The Treatment of Syphilis (Continued)
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.
[Illustration: 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 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 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 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, 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 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 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, 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, 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 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.