The September issue of the Archives of Dermatology and Syphilology presents a number of significant features regarding the use of arsphenamin and related compounds that are at present being widely employed in the treatment of syphilis. To one who studies these statements of laboratory and clinical investigators in the special field involved there must come the conviction that many therapeutic perplexities still remain at the end of nearly a decade of trial for the types of compounds which Ehrlich introduced. It is well for the practitioner to realize this, especially when expert workers still make an appeal for conservative interpretations. Stokes forcefully summarized the situation when he stated at the New Orleans session of the American Medical Association:
Too short a time has elapsed since the discovery of these drugs, and too little is as yet known about the ultimate problems of the pathology, immunology and parasitology of syphilis, to justify the announcing of new infallibilities. The necropsy pathologist of the next fifty years may well, like Warthin, upset our most plausible generalizations of today. Seasoned tradition and conservatism are still the wisest guides in our interpretation of clinical cure. Arsphenamin has made it apparently possible and even probable, but only to the inexperienced has cure been made absolute and inevitable.
It is recognized that the exact composition of arsphenamin in its available form is not fully determined. As has been emphasized again, the quantitative determination of arsenic alone in arsphenamin is insufficient to estimate its purity; in fact, the interstate sale of arsphenamin is controlled by toxicity tests on guinea-pigs made by the Hygienic Laboratory of the United States Public Health Service. Consequently, practical medicine must be on its guard to employ a product which is carefully controlled by such toxicity tests as well as by other criteria. It will not do to charge untoward results offhand solely to idiosyncrasy of the patient, faulty administration or other errors in technic. The drug itself still has inherent dangers. It should be borne in mind also that neo-arsphenamin behaves differently in the animal organism from arsphenamin, and should not be regarded simply as arsphenamin in a convenient form for administration.
It is gratifying to learn from a government expert that after the long struggle to produce satisfactory products, arsphenamin preparations made in the United States are generally less toxic than those of foreign manufacture. Neo-arsphenamin preparations made in the United States compare favorably, and in certain instances are decidedly less toxic than most of the foreign products. Timely presentations of the faults and dangers as well as the undisputed advantages of current therapy in the management of syphilis should be welcomed.—(Editorial from The Journal A. M. A., Oct. 9, 1920.)
Pharmacology of Arsenicals
The Public Health Service some time ago[262] warned against the use in syphilis of new arsenicals which are not related to arsphenamin; it was stated that a number of such were being sold with unwarranted claims as to their value. At least three such arsenicals have in recent years been the subject of some exploitation for use in this disease: sodium cacodylate, the sodium salt of methyl arsenic acid (“Arrhenal”) and the sodium salt of ethyl arsenic acid (“Mon-Arsone”).[263] As regards the first two, Castelli showed several years ago that neither has any action on experimental trypanosomiasis and spirochete infections; careful clinical observations in this country have confirmed the inefficacy of sodium cacodylate in human syphilis.[264] Voegtlin and Smith[265] of the Hygienic Laboratory have now shown in animal experiments that ethyl arsenic acid (“Mon-Arsone”) is devoid of any practical trypanocidal action. Thus the “therapeutic ratio” (the ratio of the minimal effective dose to the lethal dose) was about 1, that is, it was effective therapeutically only in approximately fatal doses, the therapeutic ratio for arsphenamin in similar conditions was 17, and that of neo-arsphenamin, 28. In fact, the conditions with ethyl arsenic acid were no more favorable than were those with arsenous acid (the active constituent of solution of potassium arsenite), although it was far less poisonous. The validity of such experiments in determining the probable value of drugs in human syphilis cannot be questioned:[266] it was by such experiments that Ehrlich and his co-workers found two or three of six hundred and six arsenic preparations studied to be of value, and of the next three hundred or more studied only one (neo-arsphenamin) worthy of trial in human medicine. The time has passed when a high arsenic content of a compound and a low toxicity, and a number of cases of apparent clinical improvement, can be assumed to indicate that a drug has any real value in the treatment of syphilis. Many organic compounds of arsenic as well as other drugs may cause temporary or apparent improvement in syphilis, but to date only those related to arsphenamin have proved of real value and comparatively safe. Others which had some real value proved to have dangerous side effects; readers will recall the history of arsanilic acid (“Atoxyl” or “Soamin”) and its acetyl derivative (“Arsacetin”).—(Editorial from The Journal A. M. A., Feb. 26, 1921.)
Salvarsan: Abrogate the Patent
The Journal has already commented on the difficulty in securing salvarsan, on the moral and ethical question as to whether or not it is justifiable for one person to control the output of a drug necessary to public health. This week we publish an account of the action of the St. Louis and Chicago medical societies, which are calling on the medical profession to appeal to their senators and congressmen to abrogate this patent. The Journal believes that this patent should be abrogated, not alone because the patentees have not supplied the demand, not alone because they have dictated to the medical profession who should have the drug and how much a physician might have, not alone because of the war with Germany, not alone because of the special needs of the government at this time for the control of venereal diseases, not alone because, as some claim, the patent at Washington does not correctly describe the product, but also because the people who are supplying this product are charging prices that are exorbitant compared to the price at which others in this country can supply it. The fact is that the salvarsan one can obtain today costs $4.50 per ampule of 0.6 gram, whereas the same dose of arsenobenzol—a preparation identical with, if not better than, salvarsan—costs $2.00 at retail, and as Dr. Schamberg says: “If we are permitted to continue marketing the same drug after the war, we can sell it at $1.00 or less per tube.” To abrogate this patent would be doing an injury to no one. Certainly the patentees of salvarsan have already reaped their harvest—and a pretty rich one. The supply of salvarsan at a reasonable price in proportion to its actual cost of production is in the interest of the health of the entire population of the country, whereas to let matters rest as they are, is to the benefit of one man. While we are emphasizing here the cost, there is after all a greater question, and that is the supply necessary to help control the ravages of one of the most serious diseases which afflict humanity today. It is the duty of Congress to abrogate the patent on this preparation and, incidentally, on all medicinal preparations of importance.—(Editorial from The Journal A. M. A., April 21, 1917.)