because the prewar demand had been stimulated artificially. 2. Those few synthetics, which were in great need, are being rapidly replaced by the American-made drugs.218In connection with the second result, the Chemical Laboratory of the American Medical Association has endeavored to contribute its services.

In September, 1917, it was announced219that the A. M. A. Chemical Laboratory would make studies of American-made synthetics. Just prior to this announcement, the National Research Council established a committee on syntheticdrugs220“to facilitate the manufacture of synthetic drugs in this country and thus to relieve shortage and reduce the exorbitant prices which have resulted from the war.”221Also during this time Congress was considering the “trading with enemy” act, first known as the Adamson bill—the purpose of which was to confer authority on the President to license American firms to use U. S. patents owned by German subjects. The act became law, September 28; the Federal Trade Commission was designated by the President to carry out the provisions of the law as it referred to enemy-owned patents. As a result of a conference, Oct. 30, 1917,222with various agencies, the Federal Trade Commission decided to consider licenses for manufacturers of synthetic drugs,afterrecommendations had been made by the Committee on Synthetic Drugs of the National Research Council; this committee in turn invoked the aid of the A. M. A. Chemical Laboratory in testing the manufacturer’s products. The essence of the laboratory’s work up to July 1, 1919, is reported in this paper.

“Partly in order to help insure to licensees a market for their products after the war, in larger part inspired by the idea of encouraging the establishment of a permanent American industry in these important articles, the [Federal Trade] Commission wisely decided that American houses should be put on the same footing as competing foreign houses for after-the-war competition, by imposing on all licensees the obligation to usenew official namesfor the articles, names which after the war will be open to all competitors, domestic and foreign.”223

The new American names are:Arsphenamin224(contracted from the scientific name arsenphenolamin) for salvarsan, arsenobenzol, diarsanol, arsaminol.Barbital (contracted from the scientific name diethyl-barbituric acid) for veronal.Barbital-sodium (the sodium salt of barbital) for “veronal-sodium” and “medinal.”Cinchophen for atophan or phenylcinchoninic acid (the U. S. P. IX name).Procain for novocain hydrochlorid (from “pro” and “(co)caine”).Procain nitrate for novocain nitrate.

In testing chemically the products which had been submitted to the Federal Trade Commission, the aims were that the product should conform to a high degree of purity; at the same time the candidate for license should not be inflicted with undue hardships in making the product, such as an unnecessarily high degree of purity. It was insisted that the purity of the drugs should be equal to, if not greater than, that of the respective former German-made products, in order to uphold the name and reputation of the American manufacturers in the after-the-war competition. Consequently, in the chemical work the American product was always examined parallel with the German-made product, authentic samples of the latter of which the laboratory had in its possession. Whenever possible, the tests described in books of standards were carried out.

Barbital was introduced into medicine under the proprietary name “veronal,” and was manufactured in Germany by Friedr. Bayer & Co., Leverkusen, and E. Merck & Co., Darmstadt, Germany. Barbital is described in New and Nonofficial Remedies, 1919,225as diethylbarbituric acid (diethylmalonyl urea) having the formula:

It is official in the British Pharmacopeia under the name “barbitone,” and in the German Pharmacopeia as “acidum diethylbarbituricum.” Barbital “may be prepared by the interaction of esters of diethylmalonic acid with urea inthe presence of metallic alcoholates.... It is also obtained by condensation of diethylcyanacetic ester with urea by means of sodium alcoholate.” Barbital is used in medicine chiefly as a hypnotic.

The different brands of barbital which were submitted to the laboratory were subjected to the tests given in the books referred to above.226The products were:

1. Barbital (Abbott) Sample A, to Federal Trade Commission.

2. Barbital (Abbott) Sample B, to Federal Trade Commission.

3. Barbital (Abbott) Sample C, to Red Cross.

4. Barbital (Antoine Chiris), to Federal Trade Commission.

5. Barbital (V. Halter), to Federal Trade Commission.

6. Barbital (Rector Chemical Company) to Federal Trade Commission.

7. Diethylbarbituric acid (Merck), to Council.

8. “Veronal,” manufactured by Farb. vorm Fried. Bayer & Co., Germany.

