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.