Part I of the Volume Contains Formulas, Good, Bad and Indifferent,

including the equivalents of a large number of shotgun proprietaries. Part II contains descriptions of drugs. This is a new feature. The purpose is to provide standards for those drugs not described in the Pharmacopeia but used in N. F. preparations. Many of these drugs were described in the U. S. Pharmacopeia VIII, but have not been included in the ninth revision. Practically all are either worthless or superfluous. Part III contains descriptions of special tests and reagents.

Among the therapeutically useful formulas are those for aromatic castor oil, emulsion of castor oil, sprays or nebulae, solution of aluminum acetate, solution of aluminum subacetate and wine of antimony. The two last named are also included in “Useful Drugs.” Several formulas for new classes of preparations which may or may not be found superior to old forms are paste pencils for the application of medicaments to limited areas of the skin, mulls, which are ointments spread like plasters, and fluidglycerates, which are fluidextracts in which glycerin takes the place of alcohol. It should be noted also that, as a result of criticism, the alcohol content of some preparations has been reduced.

As a whole, the present edition of the National Formulary, like its predecessors, is “pharmaceutically useful but not a therapeutic necessity.” To say that it is not a therapeutic necessity is to state the matter mildly, since most of the formulas and almost all of the drugs described have been discarded long since by rational therapeutists. So long as there are physicians who prescribe therapeutic monstrosities, however, the druggist should have the aid that is furnished by this book in compounding them. From the pharmacist’s point of view, therefore, the book is a valuable one. Physicians who have a scientific training in the pharmacology of drugs will not want it; others will be better off without the temptations offered by its many irrational formulas.--(Book Review in The Journal A. M. A., Sept. 2, 1916.)

NONSPECIFIC PROTEIN THERAPY

The treatment by nonspecific methods in a series of cases of influenzal pneumonia has been the subject of two recent papers. These methods are a development of the work of Ichikawa, Kraus, Lüdke, Jobling and Petersen, and others on the treatment of typhoid fever and of Miller and Lusk’s work on arthritis. In the original work in this field it was recognized that there were certain inherent dangers in the method and that wide application would be permissible only with the greatest caution and under careful control.

Roberts, Dudley, and Cary, E. G.: Bacterial Protein Injections in Influenzal Pneumonia, J. A. M. A. =72=:922 (March 29) 1919. Cowie, D. M., and Beaven, P. W.: Nonspecific Protein Therapy in Influenzal Pneumonia, J. A. M. A. =72=:1117 (April 19) 1919.

When vaccines and other toxic protein substances are injected intravenously a train of reactions takes place that includes: (a) a primary leukopenia, followed by a leukocytosis; (b) a primary lessening of the coagulability of the blood, followed after some interval by a reduction of the coagulation time; (c) a pronounced lymphagogue effect, the flow of lymph from the thoracic duct being increased threefold; (d) a hyperperistalsis of the intestinal tract, and (e) a marked splanchnic engorgement with a resulting lowering of the systemic blood pressure. The alteration of the coagulability of the blood, together with the vascular engorgement of the splanchnic area and the coincident increase in motility of the intestinal tract that follow the therapeutic injection, all tend to increase the possibility of intestinal hemorrhage. Protein therapy is therefore not a safe procedure in this particular disease. That we are able to terminate a certain number of cases of typhoid fever by crisis by means of such injections is of very great interest from a theoretical point of view.

In the treatment of arthritis, the results seem much more satisfactory. The work of Miller and Lusk has been confirmed by a number of observers, among them Culver, Cecil, Snyder, Cowie and Calhoun; and there seems little doubt that we may be able to give prompt relief and even permanent freedom from symptoms in a considerable percentage of cases of acute and subacute arthritis, especially those classed as of rheumatic origin--and this with practically no risk to the patient.

Miller, J. L., and Lusk, F. B.: The Treatment of Arthritis by the Intravenous Injection of Foreign Protein, J. A. M. A. 66: 1756 (June 3) 1916; The Use of Foreign Protein in the Treatment of Arthritis, ibid. 67: 2010 (Dec. 30) 1916.

As with other new therapeutic measures, there is still some uncertainty as to the proper dosage, which is a matter of considerable importance, in order to arrive at a just estimate of the relative advantage or danger in the treatment. Typhoid vaccines have been extensively used because they are readily procured and give a prompt and sharp reaction. However, they have the disadvantage of inexactitude in the bacterial count, as well as being of varying degrees of toxicity, the latter factor depending not only on the use of different strains of bacteria in their preparation but on the age of the vaccine. Synder, as well as other workers, is of the opinion that the primary dose should be small--from five to ten million organisms--and that the dose of typhoid bacilli injected should never exceed two hundred and fifty million. While a sharp reaction on the part of the patient is apparently a desideratum, a sufficient response can usually be elicited with a relatively small dose. There is no object in subjecting the patient to the risk of the profound depression that follows occasionally in the wake of large doses. Indeed, the only serious results so far ascribed as due to this form of therapy have followed very large doses or the use of relatively large doses in moribund patients; or such unreasonable procedures as the intravenous injection of milk. It is true that milk injections were recommended by some of the German investigators, but they were always used intramuscularly.

Snyder, R. G.: A Clinical Report of Nonspecific Protein Therapy in the Treatment of Arthritis, Arch. Int. Med. 22: 224 (Aug.) 1918.

In the treatment of pneumonia, Roberts and Cary have employed a vaccine made up of 100 million of each of the following organisms per cubic centimeter: influenza bacilli, pneumococci, staphylococci and streptococci. Of this vaccine they injected, intravenously, first 0.5 c.c., later 1 c.c. In the series of 200 patients so treated there was no evidence of injury to the patients in any way. The mortality in this series was 9.5 per cent.; in a series of eighty-six patients not treated with vaccine, the mortality was 31.2 per cent. In the untreated series, 20 per cent. recovered by crisis; in the treated, 36 per cent. so recovered. Before any reliance is placed on such statistics they should be analyzed and compared carefully according to age periods, as the death rate may vary at different ages. Cowie and Beaven used typhoid vaccine in the treatment of their patients, and they consider the vaccine shock as indicated only in the early stages of pneumonia.

Report of International Health Board, Social Medicine, Medical Economics and Miscellany, J. A. M. A. 72: 751 (March 8) 1919.

Before applying the treatment to such diseases as pneumonia it would seem that prudence would demand a thorough familiarity with the range of the reaction and the degree of toxicity of the preparation it is intended to use by first employing it in some arthritic cases. In pneumonia we must ever keep before us the vital factor of cardiac impairment; and certainly we must not undertake any measure that may depress the function of the heart. In arthritis this danger is largely a negligible one; and, with proper precaution, nonspecific therapy is not only without risk but indeed frequently followed by gratifying clinical improvement. Only in the light of experience gained in the manner indicated would it seem permissible for us to attempt to extend this form of therapy to more acute infections.--(Editorial from The Journal A. M. A., May 17, 1919.)

WILLARD EALON OGDEN

A “Specialist in Proctology” and His “Clinics”

Within the past few weeks a number of inquiries have reached The Journal from physicians in Ohio, Indiana and Pennsylvania. Those that follow are typical:

“I am in receipt of literature from H. L. Roberts, 1126 Masonic Temple, Chicago, advertising clinic in Cleveland by Dr. Willard E. Ogden who claims to be a member of the Chicago Medical Society and the A. M. A. What can you say of this man and his methods?”

“I am enclosing a folder received a short time ago. I would be glad to know if Dr. Ogden is a member of the A. M. A. as he claims to be.”

“The enclosed folder has been sent to many doctors in Indiana. The purpose is plain. The attached post card on this one was returned to him for further literature.”

In each case the correspondents send in a four-page folder bearing the title “Proctology, A Clinic. Who? Where? Why?” Three of the four pages purport to answer the interrogations given on the title page. Under “Who?” we read:

DR. WILLARD E. OGDEN

Chicago, Ill.

SPECIALIST IN PROCTOLOGY

Member Chicago Medical Society and A. M. A.

Author of “Improved Method of Treating Rectal Diseases” Formerly associated with Drs. Burleson & Burleson Grand Rapids, Mich.

Under the question “Where?” there appears the statement that “Dr. Ogden Will Hold a Clinic for The Treatment of Rectal Diseases” and the name of the city and the dates of the “clinic” are inserted with a typewriter.

Under “Why?” we read:

“Dr. Ogden does not use the usual surgical methods. His many years of experience in the treatment of Rectal Diseases (during which time he has been associated with the leading Proctologists of America) have enabled him to develop a system of office treatment which is not taught by any other practitioner.

“Tear off, sign and mail attached postcard and I will send you a booklet giving you full particulars as to the course.

Yours truly,

H. L. Roberts, Business Manager.

“Eighty-three per cent. of the people have some Rectal trouble. THIS IS THE DAY OF SPECIALISTS. Why not fit yourself to specialize in Proctology?”

The fourth page is a post card addressed to “H. L. Roberts, Room 1126, Masonic Temple, Chicago.” On the reverse side there is a printed statement which the recipient is expected to sign to the effect that he is interested in “Dr. Ogden’s Clinic” and wishes to have “full particulars of the course.”

A visit to Room 1126, Masonic Temple, failed to disclose the name of H. L. Roberts, either on the door (or doors, for there are two rooms having this number) or on the office building directory board. In fact, Rooms 1126 seem to contain a somewhat miscellaneous assortment. The signs, either on the door or on the directory board, show that there is a public stenographer (who operates a “Mailing Service,” and does “Addressing, Mailing, Multigraphing, Mimeographing”), a bookstore, a chocolate company, a publishing company, a lumber company, and one or two other concerns; but the name of “H. L. Roberts” does not appear. Incidentally, no “H. L. Roberts” is to be found listed in the Chicago telephone directory.

A few yards away from Rooms 1126 and on the same floor there appears the name, “Dr. Willard E. Ogden” on Room 1102.

According to our records, Willard Ealon Ogden was born in 1866. Before taking up the study of medicine he seems to have been a preacher. In 1899 he was graduated by the Saginaw Valley Medical College, Saginaw, Mich. He was licensed in Michigan in 1900, in Illinois and Indiana in 1913, and in Wisconsin in 1921. From 1900 until 1904 he practiced in Lyons, Mich.; from 1906 until 1911 he was at Ionia, Mich.

In 1911, he was in Grand Rapids, Mich., and was associated with Burleson and Burleson, an advertising pile cure concern. From some of the voluminous Burleson advertising on file, we learn that they “cure all diseases of the rectum (except cancer);” and claim to have “the most successful method ever discovered,” and to have cured “many desperate cases that have been given up to die.” Furthermore, they “guarantee to cure in every case or make no charge.”

On Jan. 1, 1914, Ogden was sending out a card to physicians in which he stated that he had removed from Grand Rapids, Mich., and LaPorte, Ind., to 36 W. Randolph St., Chicago, and that he would limit himself “exclusively to the treatment of diseases of the rectum.” Later, Ogden was sending out an advertising booklet filled with testimonials.

In 1914, Ogden was carrying display advertisements in Chicago papers reading, in part, in large back-faced type: “Piles Cured Absolutely Without Knife, Anesthetics, Pain or Loss of Time.... Cure Guaranteed or Money Refunded.”

In March, 1918, he became a member of the Chicago Medical Society and qualified for Fellowship in the American Medical Association, August, 1918.

In 1921, Ogden had a copyrighted mail-order course on the “Treatment of Rectal Diseases by Improved Method.” This “course” consisted of thirty-eight pages of foolscap printed on one side in imitation typewriting. The material abounded in typographical errors. Among the proprietary products recommended in this “course” as “essential” to those taking it, was “Mecca Ointment.” This nostrum, made by a Chicago concern, was declared misbranded in 1916 because of false and fraudulent claims made knowingly, recklessly and wantonly. The “course” was divided into ten parts, and with it, apparently, came ten consecutively numbered sealed envelops, and the purchaser was instructed to open these envelops, one at a time, as he completed the corresponding part in the “course.” He would there find questions which were to be answered and returned to Ogden. This, according to the description, was to enable Ogden to determine whether it was necessary to “enter more into detail upon that particular subject,” which, he stated, he would gladly do if necessary.

Furthermore, the purchaser had the privilege of asking questions of Ogden relative to symptoms, diagnosis and treatment for a period of six months after the purchase of the “course.” Although, in Ogden’s opinion, “you should have the subject well understood long before that time.”