All responded satisfactorily to the tests. In Table 1 are given the respective melting points and percentages of ash found. (The melting point of a mixture of the sample with the original “veronal” was always taken.)

TABLE 1.—MELTING POINT

AshAsh1188.5–189.00.015188.0–188.50.012188.5–189.00.016188.0–188.50.013188.0–188.50.017188.0–188.50.014188.0–188.50.048188.0–188.50.02

Barbital does not seem to form an insoluble salt with chlorplatinic acid; nor an ether-insoluble hydrochlorid or oxalate; nor an insoluble barium salt. It does not respond to many urea tests, and is not affected by urease as would be expected in light of the extensive investigations made on this enzyme by Van Slyke and Cullen.

As barbital is also sold in the form of tablets or mixtures, a reliable method for its quantitative determination in the presence of other substances is needed. Some experiments in this direction were made, but the press of other work did not permit their continuation. When time permits, this work will be resumed.

At the time of writing this article, licenses for manufacture had been granted by the Federal Trade Commission to the Abbott Laboratories, to Antoine Chiris Company, and to the Rector Chemical Company.

Barbital sodium, formerly sold under the proprietary names “veronal-sodium” and “medinal,” is, as the former name suggests, the sodium salt of diethylbarbituric acid. Its therapeutic advantages are stated to be that more rapid results are obtained because of its increased solubility over barbital alone.227Barbital sodium should yield, according to theory, 11.19 per cent. of sodium and 89.31 per cent. of diethylbarbituric acid. A number of years ago, when “veronal-sodium” and “medinal” were being introduced, Puckner andHilpert228found that these products yielded results corresponding closely to the theoretical amounts of sodium and diethylbarbituric acid. A recent examination of veronal-sodium, Merck, made for the Council on Pharmacy and Chemistry, showed it to be of the same composition as that previously reported.

Only one firm’s product has been submitted to the laboratory through the Committee on Synthetic Drugs, but because of the unsatisfactory results, it was not recommended for license, nor, as far as we are aware, has the firm investigated its anomalies.229The amount of moisture in this specimen was 0.04 per cent. It yielded 10.94 and 10.97 per cent, of sodium. Puckner and Hilpert found 11.02 per cent. of sodium in “medinal,” and 11.01 per cent. of sodium in “veronal-sodium.” The theoretical amount, according to the formula given for medinal by the proprietors(C2H5)2CCONNaCONHCO└─────────┘is 11.19 per cent. When an aqueous solution of barbital sodium was acidified, and the diethylbarbituric acid extracted with ether, it was found that the amount of freed acid extracted varied directly with the length of time after acidification.

It is possible that in preparing the sodium salt of diethylbarbituric acid, the ring opens up, forming a compound not so easily affected by dilute mineral acids.

TABLE 2.—EXTRACTION OF A SAMPLE OF BARBITAL-SODIUM

Length of TimeDiethylbarbituric Acidper Cent.a.Immediately75.5a1.3⁄4hour82.0b.Immediately82.0c.11⁄2hours80.5d.4 hours82.82e.4 hours83.56f.4 hours83.41g.451⁄2hours84.89h.451⁄2hours84.73Theory.......89.31Veronal-Sodium(Puckner and Hilpert)89.01 (average)Medinal(Puckner and Hilpert)88.95 (average)

Phenetidyl-acetphenetidin hydrochlorid was introduced in the United States under the name of “holocain hydrochloride” by Farbwerke, vorm Meister Lucius and Bruening, Hoechst a. M. Germany; the product apparently had not been patented in this country, although it was protected in Germany under patents No. 78868 and 80568. New and Nonofficial Remedies, 1918, describes “holocain hydrochlorid” as ethenyl-paradiethoxy-diphenyl-amidin hydrochlorid CH3:(NC6H4OC2H5)(NHC6H4OC2H5)HCl. It is used as a local anesthetic for the eye.

