_THE URIC ACID THEORY_
Uric acid is a substance about which more has been written and less
understood than many others in medicine and that is saying a great deal.
As a basis of the suboxidation theory of Bence Jones' day, as the cause
of gout with Garrod, as a step in our knowledge of metabolism and as a
popular fad, uric acid in its time has played many parts.
=Uric Acid in Hay Fever.= In 1893, Dr. Seth Bishop announced before the
American Medical Association that "excess of uric acid in the blood
causes hay fever and nervous catarrh;" and advised elimination and
control of the uric acid as the principle of treatment. The article may
be found in the _Journal of the American Medical Association_, 1893, and
abstracted with an interesting discussion on the treatment of hay fever,
in the _Philadelphia Medical News_, 1894. This position, of course, is
also that of Haig (_Uric Acid_, seventh edition, page 386) and his
followers.
Now, in 1893, the theory of uric acid poisoning flourished like a green
bay tree and all sorts of queer and misunderstood pathological processes
came and roosted in its branches. Patients came to our offices, not
complaining of headache or lumbago or cough, but asking for "something
for that uric acid." As patients will, they had already made the
diagnosis from the newspapers and wished our advice only for the remedy.
As the basis of hay fever, this theory of uric acid poisoning has
apparently made as little impression as de Mussy's theory of gout on the
nose and throat specialists of this country and Great Britain; for I
find no mention of it in their books, except the brief reference of
Professor Grayson quoted in the preceding chapter. In the _Virginia
Medical Monthly_, however, I find an interesting paper by Dr. John Dunn,
Professor of Diseases of the Nose and Throat in the University Medical
College of Richmond, Virginia. Following the suggestions of Dr. Bishop,
Dr. Dunn treated his patients with diet and alkalies according to the
uric acid theory and reports excellent results.
It may be pointed out that the successful results of the treatment by no
means prove that the condition was due to uric acid; for the diet may be
doing many other things besides controlling the movements of the uric
acid and it is probable that the effect of an alkali in the blood is not
a simple neutralizing of an acid but that it sets in motion a train of
chemical changes of great complexity. None the less, Dr. Dunn's paper is
well worth reading by every physician for its practical suggestions in
the treatment of hay fever.
The cardinal error made by the advocates of the _uric acid poisoning_ is
that they _name the poison_. If the theory were stated that an unknown
poison or poisons circulate in the blood and cause many symptoms of
disease, as headache, gouty pains, bilious vomiting, and so on, we would
all agree that this is so. Call it the X-poison, if you will, as
Roentgen did with his unknown ray. But when you name the poison _uric
acid_, you challenge the chemist and the physiologist to test your
doctrine by chemical analysis, and when the uric acid doctrine is
tested in this way it is found sadly wanting.
It is true that uric acid in the form of urates is found in the blood in
varying quantities, but there is no proof that it does any harm there.
In fact, there is good evidence that it does not. In the disease,
leukæmia, there is an enormous amount of uric acid in the blood, far
more than was ever demonstrated in gout or the so-called uric-acid
disorders; yet, in leukæmia, there are no symptoms of gout or any other
symptoms that have been attributed to uric acid poisoning.
A second error of the uric acid advocates, flowing from their first
error of naming the poison, is to pour their acids and alkalies into the
blood with the childlike faith that, like good children, the acids and
alkalies will go in there and do just what they were told to do,
neutralize the uric acid, and get out. They assume that the chemistry of
the acids and alkalies is as simple inside of the body as it is outside
of it and that the blood is simply a passive mixture of chemicals.
A third error of the uricacidites is to talk so glibly of the chemistry
of the blood and the influence of this or that food or medicine on its
chemical changes. The chemistry of blood! A subject of which the ablest
physiological chemists have but touched the fringe,--is that a knot to
be unloosed familiar as his garter by an amateur with a watch-glass and
a thread?
In his _Lehrbuch der Organischen Chemie für Mediciner_, Leipzig, 1906,
Bunge observes slyly that he had "sometimes had occasion to remark in
private that the less a physiologist knew about chemistry, the more
irresistible was his impulse to undertake the most difficult subjects."
