ill. His condition was aggravated by anxiety concerning the University;

for he was sufficiently conscious to be aware of the events which were taking place in Russia. The murder of Alexander II. caused him to foresee a political reaction of the most terrible type; already, a reactionary Rector had been appointed. Metchnikoff developed intense jaundice and had a serious relapse with alarming cardiac weakness; during the crisis he had a very distinct prevision of approaching death. This semi-conscious state was accompanied by a feeling of great happiness; he imagined that he had solved all human ethical questions. Much later, this fact led him to suppose that death could actually be attended by agreeable sensations.

His robust nature, however, triumphed over all these grave complications, and, during his convalescence, he was filled with a joy of living such as he had never experienced before; from that moment his moral and physical balance was completely restored. There was one unpleasant sequel to his illness, an acute affection of the sight (choroiditis), but it fortunately disappeared without leaving any traces, and, in fact, he never suffered again from his eyes, in spite of his constant use of the microscope.

After his recovery he had a renascence of vital intensity; the life instinct developed in him in a high degree; his health became flourishing, his energy and power for work greater than ever, and the pessimism of his youth began to pale before the optimistic dawn of his maturity. However, the relapsing fever had very probably increased, if not started, the cardiac trouble which eventually caused his death.

During the time when Metchnikoff was forbidden the use of the microscope on account of his eye weakness, he studied Ephemeridæ from the point of view of natural selection. He wished to elucidate the manner in which this selection operates during the very short life of those insects: the rudimentary structure of their buccal organs does not allow them to feed themselves, and they have no time to adapt themselves to external conditions.

During the 1875 holidays, at Gmunden and on the Danube, he observed the nuptial flight of the mayflies, a phenomenon which constitutes their short adult existence, preceded by a long period in the larval state. Thousands of these diaphanous, ephemeral insects swarm above the water in a compact cloud; now and then, dead Ephemeridæ fall like snow-flakes, and that is the final and tragic completion of the nuptial flight. Metchnikoff wished to unveil the mechanism of this sudden death, evidently due to a physiological cause; but he obtained no definite results either that year or the following, when he continued his observations in the Caucasus. He realised that the life of these insects was too short to allow him to solve the problems which interested him, and, his eyes now being cured, he went back to his studies on the origin of multicellular beings or _metazoa_.

He studied the development of inferior sponges and ascertained that they possess the three embryonic layers which correspond to those of other animal types, but that these layers have not the same degree of independence or differentiation. He found that in certain inferior sponges the mesoderm develops before the endoderm and gives birth to it. These two layers, born one from the other, manifest common primordial characters. Therefore he was in no wise surprised to discover that, in these inferior sponges, the amoeboid and mobile cells of the mesoderm fulfil digestive functions equally with, and even more than those of the endoderm; in fact, with primitive beings, functional characters are not more strictly delimitated than morphological characters. It is only a more advanced differentiation which separates them.

He connected these new facts with that which he had observed in 1865 in one of the lower worms, the earth planarian _Geodesmus bilineatus_. This worm is actually without a digestive cavity, for the latter is entirely filled by parenchymatous cells inside which digestion takes place.

By their primitive structure, lower sponges and worms come near the higher Infusoria, to which they are even more closely related by this intercellular digestion which is common to them.

This led Metchnikoff to ask himself whether this was not, generally speaking, _the primitive mode of digestion_. He carried out numerous researches on this point during the following years, and found the same intercellular digestion in other lower worms, such as the _Mesostoma_ and aquatic planarians, and afterwards in some lower Coelentera and some Echinoderma. He was thus enabled to establish definitely that the primitive mode of digestion was really intercellular, for the lower multicellular animals either do not possess any digestive cavity or else their digestive cavity develops late, as for instance with lower jelly-fish or with hydropolypi. Even when the cavity is developed in these inferior animals, the digestive functions are fulfilled by the mesodermic cells.

The question as to what are the ancestral forms of multicellular animals cannot be solved through direct observation, for there is a lacuna between them and unicellular beings, a lacuna which is due to the disappearance of intermediary forms. It can only be filled by hypotheses, based upon the embryology of those animals which, in their embryonic development, repeat the inferior forms from which they are derived, thus reflecting the general evolution of living beings. It was therefore to the embryology of lower multicellular beings that Metchnikoff turned, in order to endeavour to reconstitute their origin and to show the link between them and unicellular beings.

We know that the _ovule_ or primitive genital cell of every animal may be compared to a unicellular organism. After fertilisation the egg undergoes consecutive divisions or segmentation; each segment constitutes a new cell, and their aggregation forms a hollow sphere called a _blastula_, which is similar to a colony of unicellular beings. The blastula differentiates itself into embryonic layers, the _ectoderm_, _endoderm_, and _mesoderm_ already mentioned.

