THE CHEMICAL LABORATORY OF THE AMERICAN MEDICAL ASSOCIATION

The Chemical Laboratory of the American Medical Association was established in 1906 to assist the Council on Pharmacy and Chemistry in the investigation of proprietary remedies.

In accordance with the principle of its foundation, the Laboratory examines and checks the claims made for the composition and chemical properties of the products under examination by the Council, and when these are admitted to New and Non­official Remedies, it insures the establishment of tests and standards whereby the identity and purity of these products may be controlled. In addition, the Laboratory supplies information, secured by reference to chemical and pharmaceutical literature or by actual analytic work, in regard to proprietary and unofficial medicines, either for publication in The Journal of the American Medical Association or through direct correspondence.

Those portions of the Laboratory’s activities which are of special interest to physicians and which were not included in the Reports of the Council on Pharmacy and Chemistry were included in the Propaganda for Reform in Proprietary Medicines, ninth edition (1916), so far as they had been published up to the time when the edition was issued; those made during the last five years are included in Part II of this volume.

For a detailed report of the Laboratory’s work, the reader is referred to the article that follows on “The Work of the American Medical Association Chemical Laboratory.” Those who are interested in the analysis of drugs are referred to the Reports of the Chemical Laboratory issued annually for the details of the analyses which have been made by the Laboratory.

THE WORK OF THE AMERICAN MEDICAL ASSOCIATION CHEMICAL LABORATORY[G]

W. A. Puckner, Phar.D.

The American Medical Association Chemical Laboratory was established nearly ten years ago—in fall of 1906. The reason for its existence was primarily the fact that the Council on Pharmacy and Chemistry found it difficult to secure from outside sources such help as it needed in checking up the composition and properties of proprietary medicines under investigation. Medical schools and similar institutions were found ready to lend their assistance in pharmacologic and medical investigations; but the chemical investigation required the establishment of a laboratory under the control of the American Medical Association.

As years have passed, the scope of the laboratory has been extended: Its services have been requisitioned by The Journal in various ways. Thus, when requested, the laboratory reviews and verifies the chemical data contained in editorials and original contributions. The laboratory is often called on for information as to the character and composition of quack treatments and so-called “patent medicines.” Through the columns of The Journal and through direct correspondence, the laboratory responds to requests of physicians with information regarding the composition of medicines which they prescribe or in which they are interested. The laboratory attempts to be to the members of the American Medical Association what the prescription pharmacist is, or should be, to the prescribing physician—a storehouse of chemical and pharmaceutical information. In the belief that an insufficient familiarity with the chemistry and pharmacy of drugs constitutes the chief reason for the extensive use of unscientific, worthless or fraudulent proprietary remedies, this service is rendered by the laboratory as a contribution to the cause of rational therapy.

Since the efficiency of the American Medical Association Chemical Laboratory will increase as its activities are better known, the following more detailed statement of its work is offered:

THE LABORATORY AND THE COUNCIL

As stated in the rules of the Council on Pharmacy and Chemistry, it is “manifestly impossible for the Council to investigate the composition of every complex pharmaceutical mixture ...”; “it can only give an unbiased judgment on the available evidence.” In line with this, the laboratory does not undertake to prove the composition of constitution of all new synthetics, nor does it attempt to determine the individual composition of proprietary mixtures. It checks all claims that seem doubtful, however, and uses its best endeavors to secure correction of misstatements with regard to proprietary remedies and improvement in the quality of these products. Further, it reexamines, when this seems desirable, the products which have been admitted by the Council to New and Non­official Remedies, and thus determines, from time to time, their dependability. The fact that no product admitted to New and Non­official Remedies has later been shown to be untrue to its claimed composition is, it is believed, an indication that in this respect the laboratory has succeeded in performing the work for which it was primarily created.

