For instance, working in collaboration with MM. Roux and Salimbeni, he had found that it is by soluble poisons that the cholera vibrions harm the organism or kill it, but that small doses of the same poisons are vaccines and make the blood of the vaccinated animal antitoxic. On the other hand, a microbian vaccination is preventive against microbes only but not against toxins and the blood does not become antitoxic. This is explained by the fact that it is not the same cells which digest cholera microbes and cholera toxins: the microphages digest the vibriones whilst the macrophages digest the poisons and, probably, manufacture as products of this digestion, the corresponding antibody, the cholera antitoxins.
On the contrary, in cases of the inclusion of microbes by macrophages, as, for instance, in plague, the blood acquires an antitoxic power by injection of the microbes themselves and not by their toxins, as was demonstrated by M. Roux and his collaborators. The same fact was observed by Metchnikoff on the alligator, in whom also microbes are digested by macrophages. In those cases, when microbes and toxins are digested by the same cells, the latter manufacture antibodies against both.
These facts rendered legitimate the supposition of the macrophagic origin of antitoxins.
In 1897 an International Congress took place in Moscow. Metchnikoff read a paper on the phagocytic reaction against toxins and another dealing with the whole of the knowledge acquired concerning human plague. He ended this by a plea in favour of Science, so often accused of having contributed nothing to the solution of the most important human problems, particularly ethical ones, and of having, on the contrary, sanctioned the law of Might by tabulating the laws of the struggle for existence. Metchnikoff objected that, far from doing so, Science, by revealing the laws of Nature, applied to humanity the benefits derived from them, whilst striving to counterbalance their cruel or harmful effects. The struggle against plague and other diseases was a concrete example of this, for here medical science opposed itself to the cruelty of “natural selection.” He wound up his speech by the following words, “Just as, in order to satisfy his æsthetic tastes, Man revolts against the laws of Nature which creates races of sterile and fragile flowers, he does not hesitate to defend the weak against the laws of natural selection. Science has been faithful to her mission and to her generous traditions. Let her, then, progress unhindered.”
Metchnikoff’s friend and companion, M. Nocard, wrote to me concerning Metchnikoff’s paper:
Do not believe a word that Metchnikoff tells you. He had tremendous success. The somewhat free form of his paper contributed to its success, as it only made his conviction and enthusiasm more apparent. Thus the Sibyl on her tripod.
Metchnikoff had at this period a very talented disciple, M. I. Bordet, who opened a new path by a series of researches of the greatest importance. He found, among other things, that “the figured elements” can be destroyed outside the cells, in the humors. Thus, if red blood corpuscles from one animal are injected into an animal of a different kind, these globules are destroyed, not within the phagocytes, but outside them, in the ambient humors. Metchnikoff studied this phenomenon and proved that the explanation was the same that he had previously given of Pfeiffer’s phenomenon in the case of cholera vibrions. In Bordet’s experiments, the leucocytes which were already existing in the humors were also damaged by the experimental shock; but, if this was carefully avoided, the phagocytes, remaining intact, englobed and digested the injected red corpuscles and no phenomenon similar to Pfeiffer’s took place.
These observations led Metchnikoff to a thorough study of the destruction of cellular elements by the phagocytes. He had already observed that, whilst the struggle with microbes is chiefly undertaken by small leucocytes with a lobed nucleus—the microphages—it is the great leucocytes with a single large nucleus—the so-called macrophages—which undertake the destruction of cells, “figured” elements, as well as that of toxins. The macrophages are to be found not only in the blood but also in different organs such as the liver, spleen, kidneys, etc.; they seize upon living cells by means of mobile protoplasmic prolongations with which they draw them in and end by ingesting them completely. Not only do they thus absorb foreign cellular elements such as red corpuscles, spermatozoa, etc., but also all the weakened cells of the organism itself.
This weakening may be due to normal phenomena such as the metamorphosis of insects or tadpoles, when certain organs, as they weaken, become useless or inactive. But, oftener, this weakening is due to pathological causes, as in morbid atrophies or poisoning by microbian toxins. In any case, the enfeeblement of cells exposes them to be devoured by macrophages, which brings about the atrophy of the cells or even of the organs which contain them.