salvarsan
the discovery of salvarsan ("606").—salvarsan, or "606," is a chemical compound used in the modern treatment of syphilis. it was announced to the world by paul ehrlich, its brilliant discoverer, in december, 1910. ehrlich and his japanese co-worker, hata, had some years before been impressed with the remarkable effect certain dyes had on the parasites infesting certain animals and which resemble the germs that cause the african sleeping sickness in man. when one of these dyes was dissolved and injected into the blood of the sick animal, the dye promptly picked out and killed all the parasites, but did not kill the animal. dyes are very complex chemical substances and certain of them seem to have an affinity for germs. it occurred to ehrlich that if a substance could be devised which was poisonous for the germ and not for the patient it might be possible to prepare a specific for a given disease, acting as quinin does in malaria. by combining a poison with a dye it might be made to pick out the germs and leave the body unharmed.
paul ehrlich [1854-1915] paul ehrlich [1854-1915]
(from "year book of skin and venereal diseases," 1916, vol. ix. "practical medicine series," year book publishers, chicago.)
the poison which had already been shown to be especially effective in killing germs like those of[pg 71] syphilis was arsenic. the problem was to get arsenic into such a combination with other chemical substances that it would lose its poisonous quality for man, but still be poisonous for the spirochete of syphilis. ehrlich and hata began to make chemical compounds of arsenic in the laboratory with chemical substances like the dyes. as the compounds grew more complex they were tested on animals and some of them found to have the qualities for which their inventors were searching. some of them are even used at the present time in the treatment of certain diseases. the six hundred and sixth compound in this series, when tested on syphilitic animals, was found to be extraordinarily efficient in killing the germ of syphilis, even when used in quantities so small as not to injure the animal. among other things, there could be no better example of the importance of animal experiment in medicine. if the cause of syphilis had not been known, and the disease not given to animals, the discovery of salvarsan might never have been made. after extensive experiments on syphilitic rabbits, which showed that the drug could be given safely in amounts large enough to cure the animal at a single dose, it was tried on man, two physicians, drs. hoppe and wittneben, volunteering for the test. when it was found that the drug did them no harm, it was used on syphilitic patients for the first time. as soon as its remarkable effect on the disease in them was fully established, ehrlich announced the discovery before the medical society of magdeburg, and the results were published in one of the most[pg 72] important of the german medical journals. ehrlich then sent out from his own laboratory several thousands of doses of the new drug to all the principal clinics and large hospitals of the world for an extended trial. it was not until the results of this trial became apparent that he permitted its manufacture on a commercial scale. there could scarcely be a more ideal way of introducing a new form of treatment than the one adopted by ehrlich, or one better surrounded by all the safeguards that conservatism could suggest.
the mistaken conception of "single dose cure."—in the light of his experience with salvarsan in animals, ehrlich hoped to accomplish the cure of syphilis in man by a single dose of the new drug, as he had been able to cure it in rabbits. all the earlier use of salvarsan in the treatment of syphilis was carried out with this idea in view, and the remarkable way in which the symptoms vanished before the large doses used encouraged the belief that ehrlich's ideal for it had been fulfilled. but it was not long before it was found that syphilis had a stronger hold on the human body than on animals, and that patients relapsed after a single dose, either as shown by the blood test or by the reappearance, after varying intervals, of the eruption or other symptoms of the disease. unfortunately, the news of the discovery of salvarsan, and with it ehrlich's original idea that it would cure syphilis by a single dose, had gotten into the newspapers. numbers of syphilitics treated with it have been deceived by this notion into believing themselves cured. in those whose symptoms[pg 73] came back in severe form, the trouble was, of course, found out. but there are at the present time, undoubtedly, many persons who received a single dose of salvarsan for a syphilis contracted at this time, and who today, having never seen any further outward signs of the disease, believe themselves cured, when in reality they are not. in the next twenty years the introduction of salvarsan will probably result in a wave of serious late syphilis, the result of cases insufficiently treated in the early days of its use. it was not long before it was found that not one but several doses of salvarsan were necessary in the treatment of syphilis, and soon many physicians of wide experience began to call in mercury again for help when salvarsan proved insufficient for cure. at the present time the use of both mercury and salvarsan in the treatment of the disease is the most widely accepted practice, and seems to offer the greatest assurance of cure.