The charge for this course and “services as outlined” was $200, but in order to show his confidence in the ability of those who purchased it, Ogden was willing to take $100 down and the other $100 paid in “five per cent. of monies received from CURED patients” until the balance was paid.

Reverting to the present “post-graduate course” and “clinic”: Those who send in the postal card to “H. L. Roberts” receive a form-letter, signed “H. L. Roberts” in facsimile handwriting, stating that information was enclosed “regarding THE OGDEN METHODS” and stating that Dr. Ogden would be in Indianapolis or Cleveland or Pittsburgh, as the case might be, on a certain date and that the fee for the “clinic” would be $100. With this letter is an eight-page pamphlet entitled “Some Facts Concerning the Ogden Method of Treating Rectal Diseases.” The first page is headed in black-faced type: “About References and Endorsements.” It then states that the “usual references and endorsements are omitted from this booklet.” Further:

“As to Dr. Willard E. Ogden: The professional and social standing of Dr. Ogden is such that he does not need to offer any.

“As to ‘THE OGDEN METHOD’ and its value to you in your professional work: What others say or think has little if any weight. You are your own man. You do your own thinking. You decide for yourself--Do you not?”

The booklet gives an outline of the “Course of Instruction,” which is almost identical, word for word, with the outline given in the letter advertising the mail-order course previously referred to.

The booklet further states that “THE OGDEN METHOD has entirely eliminated the use of cautery, the ligature or any injections, in the treatment of hemorrhoids,” but that “the use of the electric current has proved to be the very correct method in such cases, as will be demonstrated at the clinic.” The booklet reiterates the statement that Ogden’s association with the Burleson and Burleson concern at Grand Rapids makes him “eminently well qualified to instruct members of the medical profession in this important branch of the medical science!”

In addition to this booklet there is a four-page advertising leaflet illustrating and describing the “Ogden Rectal Cabinet” and also the “Ogden Rectal Table and Stool.” There is also a little postcard--addressed, of course, to “H. L. Roberts”--for the physician to fill in stating that “you may enroll me as intending to attend Dr. Ogden’s Clinic in Proctology, to be held at----.” Should the recipient not fill in and mail this enrolment card he gets another form letter calling attention to the fact that the enrolment card has not been received and stating further that “available hotel facilities make it necessary to limit our enrolment to twenty students.”

Careful search fails to disclose that Dr. Willard Ealon Ogden has ever distinguished himself in the practice of the specialty in which he now wishes to instruct physicians. Equally careful search fails to show that Dr. Ogden has ever published a paper either on any proctologic subjects or on any other phase of medicine or surgery. Neither does there seem to be any evidence for the claim that Dr. Ogden “has been associated with the leading Proctologists of America.”--(From The Journal A. M. A., Feb. 4, 1922.)

“PATENTS”

Patent Laws and Patent Office Practice

The inequity of our patent laws, or possibly it would be more correct to say, of the interpretation of our patent laws, has been commented on many times in The Journal. The Journal also has had occasion to call attention to patents that have been issued for obviously unscientific and quackish devices and preparations. The cases of the preposterous gas-pipe fake “Oxydonor” and the creatinin mixture for the alleged conferring of immunity against diphtheria, pneumonia, scarlet fever, syphilis, tuberculosis, etc., are cases in point.

In a patent issued the early part of this year for the “discovery” of a method of flavoring Epsom salt, the patent office has, in fatuity, piled Pelion on Ossa. The “inventor” declares that his invention relates to a pharmaceutical preparation and a special method of treatment of the medicinal agents whereby said agent will be rendered much more efficient in character. He further avows that the “prime object” of his “invention” is to “disguise the normal taste and impart an agreeable odor or smell to salts commonly employed as a cathartic.” Parenthetically it may be said that probably not a day passes that some physician in the United States does not do substantially the same thing when writing a prescription. The “inventor” further claims that the object of his “invention” is to utilize the salts as a vehicle to carry an antiseptic and anesthetic agent whereby the salts when administered as a cathartic “will also act beneficially on the entire digestive tract” and “whereby cramped and spasmodic conditions are at once relieved with a resulting cure of flatulency, indigestion, sick and sour stomach, colic and the destruction of worms, etc.”

Such claims are so absurd that the only excuse for commenting on them is the effect they have on the public mind. The layman reading the specifications of this patent would naturally conclude that an invention of great importance had been made--of such importance as to warrant the government in rewarding its inventor by granting him a seventeen-year monopoly on the sale of his invention.

The law requires that, to be patentable, inventions shall be new and useful and shall show a higher degree of skill in their inception than is naturally to be expected from those who are skilled in the arts to which the inventions belong. It has been decided again and again that physicians’ prescriptions are not patentable because it is assumed that an educated physician will utilize his knowledge of pharmacy in devising proper compounds of medicines to meet the indications of disease. When a physician prescribes a dose of Epsom salt to be taken in one of the official aromatic waters, he does not produce or create a new invention by so doing. Of course, in one sense every prescription is an invention--an invention to meet the conditions presented by the patient--but such inventions are not patentable, because they represent the ordinary skill of a physician in carrying on his vocation.

If the patent office goes on granting patents for such “inventions” as flavored Epsom salt, and it should be found financially profitable to secure such patents and place the products on the market, it will only be a matter of time before the materia medica will be so restricted that a physician will be unable to write a prescription without infringing on somebody’s patent.

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 extention 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.--(Editorial from The Journal A. M. A., June 23, 1917.)

Our Archaic Patent Laws

In this issue we publish two reports of the Council on Pharmacy and Chemistry which illustrate the weaknesses of the present working of the United States patent laws. In the first report the Council presents an investigation of a recently granted patent, and shows that the patent was issued on the mere claims of the applicant and without the presentation of any evidence for such claims. The second report--“Need for Patent Law Revision”--is an appeal to the Patent Office for a more enlightened administration of the patent law, and it presents a few illustrations of the unfair protection which has been granted by the Patent Office. The protest of the Council appears at an opportune time. In Science the “Patent Office Society,” an association of employees of the U. S. Patent Office, announces that a committee has been created on request of the National Research Council to make a study of the U. S. Patent Office and its service to science and arts. It states that this committee will meet in Washington shortly to consider the adequacy of the present Patent Office equipment and the simplification of procedure as well as responsiveness to present national and international requirements. The committee also hopes to coordinate, in the interest of an improved public service, the endeavors of the various national societies, manufacturing interests, patent bar associations and all others aiming at genuine patent reform. Unquestionably, there is a growing conviction that in the case of medicines the monopoly given by the patent laws, if granted at all, should be granted with greater consideration of the public welfare. Too often the United States Patent Law has been used to obtain an unfair monopoly on a medicament or to abet quackery. There is no question that one of two things is needed: either a radical change in the patent law itself or the application of more brains in its administration.--(Editorial from The Journal A. M. A., Jan. 12, 1918.)

Dec. 28, 1917, p. 629.

Patents Perpetuated by Trade Names

The patent on aspirin (acetylsalicylic acid), controlled by the Bayer Company, American representative of the Farbenfabriken of Elberfeld Company, will expire next year (1917). The Journal has previously stated that the grant of this patent was regrettable and worked injustice to American citizens. It is unnecessary again to go into the grounds for this statement; neither in the Farbenfabriken’s home country, Germany, nor in any other country except in the United States, has a patent been granted for this product. Owing to their monopoly, the manufacturers have been able to exact a much higher price for acetylsalicylic acid, or aspirin, in this country, than elsewhere. Naturally, the Bayer Company, the American agents, view with disfavor the prospect of being compelled to share this rich field with competitors. The foregoing furnishes the answer to inquiries which have reached us from all over the country with regard to the campaign of publicity which the Bayer Company has inaugurated in the lay press. A presumably authentic and apparently candid exposition of the methods used and the motives behind the aspirin advertising is furnished in Printers’ Ink:

Granted Feb. 27, 1900.

Printers’ Ink, June 29, 1916, p. 189; July 13, 1916, p. 100.

“The manufacturers of aspirin are about to launch an extensive advertising campaign to clinch the market as far as possible before the expiration of their patent rights next year.... The purpose of the campaign is to identify the product with the trademark of the Bayer Company and to this extent hamper competition after the expiration of the patent.”

The business of the Bayer Company, the article goes on to say, has been hurt by the sale of worthless or even harmful imitations put on the market by irresponsible and unauthorized persons when the present war stopped importations from Germany.

“The public knew aspirin, but did not know who made it [italics ours].... When the Bayer Company, Inc., took over the manufacture of aspirin in this country, the first steps were taken to identify the product with the firm who made it.... Of course, there are good reasons why the makers were loth to advertise the product or to exploit their trademark. As every one knows, the advertising of a medical proposition is an extremely ticklish subject.... It is easy to make a misstep. Aspirin is one of those proprietary drugs that are extensively prescribed by physicians. If anything were done that might possibly associate this drug with the patent medicines that are in disfavor with the profession, the valuable influence and cooperation of thousands of doctors might be lost. It is believed that this knotty phase of the question is being answered in the present advertising.... Since nothing is mentioned about ‘medicine,’ ‘cures’ or ‘ailments,’ it is anticipated that there will be but little objection to the copy. All that the advertising attempts to do is to link up the name ‘Bayer’ with aspirin.... The nearest the copy gets to medical talk is in this sentence in very small type at the bottom of the advertisement, ‘The trademark “Aspirin” (Reg. U. S. Patent Office) is a guarantee that the monoacetic acid ester of salicylic acid in these tablets is of the reliable Bayer manufacture.’”

From this it appears that, not content with seventeen years of monopoly, the aspirin people are attempting to retain a hold on the market in perpetuo by associating the name of the company with the trade name “aspirin.” There can be no better time than the present, therefore, for the medical profession to substitute, for the nondescriptive name “aspirin,” the descriptive and correct name acetylsalicylic acid.--(Editorial from The Journal A. M. A., Aug. 12, 1916.)

Patenting Therapeutic Agents

In the past, therapeutic agents and apparatus have been controlled by patents and trademarks for profit. If there have been exceptions, they have been rare. The Principles of Medical Ethics of the American Medical Association contain this statement: “It is unprofessional to receive remuneration from patents for surgical instruments or medicines.” This does not mean that the patenting is wrong in itself; there are occasions when it is wise, if not necessary, to obtain a patent in the interest of the public, and, in the case of surgical instruments and medicines, of the medical profession. In certain instances it is absolutely necessary that the article produced shall maintain a definite standard of quality and purity--and, it may be added, shall be sold at a reasonable price. Enterprising pharmaceutical manufacturers have usually been ready to appropriate the results of scientific research by investigators or therapeutic measures suggested by practicing physicians. Not infrequently, in such instances, the desire for financial gain has caused the marketing of such products with extravagant, if not false, claims as to their value. Yet the patent laws may be used so as to protect and benefit the public and the medical profession. In research laboratories, work is being carried on resulting in the production of new therapeutic agents. It is important that these agents shall be so controlled that they may be made available without subordination to commercial interests. It has become practically necessary, therefore, for research workers to protect their products in the interest of the public welfare and scientific medicine. It has not been an easy matter to decide how best to bring about the desired results. This question has been before the Board of Trustees of the American Medical Association; and, in 1914, the House of Delegates passed a resolution authorizing the board to accept at its discretion patents for medical and surgical instruments and appliances; as trustees, for the benefit of the profession and the public, provided that neither the Association nor the patentee should receive remuneration from these patents. The Rockefeller Institute for Medical Research has solved the problem in a similar manner. In connection with the report of the discovery of several new arsenic compounds, Jacobs and Heidelberger, working in the Rockefeller Institute, say:

Jacobs, W. A., and Heidelberger, M.: Aromatic Arsenic Compounds, II, The Amides and Alkyl Amides of N--Arylglycine Arsonic Acids, J. Am. Chem. Soc. =41=:1587 (Oct.) 1919.

