We have already seen, in the preceding chapter,
that the microbes and the cells of various organisms
are capable of secreting definite products of a
toxic nature to which the names "ptomaines" and
"leucomaines" have been given. Researches,
which were begun scarcely twenty years ago,
have shown that, besides these crystallizable
and definite products, we meet with basic non-crystallizable
substances of unknown composition,
possessing special toxic properties, sometimes even
of extreme violence. These substances have been
named "toxins."
At first this generic name was extended toward
indefinite basic organic products that could be
isolated from tissues and tumors both normal and
abnormal; later on, however, the name was applied
to toxic substances, equally indefinite, isolated
from the culture media of microbes and the active
constituent of various venoms.
It is only since 1885, when Charrin called attention
to them, that investigations began to be
made regarding them. In 1888 Roux and Yersin,21
in their beautiful researches on diphtheria, pointed
out the diastatic nature of the properties of the
active albuminoid matter existing in the cultures
of the specific bacilli of this disease. From
that period, these products began to take a more
and more prominent place, from year to year, in
the study of pathological affections, and, by developing
the knowledge of immunity, they have opened
a new path to the investigations of therapeutic
technic.
It is due to the knowledge of these principles that
we have learned that the infectious microbes, far
from acting as they were believed to do only a few
years ago, and which Pasteur strongly maintained
to be by vital parasitism—such as would be the
case with the carbonizing bacteria which, according
to Pasteur, act by diverting the oxygen, or causing
capillary embolisms—owe their pathogenic action
to the toxic substances which are the products
of their secretion, and which spread throughout
the organism, even though the microbe frequently
is localized in a very circumscribed spot, as in
tetanus and in diphtheria.
The idea of intoxication by these products has
now replaced the idea of the direct action of the
microbe on the elements or the liquids of the organism.
The occurrence that takes place in diphtheria
and tetanus is one of the best examples to cite in
support of this view.
Here, in fact, the pathogenic microbe is found
only in a very limited area in the organism attacked—the
false membrane, in the case of diphtheria, or
frequently only a slight wound in the case of
tetanus, and the microbe becomes localized there
only. Now, in both cases, there are general
phenomena of toxic effects. There must hence be
a diffusion of toxic substances which, distributed
by the blood, affect the different systems and
exert a toxic action on the entire organism.
It must be observed that the toxins act as toxic
agents only when in a condition to be introduced
into the circulation subcutaneously. The
cause of this innocuousness of the toxins when
given per os has frequently been studied. It
appears to be quite probable that the cause of
the attenuation of the morbid properties is due
to the intervention of the digestive microbes.
Such is the opinion of Levaditi and Charrin22; it
is also the conclusion that is to be drawn from the
experiments of Mme. Metchnikoff and of Calmette23
on the modifications undergone by a
vegetable toxalbumin, abrin, and by serpent
venoms, when these toxalbumins are inoculated
with the bacillus subtilis chromogenus. Moreover,
Charrin and Lefèvre,24 on the one hand, and
Nencki, Sieber and Somanowsky,25 and Carrière,26
on the other hand, have discovered that the digestive
ferments, particularly trypsin, destroy, even
though but little, the toxins secreted by the Loeffler
and Nicolaier bacilli. This is practically contrary
to the opinion of Behring and of Rauson,27 according
to which the innocuousness of the microbial poisons
when administered per os is due exclusively to the
lack of absorption.
Nature of the Toxins.—The molecules of the toxins
are very nearly like those of the diastases. Like
these, the toxins appear to have a very complex,
and very unstable, internal structure. Their mode
of action frequently depends, as in the case of the
diastases, upon the medium in which they occur.
Again, like the diastases, they are generally destroyed
by the action of sufficiently prolonged heat,
but less easily, for there are certain toxins that
resist a temperature of 100° C. for an indefinite
period. They are, like the diastatic albuminoids,
insoluble in strong alcohol, and are precipitated
from their solutions on the addition of this reagent.