The standards, such as had been described, were meager and unsatisfactory. Hence when the first specimen of American-made phenetidyl-acetphenetidin was sent to the A. M. A. Chemical Laboratory through the agency of the Federal Trade Commission and the Committee on Synthetic Drugs, it was necessary for the laboratory to work out adequate standards.231As a result of the chemical work, a rather comprehensive monograph was drawn up, which was published in the 1918 Laboratory Reports. A summary of the products examined, with some of the chemical data, is given in Table 3. It will be seen that one specimen had a deficiency of about 2 per cent. of free base.

TABLE 3.—DATA ON PHENETIDYL-ACETPHENETIDIN HYDROCHLORID

ManufacturerAppearanceMoistureMeltingPointPhosphorusCompoundsPhenetidin*IndolReactionAshPer Cent.Base byWeightPer Cent.Base byTitrationMeltingPointof BasePer Cent.Platinum inPlatinumSalt +John T. Milliken Co.Whitecrystallinepowder5.13191.5 to 192AbsentNegativePositive0.0089.1689.16116 to 11719.02Synthetic Products Co.Whitecrystallinepowder2.90192 to 192.5AbsentNegativePositive0.1387.4987.26116 to 11719.3H. A. Metz Laboratories, Inc.Whitecrystallinepowder4.99192 to 192.5AbsentNegativePositive0.0089.1488.5511719.34Farbwerke-Hoechst Co. (German specimen)Slightly pinkcrystal5.09190 to 191AbsentNegativePositive0.1689.6589.64116 to 11719.00

* The phenetidin test is not very sensitive.

The melting point of the free base is given by a number of writers at 121 C. AlthoughKennert232stated it to be 117 C. and not 121 C., his findings seemingly went unheeded. It will be noted that our work shows the melting point to be in accord with that announced by Kennert.

The Federal Trade Commission has not issued any licenses for the manufacture of “holocain hydrochlorid.” The John T. Milliken Company has withdrawn its application. The H. A. Metz Laboratories (Successor to Farbwerke Hoechst Company, New York) are making the product in this country.

Cinchophen (phenylcinchoninic acid) was introduced in the United States as a medicine under the proprietary name “atophan,” by Schering and Glatz, New York City, who before the war were the American agents for the German manufacturers “Chemische Fabric auf Actien von E. Schering, Berlin.” Phenylcinchoninic acid (2 phenyl-quinolin-4 carboxylic acid) was first described by Doebner andGieseke233in 1887, who prepared it by warming together pyro-racemic acid, benzaldehyd and anilin in alcoholic solution; it has the structural formula:

The chief use of phenylcinchoninic acid is as an antiuric acid agent, especially indicated in gout.

In 1913, the German house of Schering was made the assignee of patent 1045759 granted by the United Statesgovernment234for the manufacture of phenylcinchoninic acid: at about the same time the product was admitted to the U. S. Pharmacopeia IX, under very loosely constructed standards.

Some time after the beginning of the European war the proprietary “atophan” became scarce in America. In 1917, however, Schering and Glatz, New York, placed American-made atophan on the market and submitted it to the Council on Pharmacy and Chemistry. Later, other firms began to manufacture the product and also submitted specimens. During the time it was investigating these products, the Federal Trade Commission decided that a license was needed to manufacture phenylcinchoninic acid under the patent just referred to, so that altogether the laboratory had a number of specimens to examine.

In making the examinations for the Council, the laboratory was practically confined, by virtue of the Food and Drugs Law, to limit its requirements of purity to those of the Pharmacopeia. Practically, the only tests were melting point, ash and solubility. According to the U. S. Pharmacopeia the melting point is “about 210.” In New and Nonofficial Remedies, 1918, it was explainedthat atophan “complies with the standards for phenylcinchoninic acid, U. S. P., but melts between 208 and 212 C.” The U. S. Pharmacopeia requires that no weighable ash remains on incinerating about 0.5 gm. of phenylcinchoninic acid. Considerable variations, especially in melting points, were found, as can be seen from Table 4.