It may be appropriate to mention here that this substance and related compounds, described in the present and following papers of the series, are covered by U. S. Patents Nos. 1280119-27. Patents have also been applied for in foreign countries. All discoveries made at the Rockefeller Institute are made freely available to the public, in accordance with the philanthropic purposes of the institution. In order to insure purity of product and protection against exploitation, it has been deemed necessary in certain instances to protect the discoveries by patents. It is the purpose of the institute to permit any drugs which may prove of practical therapeutic value to be manufactured under license by suitable chemical firms and under conditions of production which will insure the biological qualities of the drugs and their marketing at reasonable prices. Other than through the issuance of license, the Rockefeller Institute does not participate in any way in the commercial preparation or sale of the manufactured chemicals; and it receives no royalties or other pecuniary benefits from the licenses it issues.

Here we have medicine at its best. The altruism of pure science operating for the benefit of the general public: scientific therapeutics freed from commercial domination.--(Editorial from The Journal A. M. A., Oct. 18, 1919.)

PHARMACEUTICAL BARNUMS

Does the public love to be humbugged? We doubt it. That we, whether sage or fool, are humbugged is undeniable. We are humbugged just to the extent that we are ignorant. There lies one of the most powerful factors operating to the advantage of the “patent medicine” maker and the quack. The layman’s ignorance of the possibilities and limitations of drugs is wide and deep. Hence the ease with which he is fooled on this subject. A seeming frankness in advertising being the order of the day, the nostrum maker makes a pretense of telling what is in his stuff without disclosing any facts that will tend to lift the veil of mystery and thus destroy his greatest asset. So the exploiter of nostrums to the medical profession, realizing that at least a pretense must be made of giving the composition of medicaments offered to the physician, declares that his clay poultice has for its base “anhydrous and levigated argillaceous mineral.” This sounds much more imposing than dry and finely powdered clay, and satisfies by its very sonorousness. Now comes a product exploited chiefly to members of the dental profession but also, it seems, to physicians. Tablets, “activated tablets,” if you please! They are “an anodyne, analgesic febrifuge sedative, exorcising [sic!] antineuralgic and antirheumatic action.” And their composition? Simply “an activated, balanced combination of the mono-acetyl-derivative of para-amidophenetol together with a feebly basic substance in the alkaloidal state from the Thea-Sinensis.” As clear as the Missouri River! Some day some dentist or physician is going to investigate and find that this awe-inspiring, polysyllabic example of exuberant verbosity means nothing more mysterious than our old friends acetphenetidin (phenacetin) and caffein. In the meantime, the exploiters may smile softly and murmur, “Barnum was right!”--(Editorial from The Journal A. M. A., Jan. 1, 1921.)

THE PHARMACOPEIA

The Ninth Decennial Revision

The ninth revision of the United States Pharmacopeia became official this week, Sept. 1, 1916. It is more fully reviewed elsewhere; here we desire merely to call attention to two points; what the book is and what it is not. It is a book of standards for drugs; it is not a book of standard remedies. The Committee of Revision of the Pharmacopeia included physicians and pharmacists (retail, wholesale and manufacturing), but the pharmacists were in the majority and in control. The majority of the representatives of the medical profession on this committee would have preferred to see the bulk of the Pharmacopeia reduced and its value as a work of reference enhanced by the rejection of therapeutically worthless drugs. The representatives of commercial interests, on the other hand, argued that it was necessary for the Pharmacopeia to provide standards for drugs in more or less general use, whether worthless or otherwise. The force of this argument is somewhat impaired by the fact that the National Formulary, which has also been made a book of legal standards, now includes individual drugs as well as combinations; the new edition of the Formulary, in fact, contains a large number of drugs which had been dropped from the U. S. Pharmacopeia VIII. The principle of making use the sole criterion for admission to the Pharmacopeia, however, on the whole carried the day. It has not been strictly observed; good results from the efforts of the medical contingent are to be observed here and there, as in the deletion of elixir of the phosphates of iron, quinin and strychnin and of emulsion of cod liver oil with hypophosphites. That these instances were not expressions of policy on the part of the Committee on Revision, but merely deviations from policy, may be seen by a glance at the contents of the new Pharmacopeia. These include substances which have been shown to be inert, like the hypophosphites (calcium, potassium and sodium hypophosphites), complex and obsolete mixtures, like the compound syrup of sarsaparilla, and drugs which have been tried and found wanting, like saw palmetto berries. Even substances seldom used by the medical profession, but chiefly or altogether by the public, like sassafras, hops and peppermint (the herb), are standardized and made official. It seems difficult to discover any principle by which the sphere of the Pharmacopeia may be definitely marked off from that of the National Formulary. There is one great advantage in specifying U. S. P. drugs and preparations: Physicians who do so invoke legal standards of purity and identity. The only way to be sure of obtaining substances of therapeutic efficiency, however, is to exercise discrimination. The Pharmacopeia is no guide. Being prepared mainly by pharmacists to meet the needs of pharmacists, the Pharmacopeia of course contains much matter of little interest to physicians and entirely foreign to scientific medicine.--(Editorial from The Journal A. M. A., Sept. 2, 1916.)

J. A. M. A. =67=:764 (Sept. 2) 1916.

Review of Ninth Revision

The ninth revision of the United States Pharmacopeia, which has been in the hands of the Committee of Revision for more than six years, has just appeared. As was to be expected, the desire of medical men on the Committee of Revision to have therapeutic value made a requirement for admission to the Pharmacopeia has not been fully realized; it remains a book of standards for therapeutically good, bad and indifferent remedies. Among the drugs of little or no therapeutic importance or value are musk, arnica, eriodictyon, quassia, pumpkin seed, saw palmetto berries, sarsaparilla and couch grass. Many superfluous drugs and preparations are included. For instance, of the nine forms of quinin described (quinin alkaloid, bisulphate, dihydrochlorid, hydrobromid, hydrochlorid, salicylate, sulphate and tannate, and quinin and urea hydrochlorid), at least four might well have been eliminated. Two insoluble forms (the alkaloid and the tannate), two soluble forms (the hydrochlorid and quinin and urea hydrochlorid), and a moderately soluble form (the sulphate) are all that could reasonably be demanded by even the most extreme partisans of the doctrine of “pharmaceutic necessity.” Further, the use of quinin salicylate for its salicylic acid content and of quinin hydrobromid for its bromid content is unscientific. The inclusion of these salts in the Pharmacopeia is regrettable.

Those interested in the promotion of rational therapy will also regret the inclusion of a number of fluidextracts of violently toxic drugs, such as aconite and gelsemium (dose 1/2 minim each), belladonna root, digitalis, nux vomica and ipecac (dose 1 minim each), and lobelia (dose 2-1/2 minims). The more diluted forms, the tinctures, of these drugs are preferable. The inclusion of such fluidextracts in the Pharmacopeia is playing into the hands of certain pharmaceutical manufacturers, who recommend the tincture be prepared from fluidextracts--an unscientific procedure.

The efforts of the medical members of the committee, however, have not been entirely fruitless. Of the articles described in the U. S. Pharmacopeia VIII, 243 have been deleted; sixty-seven new articles have been added. The loss of 167 titles may be set down as a gain. Moreover, most of the new substances give promise of therapeutic usefulness. Thirty-six are taken over from New and Nonofficial Remedies; nineteen are substances which are in the edition of Useful Drugs now in the press. It cannot be said, however; that all of the additions have been judiciously selected. It is an infelicitous time to add calcium and sodium glycerophosphate just when grave doubts of their therapeutic efficiency are being felt. The addition of the extracts of aconite, hydrastis and viburnum prunifolium is likewise unfortunate. All are superfluous preparations, the first because a drug so powerful that an average dose of the extract is only 10 mg. or 1/6 grain is better given in the form of tincture; the second because hydrastis is a drug of uncertain value, already represented by three preparations, and the third because viburnum prunifolium has been discarded and discredited by the best therapeutic authorities. It must be accounted clear gain, on the other hand, that the deletions include many inert, obsolete or superfluous substances like bismuth citrate, kaolin cataplasm, pipsissewa, coca leaves, ladyslipper, wahoo, cotton root bark, compound acetanilid powder and compound syrup of hypophosphites, not to mention nine salts of iron and thirty-eight fluidextracts of various drugs. Wines, unmedicated and medicated, whisky and brandy are also among the articles dropped.

A number of new features are introduced, such as microscopic standards for powdered drugs, standard abbreviations for titles, the use of the term “mil” instead of “cubic centimeter,” and a chapter each on sterilization, diagnostic reagents, biologic assays, electrolytic determination of metals and the determination of alcohol, the melting point, the boiling point and the congealing point.

The chemical nomenclature is substantially the same as that adopted in the previous revision; so is the nomenclature of drugs. The addition of official abbreviations for the Latin titles of drugs will doubtless be found a useful feature.

Less commendable is the change from the familiar “Cc.” to “mil.” The term “cubic centimeter” is so thoroughly established and so widely used, wherever the metric system is employed, that it cannot be expected that it will be universally displaced by the word “mil.” The latter is therefore only a superfluous synonym, and as such out of harmony with the simplicity of the metric system. Perhaps it may even be taken for the abbreviation of “millimeter,” “milligram” or other words derived from “mille,” which would be equally entitled to the same abbreviation.--(Book Review in The Journal A. M. A., Sept. 2, 1916.)

PHYSICIAN’S STOCK IN PRESCRIPTION PRODUCTS

The letter that follows comes from a physician who feels that he has a grievance regarding a company in which he holds stock:

“In 1914, I bought some stock of the ---- ---- Company, and in 1917 bought some more stock in the same company. I notice that the company advertises in The Journal of the American Medical Association, and I believe it does this not so much to acquaint the medical profession with its product, as to acquaint physicians with its name in order that its stock salesmen can keep on unloading more stock to members of the medical profession.

“The company gets the doctors’ money through the sale of stocks, it gets its product on the market with the doctors’ assistance and through their influence, and it looks to me as if the doctors were getting very little in return, as the dividend checks have been few and far between since I have known anything of the company.

“It is not my idea to criticize the product; but I do believe and feel that the stockholders are entitled to a square deal from a company which in turn is expecting so much from them, and again I feel that the publishers of The Journal should be made aware of these conditions so that they do not either consciously or unconsciously foster a concern that is depriving the physician of his hard-earned money.

“If this letter is unfair, I am willing to be shown otherwise. Kindly publish it in The Journal, omitting my name and address.”

The company to which our correspondent refers put out a proprietary product prescribed by physicians and used by the public. Some years ago the company in question advertised its product in The Journal until its stock-selling scheme was brought to the attention of The Journal; the advertisements were then rejected. Some years later, on evidence that the company had discontinued its stock-selling methods to physicians, its product was again admitted to the advertising pages of The Journal. Our correspondent says that he believes that the physicians who hold stock in this company “are entitled to a square deal.” What about the public? Is it getting a square deal when physicians are financially interested in the products that they may be called on to prescribe? Is the average layman’s confidence in the medical profession likely to be enhanced when he learns that the physician to whom he went for treatment has a financial interest in the therapeutic agent which was prescribed? Our correspondent’s complaint against the company seems to be, not that the company sold stock to physicians, but that “the dividend checks have been few and far between,” the assumption being that had the dividends come regularly, there would have been no complaint. It cannot be too often emphasized that it is against public interest and scientific medicine for physicians to be financially interested in the sale of products which they may be called on to prescribe for the sick. It is perfectly true that there are many physicians who would not consciously permit financial considerations to warp their judgment; but it is not humanly possible to remain unbiased in cases of this sort. It is conceivable that a judge on the bench might make every effort to dispense impartial justice in a suit in which one of the parties was a firm in which he, the judge, had financial interest. Nevertheless, it would be obviously improper for such a judge to try a case of this kind. Yet, in this supposititious case the only harm that could result would be of a financial nature. In the case of the physician, the harm is not to the public’s purse but to the public’s health.--(From The Journal A. M. A., Dec. 11, 1920.)