the value of salvarsan.—salvarsan has done for the treatment of syphilis certain things of the most far-reaching importance from the standpoint of the interests of society at large. it has first of all made possible the control of the contagious lesions of the disease. secondly, as was said before, it has made possible the cure of the infection in the primary stage, before it has spread from the starting-point in the chancre to the rest of the body. to understand how it accomplishes these results it is important to understand its mode of action.
the action of salvarsan.—it will be recalled that ehrlich planned salvarsan to kill the germs of syphilis,[pg 74] just as quinin kills the germs of malaria. it was intended that when the drug entered the blood it should be carried to every part of the body, and fastening itself on the spirochetes, kill them without hurting the body. this is seemingly exactly what the drug does, and it does it so well that within twenty-four hours after a dose of it is given into the blood there is not a living germ of syphilis, apparently, in any sore on the body. if the same thing happened in all the out-of-the-way corners of the body, the cure would be complete. the natural result of removing the cause of the disease in this fashion is that the sores produced by it heal up. they heal with a speed and completeness that is an even greater marvel than the action of mercury. the more superficial the eruption, the quicker it vanishes, so that in the course of a few days all evidence of the disease may disappear. this is especially true of the grayish patches in the mouth and about the genitals, which have already been described as the most dangerously contagious lesions of syphilis. it is evident, therefore, that to give salvarsan in a case of contagious syphilis is to do away with the risk of spreading the disease in the quickest and most effective fashion. it is as if a person with scarlet fever could be dipped in a disinfecting bath and then turned loose in the community without the slightest danger of his infecting others. how much scarlet fever would there be if every case of the disease could be treated in this way? there would be as little of it as there now is of smallpox, compared to the wholesale plagues of that disease which used to kill[pg 75] off the population of whole towns and counties in the old days. if we could head off the crops of contagious sores in every syphilitic by the use of "606," syphilis in the same way would take a long step toward its disappearance. it is not a question, in this connection, of curing the disease with salvarsan, but of preventing its spread, and in doing that, salvarsan is one of the things we have been looking for for centuries.
the treatment of syphilis with salvarsan.—salvarsan, the original "606," was improved on by ehrlich in certain ways, which make it easier for the ordinary physician to use it. the improved salvarsan is called neosalvarsan ("914") and has no decided advantages over the older preparation except on the score of convenience. both salvarsan and neosalvarsan are yellow powders, which must be manufactured under the most exacting precautions, to prevent their being intensely poisonous, and must be sealed up in glass tubes to prevent their spoiling in the air. they were formerly administered by dissolving them or by mixing with oil and then injecting them into the muscles, much as mercury is given by injection. at the present time, however, the majority of experts prefer to dissolve the drug in water or salt solution and to inject it into the blood directly, through one of the arm veins. there is very little discomfort in the method, as a rule—no more than there is to the taking of blood for a blood test. at the present time the quantity of the drug injected is relatively small for the first injection, growing larger with each following injection. the[pg 76] intervals between injections vary a good deal, but a week is an average. the number of injections that should be given depends largely on the purpose in view. if the salvarsan is relied on to produce a cure, the number may be large—as high as twenty or more. if it is used only to clear up a contagious sore, a single injection may be enough for the time being. but when only a few injections are used, mercury becomes the main reliance, and a patient who cannot have all the salvarsan he needs should not expect two or three doses of it to produce a cure. the publicity which has been given to this form of treatment has led many patients to take matters into their own hands and to go to a physician and ask him to give them a dose of salvarsan, much as they might order a highball on a cold day. the physician who is put in a position like this is at a disadvantage in caring for his patient, and the patient in the end pays for his mistaken idea that he knows what is good for himself. the only judge of the necessity of giving salvarsan, and the amount and the frequency with which to give it, is the expert physician, and no patient who is wise will try to take the thing into his own hands. there are even good reasons for believing that the patient who is insufficiently treated with salvarsan is at times worse off than the patient who, unable to afford the drug at all, has had to depend for his cure entirely on mercury.