When the uric acid amateur chemist comes to study the real poisons of
the blood, he will be confronted with a problem even more intricate than
uric acid, though that one is intricate enough and still unsolved. For
there are "poisons in the blood," though it is improbable that uric acid
is one of them. These poisons are the blood-proteins, so many that the
physiologist has never counted them, so minute in quantity that no
chemist has ever isolated them, so complex in structure that the ablest
chemists of the world stand appalled before a molecule that contains
sixty atoms of carbon,[1] so powerful that an undetermined fraction
smaller than one-third of a grain will kill ten thousand guinea pigs or
one hundred thousand mice, and so perfectly under control that they
circulate harmlessly in the normal blood. The marvel is that any animal
remains alive; and no animal would remain alive were it not for a system
of protection by which these poisons are rendered harmless, usually by a
slight rearrangement of the atoms in their molecule which is one of the
wonders of organic chemistry.
We are far from knowing just what happens when we pour acids and
alkalies and foods into this witches' cauldron of blood. Rather than
impudently announcing the changes that are about to take place in the
blood when we administer a certain food or medicine, we should stand in
reverent awe before one of the most intricate and marvelous puzzles
with which nature ever challenged the chemist and the physiologist.
Shall we therefore stop using acids and alkalies as medicines because we
do not know each step in their mode of action? By no means. We do not
know each step in the mode of action of any medicine or of our foods,
either, for that matter; but we do not for that reason stop eating. We
should still use the acids and alkalies for their effect on the patient
as far as we can see it just as we shall still go on eating food because
it nourishes us; but we shall be wise to stop talking so glibly about
what we cannot see and do not yet know, the effect of those acids and
alkalies on the chemistry of the blood.
=Uricacidæmia and Gout.= Now, why do I speak with respect of de Mussy's
theory of gout as a cause of hay fever and so disrespectfully of the
uric acid doctrine? Are not gout and uric acid poisoning the same thing?
No. They are not; though the two ideas are usually confused by medical
men since Garrod's time and his demonstration of the increase and
decrease of uric acid in the blood of gouty patients. Gout is something
more than a simple accumulation of uric acid in the blood because of its
imperfect elimination by the kidneys. What that something is, we do not
know; but gout is, at least, a clinical entity, a definite group of
symptoms known since Hippocrates' time. Take away the uric acid theory
and you still have the disease, gout, that any of us can recognize, as
the Greeks and Romans recognized it when the word uric acid was unknown.
It is on these symptoms of gout, the clinical picture of disease, not on
any hypothetical uric acid, that de Mussy based his theory and thus far
he is on solid ground. On the other hand, _uric acid poisoning_ is
largely a figment of the imagination. Take away the uric acid, which has
never been satisfactorily proved to be there, and there is nothing left.
In not one one-hundredth part of the cases of so-called uric acid
poisoning is it proved that uric acid has anything to do with the case.
=The Deposits of Uric Acid in Gout.= The deposit of uric acid in the form
of urates in the gouty joint has always been a strong argument for the
theory that gout, at least, is due to an excess of uric acid (urates)
in the blood. At one time, in a humble way, I was a pathologist, and
this theory of a blood overloaded with uric acid as the only thinkable
cause of its deposition in the joints never impressed me as
pathologically sound. I often compared these deposits of urates in the
joints with the deposits of lime salts so often found at autopsies in
caseous glands or small necrotic areas. The superficial observer says:
"See what an excess of lime salts there must have been in the blood." He
is thinking of laboratory glassware and the ground around a mineral
spring that becomes encrusted with salts as the solutions evaporate.
But, in animal pathology, this is a false conclusion. The animal body is
not a test-tube and, in it, the laws of physics are modified by those of
physiology. Lime salts are deposited in the caseous gland or tubercle
not because they are in excess in the blood but because lime salts are
attracted to all caseous material from normal blood. Whether or not this
calcification is an intentional provision of nature to protect the body,
to petrify the necrotic material and make it harmless, is not the
question here, though the calcification has this effect. The point here
is that calcification of caseous glands or necrotic areas does not
presuppose an excess of lime salts in the blood. The first step is not
an excess of lime in the blood but a necrosis, after which the lime
salts will be deposited from normal blood.
So, it has seemed to me that the deposit of urates in and around a joint
is no proof of their excess in the blood. Just as in calcification, so
in gout, the first step may be a minute area of necrosis or other local
degeneration that attracts the urates that are always present in normal
blood; or the secret of the gouty inflammation, like that of urticaria
and hay fever, may at last be found in Anaphylaxis, as described in the
next chapter.
FOOTNOTES:
[1] Wenn mehr als 60 Atome Kohlenstoff im Molekül sind, dann ueberlasse
ich das Object zu andern. Bunge, page 262, quoting "einen hervorragenden
Forscher auf dem Gebiete der organischen Chemie." See Bunge for
authority of these statements.