In this connection the question may be asked, Are many proprietary medicines exploited to the medical profession with false claims in regard to their composition? Also it may be asked, Has the number of proprietaries marketed with false statements of composition decreased since the Council and the laboratory began their work? Answering the latter question first: There is no doubt that today fewer proprietary medicines are being sold with false claims as to composition than there were ten years ago. When the Council began its work, medical journal advertising teemed with statements regarding the composition of medicines which any chemist familiar with medicine would not hesitate at sight to brand as untrue. Today such manifestly false claims are rare. Coming to the former question: Many false statements regarding the identity and composition of remedies have been made in ignorance. This is not surprising when it is remembered that the most ignorant may and do engage in the manufacture of medicine. Besides ignorance, however, an accommodating conscience on the part of the manufacturer and a failure on the part of the medical profession to appreciate the danger which lies in the use of medicines of unknown composition unquestionably have greatly encouraged the marketing of falsely declared medicines. A glaring illustration of the ignorance of manufacturers—for it is hard to believe that any business concern would deliberately court prosecution by the federal authorities through false statements on labels—is the fact that nearly thirty years ago A. B. Lyons published a report[147] pointing out that the proprietary Iodia was falsely declared as to composition and that in 1914 when the Council examined this preparation such incorrect declaration appeared on the label.[148] That many physicians do not recognize the danger to their patients and their reputation in the use of medicines, the composition of which they do not know, is illustrated by the fact, disclosed by inquiries sent to the laboratory, that physicians were found willing to employ an arsenical preparation (Venarsen), advertised for intravenous use, although its promoters vouchsafed no information in regard to the nature of the arsenic compound contained therein.

UNRELIABILITY OF LITTLE USED DRUGS

The purpose of the federal Food and Drugs Act is to secure the prosecution and punishment of all who sell medicines which are adulterated or misrepresented as to composition. As a matter of fact, the wording of the law relating to the adulteration and misbranding of drugs is such that the federal authorities have been able to do little more than to require that the drugs for which standards are provided in the Pharmacopeia shall when sold comply with those standards. Similarly, those states which attempt to improve the quality of drugs sold within their borders—few states do efficient work along these lines—limit their work to the enforcement of the Pharmacopeial standards. This leaves the vast number of unofficial drugs and medicaments beyond the control of federal or state authorities. While most of these drugs are relatively unimportant, and while the amounts of them which are used are not great individually, the total consumption of them is large. With a view of furnishing to physicians standards for drugs of this sort the Council has described in New and Non­official Remedies not only distinctly proprietary drugs, but also some of the unofficial drugs which are apparently of therapeutic value and used to a considerable extent. Aiding the Council in this line of endeavor, the laboratory has attempted to establish standards for these little used drugs, and New and Non­official Remedies, 1916, provides standards for such unofficial and non-proprietary drugs as quinin and urea hydrochlorid quinin, tannate, sodium acid phosphate, and sodium perborate. An example of work which furnished much needed standards for an unofficial article is the investigation of zinc permanganate by W. S. Hilpert.[149] Reference to the published reports of the laboratory will give an idea of the amount of work such standard­ization entails. A reference to the new U. S. Pharmacopeia, when this comes from the press, will show that a considerable number of unofficial articles described in New and Non­official Remedies have been admitted to the Pharmacopeia along with the standards worked out in this laboratory.

While in a way the work done in connection with these less important drugs has attracted little attention from the medical profession, it has had an effect on pharmaceutical manufacturers. In the past, pharmaceutical houses, ever anxious to market something new, on the slightest provocation have placed on the market, in the form of pills, powder, elixir, ampule, etc., every drug for which some sort of medical recommendation could be found. In marketing these dosage forms, the manufacturer has too often been little concerned about the quality of the drugs used.[150] Just at present, for instance, some interest is being shown in iron cacodylate; but while manufacturers appear to be most ready to take advantage of this interest by offering the drug in the form of ampules, etc., they have given little help toward the establishment of standards for this arsenic compound. Manufacturers are ever ready to sell drugs of all sorts, but in view of the small demand they cannot or will not safeguard the identity and purity of such drugs. A further illustration of the unreliability of unofficial drugs is the recent report by Levy and Rowntree[151] showing not only that the various dosage forms of emetin hydrochlorid obtained from different manufacturers varied from manufacturer to manufacturer, but also that the product of the same manufacturer was variable and that the supply furnished by one pharmaceutical firm was so toxic as to make its use dangerous.