PITUITARY GLAND PREPARATIONS

The importance of the standardization of preparations of the posterior, or infundibular, lobe of the pituitary gland (the liquor hypophysis of the new United States Pharmacopeia, pituitary solution, pituitary extract, etc.) is exemplified by a recent publication of Roth. As is well known, the active constituent or constituents of this gland have not been isolated, and there is no chemical method of determining the activity and therapeutic value of various preparations. There are, however, certain physiologic methods by which the activity of such preparations may be determined with a considerable degree of exactness. The last revision of the Pharmacopeia, recognizing that the best attested field of usefulness for such preparations is in obstetrics, adopted as a test their activity on the uterus of the guinea-pig; the details of the method adopted by the Pharmacopeia are those described by Roth. Roth now reports on the activity of seven samples of commercial infundibular extracts, the products of five American manufacturing pharmacists. Four of these samples were found to be of Pharmacopeia strength; the other three were much weaker. Of the latter, one had but one tenth, another but one fifth and the third but one fourth of the required activity. Those preparations which had been accepted by the Council on Pharmacy and Chemistry for inclusion in New and Non-official Remedies corresponded to the Pharmacopeia requirements. Roth also compared the activity of these seven preparations on the blood pressure, another method by which it has been proposed to standardize infundibular extracts. The four preparations which were equally active on the uterus were found to be equally active on the blood pressure; the other three were much weaker. Roth points out, however, that the results of the two methods are not necessarily parallel; in one instance, for example, two samples caused equal rises of blood pressure, but one was twice as active as the other on the uterus. Hence it is evident that the blood pressure test is not a satisfactory method for determining the activity of a preparation on the uterus, and vice versa.

Roth, G. B.: Pituitary Standardization, Bull 109, Hyg. Lab., U. S. P. H. S., 1917.

Roth, G. B.: Bull 100, Hyg. Lab., U. S. P. H. S.

The subject of pituitary standardization, or perhaps it may be said the application of the present method is, however, in need of further study. Thus the statement has recently been made that commercial preparations are on the market which have from three to five times the activity of the Pharmacopeia standard; this was not the case, however, with the preparations examined by Roth. It is probable that some have used for comparison a weaker standard than that proposed by the Pharmacopeia; this, of course, would lead to the conclusion that the commercial preparations were stronger than the Pharmacopeia standard. Roth suggests that the employment of standards of unequal activity by the various supply houses could easily be eliminated by having a central laboratory distribute material for use as a standard. It will be recalled that before the United States Public Health Service established and began the distribution of standards for diphtheria and tetanus antitoxins, the commercial preparations of these varied even more in activity than do those of the pituitary extracts at present.

Pittenger, P. S., and Vanderkleed, C. E.: Jour. Am. Pharm. Assn. =6=:131, 1917.

It is unnecessary to emphasize the importance of this subject; this is sufficiently evident to those who have followed the recent clinical literature on the use of pituitary extracts in obstetrics. These preparations are used in times of emergency; a weak preparation is valueless, whereas overdosage, either from too strong a preparation or from too free use of a preparation of the official strength, is often followed by disaster to the mother or child or both. Roth cites a number of cases of ruptured uterus and other injuries resulting from their use.--(Editorial from The Journal A. M. A., May 5, 1917.)

PROPRIETORSHIP IN MEDICINE

To the Editor:--I am enclosing a reprint of my article on the “Present Status of Pituitary Extract in Labor,” which appeared in The Journal, June 2, 1917, p. 1601, and also the September issue of Parke, Davis and Company’s Therapeutic Notes, on page 89 of which they quote this article, that you may compare the two. The Therapeutic Notes article is ostensibly a copy, but as a matter of fact, it gives it only in part, which seems to me to be a gross misrepresentation, and one which I do not think should go unnoticed.

Joseph J. Mundell, M.D., Anacostia, D. C.

“Used here in properly selected cases, after due consideration by one who has good obstetric judgment, its results are usually happy, and it is a boon to the tired mother and her attendants.”

“To step beyond these narrow confines of indications is indeed entering on dangerous territory. Especially is this true as regards the life of the baby. It is recommended in small doses by some good authorities and is frequently used in cases of slight contraction at the brim with sometimes very good results if the birth occurs within a few minutes, but frequently with disastrous results to the baby if delivery is delayed. In such cases, forceps are urgently indicated. Its use in such cases is risky beyond question. Pituitary extract is recommended in cases of postpartum hemorrhage, but ergot is undoubtedly to be preferred.”

“All means should be exhausted to arrive at a definite diagnosis, and the dangers of its use should be fully appreciated and due consideration given before its administration in any case, for such a powerful drug, used indiscriminately, will surely produce sad results to mother or child or both.”

“During the past two years a number of untoward effects and consequences of severe character have arisen. As far as the maternal accidents and complications are concerned, I firmly believe that were the slogan of the hour “safety first” borne in mind, a number of them could have been prevented, for beyond question this drug has been greatly abused, as it has been given in too large doses, in cases in which its use was strongly contraindicated, and often, I am sorry to say, for no reason other than the accoucheur’s expediency. Its use has been reckless and careless. The many reports of its rapid and safe action have been one of the greatest dangers. DeLee says, ‘It provides for the physician and his brother gynecologist a lot of chronic sufferers, often incurable, even after mutilating operations.’”

“An analysis of the detailed reports of all these cases of ruptured uterus with one or two exceptions reveals the fact that pituitary extract was abused, being given to patients who should not have had it. To my mind, to give a dose of pituitary extract to a woman who has a contracted pelvis, mild or severe, when the head has not passed through the pelvis, is criminal and, if the obstetrician is not aware of the contraction, he is still little short of being a criminal.”

In the latter part of his article in The Journal, Dr. Mundell analyzes the reports of twelve cases of rupture of the uterus, thirty-four cases of fetal deaths, and forty-one cases of asphyxia pallida in which “resuscitation was effected only after prolonged and vigorous efforts.” These also were not excerpted.--Ed.]--(Correspondence in The Journal A. M. A., Nov. 24, 1917.)

The Manufacturer’s Protest

To the Editor:--The article in The Journal, November 24, page 1818, on proprietorship in medicine does us a gross injustice, and in reply thereto we beg leave to submit the following:

For reasons which every publisher (yourself included) understands, it is not practicable for us to reproduce in full, in the columns of Therapeutic Notes, all the clinical papers to which we wish to direct the attention of our readers. But that the article of Dr. Mundell was not garbled to make capital for Parke, Davis & Co. is quite apparent on comparison of the omitted portions with a previous paper by the same author, reprinted in the January (1917) issue of the Notes, and herewith submitted together with clippings from other issues of the Notes which prove that we have not hesitated to present to our readers the dangers incidental to the misuse of Pituitrin as well as the advantages of its proper use.

Therapeutic Notes, in quoting other journals, puts into its readers’ hands the means of investigating the fairness of its quotations. It is a house organ--true enough; but the organ of a house which has always appealed to the honor as well as to the progressiveness of the medical profession. Its publishers could not afford to resort to deception in advertising their products, through this or any other medium.

The profession is indebted to Parke, Davis & Co. for Pituitrin (among other medicaments), and it is to the profession that the manufacturers look for the ultimate verdict. The contraindications are quite as important as the indications, and, as the excerpts submitted show, we have taken account of these, not only in forming our own estimate, but in presenting the evidence to the readers of Therapeutic Notes.

We cite these facts that you may give us a square deal in an early issue of The Journal if so disposed.

Parke, Davis & Co., Detroit.

Why Proprietaries Flourish

To the Editor:--The following experiences seem to add one more to the many reasons offered to explain why proprietaries and ready-made preparations flourish at the expense of the official drugs and preparations: A few days ago I prescribed Troches of Ammonium Chloride, U. S. P., for a patient of exceptional perseverance. The next day he had not yet secured the troches and told me that he had submitted the prescription to seven pharmacies, including the largest, and three of the best known and admittedly the best equipped in New York. All told him that these troches were “not being made any more,” and that they were therefore unable to supply him. He thereupon communicated with one of the largest wholesale manufacturing pharmaceutical houses in America and received precisely the same answer. I then took the matter up with a first class pharmacist whom I knew and induced him to prepare this difficult (!) troche, for which the U. S. Pharmacopeia gives the following directions: “Rub the powders together until they are thoroughly mixed; then form a mass with syrup of tolu and divide ...”

Seven pharmacists declined to fill a prescription for an official preparation because they could not buy the preparation from a wholesaler, and it required some persuasion to get the eighth to make the preparation. But even worse, several of the pharmacists offered my patient some ready-made troche more or less resembling the official, or offered compressed tablets of ammonium chlorid.

That this is not an isolated example of what often poses as pharmacy is shown by the fact that I have found it extremely difficult to find a pharmacist who would extemporaneously coat pills with gelatin. Most want the physician to alter his prescription so that one of the ready-made gelatin coated pills can be dispensed, if a gelatin coating is necessary. Some gelatin, hot water, a large cork, and a few domestic sewing needles are all that is required for very satisfactory coating of pills with gelatin, yet few pharmacists seem willing to perform this simple procedure.

Two other illustrations, not so recent, have come to me from a colleague. A few years ago he was unable to obtain from either of two pharmacists an emulsion of cod liver oil without the hypophosphites because, as both said, “It does not come without hypophosphites.” On another occasion four of the best drug stores in Boston were asked for the Compound Laxative Pill, U. S. P., then official in the Pharmacopeia. In every case he was told that he must have meant the compound cathartic pill, which in no way resembles the pill he sought.

With this attitude on the part of the men supposed to be serving the public and the medical profession by the practice of pharmacy, is it any wonder that it is difficult to induce the medical profession to prescribe official preparations or combinations of official drugs in place of ready-made commercial substitutes largely drawn from among the proprietaries or specialties? Real pharmacy by real pharmacists is a necessity if we are to succeed in combating the proprietary evil.

Cary Eggleston, M.D., New York.

--(Correspondence in The Journal A. M. A., Aug. 21, 1920.)

PHILIP RAHTJEN AND HIS DISCOVERIES

Recent newspaper reports regarding the alleged “discovery of the Germ of Pernicious Anemia” and the development of “an antitoxin and serum” by Dr. Philip Rahtjen of Pasadena, California, have brought inquiries of which the two that follow are typical. This from a physician in Indiana:

“Please let me know about the supposed recent discovery of Dr. Philip Rahtjen concerning pernicious anemia. The information I have is from a newspaper clipping of October 21, Pasadena, California. Kindly omit my name.”

A New York physician writes:

“If you could send me any information as to the enclosed I would appreciate it. The article impresses one as absolutely inconclusive. However, I promised the patient I would investigate the matter.”

The enclosures referred to consisted of a reprint and a letter from “Ph. Rahtjen, M.A., Ph.D.,” Pasadena, Calif., both of which had been sent to a layman who had written to Rahtjen. The reprint was a translation of a brief article by Rahtjen “On the Etiology of Idiopathic Anemia,” translated from the Centralblatt für Bakteriologie Parasitenkunde und Infektionskrankheiten. Rahtjen’s letter to the layman read:

“Your inquiry relative to my isolation and classification of the Germ of Anemia received.

“I herein enclose my paper published in August in the Central Magazine of Bacteriology.

“I have succeeded in immunizing goats against the Germ therein described. Five thousand injections of the Serum have been given. Three hundred cases diagnosed as Anemia and Chlorosis were treated under observation. Six cases of Pernicious Anemia were observed under treatment. All responded favorably.

“The Serum is at your disposal from my laboratory here for the use of your physician. The price is five dollars for twelve ampoules each containing 1 ccm., the amount of one injection.

“The treatment consists of intramuscular injection every second day accompanied with a nitrogenous free diet, preferably milk diet. Your attending physician should very easily give them.”

Just what Rahtjen’s serum is we do not know. Nor have we been able to find any information on the subject in any available medical literature. In fact, a rather careful search of American medical literature for some years past fails to reveal any article by Rahtjen on any subject.

Philip Rahtjen is not a physician. In the Propaganda files is a circular issued in 1917 by the “Rahtjen Tuberculosis Sanatorium” of San Francisco, Calif. This exploits “The Rahtjen Cure for Tuberculosis” and tells of “The Discovery of Dr. Philip Rahtjen.” The circular states that:

“Dr Rahtjen studied in Heidelberg, Berlin, Munich, Marburg, and Rostock, Germany, from which latter school in 1904, he graduated in chemical pathology as Doctor of Philosophy. He became assistant professor of pathology at the Imperial Biological Station at Heligoland, and was later appointed assistant to Dr. Piorkowsky, head of the Deutsche Schutz und Heilserum Gesellschaft.”

The same circular summarizes the potentialities of “Rahtjen’s Cure for Tuberculosis” thus:

“The remedy seems to cure tuberculosis in all its forms with equal celerity and certainty. The evidences indicate that it does not matter how far the disease has progressed, if there be tissue of the attacked organ remaining sufficient to sustain life, the disease can be wholly eradicated and the patient restored to health. This is indicated alike in tuberculosis of the lungs, of the throat, of the bladder, of the kidneys.”

