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. These observations suggested to Metchnikoff the idea that senile atrophy might be due to the same mechanism, and his thoughts turned towards the problem of the causes of old age. But, before undertaking researches in a new direction, he wished to conclude those he had been pursuing for twenty years on the phenomenon of phagocytosis. He therefore started to complete his investigations on immunity in order to epitomise them and to give a definite form to his doctrine on that subject. CHAPTER XXVI 1900. Immunity--Natural Immunity--Artificial Immunity. For centuries the question of immunity has occupied the human mind because the prevention of disease has ever been one of the greatest preoccupations of Man. Savages had already observed that man can become refractory to the venom of serpents, either through a slight bite or by the application of certain preparations of that venom on scarified skin. It was also a popular and very ancient notion that the contact of a slightly scratched hand with the pustules of cow-pox conferred immunity against human small-pox. It was on this observation that Jenner founded his method of antivariolic vaccination. The latter, in its turn, suggested to Pasteur the idea of attempting antimicrobian vaccinations. Having ascertained that old cultures of chicken cholera, previously very virulent, had become harmless, he wondered whether they had become a vaccine and proved by experiment that they had. That led him to the principle of the attenuation of viruses and to that of vaccination by attenuated microbes. Thus the problem of the mechanism of immunity was stated.