TABLE 4.—MELTING POINTS AND ASH

ProductNo.ManufacturerMeltingPoint, C.Ash,%1Abbott Laboratories, Chicago208.5–210.50.052Abbott Laboratories, Chicago212 –2130.051Calco Chem. Co., Bound Brook209 –210.50.071Morgenstern, New York204.5–207.52.82Morgenstern, New York208.5–211.5None1Schering and Glatz, New York206 –208None2Schering and Glatz, New York209 –211None3Schering and Glatz, New York208.5–2100.174aSchering and Glatz, New York (1)208.5–2100.24bSchering and Glatz, New York (2)208.5–209.50.34cSchering and Glatz, New York (3)208.5–2100.0251Wm. H. Sweet and Co., Columbus204 –208None2Wm. H. Sweet and Co., Columbus209.5–211.50.041German specimen from Schering and Glatz210 –212None

Abbott Laboratories, Chicago

Calco Chem. Co., Bound Brook

Morgenstern, New York

Schering and Glatz, New York

Schering and Glatz, New York (1)

Schering and Glatz, New York (2)

Schering and Glatz, New York (3)

Wm. H. Sweet and Co., Columbus

German specimen from Schering and Glatz

By referring to this table on melting points and ash content it will be noted that the production of a better grade of products resulted after the respective firms had submitted samples to the A. M. A. Chemical Laboratory for criticism, and from a chemical standpoint, the last products examined were found to be as satisfactory as the German-made “atophan.”

Solubility of Cinchophen (Phenylcinchoninic Acid).—As methods of determining impurities, or estimating the degree of purity of phenylcinchoninic acid were not described in the U. S. Pharmacopeia, it was decided to try extraction methods.235This in turn led to the question of solubilities. The U. S. Pharmacopeia gives the solubility of phenylcinchoninic acid only in general terms; hence it was deemed advisable to determine its solubilities and describe them in more definite terms. The sample of phenylcinchoninic acid employed to determine the solubility was obtained by repeated recrystallization from alcohol of a commercial specimen. Solubilities were determined in water; 95.0 per cent. alcohol; 48.5 per cent. alcohol;236chloroform and ethyl acetate.237Complete saturation of the solvent was attained according to the U. S. P. IX method (p. 599). The bath was maintained at a temperature of 25 C., with a range of ± 0.2 degrees. The solution was analyzed by the method of Seidell.238The data obtained for the solubility of phenylcinchoninic acid are given in Table 5.

TABLE 5.—SOLUBILITY OF CINCOPHEN

SolventGm. per Hun-dred Gm. ofSat. SolutionSolubility,Parts byWeightDistilled water0.01601 in6,216.095 per cent. ethyl alcohol0.83431 in119.0Dilute ethyl alcohol0.08751 in1,142.6Chloroform0.10751 in929.7Ethyl acetate1.41511 in70.6

Distilled water

95 per cent. ethyl alcohol

Dilute ethyl alcohol

Chloroform

Ethyl acetate

The Abbott Laboratories, Chicago, have been licensed by the Federal Trade Commission to manufacture cinchophen. Other firms, however, have decided to manufacture it without the formality of obtaining a license, evidently considering the German-obtained patent not to be valid.239

Procain was introduced in medicine under the proprietary name “novocain,” and before the war was obtainable in this country only through the Farbwerke Hoechst Company, the American representative of the German establishment, Farbwerke vorm Meister Lucius Bruening, Hoechst a. M. Chemically it is the mono-hydrochlorid of para-amino-benzoyl-diethyl-amino-ethanol, having the structural formula:

NH2—COO-CH2-CH2—N(C2H5)2.HCl

It is prepared according to U. S. patent No. 812554 (issued to Alfred Einhorn, Munich, Germany) by treating para-nitro-benzoylchlorid with ethylene chlorhydrin and diethylamin with subsequent reduction of the nitro groups, the resulting product being purified by recrystallization.