The booklet stated further that patients might be treated at one of two places: at the offices of the sanatorium in the city of San Francisco, or at the sanatorium itself near Glenwood. The cost of treatment at the sanatorium was to be $1,000, which would entitle “the patient to residence and attention there for four months.” According to the leaflet, “This is regarded as a period sufficient to restore the patient to health whatever be the stage of his disease; provided only, as we remark, that he has enough left of the infected organ to sustain life with the T. B. expelled.”

“At the end of four months the patient is sent to his home, not alone relieved of his disease, but in a highly vigorous state of health.”

All this, as stated previously, was in 1917. And yet people are still dying of tuberculosis!

In March, 1920, Rahtjen (so the newspapers have it) was offering a “New-Life Fluid.” According to a San Francisco paper, Dr. Philip Rahtjen “announces the discovery that by the injection of secretions from the ductless glands the human body may be reinvigorated.” The paper described the discovery “as a long step forward in the fight to counteract old age” and stated that a syndicate was being formed by Rahtjen and others to “produce the extract in such quantity that it may be available for every one.” The newspaper article showed the learned doctor in a laboratory apron in the characteristic pose of the newspaper “scientist” pouring something from a beaker into a test tube--and gazing intently at the camera while doing it! This was in March, 1920; yet people still grow old.

Within the last month the Los Angeles Examiner has heralded some more wonderful accomplishments of Rahtjen. According to this paper Rahtjen has:

1. Isolated the “germ of pernicious anemia.”

2. Found the “serum” for the cure of this disease.

3. Discovered the secret of human virility.

4. Evolved a fluid “from the glands of selected bulls and cows” which will “restore ‘pep’ for worn-out human bodies! Give added weight, clearer eyes, brighter minds, quicker bodies and a generally ‘firmer grip’ on oneself!”

This “amazing discovery” was, according to the Los Angeles paper, the culmination of “five years of continuous study” and had only just been revealed by Rahtjen.

“Dr. Rahtjen has for years been working silently in a bio-chemical laboratory in Pasadena, surrounded by microscopes, scales, test-tubes, acids, alkalis, reagents and all the accompanying stage settings that spell bio-chemical science.”

All of these wonders might still have been a closed book to the public had not “friends” of Dr. Rahtjen brought the matter to the attention of the Examiner.

“Dr. Rahtjen yesterday, with the usual reserve of the ethical scientist, was disinclined to talk of his work until publication of it in a scientific journal.”

Fortunately for a palpitating public, the Los Angeles Examiner “was able to learn the essence of his study” and pass the information on. It seems from this newspaper report that Rahtjen first made his extracts from the glands of goats and sheep but these extracts “were found to be too strong.” As a result “Dr. Rahtjen is now using the glands of specially selected Mexican bulls and cows.” The male patients who are “weak, uninterested in life, unable to concentrate in thought” are given the extract of bull; the female patients who are in a similarly deplorable condition receive an “injection of the cow gland extract.”

We have not yet learned whether the Los Angeles Examiner has deprecated Dr. Rahtjen’s use of Mexican bovines. Remembering the attitude of the Hearst papers toward all things Mexican, one may look for the suggestion that Mr. Rahtjen use 100 per cent. American bull.--(From The Journal A. M. A., Nov. 26, 1921.)

SODIUM CACODYLATE IN SYPHILIS

To the Editor:--I was much interested in the study of this subject by Dr. H. N. Cole (The Journal, Dec. 30, 1916, p. 2012.)

In 1913 I treated a series of cases of syphilis with sodium cacodylate; but, not getting the desired results, I discontinued its use. In 1915, I became interested again because of the writings of Dr. J. B. Murphy, and applied it in three cases in which the patients had initial lesions:

CASE 1.--J. M., man aged 21, single, shoeworker, came to me with an initial lesion of the penis to the right of the frenum. I began intramuscular injections of sodium cacodylate, 5 grains, in ampules made by Parke, Davis & Co., every day for ten days. Then I halted for ten days and repeated ten more injections. The sore on the penis entirely disappeared about the ninth day. There was a slight, faintly macular eruption of the forearms and abdomen, which soon disappeared. There was no alopecia. When he returned, after the last series of ten injections, there were mucous patches in the throat and some involvement of the left tonsil. I put the patient on mixed treatment, which cleared his throat. He had, at end of twenty doses of 5 grains of sodium cacodylate each, a positive Wassermann reaction. After mercury and potassium iodid for two months there was a positive Wassermann reaction. To date, after three salvarsan treatments intravenously there have been two negatives.

CASE 2.--F. S., man, aged 28, married, machinist, had an initial lesion on the penis. Treatment with sixty injections of 5 grains of sodium cacodylate gave results as follows: The initial sore on the penis disappeared in ten injections; there were severe mucous patches of the mouth; the tonsils were badly infected. There was a positive Wassermann reaction. There were syphilids of both arms and shins; marked papular eruption; malaise, and a slight trace of albumin in the urine. I placed the patient on mercurials and at last give him three salvarsan injections three weeks apart. The result was a negative Wassermann reaction, the skin was clear and the patient felt fine.

CASE 3.--D. C., woman, aged 21, single, seamstress, had an initial lesion on the left side of the cervix, and a macular eruption on the face, neck and shoulders, and also, though faint, on the forearms. Thirty injections of sodium cacodylate of 5 grains each were given. The initial lesion disappeared in one week. Mucous patches of the mouth appeared and persisted. The Wassermann reaction was positive. I gave mercurials and potassium iodid for seven months, and salvarsan once. The Wassermann reaction is now negative.

My conclusion after two trials of the use of sodium cacodylate in small or large doses is that it has no effect toward curing the condition; in fact, the throat symptoms were seemingly increased in severity by its use. It has no effect on syphilids of the forearms and shins, and if anything makes them worse.

It improves the appetite, as one would expect. It has some effect on the kidneys, as noted in Case 2; it has some effect in healing the initial lesion, as noted in all three of this series; why, I do not know.

I am entirely satisfied that it has no beneficial effect on syphilitics and have discontinued its use entirely in my practice.

I am glad to have read Cole’s excellent article, as it shows me that I was correct in my decision not to use it again, as it was worthless.

William G. Ward, M.D., Lynn, Mass.

To the Editor:--Dr. William G. Ward’s letter (The Journal, Feb. 3, 1917, p. 390), and the recent admirable article by Dr. Harold N. Cole (The Journal, Dec. 30, 1916, p. 2012) recall to mind Dr. J. B. Murphy’s clinical note on the use of sodium cacodylate in the treatment of syphilis (The Journal, Sept. 24, 1910, p. 1113), and the experimental work of Cap. H. J. Nichols, U. S. Army (The Journal, Feb. 18, 1911, p. 492). The results of Nichols’ work conclusively proved, at least from a laboratory standpoint, that this drug was of very little value as a spirocheticide in combating syphilis. Prior to the publication of Dr. Murphy’s letter I had employed sodium cacodylate extensively as a remedy in psoriasis, and I still continue to use it in selected cases of the disease.

Adopting Dr. Murphy’s suggestion, I gave the agent an extensive trial in syphilis in all stages of the disease. The results were extremely disappointing, from both clinical and serologic points of view. More recently, during the scarcity of salvarsan, I gave the drug a second trial, employing it in large dosage in the hope that the previous failure had been due to the employment of insufficient amounts. The results were not tabulated, but, judging roughly from my experience in a score of cases, its therapeutic value as an antisyphilitic was nil. A few of the patients underwent a temporary improvement, probably owing to the tonic effect of the drug, but in every instance the serologic findings were unaffected.

R. L. Sutton, M.D., Kansas City, Mo.

--(Correspondence in The Journal A. M. A., Feb. 3, 1917.)

TABLETS: DEPENDABILITY OF DOSAGE

The tablet form of administering medicines is popular among many physicians because of its convenient availability and dosage. There is no doubt about the convenience of tablets, but the accuracy of the dosage content is not always to be depended on. One reason for this is that the demand for palatable and convenient “medicaments has led manufacturers to attempt to produce in tablet form mixtures which, from the nature of the case, are not suited to that method of compounding.” In a series of painstaking experiments on bismuth, opium and phenol tablets, conducted a number of years ago in the A. M. A. Chemical Laboratory, it was shown that no tablets on the market then contained the amount of phenol the label indicated, the variation being from 12.3 to 112.5 per cent. Similarly, the laboratory found that in the case of several different brands of Aromatic Digestive Tablets, the amount of hydrochloric acid present in these absurd combinations was true to label in only one half of the specimens, notwithstanding the fact that the amounts claimed to be present were ridiculously small; in two specimens, there was no hydrochloric acid whatever present, while a third contained only a trace. These examples illustrated clearly the very evident unwisdom of attempting the pharmaceutically impossible merely for the sake of convenience or pharmaceutical “elegance.”

Puckner, W. A., and Clark, A. H.: Examination of Tablets of Bismuth, Opium and Phenol, The Journal A. M. A., July 25, 1908, p. 330. Puckner, W. A., and Hilpert, W. S.: Tablets of Bismuth, Opium and Phenol, Dec. 17, 1910, p. 2169, May 6, 1911, p. 1344. Unreliable Pharmaceutical Products, editorial, May 6, 1911, p. 1335.

Puckner, W. A., and Warren, L. E.: Aromatic Digestive Tablets, The Journal A. M. A., Aug. 20, 1910, p. 710.

Another reason for doubting the accuracy of dosage, irrespective of the characteristics of the drugs composing the tablets, has been the manifest lack of care in their manufacture. In 1914, Kebler reported the results of a far-reaching investigation of tablet compounding in which he pointed out that tablets on the market were not as uniform or accurate as was generally believed, the variations being “unexpectedly large in numbers and amount.” During the past year, the Connecticut Agricultural Experiment Station undertook the examination of tablets--proprietary and nonproprietary--taken from the stock of dispensing physicians. The variations found in weights of the tablets were strikingly similar to those reported by Kebler.

Kebler, L. F.: The Tablet Industry, Jour. Am. Pharm. Assn., 1914, 3, 820, 937, 1062.

Bull. 200, Connecticut Agricultural Station, Food and Drug Products, 1917, p. 161.

VARIATION IN WEIGHTS OF TABLETS

Kebler Connecticut Variation Per Cent. Per Cent. Less than 10 per cent. 43 44 More than 10 per cent. 57 56 More than 12 per cent. 44 35 More than 15 per cent. 28 26 More than 20 per cent. 9 10

The determinations of the composition of the tablets when compared with that claimed for them showed wide variation--from 54 per cent. above to 70.5 per cent. below; in almost two thirds of the tablets examined, the variation amounted to more than 10 per cent.; in three fifths of the tablets, the variation was more than 15 per cent.; in one fourth, more than 20 per cent., and in one twentieth, more than 50 per cent.; only in one eighth of the tablets was the variation less than 5 per cent.

The Connecticut investigators substantiate once again the work previously reported, namely, that there are a number of firms who are either incompetent or careless. For tablets of simple composition, a variation from the declaration of 10 per cent. should be amply sufficient to compensate for the errors of careful manufacture. It may be added that the best tablets originate generally from firms having competent chemical control.--(From The Journal A. M. A., July 27, 1918.)

THERAPEUTIC EVIDENCE: ITS CRUCIAL TEST

Torald Sollmann, M.D., Cleveland

Read before the Section on Pharmacology and Therapeutics at the Sixty-Eighth Annual Session of the American Medical Association, New York, June, 1917.

This article clearly states the difficulties experienced by the Council in estimating the merits of a proprietary medicinal product and clearly defines the method which has been found to be practical in judging of the therapeutic value of such preparations. The Council has approved this discussion of the subject and has directed that the paper be published in the annual Council reports.

W. A. Puckner, Secretary.

According to the good old truism, the last and crucial proof of the pudding is in the eating thereof; and so, the last and crucial test of a therapeutic agent is its consumption by a patient. There is, however, one essential difference: When the pudding is eaten, with a sense of satisfaction, we know that it was a good, or at least an eatable, pudding.

If the patient improves after taking a remedy, we do not yet know that he improved on account of the remedy. The post hoc type of reasoning or logic is not respectable; but it is all too apt to creep in unawares, unless one takes great precautions indeed.

