At Messina, we settled in a suburb, the Ringo, on the quay of the Straits, in a small flat with a garden and a splendid view over the sea. We did not have much room, and the laboratory had to be installed in the drawing-room, but, on the other hand, Elie only had to cross the quay in order to find the fisherman who provided him with the material needed for his researches and with whom we frequently went sailing.

Metchnikoff loved Messina, with its rich marine fauna and beautiful scenery. The splendid view of the sea and the calm outline of the Calabrian coast across the Straits delighted him. He enjoyed it all the more after the many excitements of life at the University, and eagerly gave himself up to his researches. Often, in later years, he delighted to recall memories of that period, the more so that this was connected with the principal phase of scientific activity which led to the formation of his phagocyte theory. After the earthquake in 1908, he wrote a few pages on Messina and ended his article by the following lines:

Metchnikoff continued to study intracellular digestion and the origin of the intestine. He foresaw that the solution of those problems would lead to general results of great importance. The study of medusÆ and of their mesodermic digestion confirmed him more and more in the conviction that the mesoderm was a vestige of elements with a primitive digestive function. In lower beings, such as sponges, this function takes place without being differentiated, whilst with other Coelentera and with some Echinoderma the endoderm gives birth to a digestive cavity; yet, the mobile cells of the mesoderm preserve their faculty of intracellular digestion. As he studied these phenomena more closely, he ascertained that mesodermic cells accumulated around grains of carmine introduced into the organism.

All this prepared the ground for the phagocyte theory, of which he himself described the inception in the following words:

This very simple experiment struck Metchnikoff by its intimate similarity with the phenomenon which takes place in the formation of pus, the diapedesis[15] of inflammation in man and the higher animals. The white blood corpuscles, or leucocytes, which constitute pus, are mobile mesodermic cells. But, while with higher animals the phenomenon is complicated by the existence of blood-vessels and a nervous system, in a star-fish larva, devoid of those organs, the same phenomenon is reduced to the accumulation of mobile cells around the splinter. This proves that the essence of inflammation consists in the reaction of the mobile cells, whilst vascular and nervous intervention has but a secondary significance. Therefore, if the phenomenon is considered in its simplest expression, inflammation is merely a reaction of the mesodermic cells against an external agent.

Metchnikoff then reasoned as follows: In man, microbes are usually the cause which provokes inflammation; therefore it is against those intruders that the mobile mesodermic cells have to strive. These mobile cells must destroy the microbes by digesting them and thus bring about a cure.

Inflammation is thus a curative reaction of the organism, and morbid symptoms are no other than the signs of the struggle between the mesodermic cells and the microbes.

In order to verify these conjectures, he started studying the englobing of microbes by mesodermic cells in larvÆ and in other marine invertebrates which he inoculated.

At that time, a well-known German scientist, Kleinenberg, was Professor of Zoology at Messina. Metchnikoff imparted his ideas to him and showed him his experiments. Kleinenberg encouraged him very much; he looked upon his theory as “an Hippocratic thought” and advised him to publish it at once.

Metchnikoff was also greatly encouraged by Virchow, who happened to pass through Messina and came to see his preparations and his experiments, which seemed to him conclusive. However, Virchow advised him to proceed with the greatest prudence in their interpretation, as, he said, the theory of inflammation admitted in contemporary medicine was exactly contrary to Metchnikoff’s. It was believed that the leucocytes, far from destroying microbes, spread them by carrying them and by forming a medium favourable to their growth.

Metchnikoff always preserved a deep gratitude towards Virchow and Kleinenberg for the moral support which they gave him at that time.

When the hot weather came, we left Messina for Riva, a delicious summer resort on the shores of the Lake of Garda. There, Metchnikoff wrote his first memoir on the reaction of inflammation and on the digestion of microbes by the mesodermic cells of lower invertebrates. On the way back to Russia through Vienna, he went to see the Professor of Zoology, Claus; he found other colleagues with him and expounded his theory to them. They were much interested, and he asked them for a Greek translation of the words “devouring cells,” and that is how they were given the name of phagocytes.

Claus asked him for his memoir for the Review which he edited and in which it appeared soon afterwards, in 1883.[16] The new-born “phagocyte theory” was thus very well received by naturalists and by Virchow, the father of cellular pathology.

Having returned to Russia, we went to the country, where Elie had to attend to family business; nevertheless, he continued his researches in every leisure moment. He had observed in Echinoderma that, during the transformation of their larvÆ, the parts becoming atrophied were englobed by mesodermic mobile cells. In those observations he was delighted to have found an example of physiological inflammation, i.e. one which presented itself in normal and non-morbid conditions. He thought he might observe it also during the metamorphosis of the tadpole into a frog, whilst the tail was being atrophied. But he found that, instead of the leucocytes of the blood, certain cells from the muscular tissue were those which devoured the enfeebled elements of the tail; he thus learnt that phagocytes might be, not only the white blood corpuscles, but other cells of mesodermic origin.[17]

In autumn 1883 he read his first paper on phagocytosis to a congress of physicians and naturalists at Odessa.[18] He compared the phagocytes to an army hurling itself upon the enemy and looked upon the phagocytic reaction as a defensive force of the organism.

In that paper itself and from that moment onwards, the trend of his ideas towards optimism becomes visible. By discovering the phagocytic reaction of the organism, he made a first breach in his philosophy of human nature, hitherto so pessimistic; he discovered within it a salutary element which could be utilised by science to combat its discords. He began to have some faith in the power of knowledge, not only for this struggle, but also for the establishment of a rational conception of life in general. Thus he said in his paper to the Odessa Congress:

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.

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.