They easily adhere to precipitates that form in
liquids in which they occur in solution, and possess
the remarkable property of diastases in that imponderable
masses produce considerable results.28
Although closely allied to certain alkaloidal bases,
the toxins are sharply distinguished by the remarkable
fact that their action is never immediate, but
is always preceded by a period of incubation, which
may be quite long.
Like the alkaloidal bases, they appear to result
from the hydrolyzing breaking down of albuminoids
and nucleo-albumins, and they appear to
be intermediary, from a chemical point of view,
between these bodies, the general characters of
which they retain, and the alkaloids proper, or
ptomaines, to which we have called attention, and
the principal chemical and physiological properties
of which they possess.
No absolutely precise knowledge is had regarding
the chemical nature and constitution of these
remarkable substances. A number of analyses of
these substances have been published which, in
general, permit no definite conclusion to be drawn.29
I have, however, elaborated several speculative
ideas regarding this subject.30
We must here call particular attention to the
ideas of Ehrlich regarding the constitution of the
toxins. According to this scientist, their molecules
contain two functional groups; the one, to which
he has given the name "haptophore," is that
which enables the toxin to attach itself to any
cellular element whatever, and which it then
renders non-toxic by means of the other, or "toxophore,"
group. We will particularize farther on
regarding this very important conception.
Origin of the Toxins.—These toxic bodies result
either as the products of the secretion of microbial
life, or as the result of the normal functionation of
cellular life in the higher vegetable or animal
organisms.
They are the direct products of life, and do
not result, as was formerly believed, from a more
or less profound modification of the more or less
complex albuminoids that serve as a food for the
various species of microbes, or for the cellular elements.
The vegetable toxins are less numerous than
the animal toxins. They are met with, nevertheless,
in almost all mushrooms which are reputed
or known to be toxic; the seed of the castor plant
contains a very toxic vegetable albuminoid, as is
likewise the case with Abrus precatorius (jequirity-bean),
and certain others.
The true physiological toxins occupy a very
important place in the realization of the conditions
that govern health, sickness, and death.
We will see later on that they are met with in
quite large number in the bladder, whence they
are voided in the urine. Their number varies considerably,
according to diverse influences (waking,
slumber, eating, fasting, fatigue, oxygen, brainwork,
health, disease, etc.). It is necessary here to
observe that the renal system serves for the purification
of the entire organism, and that in the
case of normal life we will find in the renal system
a large portion of the products of the cellular secretion
of the organism, and among the number there
are found, as we know, a certain number of alkaloidal
bases. We will take up later the subject of
urinary toxicity.
Autointoxications.—The toxins are also encountered,
and often in some number, in the muscular
tissues and in the blood, particularly in those
of batrachians, mureids, and saurians. In the
organism these toxins, developed by the activity
of the various cells, may cause autointoxication
whenever, for one cause or another, their normal
elimination ceases. "Although there are an
infinity of diseases," remarked Prof. Bouchard,
"there are but a few ways of becoming ill." Of
these ways that of autointoxication is the most
frequent. "What else is it, then," says Prof.
Charrin, "in the last analysis, but to die from
affections of the kidney, the liver, the heart, the
lung, etc., if it be not to succumb because of the
lack of oxygen, the accumulation of carbonic acid,
the influence of the numerous urinary poisons,
the action of acids, of salts, of biliary pigments, or
the effect of noxious principles, which the hepatic
cell must normally destroy or at least attenuate."
These autointoxications, always due to poor
elimination of toxic principles, toxins formed in
very great number in the organism, and which
the normal modes of evacuation or destruction do
not eliminate, are always found to be the cause
of all diseases, even those that are manifested by
attacks of the cerebro-spinal axis, and that exhibit
variously mania, insanity, symptoms of hyperexcitability,
etc.