Clinical evidence needs especially to be on its guard against this pitfall, for the conditions of disease never remain constant; nor is it possible to foresee with certainty the direction which they are going to take. It is just this point which makes the clinical evidence so much more difficult to interpret than laboratory evidence, in which the conditions can be more or less exactly controlled, and any changes foreseen. It is on this account, also, that clinical experiments must be surrounded with extra painstaking precautions.

In brief, while the “proof” of a remedy is on the patient, that is not the whole story, but merely an introduction. The real problem is to establish the causative connection between the remedy and the events. The imperfect realization of this has blocked therapeutic advance, has disgusted critical men to the point of therapeutic nihilism, and has fertilized the ground for the commercial exploitation of drugs that are of doubtful value or worse.

This has been impressed on me particularly by my service on the Council on Pharmacy and Chemistry. In the course of its work of passing on the claims advanced for commercial remedies, this Council is forced to inquire critically into the basis of the claims of manufacturers.

It is interesting to note the qualitative differences in the evidence for the various kinds of claims: The chemical data are usually presented in such a form that it is possible to tell at a glance whether or not they are based on demonstrated facts, which could usually be verified or refuted without special difficulty. The deductions are usually such as can be legitimately drawn from the data, or else they are obviously absurd. All this agrees with the relatively exact status of chemical science.

In passing to data and deductions from animal experiments, a distinct change is noticeable: Not only are the data less reliable, and less worthy of confidence, but they are more often stated in a less straightforward manner. The presentation of the data often shows evidence of manipulation of the results, so as to make them most favorable to a preconceived conclusion that would recommend the drug. This is not always intentional, but is partly due to the less exact nature of animal experimentation, which leaves a wider play to the arbitrary interpretation of the reporter. A certain amount of this is unavoidable. No serious objection can be raised, provided the experimenter presents all the essential data, and discusses fairly all of the interpretations that would apply to them.

On the whole, it is usually possible to form a fairly definite estimate of the value of experimental data.

When one comes to the clinical evidence, an entirely different atmosphere obtains. When the Council demands evidence of the usefulness of a remedy, the manufacturers generally respond with every sign of enthusiasm. They may have ready a series of articles already published, or they instruct their agents to bring in letters from physicians. The last method seems to meet the most cordial response, judging from the deluge of letters and opinions that floods the Council.

The quality of the published papers is a fair reflection of the deficiencies of what is still the common type of clinical evidence. A little thought suffices to show that the greater part cannot be taken as serious evidence at all. Some of the data are merely impressions--usually the latest impressions of an impressionable enthusiast--the type of man who does not consider it necessary to present evidence for his own opinions; the type of man who does not even realize that scientific conclusions must be based on objective phenomena.

Some of the papers masquerade as “clinical reports,” sometimes with a splendid disregard for all details that could enable one to judge of their value and bearing, sometimes with the most tedious presentation of all sorts of routine observations that have no relation to the problem.

The majority of reports obtained by the agents belong to these classes, notwithstanding the fact that they are often written for the special use of the Council, and therefore with the realization that they are likely to be subjected to a thorough examination, and therefore presumably representing the best type of work of which the reporter is capable. So, at least, one would suppose.

It is also possible, however, that some of these reports are written merely out of thoughtlessness, or perhaps often to get rid of an importunate agent. This is illustrated by the following correspondence, taken literally from the files of the Council.

A letter from a prominent physician “A,” endorsing a certain preparation “D,” having been submitted to the Council, the secretary was directed to write to Dr. A as follows:

Dear Dr. A:--The B Company of C has requested the Council on Pharmacy and Chemistry to admit its preparation D to New and Nonofficial Remedies. As part evidence for the value of the preparation, the company submitted a letter from you which contains the following:

So far as my experience has thus far gone, they are certainly superior to a number of other iodine compounds now on the market, and I should judge that they ought to take a superior place in therapy involving the use of iodine.

The referee of the Council in charge of D writes that he was interested by your letter and asks that I inquire: As compared with sodium or potassium iodid, what would you say are the differences between, and real advantages of, D and the alkaline iodids? Did you make any comparative experiments and keep a record of them? If so, the referee would like to receive an account of your trials. In what direction could D be expected to occupy a superior place in iodin therapy?

I hope that you can give the information asked by the referee and thus aid the Council in arriving at a correct estimate regarding the value of D.

The following reply was received from the physician in response to the foregoing:

Dear Professor Puckner:--In reply to yours of January 19, I did not proceed far enough in the investigation of D to draw conclusions of any particular value for the purpose of the Council on Pharmacy and Chemistry; and I so stated in my letter to the proprietors of that remedy.

Answers to the questions you put in your letter require an amount of investigation of the remedy far beyond anything I undertook. As a matter of fact, I returned about five sixths of the capsules sent me, because of lack of time and opportunity to carry out the extensive clinical experiments that I plainly saw would be required to give an opinion at all worth while. I believe you had better not consider me in the matter at all.

The report was furnished by a physician for whom I have a high personal regard. I introduce it here, not so much in a spirit of criticism, but as a justification of the opinion that I have formed of clinical evidence obtained by manufacturers through their clinical adjutors.

When commercial firms claim to base their conclusions on clinical reports, the profession has a right to expect that these reports should be submitted to competent and independent review. When such reports are kept secret, it is impossible for any one to decide what proportion of them are trustworthy, and what proportion thoughtless, incompetent or accommodating. However, if this were done it is quite possible that such firms would find much more difficulty in obtaining the reports. Those who collaborate should realize frankly that under present conditions they are collaborating, not so much in determining the scientific value, but rather in establishing the commercial value of the article.

Often the best type of clinical reports--those in which the observations are directed to the significant events and not to mere side lines, and in which the significant events are correctly and adequately reported--generally lack one important essential, namely, an adequate control of the natural course of the disease.

Since this cannot be controlled directly, it must be compensated indirectly. For this purpose, there are available two methods:

The first is the statistical method, in which alternate patients receive or do not receive the treatment. This method can usually only be of value when a very large series of patients is available. Even then, its value is limited or doubtful, because it cannot take sufficient account of the individuality of cases.

The second method consists in the attempt to distinguish unknown preparations by their effects--the method that might be called the “comparative method” or the “blind test.”

In this, the patient, or a series of patients, is given the preparation which is to be tested, and another preparation which is inactive, and the observer aims to distinguish the two preparations by their effects on the patient. Surely if the drug has any actions at all it will be possible to select correctly in a decided majority of the administrations.

The same principle can be applied in distinguishing the superiority of one preparation over another. In this case, the two preparations would be given alternately to different patients, and the observer would try to distinguish them by their effects. Here again, if one drug is really superior or otherwise different from another, to a practically important extent, the observer will surely be able to make the distinction.

This method is really the only one that avoids the pitfalls of clinical observation; it is the only method that makes the results purely objective, really independent of the bias of the observer and the patient. It is the only method, therefore, which determines whether it was really the pudding that was eaten and not some other dessert.

In principle this method does not usually offer any very great difficulties. It is, of course, necessary that the two preparations to be compared shall resemble each other so closely or shall be flavored, etc., so that they cannot be distinguished by their physical properties. This is usually not a very difficult matter. The method does not jeopardize the interests of the patient, for it is understood that no drug would be tested in this way unless there is some reason to believe that it has a value. When the patient’s condition is such as to demand treatment, then he would be receiving either the standard drug or the drug which the experimenter believes may be superior to the standard.

CONCLUSIONS

The final and crucial test of a remedy is on the patient; but the test must be framed so as to make it really crucial. Most clinical therapeutic evidence falls far short of this. The “blind test” is urged to meet the deficiencies.--(From The Journal A. M. A., July 21, 1917.)

“VACCINES IN TOXIC CONDITIONS”

Commercialized Propaganda in the Guise of Science

Under the title “Vaccines in Toxic Conditions,” what purports to be a scientific contribution appears in the original department of the official organ of a state medical society. The apparent purpose of the article is to overcome any hesitancy on the part of practitioners to use vaccines in toxic infectious conditions for fear that they might thereby cause harm. Such a thesis is interesting and might be important--if true. Two outstanding facts, however, give pause. First, the theory promulgated is contrary to the experience of those who have studied the subject; second, the man who writes the article is in the business of making and selling vaccines! The former fact is a matter of fairly general knowledge among the better informed members of the medical profession; the latter fact is nowhere made evident in the article, which the reader might infer came from a disinterested investigator in the realms of immunology.

Sherman, G. H.: Vaccines in Toxic Conditions, Illinois M.J. 38: 314 (Oct.) 1920.

The article purports to prove that the special investigations carried on by its author show that there is no basis for the well-grounded fear that vaccines might be harmful to a patient suffering from toxic infectious conditions. Thus:

From a closer study of these infective processes we find that this toxic condition is due to the rapid multiplication of the infecting organisms with the incidental production of ferments which the germs secrete to digest the food on which they live. These toxic ferments have a distinct destructive tendency on tissue cells, without any marked influence in stimulating tissue cells for antibody production. The crying need, however, in these extensive acute infections is rapid antibody formation to neutralize these germ-produced poisons and to eliminate the germs.

Now vaccines, we are informed, are not toxic and so stimulate the production of antibodies. In other words, the same organism that in the body is toxic and without marked antigenic properties becomes nontoxic and actively antigenic when converted into a vaccine. The details of the experiments of the “closer study” made by the author of this paper (and the manufacturer of vaccines) which give such definite and convincing results are not published. Possibly the article is a preliminary contribution, and future issues of the same publication will carry further articles on the same subject. The follow-up system is well recognized in the advertising world. At all events, this “closer study” has convinced the author of the article that:

... even in extreme toxic conditions, in acute infections, bacterial vaccines may be employed without the least fear of doing any harm. In fact, we find that in extreme acute infections, bacterial vaccines not only give the best clinical results, but they may also be given in larger doses at shorter intervals with less reactions than in minor or chronic infections and the earlier they are given the better the results.

Here again no details are given; there are no comparative results of the careful study of a series of cases. The sum and substance of this remarkable contribution to a scientific publication is to the effect (1) that the organism that in the body is toxic becomes nontoxic when introduced in vaccine form; (2) that the organism that in the body is but little antigenic becomes when introduced in vaccine form actively antigenic, and (3) that “in extreme acute infections” when the body is affected profoundly by the infectious agent and its product, the oftener and the more one injects of these very materials, the better the results!

And this astounding plea for the use of vaccines in conditions in which vaccines are generally held to be contraindicated, or even injurious, is made by one whose business is the manufacture of vaccines and selling them to the medical profession!--(Editorial from The Journal A. M. A., Oct. 23, 1920.)

VITAMINS: THEIR DISTRIBUTION

Our knowledge of the accessory food factors, commonly spoken of as vitamins, is so recent, comparatively speaking, and the exact nature of these factors still so enveloped in mystery, that it was inevitable that the public’s lack of knowledge on the subject should be capitalized. It is not surprising that there are on the market a number of preparations of the “patent medicine” type that are being sold under the claim that they are rich in vitamins--although the exploiters of these fail to explain which, if any, of the three accessory food factors their products contain. The renaissance of yeast as a therapeutic agent has given an opportunity to the manufacturers of this product of unduly stressing the fact that yeast is particularly rich in the antineuritic vitamin (water-soluble B). Because milk and certain milk products are rich in the fat-soluble A factor, the dairy interests would apparently have the public believe that this particular vitamin is to be obtained only from their products. Thus, a journal devoted to the dairy interests recently claimed that those who want vitamins must get them in their milk, butter, cheese and other milk products. The truth is, the accessory food factors are so well distributed throughout the dietary of modern man that, generally speaking, the individual who uses ordinary judgment in selecting his food is in no danger of suffering from a deficiency of any of these three factors. It would be well if every physician might read the excellent monograph on the present state of knowledge concerning accessory food factors written by a committee appointed jointly by the Lister Institute and Medical Research Committee. In this report the distribution of the vitamins in our common foodstuffs is thus briefly summarized: “... broadly speaking it is safe to say that the individual always finds sufficient supply of vitamins in his food so long as that food is reasonably varied and has received no artificial or accidental separation into parts, and so long as no destructive influence has been applied to it.” At the end of the committee’s report is a table (reproduced on page 562) which shows the distribution of the three accessory factors in the commoner foodstuffs.--(Editorial from The Journal A. M. A., Aug. 13, 1921.).