Procain is employed largely in infiltration anesthesia. It is less toxic than cocain, but its anesthetic action is not sustained. This drawback is overcome by the simultaneous injection of epinephrin, and for this reason procain is often compounded with epinephrin in tablets, thus obviating the necessity of separate solutions.

When the first specimens of the American-made product were submitted through the channels of the Federal Trade Commission, it was necessary to compile a monograph.240This was prepared from descriptions in the available literature, mostly from tests described in New and Nonofficial Remedies, 1918, and the German Pharmacopeia V.

The submitted products were found satisfactory chemically. The toxicity determinations made by Dr. R. A. Hatcher, with the assistance of Dr. CareyEggleston241indicated that none of the specimens are to be considered dangerous when used in ordinary dosage for normal individuals. Therefore the Federal Trade Commission, on recommendation of the Committee on Synthetic Drugs of the National Research Council (aided by the A. M. A. Chemical Laboratory), issued licenses for the manufacture of procain to the Farbwerke-Hoechst Company (which license was later transferred to the H. A. Metz Laboratories), to the Abbott Laboratories, to the Calco Chemical Company and to the Rector Chemical Company.

Subsequently the products of the licensed firms were submitted to the Council on Pharmacy and Chemistry, which in turn invoked the aid of the A. M. A. Chemical Laboratory and the Cornell University Pharmacologic Laboratory. Later the Council asked the laboratory to examine themarketsupply. Altogether, therefore, a number of products were examined which were found to respond satisfactorily to the tests outlined (Table 6).

TABLE 6

BrandDateReceivedColorMeltingPoint, C.*Ash, %Procain (Abbott), from Committeeon Synthetic Drugs12/21/17White154–155NoneProcain (Abbott), submitted toCouncil P. and C.1/29/18White153.5–154.5NoneProcain (Abbott), Gen. Pur. Off.U. S. Army8/31/18White152.5–153.5NoneProcain (Abbott), Gen. Pur. Off.U. S. Army, No. 899999/30/18Slightbrownish tint153–154.5NoneProcain (Abbott), Gen. Pur. Off.U. S. Army, No. 899989/30/18Slightbrownish tint153–154.50.005Procain (Abbott), Gen. Pur. Off.U. S. Army, No. 8999710/ 8/18Slightbrownish tint153–154NoneProcain (Abbott), Gen. Pur. Off.U. S. Army, No. 8999611/ 4/18Slightbrownish tint153.5–154.5NoneProcain (Abbott), Gen. Pur. Off.U. S. Army, No. 81099511/ 4/18Slightbrownish tint153.5–154.5NoneProcain (Calco), from Committeeon Synthetic Drugs2/ 7/18White153.5–154.5NoneProcain (Farbwerke-Hoechst Co.),submitted to Council10/24/18White153–154NoneProcain (Farbwerke-Hoechst Co.),submitted to Council12/10/17White153–154.5NoneProcain (Farbwerke-Hoechst Co.),submitted to Council, market spec. “A 56”8/ 9/18White153.5–154.5NoneProcain (Farbwerke-Hoechst Co.),submitted to Council, market spec. “A 57”9/ 9/18White153.5–154.5NoneProcain (H. A. Metz Lab.),market spec. “A 63”8/23/18White153–154NoneProcain (H. A. Metz Lab.),market spec. “A 57”9/23/18White153–154NoneProcain (Rector), fromCommittee on Synthetic Drugs12/18/17White153–154.5NoneProcain (Rector), fromCommittee on Synthetic Drugs5/ 2/18White152.5–153NoneProcain (Rector), market spec8/20/18Slightbrownish tint153–155NoneProcain (Rector), market spec8/23/18Slightbrownish tint153–155NoneProcain (Rector), market spec8/23/18Slightbrownish tint153–154.5None

on Synthetic Drugs

Council P. and C.