These autointoxications are controlled by the
nervous system, and the latter alone is the cause
of a larger number of maladies than is generally
believed; in fact, if the mechanism of nutrition be
reduced to its most simple elements, it will be
seen to consist of the penetration of the foods, of
the plasmatic principles, to the cells; of their
transformation within the interior of the cells,
and finally the rejection of all the matter that
could not be utilized. It is the nervous system
that commands or dominates this mechanism, that
controls the taking-up of assimilable elements and
the elimination of toxic principles, the fruit of
assimilation or disassimilation, and in such a manner,
in fact, that this same nervous system can,
at its will, cause starvation, or intoxicate.
The marvelous cures obtained by magnetic
methods are due to no other causes than favorable
changes in the nervous system.
General Mode of Action.—The toxins, of whatever
kind, always behave like diastases, in the sense
that their definite action appears to be absolutely
independent of their mass, and that imponderable
quantities suffice to cause serious morbid affections
and profound modifications in nutrition.
Koch has shown that tuberculin is capable of affecting
60 trillion times its weight of the living human
being. According to Vaillard one milligramme of
tetanus toxin will kill a horse weighing 600 kilos.
These two examples show what an enormous power
the toxins possess.
My views regarding the manner in which diastases
act I have developed at length in my work
Nature des Diastases. The close analogy between
these substances and the toxins, an analogy upon
which, moreover, I have dwelt at some length, permits
me to refer the reader who is desirous of fuller
details to the small work just mentioned.
The mode of action of diastases resembles singularly
closely that of the catalytic substances,
and we will admit, for the moment, that they
act by intermediary combination, resulting in their
rapid decomposition.
We owe to Ehrlich31 a new conception relative
to the nature and mode of action of the diastases,
and which to-day plays an important rôle in all
our conceptions regarding immunity.32
According to this scientist, the complex molecule
of albuminoid substances is constituted by
a fixed central nucleus, and by a number of lateral
chains or receptors, fixed to this nucleus, which
possess diverse accessory functions, and which
serve, particularly, for the nutrition of the cells.
These receptors have a great affinity for the various
substances necessary for the support of the
living elements, and they seize upon the alimentary
substances, in normal life, just as a leaf of the
Dionæa seizes a fly which serves as its food.
In these special conditions the receptors may
attach themselves to the complex molecules of
albuminoid substances, such as the different
toxins.
Ehrlich supposes, as we have already seen, that
a toxin contains two special groups—a toxophore
group, which poisons, and a haptophore group,
which combines with the receptor. According to
this theory, the toxophore group of a toxin can act
on an organism only when the haptophore group
of the toxin encounters a suitable attachment or
receptor.
The receptors attached to the living protoplasmic
molecule attract the toxin, just as a lightning-rod
attracts the lightning.
It is hence clearly proved that the toxigenic
poisons exert their noxious action on the cellular
elements of sensitive organisms, by entering into
combination with these.
Experience has shown that they attach themselves,
in a most rigorously elective manner, to the
tissues, and rapidly disappear from the general
circulation. Numerous facts, clearly established, attest
the reality of this fixation or attachment.
It is thus that von Behring and Wernicke33
sought to ascertain the quantity of antitoxin (we
will see farther on that this name is given to those
substances which neutralize the activity of toxins
under certain conditions) which, introduced a certain
time after the introduction of the poison,
will save the life of the animal. They have experimented
with diphtheria toxin, which we will study
later, and they have demonstrated that, if the
antitoxic serum be introduced immediately after
the toxin, a dose of antitoxin twice as large as
that of the toxin suffices to effect a cure.
Eight hours after the administration of the toxin
the dose must be trebled, while after thirty-six hours
it is necessary to have recourse to a quantity of
antitoxin eight times as great. These experiments
show that the curative action of the antitoxin is
so much the less the longer the period of time
that has elapsed between the introduction of the toxin
and the antitoxin. This is because the toxin has
become so intimately attached to the tissues that
the antitoxin introduced has not the power to
destroy the combination. These facts have been
confirmed by Donitz34 and by the classic experiments
of Decroly and Rousse.35
This is not, however, the case with cold-blooded
animals, which, generally, are not affected by injections
of poisonous toxins. Thus Metchnikoff36 and
his pupils have been able to show that the toxins
introduced into certain cold-blooded animals
(Oryetes nasicorius) may remain for several months
without alteration in their circulation.