DISTRIBUTION OF THREE ACCESSORY FACTORS IN COMMONER FOODSTUFFS

Classes Fat-Soluble A Water-Soluble B Anti- of or Anti- or Antineuritic scorbutic Foodstuff rachitic (Antiberiberi) Factor Factor Factor

Fats and Oils: Butter +++ Cream ++ Cod-liver oil +++ Mutton fat ++ Beef fat or suet ++ Peanut oil + Fish oil, ++ whale oil, etc. Margarin prepared Value in from animal fat proportion to amount of animal fat contained Nut butters + Meat, Fish, etc.: Lean meat (beef, mutton, etc.) + + + Liver ++ ++ + Kidneys ++ + Heart ++ + Brain + ++ Sweetbreads + ++ Fish, white very slight, if any Fish, fat (salmon, herring, etc.) ++ very slight, if any Fish roe + ++ Canned meats ? very slight Milk, Cheese, etc.: Milk, cow’s whole, raw ++ + + Milk, skim, raw + + Milk, dried whole less than ++ + less than + Milk, boiled, whole undetermined + less than + Milk, condensed, sweetened + + less than + Cheese, whole milk + Eggs: Fresh ++ +++ ? Dried ++ +++ ? Cereals, Pulses, etc.: Wheat, maize, rice, whole grain + + Wheat germ ++ +++ Wheat, maize, bran ++ Linseed, millet ++ ++ Dried peas, lentils, etc. ++ Soy beans, haricot beans + ++ Germinated pulses or cereals + ++ ++ Vegetables and Fruits: Cabbage, fresh (raw) ++ + +++ Cabbage, fresh (cooked) + + Cabbage, dried + + very slight Cabbage, canned very slight Swede (rutabaga) raw expressed juice + +++ Lettuce ++ + Spinach (dried) ++ + Carrots, fresh raw + + + Carrots, dried very slight + Beetroot, raw, expressed juice less than + Potatoes, raw + + Potatoes, cooked + Beans, fresh, scarlet runners, raw ++ Onions, cooked + at least Lemon juice, fresh +++ Lemon juice, preserved ++ Lime juice, fresh ++ Lime juice, preserved very slight Orange juice, fresh +++ Raspberries ++ Apples + Bananas + + very slight Tomatoes (canned) ++ Nuts + ++ Miscellaneous: Yeast, dried +++ Yeast, extract and autolyzed ? +++ Malt extract + in some specimens

Our Knowledge of Vitamins

Commenting on the trend of medical research concerning vitamins, the latest report of the British Medical Research Council says:

The present situation is a curious one, upon which posterity will probably look back with great interest. We still have almost no knowledge of the nature of these elusive food substances or of their mode of action, but we have gained empiric knowledge already of the greatest practical value for the prevention of scurvy and of other grave diseases and for the promotion of health and beauty in the population.

This statement, it will be noted, emphasizes the foundation on which rests our present use of vitamins. From time to time The Journal has commented on our lack of actual knowledge of these mysterious substances, emphasizing particularly the generally accepted fact that the taking of a well-balanced diet results in providing the individual with such vitamins as are necessary to his growth and nutrition. Last week appeared a brief report of a meeting of the Chicago Medical Society devoted to this subject, and it was gratifying to have the conservative view which The Journal has emphasized substantiated by many of those who took part in the discussion. Moreover, the British Medical Journal, in its leading editorial for February 11, reiterates that an abundant supply of vitamins exists in all fresh vegetables, and that a considerable quantity occurs in milk and meat, provided the latter substances are obtained from animals fed on fresh foods. “A normal adult,” it says, “living on an ordinary diet containing a reasonable proportion of fresh vegetables is, therefore, certain of obtaining a plentiful supply of vitamins.” Of all the mass of evidence which has accumulated relative to these substances, this fact is the point of greatest importance. It is, however, very unfortunately, the one point which those commercially inclined are unwilling to recognize.--(Editorial from The Journal A. M. A., March 11, 1922.)

The Demand for Vitamins

Thus the British Medical Journal in its current issue:

In spite of the fact that ordinary fresh foods are the simplest, cheapest and richest sources of vitamins, the public apparently demands to be supplied with vitamins in the form of medicinal products.

The public “demands” vitamins in pill form! Why? For the same reason that the public, lay or medical, demands many things today that it does not need--because the whole trend of modern advertising is toward creating demands, rather than supplying needs. Vitamin concentrates are being “demanded” by the public because shrewd and forward-looking “patent medicine” exploiters are using all the subtle arts of modern advertising to convince the public that it is in serious danger of vitamin starvation, and that the only hope lies in buying these alleged concentrates to make up a hypothetical deficiency. It seems inconceivable that a rational man would pay a tremendously high price for certain food factors which are already present in his ordinary diet. But he will; and advertising is the reason. Advertising campaigns such as these of the vitamins constitute a vicious circle; an artificial demand is created and then the manufacturer excuses his business on the ground that he is merely supplying a demand! As our British contemporary says, “ordinary fresh foods are the simplest, cheapest and richest sources of vitamins.”--(Editorial from The Journal A. M. A., March 18, 1922.)

THE WILLIAM A. WEBSTER CO. AND THE DIRECT PHARMACEUTICAL CO.

The following letter from a Detroit physician was received a few days ago.

To the Editor:--I have just received a letter from the Direct Pharmaceutical Co. of St. Louis, Mo., quoting prices on drugs which are not more than one half what the leading manufacturers are quoting on the same drugs. I have received previous literature from this company but have not done business with them. I would be unwilling to prescribe their drugs unless I were satisfied that they are what is claimed for them. I would be glad to receive any information regarding this firm that may be available.

The Journal has also received some letters from physicians regarding the William A. Webster Co. of Memphis, Tenn., relative to a letter the concern was sending physicians in the form of a testimonial (reproduced in miniature on this page) and alleged to be from Dr. F. W. P. Butler of Columbia, S. C. Typical letters on the Webster advertising follow:

To the Editor:--Is there not some way through which the dignity of the medical profession can be protected from the circulation of such idiotic drivel as the enclosures display?

To the Editor:--I am sending you an example of the sort of “evidence” which some so-called ethical pharmaceutical houses expect physicians to take for scientific proof. It is pathetic that there are some in our profession who “fall for” such rot. I trust you will continue your campaign for honest and intelligent medicine.

The “evidence” to which one of the correspondents refers and which another characterizes as “idiotic drivel” is reproduced on the following page in miniature. It is a testimonial for William A. Webster Company’s “Ferritonic-Woods.”

Our readers may wonder why we are discussing in one article the William A. Webster Company of Memphis, Tenn., and the Direct Pharmaceutical Co. of St. Louis. The reason is that the Direct Pharmaceutical Co. of St. Louis is apparently merely a sales agency for the William A. Webster Company of Memphis. It appears that orders sent in to the Direct Pharmaceutical Co. go to Memphis to be filled.

The following information regarding some of the products that have in the past been put out by the William A. Webster Company should be of interest to the profession. In government bulletins issued by the Department of Agriculture in October, 1913, there were reported some cases of adulteration and misbranding on the part of the William A. Webster Co., of Memphis, Tenn. A “Pure Concentrated Extract of Lemon” shipped by this concern was found by the federal chemists to be colored with a coal-tar dye “whereby inferiority was concealed,” and while purporting to be a concentrated lemon extract, “in fact, it was not a concentrated lemon extract.” Some “Pure Concentrated Extract of Banana” was found to have mixed with it an imitation banana flavor and an artificial color so as to “injuriously affect its quality and strength” and so that “its inferiority was concealed.” “Pure Concentrated Extract of Pineapple” was found to have had mixed with it “an imitation extract of pineapple artificially colored.” “Pure Concentrated Extract of Strawberry” had been mixed with “an imitation strawberry extract artificially colored.” The same bulletins described the case of the government against a shipment of “Syrup Iron Iodide” made by the Webster concern in which the amount of iron iodid was less than half that claimed on the label. In each of the cases just described, the company pleaded guilty and was fined.

In a similar bulletin issued August, 1914, there were recorded several more cases of adulteration and misbranding charged against the William A. Webster Company. Some “Wine Coca Leaves” was held adulterated in that the amount of alcohol present was wrongly declared on the label; it was held misbranded in that while it contained cocain, the label failed to bear any statement regarding the quantity of proportion of this drug. Tablets of “Acetanilid and Sodium Bromid Compound” were found deficient in strength. “Anti-Vomit Tablets,” “Aspirin Tablets,” “Bismuth and Calomel Tablets,” “Quinin Laxative Tablets,” “Salol Tablets,” “Sodium Salicylate Tablets,” “Neuralgic Tablets,” “Diarrhea Calomel Pills” and “Morphin Sulphate Hypodermic Tablets” were also misbranded in that the amount of certain ingredients found in them failed to tally with the amount declared on the label. In all of these cases also the William A. Webster Company pleaded guilty and was fined.

In a government bulletin issued in June, 1917, the same company was charged with adulterating and misbranding a quantity of Aspirin tablets which, instead of containing 5 grains as labeled, contained only a fraction over 1 grain. In this case, too, the company pleaded guilty and was fined. The table that follows briefly summarizes some of the cases just referred to:

Amount Claimed Amount Found “Syrup Iron Iodid, U. S. P.” Ferrous Iodid 10% 4.6% “Acetanilid and Sodium Bromid Tablets” Acetanilid 3.50 gr. 2.94 gr. “Anti-Vomit Tablets” Bismuth subnitrate 2.50 gr. 1.76 gr. Cerium Oxalate 2.50 gr. 1.78 gr. Cocain Hydrochl. 0.0833 gr. 0.0637 gr. “Aspirin Tablets” 5.0 gr. 3.82 gr. “Bismuth and Calomel Comp. Tablets” Bismuth subnitrate 0.1 gr. 0.22 gr. Calomel 0.1 gr. 0.22 gr. “Quinin Laxative Tablets” Acetanilid 2.0 gr. 1.69 gr. “Salol Tablets” 2.50 gr. 2.05 gr. “Sodium Calicylate Tablets” 5.0 gr. 3.88 gr. “Neuralgic Pills” Morphin sulphate 0.05 gr. 0.015 gr. “Diarrhea Calomel Pills” Morphin sulphate 0.062 gr. 0.05 gr. “Morphin Sulphate Hypodermic Tablets” 0.25 gr. 0.21 gr. “Aspirin Tablets” 5.00 gr. 1.13 gr. X/

--(From The Journal A. M. A., Oct. 18, 1919.)

YEAST

From time to time yeast has attained a transitory popularity as a therapeutic agent. Its use in this way in practical medicine has been based essentially on empiric considerations. Yeast is rich in nucleic acid, but this has not found any special applications. The fatlike substances obtainable from yeast have been recommended in certain alimentary conditions, without finding any widespread acceptance.

More recently yeast has acquired interest from somewhat different angles. In these days of food shortage and enforced conservation, it has come to be realized that the minute yeast cells are endowed with a remarkable capacity of synthesizing one of the most valued nutrients, namely, protein. This substance can be built up out of the simplest forms of nitrogenous compounds by yeasts, in contrast with the incapacity of the higher organisms to construct protein out of anything less complex than the ready made aminoacids. It is reported that in Europe yeast has actually been grown on a large scale in solutions of sugar, salt and simple nitrogenous compounds for the sake of securing the much desired proteins. The utilization of yeast protein for cattle feeding is a current practice abroad; and the satisfactory digestibility and availability of the same product by the human organism has repeatedly been announced since the beginning of the war. In this country the yeast which is produced as a by-product of the brewing industry is for the most part discarded as waste; in the distilleries it becomes a part of the distillers’ grains that are extensively employed as feeds in the dairy industry.

Still newer is the indication that yeast is comparatively rich in at least one of the as yet unidentified accessory factors in nutrition now popularly spoken of as vitamins. Hopkins of the University of Cambridge, England, first directed attention to this unique property of yeast. It has been verified by Funk and Macallum, and recently Osborne and Mendel have given substantial evidence of the potency of yeast to render a diet not otherwise capable of inducing maintenance effective in nutrition.