U. S. Army

U. S. Army, No. 89999

U. S. Army, No. 89998

U. S. Army, No. 89997

U. S. Army, No. 89996

U. S. Army, No. 810995

on Synthetic Drugs

submitted to Council

submitted to Council, market spec. “A 56”

submitted to Council, market spec. “A 57”

market spec. “A 63”

market spec. “A 57”

Committee on Synthetic Drugs

Procain (Rector), market spec

* U. S. Patent 812,554—the novocain patent—declares that the salt melts at 156 C. Evidently based on this, both the German Pharmacopeia and past editions of New and Nonofficial Remedies give this melting point. Two specimens of German-made novocain obtained from our files, stated to be manufactured by Farbwerke-Hoechst vorm. Meister, Lucius and Bruening, Hoechst a. M., were found to melt, respectively, between 154 and 155 C. and between 153.5 and 154.5 C. when the melting point was determined according to the direction of the U. S. Pharmacopeia, ninth revision. The various specimens examined at that time melted between 153 and 155 C., and it was decided to permit this range.

An examination of some American-made procain-suprarenin tablets was also made. The procain was determined by liberation of the alkaloid with ammonia water, extraction with chloroform, evaporation of the chloroform, dissolving the alkaloid in one hundredth normal sulphuric acid solution and titrating excess acid with one hundredth normal sodium hydroxid solution. The epinephrin was determined according to the method employed by Seidell,242with slight modifications. The tablets contained the claimed amounts of ingredients.

Before the war, the American physician was literally bombarded with new and wonderful (?) coal-tar synthetics, most of which were originated in Germany. In fact, it seemed that if a by-product in the manufacture of dyes could not be used for a dye per se, then a place might be found for it in the ever increasing lists of medicaments. By clever advertising and propaganda among physicians, an artificial stimulation for coal-tar drugs was created which evidently yielded lucrative financial returns. As a result of the war, it is interesting to observe that of all the synthetic drugs imported into this country from Germany and on which the American patents were controlled by the Germans (up to the time of our entrance into the war), the demand was really sufficient enough to warrant the commercial manufacture of only four of them by American firms. Of course, a larger number ofnonpatented drugs, also imported from Germany, are now being made in sufficient quantities in this country;many of the drugs in this class were never patented or are the ones which have survived after the patent had expired, such as acetanilid, acetphenetidin, and acetylsalicylic acid.

In view of the agitation to found an institute for cooperative research as an aid to the American drug industry under the auspices of the American Chemical Society, it will be well for the medical profession to be on its guard against too enthusiastic propaganda on the part of those engaged in the laudable enterprise of promoting American chemical industry. Unless it is, it may be inflicted in the future, as in the past, with a large number of drugs that are either useless, harmful or unessential modifications of well-known pharmaceuticals. It will be well also for the chemists—those engaged in this enterprise—to be sure that the product is of therapeutic value before asking its use as a medicine. The American medical profession has learned that relatively few of the many German synthetics were really valuable or decided improvements over established drugs. If American chemists desire to retain their prestige with the medical profession, they should earnestly endeavor to see that the advantages derived from the war and from such an institute as proposed are not abused in the worthy desire to popularize chemistry both educationally and commercially. They should realize that physicians are in no receptive mood for a flood of synthetics, even though “American-made.”