If we consider the facts of the theory of Ehrlich's
lateral chains, which we have mentioned, we are
led to well-defined conclusions regarding the mode
of action of the toxins. In fact, since these toxins
exhibit a pronounced chemical affinity for the tissues,
and while, on the other hand, they can attach
themselves only because of the presence of certain
functional groups of the protoplasmic molecules,
this union can take place only in certain specific
centers. This has been fully confirmed by experiments
in vitro.
It is known, since the researches of Ehrlich,37
Wassermann and Takaki,38 Marie,39 Metchnikoff,40
and a host of other scientists, that this fixation is
due to a clearly elective property. It is for this
reason that the tetanus toxin fixes itself only upon
the nervous tissue, and that in this action all passes
as if the nervous tissue had been provided with
functional groups possessing an elective affinity
for the tetanic poison.
Means of Defense Possessed by the Organism
against the Action of Toxins.—We have already seen
that the renal organs serve for the elimination of
the toxins normally produced in the organism by the
simple play of its cellular mechanism. Experience
has shown that the toxins introduced from without
into the circulation are generally finally eliminated,
even though in the meantime the modifications
they have imprinted on the economy may
be transmitted hereditarily; and that their influence
on the general nutrition and the normal functionation
of the entire organism persists even after
their elimination.
Much has been said regarding the elimination of
these toxins by the urine, but the experiments made
by Métin, at the Institut Pasteur, have shown the
inaccuracy of this assumption, and it has been
necessary to seek another.
It has been remarked that oxidation destroys
the toxins in vitro, and it has been thought that
a process resembling disinfection may well take
place within the tissues of the animal economy,
but no decision has been arrived at regarding the
possible mechanism of this action, which some
attribute to the action of the oxidizing ferments
of the organism, or to the action of certain special
cells.
According to Poehl, there is developed as
destroyer a substance possessing energetic oxidizing
properties, which he has isolated and named
spermine, and which is found in most of the organic
fluids and particularly in the leucocytes, the special
rôle of which we will presently study.
There develops still another cause of elimination,
or, to be more exact, of the neutralization of
the toxic principles in defense of the organism
against the toxins, and that is the formation of
antitoxins.
It is well known that the term virus has been
reserved to designate physiological liquids which
were characterized, when first they were known,
by their property of transmitting to an organism
certain functional affections, but the true character
of which is to expend their toxicity upon the
microbes which occur and are reproduced in the
organism, or upon the organized plastidulary granulations,
as in the case of the rabic virus, the special
microbe of which has not as yet been isolated.
Pasteur, when studying rabies, found that the
brain and spinal marrow of rabid animals contained
the pure rabic virus in considerable quantity, and
that every particle of the marrow was capable of
imparting rabies to a perfectly healthy dog. After
having ascertained this fact, he found that he
could attenuate the action of the virus, either by passing
the virus through certain animal organisms, such
as the monkey or rabbit, by gently heating, or even
by allowing it to oxidize and partially dry in the
air, or else by submitting it to the action of antiseptics
or alternating electric currents of very high
tension.
Experiments have shown that a deadly virus,
attenuated by one of the means mentioned, may
be injected, without danger of death, into the living
animal; and what is still better, the animal thus
treated acquires the power of resisting large doses
of the virus, less and less attenuated, and that it
is possible to reach a point where the animal
economy may become habituated to very large
doses of a highly virulent virus without the organism
experiencing any visible illness—that is, the
organism has been vaccinated with regard to the
particular virus.
Experiments have shown that this property is
not peculiar to microbial virus alone, but that it
is common to the venoms the toxicity of which is
essentially due to some toxins, with the exception
of those agents noted.
