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 Roux[46]; 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.