THE ANALYSIS OF “PATENT MEDICINES”

In the preface to the first annual report of the chemical laboratory it was stated that the laboratory “occasionally takes up the examination of ‘patent medicines’ ...” At that time it was felt that the widespread use by the medical profession of irrational and even secret medicines made it necessary to devote the laboratory’s attention to the correction of this evil. As the years have passed on, these conditions have been remedied to some extent, at least so far as chemical analysis can correct them. On the other hand, public opinion has been aroused to the many evils connected with the exploitation of “patent medicines,” and has more and more insistently demanded that the medical profession aid in the correction of this evil. Accordingly, the laboratory has paid much attention to the analysis of “patent medicines” during the last few years. As the chief asset of “patent medicines” is the element of secrecy which surrounds their composition, it is hoped that the laboratory’s analysis of such widely used “patent medicines” as Nature’s Creation,[152] Mayr’s Wonderful Stomach Remedy,[153] Sanatogen,[154] Eckman’s Alterative,[155] Tonsiline,[156] and Bromo-Quinin[157] has been worth the labor. In addition, the work of this laboratory has been published, including not only the results of its analyses, but also the methods which are used. In view of the dearth of published reports regarding the methods used in the analysis of “patent medicines,” it is hoped that this feature of the laboratory’s work has been of aid to chemists engaged in similar work.

The laboratory’s activities along these lines have done much to discount the claim of proprietary manufacturers that chemical analysis is unable to determine the character of “patent medicines.” The recent Wine of Cardui trial has brought it out prominently that chemical analysis can determine the presence of potent constituents, and that “patent medicines” which fail to reveal such potent ingredients to the analyst may safely be put down as worthless. The demonstration that the essential composition of medicinal preparations may be determined by chemical analysis should also prove an effective answer to the manufacturers in their protest against the requirement, now being urged for enactment into law in various states, that the medicinal ingredients of their wares must be declared on the label. Manufacturers have held that this would lay them open to competition with imitations and substitutions. The possibility of chemical identification proves, however, that secrecy of composition, though it prevents consumers from knowing the character of a “patent medicine,” will not be a hindrance to the imitator and substitutor.

IDENTITY OF DRUGS USED IN INVESTIGATIONS

In the past, much of the experimental work in medicine has seriously suffered in that the identity of the material used in such investigations was not established. In view of this the laboratory has watched the contributions submitted to The Journal, and whenever necessary and feasible has urged the authors to identify their material before publication of the findings. For instance, a number of staining agents—so-called “anilin dyes”—have been found to possess therapeutic action. Since the identity of many of these staining agents is today essentially secret, the laboratory has urged through The Journal that those who experiment with these substances make an effort to determine their identity whenever possible and to give preference to those the chemical identity of which is known. The need for such identification has been discussed in the reports of the laboratory.[158] The amount of work involved in the chemical identification of drugs used for experimental work is illustrated in a contribution entitled “An Examination of Several Commercial Specimens of Opium Alkaloids or Their Salts.”[159] by L. E. Warren, in which was determined the identity of the various opium products used in an investigation by D. I. Macht, carried out under a grant of the Therapeutic Research Committee.

THE LABORATORY AND PHARMACEUTICAL LITERATURE

In the past much of the information in regard to the composition and properties of medicines which has appeared in pharmaceutical journals has not become available to medicine. In many cases medical journals could not afford to publish such data because this would have been contrary to the interest of their advertisers, and hence the publications regarding the irrational character of Lactopeptine, of Bromidia, etc., which appeared in the pharmaceutical journals did not become a matter of common medical knowledge. Through the laboratory an attempt has been made to keep the medical profession informed in regard to pharmaceutical literature. The laboratory has a good working pharmaceutical and chemical library, and subscribes to the important American and foreign pharmaceutical and chemical publications. The discussion of new remedies, such as medinal and sodium veronal,[160] salvarsan, atoxyl and arsacetin,[161] and neosalvarsan[162] soon after their introduction, illustrates the work of the laboratory along these lines.