The attenuated viruses act, as vaccins, through
their soluble constituents, which, either directly, by
modifying the nutrition of certain cells, or indirectly,
by inducing reactions of the nervous centers which
preside over this nutrition, profoundly change the
conditions of life and give rise to the pathological
condition—the vaccined state.
Experiments by Behring and Kitasato41 have
shown that the tumors of a vaccinated animal,
freed from all organized matter visible under the
microscope by filtration through porcelain, contains
principles capable of directly or indirectly protecting
other animals from the disease caused by the
corresponding virus. Meanwhile, experiments have
shown that the vaccinating matters are totally
eliminated; nevertheless, after their elimination,
the immunity acquired remains with the animal,
which then continues to be protected against the
corresponding virus.
Interest in this subject has incited numerous
researches with a regard to bringing to light the
mechanism of this immunization; and this will
form the subject of another volume of this collection.
We may state here, however, that there
have been recognized two concurrent causes of
this preservative action; the one, called phagocytosis,
results from the fact that the microbe introduced
into the vaccined organism becomes incapable
of producing its usual toxins, while on the other
hand the immunization renders the organism
capable of secreting substances possessing an
activity contrary to that of the virus, in fact true
counter-poisons, comprised under the general name
antitoxins.
Phagocytosis.—We have seen that an organism
subjected to a toxic invasion tends to protect itself
by proper means of defense; and one of those is
the direct putting into activity of the living cellular
elements themselves, and in particular, the leucocytes,
or white corpuscles, found in more or less
number, according to pathological conditions, in
the blood and lymphatic fluids.42
Metchnikoff has shown that the moment a
foreign element, particularly a microbe, enters the
organism, these leucocytes come flocking from
all parts of the body, collect around the bacterial
element, penetrate it, and begin to digest it.
These elements have received the name phagocytes.
The name chemotaxis has been given to the property
by virtue of which they approach (positive
chemotaxis) or move away from (negative chemotaxis)
certain substances which affect them powerfully.
Experiments have shown that the leucocytes
are attracted by the products secreted by pathogenic
microbes, or saprophytes. Attracted by
the latter, the white corpuscles surround, envelop,
and finally digest them; and when it happens that
all the pathogenic microbes within an organism
are absorbed, the organism survives, while in the
contrary case it succumbs.
Attention must be called to this attack by the
white corpuscles within the limits where they are
normally confined. It is a pathologic diapedesis—a
leucocytosis provoked by the irritation of the
tissues—and caused either by the presence alone
of foreign elements, or by the soluble products
secreted by them.
When, for any reason whatever, this phagocytic
action is impeded, the resistance of the organism
to pathogenic infection ceases to be effective,
and the organism may therefore be invaded by
the microbe. Numerous causes may contribute to
impede this action.
The Antitoxins.
We have seen that the second means of defense
possessed by the organism resides in the action of
special products, true defensive secretions, possessing
an activity contrary to that of the toxins,
and which are secreted by the cells of the organism
under the influence of the vaccins.
This is a property common to every organism,
and which is observed even in non-vaccinated
subjects, although in this case the secretion forms
with great difficulty and in small quantity.
When an organism subjected to the toxic action
of a bacterial infection does not succumb to the
intoxication, it emerges from the test gifted with a
new property, which may be augmented by habituation,
and which borders on immunity.
At first we were content to vaccinate small
animals in the laboratory, but in proportion as the
discoveries in this domain extended, and there
developed a need for large quantities of antitoxins,
recourse was had to the larger animals, particularly
horses and cattle. From the moment that large
quantities of blood and antitoxic serum were at
command, search was made for a means of isolating
the antitoxin and determining its properties.
Experiments so far made have shown that the
antitoxins are substances of an albuminoid nature,
of unknown composition, and which are very closely
united to the albuminoid substances of the serum.
It must be observed, however, that Behring and
Knorr oppose the assertion regarding the albuminoid
nature of tetanic antitoxin, but their reasons for
this do not appear to be well founded.