On the other hand, the constructive possibilities of chemistry in the service of medicine should serve as a stimulus for American research. Notwithstanding all the pharmaceutical shrubbery which Germany sent to us, still it did contain some synthetics that were worth while. As therapeutics has been benefited by these organic chemicals, it is logical to reason by analogy that there remain other synthetics to be discovered which will occupy places of equal distinction in the modern materia medica. For example, vaccines are of undoubted merit in the field of immunology, but their action is, in the end, chemical; as soon as chemical technic is refined by medicochemical research, it is quite possible that a definite chemical agent (synthetic) will supersede the indefinite bacterial vaccine. Obviously the American chemist has the opportunity of showing his resourcefulness in aiding the public health of America and the world. In this connection, a cooperative institute devoted to purely scientific drug research, and governed in such a manner as to inspire confidence in its humanitarianism and unbiased judgment, should serve a most commendable purpose. The hopes of American men of science are for a monumental research institution—cooperative with all the allied professions—and, as theChicago Chemical Bulletin stated, “Stripped of all professional or commercial pettishness and not dominated by any one group of scientists.”243

As for the results of the work so far, they can be summed up in two sentences.

1. American chemists are producing synthetic drugs formerly controlled by Germany, and thus have declared their independence of German chemicals.

2. Judging from the evidence at hand, we can feel assured that the quality of American synthetics will be second to none.—(From The Journal A. M. A., Sept. 6, 1919.)

S. Q. Lapius, M.D.

[Foreword.—It is more than twelve years since the Council on Pharmacy and Chemistry of the American Medical Association was created. Since then there have been but few issues ofThe Journalthat have not called the attention of the medical profession to the debasing influence on scientific medicine of unscientific or worthless proprietary mixtures advertised to physicians for their use in prescribing. The Council on Pharmacy and Chemistry has investigated and shown many of these preparations to be fraudulent in one way or another, and these reports have been published inThe Journal. In spite of this, these preparations have been advertised continuously to physicians, through medical journals and otherwise, and prescribed by a large number of physicians. One reason for this is that there are many physicians who have never seen these reports—who were not in active practice at the time, or who were not readingThe Journal. We probably have among our readers at the present time 35,000 or 40,000 physicians who were not among the readers ofThe Journaltwelve years ago. It is desirable, then, that we should take up, in more or less detail, several of the more widely advertised products that have been the subjects of previous reports. It has been repeatedly stated inThe Journalthat many of the proprietary mixtures—the so-called ethical proprietaries advertised to physicians—were no better and no worse than “patent medicines” advertised to the public.

Every physician who has the welfare of medicine at heart should put these questions squarely to himself if he has not already taken a firm stand on this whole problem: What is my attitude toward the work of the Council? Are its reports worthy of acceptance? Am I upholding the Council in its efforts to place therapeutics on a rational basis, not by blind faith alone, but by an honestly critical attitude toward it? Am I following the path of indolence by taking the advice of nostrum makers without any serious effort to determine whether they are true or false? In a word, am I really practicing medicine, or am I an unpaid agent and a dupe of nostrum makers? There are other revolutions than political. The public can be wronged just as certainly by the abuse of its confidence in clinicians as by the usurpers of political power, and when the public is thoroughly aroused the heavy hand of retribution is not likely to be too discriminating. That the sins of clinicians are standing out plain for any one who wishes to read is becoming more and more evident. There is but one short and ugly word that properly characterizes the physician who accepts a fee for prescribing that about which he has no more knowledge than has the one for whom he prescribes it. Are you with the nostrum makers or with decent medicine?

The article below is the first of a series written forThe Journalby one who is thoroughly conversant with the work of the Council on Pharmacy and Chemistry and can speak authoritatively on questions dealing with the action of drugs and the treatment of diseases. We believe that these articles will prove of interest and profit and that they will help physicians to answer the questions just propounded.]

Bell-ans, for years advertised only in medical journals under the name “Pa-pay-ans (Bell),” is now advertised in newspapers as a remedy that “Absolutely Removes Indigestion.” As it is still being advertised to physicians, we propose to analyze the claims made for it with as much care as would be exercised in the discussion of the newest discovery in medicine, because we believe that it is desirable to show the trend of exploitation of a certain type of preparation in the medical press.

In theNew York Medical Journalthe following advertisement recently appeared on the front cover:

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