it is one of the tragedies of the modern private practice of medicine that the physician has so often to consult the patient's purse in giving or withholding salvarsan, and for that reason, except in the well-to-do,[pg 77] it is seldom used to the best advantage. such a drug, so powerful an agent in the conservation of the public health, should be available to all who need it in as large amounts as necessary, without a moment's hesitation as to whether the patient can afford it or not. it is not too much to urge that private patent rights should not be allowed to control the price and distribution of such a commodity to the public. upon the payment of suitable royalties to the inventor the manufacture of such a drug should be thrown open to properly supervised competition, as in the case of diphtheria antitoxin, or be taken over by the government and distributed at cost, at least to hospitals. to bring about such a revision of our patent law every thinking man and woman may well devote a share of personal energy and influence.
the manner of giving salvarsan is as important for the patient as the correct performance of an operation, and the safeguards which surround it are essentially the same. the drug is an extremely powerful one, more powerful than any other known, and in the usual doses it carries with it into the body for the destruction of the germs of syphilis many times the amount of arsenic needed to kill a human being. if something should go astray, the patient might lose his life as promptly as if the surgeon or the anesthetist should make a slip during an operation. to make the giving of salvarsan safe, the judgment, experience, and training of the specialist are not too much to ask.
the dangers of salvarsan are easily exaggerated,[pg 78] and some people have a foolish fear of it. the wonderful thing about the drug is that, with all the possibility for harm that one might expect in it, it so seldom makes any trouble. it is, of course, first carefully tested on animals when it is manufactured, so that no poisonous product is placed on the market. it is as safe to take salvarsan at the hands of an expert as it is to take ether for an operation or to take antitoxin for diphtheria, and that is saying a good deal. most of the stories of accidents that go the rounds among laymen date back to the days when first doses were too large and made the patients rather sick for a time. present methods and cautions about administering the drug are such that, except for the improvement in their condition, patients seldom know they have received it. the first dose may light the eruption up a little, but this is only because the drug stirs the germs up before it kills them, and improvement begins promptly within a few hours or a day or two.
the first characteristic of salvarsan which we should bear in mind especially, in our interest in the social aspects of syphilis, is then the rapidity rather than the thoroughness of its action. it is a social asset to us because it protects us from the infected person, and it is an asset to the patient because it will set him on his feet, able to work and go about his business, in a fraction of the time that mercury can do it.
the efficiency of salvarsan in the cure of syphilis in the early stages is due, first, to the large amount of it that can be introduced into the body without[pg 79] killing the patient, and second, to the promptness with which it gets to the source of trouble. in the old days, while we were laboriously getting enough mercury into the patient to help him to stop the invading infection, the germs marched on into his blood and through his body. with salvarsan, the first dose, given into the blood, reaches the germs forthwith and destroys them. there is enough of it and to spare. twenty-four hours later scarcely a living germ remains. the few stragglers who escape the fate of the main army are picked up by subsequent doses of salvarsan and mercury, and a cure is assured. there is all the difference between stopping a charge with a machine gun and stopping it with a single-shot rifle, in the relative effectiveness of salvarsan and mercury at the beginning of a syphilitic infection.
in syphilis affecting the central nervous system, salvarsan, modified in various ways, may be injected into the spinal canal in an effort to reach the trouble more directly. the method, which is known as intradural therapy, has had considerable vogue, but a growing experience with it seems to indicate that it has less value than was supposed, and is a last resort more often than anything else. it involves some risk, and is no substitute for efficient treatment by the more familiar methods. if necessary, a patient can have the benefit of both.
the luetin test was devised by noguchi for the presence of syphilis, and is performed by injecting into the skin an emulsion of dead germs. a pustule forms if the test is positive. it is of practical value only in late syphilis, and a negative test is no proof of the absence of the disease. positive tests are sometimes obtained when syphilis is not present. for these reasons the test is not as valuable as was at first thought.