In general, these antitoxins are precipitable with
the globulins, and possess quite considerable powers
of resistance towards physical and chemical agents.
Thus they are destroyed only at a temperature
above 60-65° C. Kept in the dry state, in the
residue of evaporated serum, and away from the
light and all oxidizing action, it is possible to preserve
their activity for a very long time.
They are essentially humoral substances; they
are found in the blood of vaccinated animals, from
which may be obtained antitoxic serums with a
specific but transient immunity; and they are also
found in the plasmas of the lymph and exudates,
in aqueous tumors, and in the milk. They are
seldom found in the cells.
Mode of Action.—Frequent attention has been
paid to the mode of action of the antitoxins upon
the toxins, a phenomenon of great importance in
relation to the phenomenon of immunity acquired
against the toxins. At the beginning of our
knowledge on this subject, the idea of a destruction
of the toxin immediately suggested itself, and was
advanced by von Behring.43 According to this
scientist the antibody inhibits the morbigenic action
of the toxin by neutralizing the toxin, combining
with the latter to form a compound of a chemical
nature which is devoid of toxicity and without
action on the organism. According to this theory,
the influence of the antitoxin on the toxin is direct,
and does not require the intervention of the living
cellular protoplasm. Such was also the belief of
Prof. Ehrlich.44
Buchner, a little later, believed that the antitoxin,
instead of acting directly on the toxin,
exercised a direct influence on the living elements
of the organism, preserving them from intoxication.45
Such was also the opinion of Roux46; and Calmette
demonstrated that a mixture of venom and
of a non-toxic antivenom recovered its toxicity on
being heated to 68° C, whereby the antivenom
was destroyed (Calmette: Le Venin des Serpents,
Paris, 1897, p. 58); and Wassermann arrived at
the same result.47
The array of proofs offered by these scientists,
which we cannot here enlarge upon without uselessly
extending our subject, would tend to make
one believe, at first glance, that the antitoxin does
not act directly on the toxin, but at the present
time Buchner's theory appears untenable. Numerous
researches have proved conclusively that the
toxin and the antitoxin have a specific affinity
for each other, by virtue of which these principles
combine to form a substance free from all toxicity,
but unstable, and which may be decomposed by
heat or certain other factors.48
Some recent experiments by J. Martin and Cherry
(Proceedings of the Royal Society, 1898, LXIII, p.
423) have clearly brought out this fact. These
authors made mixtures of serpent venom with its
antivenom, which they filtered through a layer of
gelatin, under the supposition that, if the venom
and its antivenom were not chemically combined,
the former alone would be able to pass through
into the filtrate, because its molecules are so much
smaller. Martin and Cherry allowed the venom
and its antivenom to remain in contact for varying
periods before filtering. As the result of a series
of experiments carried out with this idea, they
have demonstrated that the filtrate obtained after
allowing a few minutes' contact between the two
substances, was decidedly toxic, while that obtained
after a contact of half an hour was absolutely non-toxic.
From this the authors conclude that the
antitoxin enters into chemical union with the
venom, but that the combination does not take
place immediately, and requires a certain length
of time for its accomplishment.
Ehrlich and Knorr have demonstrated that the
neutralization is less rapid in dilute solutions than
in concentrated ones.
Prof. Svante Arrhenius has completed our knowledge
regarding the mode of combination between
the toxins and the antitoxins, by demonstrating the
occurrence of limited reactions analogous to the
etherification of an alcohol by an acid, and in
such a manner that there always exists, in a mixture
of these two substances, a certain quantity of
free toxin and antitoxin. This is an important
modification of the general ideas held in this
respect.49
It appears necessary to bring here more clearly
in evidence the fact that the antitoxin inhibits the
noxious action of the toxin, even outside the living
organism, by uniting with it to form a compound
in identically the same manner as when a strong base
and a strong acid are brought together. As we have
seen, all the conditions of environment that favor
or retard the formation of salts, in a like sense
influence the neutralization of the toxin by its
antitoxin.
