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 Donitz[34] 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 Metchnikoff[36] 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.