The first theories propounded on the subject concerned the humors. Pasteur supposed that immunity was due to the absorption, by the vaccinating microbes, of certain nutritive substances in the humors, which, not being renewed for some time, were missed by the microbes afterwards introduced into the organism, which therefore could not develop completely. Chauveau, on the other hand, thought that, in cases of immunity, the humors contained substances which were unfavourable to microbes. Those theories explained particular facts, but were not applicable to the generality of cases. Other theories,[21] whilst attributing an active part to the organism itself, failed to account for the mechanism of immunity in general. This was due to the fact that knowledge at that time lacked the two essential elements, _i.e._ the modifications suffered by the organism which was becoming immunised, and the fate of the microbes in the refractory organism. [21] Naegeli, Büchner, Gravitz. The disappearance of the microbes in the cured or refractory animal had indeed been observed;[22] the inflammatory reaction of the organism in the course of immunisation had been noted;[23] microbes had long ago been observed inside the white globules of pus;[24] but, either an erroneous interpretation was given to the facts observed, or, rather, the links of causality between those factors failed to be established because they were observed solely in the complicated organism of superior beings. Humoral theories, less easy to test, preserved an appearance of generality and were easily admitted. [22] Chauveau. [23] Büchner. [24] Hayem, Birsch, Hirschfeld, Kleps, Recklinghausen, Waldeyer, and Virchow. Such was the state of the question when Metchnikoff approached it from a naturalist's point of view. He knew the life of unicellular beings and that of the lower multicellular organisms in their complete simplicity; he knew their mode of defence by ingestion and intracellular digestion. Having become familiar with these phenomena, visible in the single cell, he was better able to see his way in the complicated _milieu_ of higher beings. He was therefore able to discover the connection between the divers factors which other scientists had observed singly. He was able to prove that it is the combination of these factors, _i.e._ inflammation, the ingestion of living and virulent microbes, and their disappearance by means of intracellular digestion which makes immunity possible. He demonstrated that "there is but one permanent element in natural or acquired immunity, and that is phagocytosis." The extension and importance of this factor, applicable to the whole animal kingdom, proved the truth and general scope of the phagocyte doctrine of immunity.