THE LABORATORY’S EFFORTS TOWARD RATIONAL PRESCRIBING

The laboratory naturally is in thorough sympathy with the present day efforts toward a more rational use of drugs, as exemplified in the Council’s publication “Useful Drugs.” Two recent contributions of the laboratory may be cited as a further support of the movement for limiting prescribing to the more widely used drugs. In line with the general tendency of manufacturers to put out all sorts of modifications and asserted improvements over official substances, there have been placed on the market a number of preparations said to represent some improvement over the pharmacopeial Blaud pills. The report, “The Quality of Commercial Blaud’s Pills,”[163] by L. E. Warren, shows that the ordinary pharmacopeial Blaud pill is in every way the equal of the semiproprietary preparations claimed to be improvements. Further, the examination of the various brands of sodium and theobromin salicylate as compared with the preparation diuretin by P. N. Leech[164] shows that the former preparations, sold at 35 cents per ounce at the time the examination was made, are fully the equal of the proprietary Diuretin, which then cost the druggist $1.75 per ounce.

THE LABORATORY AS AN INFORMATION BUREAU

It is generally admitted that the proprietary medicine business, particularly the exploitation of complex mixtures, attained the extensive vogue which it has or had because instruction in medical schools was deficient in materia medica, pharmacy and chemistry. As a result of lack of knowledge along these lines, the young graduate after some trial became fearful of formulating his own prescriptions, and in time became dependent on pharmaceutical firms which provided him with medicines ready to dispense. That physicians have been insufficiently trained in regard to the pharmacy and chemistry of drugs has often been emphasized in pharmaceutical journals where prescriptions containing incompatible drugs are reported and where even plans are brought forward whereby the pharmaceutical profession may aid in remedying this difficulty.

During my pharmaceutical experience I was often sorely vexed as to what to do when prescriptions contained drugs which on mixing would undergo decomposition which the physician surely did not anticipate. I remember well a prescription directing that potassium permanganate be made into pills with extract of gentian and other things, and how, the physician having spurned the suggestion to modify the prescription so as to avoid decomposition of the permanganate, I was obliged to select a mortar, gently triturate the drugs until a conflagration was started, and to finish the prescription after the combustion had subsided. However, in my pharmaceutical experience I generally found the physician most ready to receive suggestions from the pharmacist which would prevent incompatibilities, improve the palatability and appearance of his prescriptions, and protect the patient from unnecessary expense.

Similarly it has been my experience since the establishment of the Association’s laboratory that physicians are anxious to receive information in regard to the materia medica, pharmacy and chemistry of drugs. As the druggist earns the respect and support of the physician when he makes available to him the pharmaceutical knowledge and experience which he has, so this laboratory has aimed to gain the endorsement of the American Medical Association membership by furnishing to physicians information in regard to the composition, chemistry and pharmacy of drugs through replies in the Query and Minor Notes Department of The Journal as well as through direct correspondence. It has been most gratifying to the laboratory that The Journal receives an increasing number of inquiries both as regards the chemical and pharmaceutical questions involved in the writing of prescriptions and as regards the composition of secret and semisecret proprietaries (often because they are prescribed by the inquirer’s colleague) and “patent medicines” (which are taken by his patient). The laboratory has tried its best to answer the many inquiries received. Many of the questions which come in can be answered by a pharmacist or chemist without hesitation. Others, particularly as to the composition of medicines, the laboratory has been able to answer by reference to its library and its extensive card index. Still others have required experimentation and chemical analysis.

While, as stated a moment ago, the laboratory has encouraged the sending of inquiries and has earnestly striven to furnish the information asked for, it is obvious that the amount of chemical work which can be done is limited. The small size of the laboratory force, consisting of three chemists engaged in actual analytical work, makes it necessary to select for investigation those problems which shall be of general interest to the medical profession. As the American Medical Association is national in its scope, the laboratory has held that it can do analytical work only when such work will be of general interest to physicians and of value both to the medical profession and the public. In view of this it has refrained from undertaking analyses which would benefit only the physician making the inquiry and possibly his patient. The laboratory further has not felt justified in undertaking work of merely local interest; instead it has used its endeavors to secure the investigation of such local problems by municipal or state authorities.—(From The Journal A. M. A., Nov. 25, 1916.)