Thus the researches made in recent years and the results of the London Congress allowed us to consider the phagocyte theory of immunity as being solidly established.
Yet, Behring’s discovery of antitoxins still hung over it like a sword of Damocles; it was imperative that the respective parts played by antitoxins and by phagocytes should be elucidated. With that object in view, Metchnikoff undertook new researches and succeeded in ascertaining once for all the narrow link between immunity and the function of the phagocytes which probably elaborate the antitoxins as a product of their digestion of vaccinal toxins. He drew this conclusion from the fact that, in a rabbit vaccinated against hog-cholera, the exudate devoid of phagocytes[20] is neither bactericidal, nor antitoxic, nor attenuating, while it is so if it contains phagocytes. Therefore a relation of causality exists between cells and the acquired properties of humors. And the resistance of the animal is in visible correlation with the degree of phagocytosis which is manifested by it.
These results having been established, it seemed as if the last rampart of the humoral theory had been taken by storm.
In the meanwhile the persistent and bitter opposition of physicians to the phagocyte theory made a great impression on Metchnikoff, and, while stimulating his energy in defence of his ideas, it maintained him in a state of nervous excitement and even depressed him.
He asked himself why this obstinate opposition to a doctrine based on well-established facts, easily tested and observed throughout the whole animal kingdom? To him, a naturalist, it seemed clear and simple and all the more admissible that it was confirmed by the generality of its application to all living beings.
But, he thought, perhaps the real cause of the attitude of the contradictors lies in the very fact that medical science only concerns itself with the pathological phenomena of higher animals, leaving their evolution entirely out of account, as well as their starting-point in lower animals—whilst it is the very simplicity of the latter which allows us to penetrate to the origin of the phenomena.
Perhaps a general plan of the whole, in the shape of a comparative study, embracing the whole animal scale, would throw light over the generality of phagocytic phenomena and would make their continuity understood through normal and pathological biology. He determined to make this effort. In order to place in a fresh light the biological evolution of phagocytosis phenomena in disease, he chose one of the principal manifestations of pathological phagocytosis, inflammation, and, in 1891, gave a series of lectures on this subject which he afterwards published in a volume. According to his usual method, he began by the most primitive beings, taking as a starting-point the lower organisms which do not yet possess differentiated functions, and whose normal digestion is, if necessary, used as a means of defence against noxious agents. Then, by a comparative study in every grade of the animal kingdom, he proved that the same mode of struggle and defence persists in the mesodermic cells, the phagocytes in all animals in general. In all of them, thanks to a special sensitiveness, Chimiotaxis, phagocytes move towards the intruder, to englobe it and digest it if they can. This reaction for defence by the organism takes place in beings endowed with a vascular system by the migration of the blood-phagocytes which traverse the walls of the blood-vessels in order to betake themselves to the invaded point.
In higher animals, all the symptoms which accompany this phenomenon of defence and which constitute the classical picture of inflammation (a heightened temperature, pain, redness, tumefaction) are due to the complexity of the organism; but the essence, the primum movens of inflammation, with them also, is a digestive action of the phagocytes upon the noxious agent, therefore a salutary reaction of the organism, essentially similar to the normal digestion of inferior beings. Metchnikoff adduced numerous examples giving evidence of the genetic link which exists between inflammation and normal intracellular digestion, and while establishing the evolution of the former on biological and experimental bases, he showed at the same time the close connection which binds normal biology and pathological biology.
This series of lectures formed a volume which appeared in 1892 under the title of Leçons sur la pathologie comparée de l’inflammation, a book which contributed to the acceptation of the phagocyte theory and which showed the importance of Natural History applied to Medicine.