Yeast has been used, like extracts of rice polishings, to cure the experimental polyneuritis induced in birds by a diet of polished rice. From the experiments of Osborne and Mendel it appears that less than 2 per cent. of dried brewers’ yeast suffices to induce small experimental animals to grow on artificial food mixtures on which alone they fail to thrive. How the use of yeast as an adjuvant to otherwise inadequate food mixtures exerts its beneficial effect is not yet made clear. Satisfactory growth in these cases is promoted by liberal eating. Anything which renders food more palatable may stimulate one to eat more liberally of it. This can scarcely be the explanation of the potency of the yeast as it is effective even when fed apart from the rest of the food. It may have a favorable effect on the metabolism and thus improve the general condition so that more food is consumed. Small quantities of milk and extracts of many of the common plant foods, such as the cereal grains, have been found to act in the same way. There seems to be little doubt, therefore, that yeast also contains something comparable with the so-called water-soluble vitamins of the diet. A specific need for yeast can scarcely be predicated on this fact, however; for any well selected human dietary containing the usual variety of animal and vegetable foods is not likely to be devoid of the widely distributed water-soluble type of vitamin. We mention this to check premature enthusiasm for a new vitamin.--(Editorial from The Journal A. M. A., Sept. 8, 1917.)

Yeast and Its Uses

To the Editor:--Is there available information concerning the medicinal use of yeast? How is it taken? I should like to know whether the use of it would cause any digestive disturbance, and whether the flesh gained is normal and permanent.

S. E. L., Bridgeport, Conn.

ANSWER.--Yeast is one of those remedies that have undergone alternating cycles of use and of disuse; just at present it appears again to be in its ascendency. No doubt, the reason for these cycles has been excessive praise and uncritical use, followed by disappointment and consequent discard.

Hawk and his associates (Hawk, P. B.; Knowles, F. C.; Rehfuss, M. E., and Clarke, J. A.: The Use of Bakers’ Yeast in Diseases of the Skin and of the Gastro-Intestinal Tract, The Journal, Oct. 13, 1917, p. 1243) have recently called renewed attention to its laxative qualities. When from one-half to one cake of yeast was given three times daily before meals, it produced regular bowel movements in a number of patients suffering from constipation. That this result is not due to any vital processes in the yeast is shown by the fact that yeast killed by boiling water was employed with success. It is suggested that such yeast might be preferred for patients troubled with flatulence. Aside from the tendency of living yeast to produce diarrhea, and the possibility that it may aggravate flatulence, no digestive disturbance has been charged against it. Aaron, in his “Diseases of the Digestive Organs,” speaks favorably of its use in atonic constipation.

The much debated question whether yeast may serve as a food can be answered in the affirmative in view of such work as that of the Germans on “Nährhefe”--yeast food (Schottelius, Deutsch. med. Wchnschr., July 8, 1915, p. 817) and Boruttau (ibid., July 29, 1915, p. 924) and of Hawk and his associates. There is no reason to assume that weight gained under its use would be more readily lost than weight gained from any other food. However, in view of its laxative action, the average individual can ingest only from 1 to 2 gm. of nitrogen a day in this form. This obviously greatly limits its value as a food. Owing to its high nuclein content, it is contraindicated in gout.

As a source of water soluble growth promoting as well as antineuritic vitamin, yeast has become thoroughly established as the result of the recent works of numerous investigators. However, as such common foods as milk, rice, wheat, oats and beans also contain such vitamin, there is little likelihood of its proving of therapeutic value on that account. In other words, yeast and other vitamin containing foods have specific growth promoting qualities only when the stunting is due to lack of vitamin. A minute amount of this substance suffices to produce maximal results. More is of no use. Hess (Proc. Soc. Exper. Biol. & Med. =13=:145, 1916) found yeast of no value in infantile scurvy.

The most important question in connection with yeast therapy is to what extent it is endowed with “antibiotic” power, that is, to what degree it is capable of inhibiting the growth of other organisms. That this frequently occurs in cultures in vitro is shown by the fact that yeast contamination may practically eradicate the growth of certain other organisms. That, on the other hand, this is not true for all forms of bacterial life is shown by the fact that there is definite symbiosis between yeast and lactic acid bacilli (Northrup: Soc. Tech. Bull. 15, Mich. Agr. Expa. Sta., 1912).

That its “antiseptic power is, on the whole insignificant” has been shown by Palier (Diet. & Hyg. Gaz., March, 1906), who found commercial yeasts commonly contaminated with numerous bacteria, the most frequent being Bacillus coli-communis or one of its congeners. An antagonistic action by yeast is claimed against Staphylococcus pyogenes, and on the strength of this, Buchholtz (Ueber Acne und eine neue erfolgreiche Behandlung derselben, Berl. klin. Wchnschr., Feb. 2, 1914, p. 215) employed it locally in the treatment of acne and obtained a positive but temporary effect. He believes that the effect is improved by the combination of yeast with an equal quantity of boric acid. He employed this as a dusting powder applied freely to the skin once daily, after the application of a thin layer of a boric acid salve (boric acid powder from 40 to 50, glycerin and water, of each 100) to make it stick better. In cases in which the nose was markedly involved, he also used this as a snuff. Yeast poultices have been employed with asserted great benefit in the treatment of wound infection of all kinds (Kempf, E. J.: Ind. M. J., September, 1904, p. 97).

The use in leukorrhea was recommended by Hippocrates Abraham (Mon. Geb. Sym., 1910) and many others report favorable results from yeast in the treatment of gonorrheal vaginitis. In various gastro-intestinal infections, yeast has been lauded by many, among others, Thiercelin and Chevrey. It has been given by mouth, but most especially in high rectal enemas.

Still more from a theoretical standpoint is the reassertion of the curative value of the oral administration of yeast in various cutaneous disorders. Thus Hawk and his collaborators report cure or improvement in all of seventeen cases of acne vulgaris and eight cases of acne rosacea. They also report seventeen cases of furunculosis, in all but one of which there was cure or improvement from yeast treatment. They are unable to decide whether the result is due to the laxative action, the production of leukocytosis, or to other influences.

Yeast is probably best taken incorporated in food. Hawk and his associates found that yeast may well be incorporated in wheat biscuits, and that in this way a yeast-wheat combination of most agreeable flavor was produced: that, in fact, the biscuits with the yeast tasted better than those without it. They found by tests that in bread making as much as 20 per cent. of the flour might be replaced by dry yeast, and that thereby a loaf would be produced that was excellent in every way and possessed of an attractive flavor. The dry yeast was prepared by desiccating compressed yeast at 105 C. in a current of air, and then milling it to produce a flour of the approximate fineness of ordinary wheat flour. They also found that yeast may be added to meat preparations, such as Hamburger steak, to the extent of 2.5 per cent., yielding a preparation of very satisfactory taste.--(Query in The Journal A. M. A., Aug. 23, 1919.)

BRIEFER PARAGRAPHS

Laxol and Lysol--The Short and Catchy Proprietary Name

A laborer went to a Brooklyn physician for treatment and was given three prescriptions. One of the prescriptions, according to the Food and Drug Bulletin of the Department of Health, City of New York, called for “Laxol,” the word being written on a piece of blank paper without directions. The drug clerk misread the prescription and dispensed an “original” bottle of “Lysol” which bore the usual poison label with skull and cross bones. The man drank the entire 3 ounces of Lysol and died half an hour later. The case is now in the hands of the District Attorney, the drug clerk being held under $10,000 bail. “Laxol,” as our readers know, is castor oil sweetened with saccharin and flavored with peppermint. There is no excuse for prescribing the product. The official Aromatic Castor Oil (Ol. Ricin. Arom.) of the National Formulary would answer every purpose served by the proprietary preparation.--(Editorial from The Journal A. M. A., May 29, 1920.)

Look Up Its Rating

Modern business has become so complex that it is no longer possible for those engaged in trade to know, offhand, the financial responsibility of their prospective customers. The commercial agency is a natural development; it aims to supply the technical (financial) information which the conservative business man needs but is otherwise unable to get. When John Doe & Co. contemplates entering into business arrangements with Henry Roe & Son to a degree that involves financial obligations, it looks up Roe in the rating book of Dun or Bradstreet and probably calls for a special commercial report on the concern. These facts are so elemental and obvious as to be trite. The complexity of modern medicine, especially in the pharmacologic field, has made it a physical impossibility for physicians to know the scientific status of scores of pharmaceutical products put out under proprietary or brand names. It was recognition of this fact that brought about the creation by the American Medical Association of the Council on Pharmacy and Chemistry. This body of experts, serving without remuneration and reporting without fear or favor on the newcomers to the pharmaceutical world, places at the disposal of physicians unbiased information, free alike from prejudice or prepossession. As the commercial agency reports on the commercial probity of individuals and firms, so the Council on Pharmacy and Chemistry reports on what might be called the scientific probity of proprietary and unofficial pharmaceutical products. The commercial agency issues, at no small expense to its customers, rating books; the council on Pharmacy and Chemistry issues, at a nominal price, “New and Nonofficial Remedies.” The commercial agency, for a substantial fee, will furnish reports on business concerns; the Council on Pharmacy and Chemistry will, without any expense to the profession, furnish reports on proprietary products used for the relief or cure of human ailments. The careful business man avails himself of the services of the commercial agency; there are financial interests at stake. The conscientious physician will avail himself of the services of the Council; there are, it may well be, lives at stake.--(Editorial from The Journal A. M. A., April 24, 1920.)

The Medical Profession and Commercial Interests

Last week The Journal published a letter received by a physician in Milwaukee from a firm of lawyers representing the Farbwerke-Hoechst Company. In this communication the physician was threatened with suit if he published further unfavorable reports regarding that firm’s preparation. Quoting from the attorney’s letter:

“Mr. Metz directs us to inform you that the publication of this article and the statements therein were seriously damaging to the Farbwerke-Hoechst Company, and directs us to say further to you that he and the corporation will hold you personally responsible for any repetition, oral or written, of the same or of similar statements to the same effect.”

We were under the impression that the time had passed when a proprietary medicine manufacturer would presume to threaten a physician for making an honest report of his results with any therapeutic agent. Such condition did exist once, before the Council on Pharmacy and Chemistry undertook its work. Now comes Mr. Metz to revive this relic of an historic but infamous period in the history of American proprietary medicine manufacturing. Even Mr. Vanderbilt regretted that he ever said “The public be d----.” One of the elementary principles in the practice of medicine is that the individual physician shall let others know his results, whether good or bad, in any line of treatment. It is by such interchange of knowledge and experience that progress in medicine is possible. Yet Mr. Metz would interfere with the diffusion of such knowledge and experience when it applies to proprietary medicines. His legal threat against Dr. Sargent is “terrorism” applied to the medical profession.--(Editorial from The Journal A. M. A., June 8, 1918.)

Rabbit-Foot Therapy

Few but ignorant darkies have any great faith in the therapeutic efficacy of the left hind foot of a rabbit caught in the churchyard in the dark of the moon. In the light of modern therapeutics one is tempted to believe, however, that had some one person or firm an exclusive proprietary right to this particular brand of rabbits’ feet, there would be many intelligent people--and not all of them laymen--ready to swear by rabbits’ foot therapy. In medical journals (whose advertising pages set forth the virtues of the pedal extremities of Lepus sylvaticus) many solemnly scientific articles would probably appear relating the success that the writers had had with this form of therapy in the treatment of some distressing stubborn conditions that had failed to respond to all previous efforts. Is it ubiquity that has saved the homely cotton-tail from being a therapeutic hero?--(Editorial from The Journal A. M. A., Sept. 29, 1917.)

Secret Remedies and the Principles of Ethics

Many hundreds, possibly thousands, of inquiries are received each year by The Journal from physicians asking for information on, or an opinion of certain proprietary remedies. In many instances the preparations in question are essentially secret in composition, although advertised to the profession under a fair-seeming exterior of apparent frankness. There are on the market today--and used by members of the American Medical Association--dozens, yes scores, of widely advertised proprietaries that are, to all intents and purposes, secret. The physicians who prescribe them do not know and cannot know what they are giving their patients. On this point Section 6 of Chapter II of the Principles of Medical Ethics of the American Medical Association says:

“... it is ... unethical to prescribe or dispense secret medicines or other secret remedial agents, or manufacture or promote their use in any way.”

The inherent and basic reasonableness of the various requirements of the Principles of Medical Ethics needs no exposition or defense. A large number of proprietary remedies which at present degrade medicine would be wiped out of existence or, at any rate, go over to the “patent medicine” class, where they belong, if physicians would live up to