Formation of Antitoxins.—Ehrlich's theory of
side chains, to which reference has already been
made, furnishes us with an explanation of the
formation of the antitoxins in tumors. Let us
suppose that, in the organism, a cell had come
into contact only with certain toxic molecules incapable
of compromising its life, and that the only
result was the immobilization of the receptors
which are united with the haptophore groups of
the opposing toxins. It is known that, by virtue
of a property inherent in all living organisms,
during the phenomena of reparation, there is
generally an overproduction of the neoformed
parts. In the case we here speak of, as the receptors
fill an important function in the nutrition of the
opposing cellular elements, once they become united
with the toxic haptophores, they become incapable
of filling their normal function of nutrition. Under
these conditions the cells develop so large a quantity
of receptors that, filling the cells, and not finding
any more room, they spread into the blood and
other liquids of the organism.
Under these conditions, every new injection of toxin
into the organism is absorbed into the blood where
it meets with the free receptors which possess great
avidity for the haptophore group of its molecule,
and the two groups immediately unite, before the
haptophore group of the toxin has been able to
attack and intoxicate a cellular element.
We thus see that the receptors which, when in a
free state in tumors, play the rôle of antitoxics or
antitoxins, become, within the cellular elements
themselves, the vehicle of intoxications. Figuratively
speaking, so long as these fixators are
attached to the molecule of the living protoplasm
they attract the toxin.
According to this ingenious conception, the
formation of antitoxins is hence absolutely independent
of the action of the toxophore elements
on the cellular elements, and it suffices that these
possess receptors or side chains capable of uniting with
the haptophore groups of the toxin. This explains
why it has been possible to produce antitoxins from
toxins which have lost some of their toxic properties,
but which have preserved their property of
uniting with antitoxic substances. Ehrlich gives
the name toxoids to those modified toxins that
have lost their toxophore groups, while the haptophore
group, the producer of the immunizing substance,
is still preserved intact.
According to Metchnikoff's theory, which is
very similar, it seems quite possible that the
phagocytes, thanks to the facility with which they
absorb poisons, occupy an important place as
producers of antitoxins. It has not been possible
so far to verify this theory in our at present imperfect
knowledge regarding this subject. The
domain of immunity has, however, made brilliant
conquests during these last few years, so that we
should not despair of arriving at a definite solution
before long.
In the vaccinated animal the antitoxin is reproduced,
and it is possible to obtain several
times, from the vaccinated animals, successive
portions of antitoxic serum.50 The protective power
of these antitoxins is absolutely marvelous. An
animal accustomed gradually to the tetanic virus
yields a serum containing an antitoxin a thousand
times more active than the virus.
According to Vaillard, a quintillionth of a cubic
centimeter of this antitetanic serum suffices to
preserve one gramme of living mouse from the
effects of a dose of tetanic serum that would otherwise
be surely fatal.
In the animal, the antitoxins are eliminated
mostly by the fluids of the body, and particularly
by the urine. Ehrlich has demonstrated that they
also pass into the milk, and this fact is confirmed
by a large number of observers. It explains the
immunity acquired by nurslings, and which is
transmitted by the milk.
Serotherapy.—The search for antitoxins and their
rôle in the etiology of infectious diseases are fundamental
points in actual therapy. It has been demonstrated
that the serums of certain vaccinated animals
enjoy very extended antitoxic therapeutic properties;
for instance, the serum of vaccinated rabbits is an
antivenom towards erysipelas; and the sterilized cultures
of the pneumococcus or of the Bacillus pyocyaneus
prevents infection of carbuncle (anthrax).
The antivenomous serum of the ass immunized
by injections of increasing doses of the venom of
the terrible naja is a perfect prophylactic and curative,
not only as regards the venom of this serpent,
but also against that of the crotalus, trigonocephalus,
and viper.
We shall take up the study of serotherapeutics in
another volume of this collection.