In the majority of animals the origin of the first two layers, ectoderm and endoderm, is due to the invagination of one of the poles of the blastula; the invaginated part of the walls forms the internal layer, the endoderm, and lines the cavity produced by invagination; this cavity thus becomes a _digestive_ cavity. This stage of development, called _gastrula_, is similar to a cup with a double wall, of which the outer is the ectoderm and the inner the endoderm.

This stage, discovered by Kovalevsky, is to be found in the evolution of most animals and corresponds to the adult stage of some of them. It was consequently considered as the _primitive type_ of multicellular beings.

Haeckel founded thereupon his theory of the _gastræa_, according to which the common ancestor of animals was a lower animal, now disappeared, and similar to that stage of development. He therefore gave to this hypothetical animal the name of _gastræa_.

Metchnikoff, however, discovered among primitive multicellular animals, such as sponges, hydroids, and lower medusæ, a stage of development still more simple than the gastrula; this stage is without a digestive cavity and only assumes the gastrula form in its ulterior evolution. He also made the remarkable discovery that, in the most primitive multicellular animals, the endoderm is formed, not by means of invagination, but by the _migration_ of a number of flagellated cells from one pole of the wall of the blastula into the central cavity. These cells draw in their flagellum, become amoeboid and mobile, multiply by division, fill the cavity of the blastula, and become capable of digesting. They originate the digestive cells of the complete organism and give birth to the mesoderm, which explains how the latter comes to contain a number of devouring cells even though these do not constitute digestive organs properly so called. Metchnikoff gave to that stage the name of _parenchymella_, for the migrating cells constitute the endoderm in the condition of a parenchyma.

The invariable presence of this stage in the simplest multicellular animals, the primitive amoeboid state of the endodermic cells, cases of ulterior transformation of the parenchymella into the gastrula form in certain animals, the absence of a differentiated digestive cavity,--all that proved, according to Metchnikoff, that the parenchymella is more primitive than the gastrula, and is therefore entitled to be considered the prototype of multicellular beings.

He saw a confirmation of this in the fact that primitive adult animals also have no digestive cavity but merely an intracellular digestion (sponges, turbellaria).

He concluded that the common ancestor of multicellular beings was a being constituted by an agglomeration of cells without a digestive cavity, but endowed with intracellular digestion, like that of the "parenchymula" stage of development. He therefore gave to that hypothetical ancestor the name of _parenchymella_.

Later, in 1886, he definitely formulated his theory of the genesis of multicellular beings, and having already stated the phagocyte theory, he substituted for the name _parenchymella_ that of _phagocytella_, which indicated at the same time the primitive mode of digestion of that hypothetical ancestor.

Reduced to its simplest form, it presented, according to Metchnikoff, a certain analogy with a colony composed of unicellular beings of two kinds: the first, flagellated, forming the external layer, and the others, amoeboid, occupying the centre of the colony and capable of digesting.

It may be interesting to mention here that, in this hypothetical description, Metchnikoff foresaw the existence of similar, but real, beings discovered a year later by Saville Kent, namely, the flagellated colonies of _Protospongia_.

Thus the link between the unicellular and the multicellular beings could be constituted through the intermediary of flagellated colonies on the one hand and, on the other hand, of beings similar to a _phagocytella_. The _indivisible colony_ became the _multicellular individual_.

While studying the genealogy of beings, Metchnikoff continued his researches on intracellular digestion. In 1879, at Naples and at Messina, he was able to establish the fact that the mesodermic cells of many larvæ of Echinodermata and Coelenterata, endowed with a digestive tube, nevertheless contained strange bodies. Therefore, even complicated organisms with a differentiated digestive system could still contain at the same time some primitive cells with an autonomous digestion.

All these researches on the unity of the origin of multicellular beings and their morphological elements, and also those concerning intracellular digestion, were gradually preparing Metchnikoff's mind for the conception of the phagocyte theory.

* * * * *

We spent the summer of 1880 with my family in the country. The cereals were invaded by a harmful beetle, the _Anisoplia austriaca_, which was devastating the country. Metchnikoff took the study of this scourge to heart and tried to find a remedy. He had, the preceding year, observed a dead fly enveloped with a sort of fungus which had evidently been the cause of its death. Hence he conceived the idea that it might be possible to combat harmful insects by provoking epidemics among them. He now returned to this idea; on dead bodies of _Anisoplia_ he found a small fungus, the _muscardine_, which was invading the insects by means of filaments, and he succeeded in infecting healthy beetles.

At first he confined himself to laboratory experiments; then a great landowner, Count Bobrinsky, placed experimental fields at his disposal. As the acquired results were very encouraging, Metchnikoff, forced to leave the neighbourhood, left a young entomologist in charge of the application of his method. So far as he himself was concerned, this study proved the starting-point of his researches on infectious diseases.