The theoretical study of Natural History problems (in the largest sense of the word) alone can provide a critical method for the comprehension of truth and lead to a definite conception of life, or at least allow us to approach one. And yet, until then, the theory of phagocytosis as a curative force of the organism was but a hypothesis, for he had not yet observed _spontaneous phagocytosis in diseases_ and did not know pathogenic microbes. He therefore sought to study them in lower animals, whose simple structure made the observation easier. He found some small, transparent, fresh-water crustaceans, called _daphniæ_, which were diseased and easy to place alive under a microscope. These crustaceans are often infected by a parasite fungus (_Monospora bicuspidata_), of which the spores, shaped like sharp needles, are introduced with food into the digestive tube, traverse the walls of it, and thus penetrate into the general cavity of the body. They are immediately attacked by mobile phagocytes, which either singly or in groups englobe them; if the phagocytes succeed in digesting the spores, the daphnia recovers; in the contrary case, the spores germinate and develop into small fungi which invade the organism and kill it. The recovery or death of the daphnia depends therefore on the issue of the struggle.[19] This observation gave final confirmation to the hypothesis of the curative forces of the organism. [19] Virchow's _Archiv_, vol. 96, p. 177. Metchnikoff was not content with observing lower animals but wished to study the reaction of the organism of mammals in infectious diseases. At that time, the best-known microbe was the bacillus of anthrax. He therefore chose that for his researches and ascertained that phagocytosis varied with the virulence of the microbes; thus, while phagocytes did not attack virulent bacteria, they attacked and rapidly digested attenuated bacteria. Moreover, he observed a very active phagocytosis in refractory animals and the reverse in sensitive ones. He thus came face to face with the question of _immunity_. He approached it by a comparative examination of the reaction of the organism of vaccinated rabbits and of non-vaccinated ones, and ascertained that an active phagocytosis was only manifested in a previously vaccinated organism. Metchnikoff explained these facts by the theory that the phagocytes became accustomed, gradually, through vaccination, to strive against more and more virulent microbes. From that moment, immunity appeared to him as being no other than this progressive hardening. He published his researches in 1884 in Virchow's _Archiv_, and impatiently awaited medical reviews, hoping to find some answer, but the memoir passed unnoticed; the full significance of it had not been grasped. CHAPTER XIX Ill-health of his wife and sister-in-law--Journey to Tangiers through Spain--Villefranche--Baumgarten criticises the phagocyte theory.