In his last summary of the question, presented to the International Congress of Medicine at Paris in 1900, Buchner[912] maintains his theory of leucocytic secretions. But he already takes one step more towards the theory of phagocytosis, at least as regards natural immunity. He consents to accept the fact “that phagocytic activity is in many cases of decisive importance in overcoming the infective processes, especially in those cases in which the secreted alexins were unable to bring about more than a temporary attenuation of the vital functions of the bacteria. Under these conditions the bacteria could only be modified in so far as their chemical functions were transformed into a latent state, from which they would be ready to regain their full vital activity should it happen that the phagocytes were not there to prevent them from doing so.” In any case this view is widely removed from the old theory, according to which phagocytes were regarded as capable of ingesting dead and inoffensive bacteria only.
A second adversary of the theory of phagocytosis, von Behring[913], gives a place to this theory not only in certain examples of natural immunity but even in some cases of acquired immunity, e.g. in the immunity of sheep vaccinated against anthrax, an example I have already cited in Chapter VIII (cf. supra, p. 242).
It would take too long to describe the change of opinion on the theories of immunity that has taken place during recent years. I will content myself with citing certain examples which shall be taken from the works of declared adversaries of the theory of phagocytosis. Thus, Flügge, who early declared against the cellular theory completely and categorically and at the same time argued strongly in favour of the humoral theory, has been gradually led to depart from his first position. We may follow the steps of his conversion in the different editions of his Outlines of Hygiene. In the first edition published in 1889 he expresses himself in the following manner[914]: “Recent researches indicate the probability, however, that the phagocytes in by far the greater majority of cases seize the infective agents which, already dead, are not in a condition suitable for the performance of a defensive function. On the other hand, it is proved that the blood and blood plasma of warm-blooded animals possess the property of destroying, very quickly, enormous numbers of pathogenic bacteria,” ... etc. In the fourth edition of the same work, published in 1897, we find at the corresponding place the following passage[915]: “Recent researches indicate the probability, however, that the theory of Metschnikoff ... is not in a position to offer a complete explanation of the process of immunity.” This passage is followed by a somewhat conciliatory and eclectic development of the theory.
Let us take as a second example Günther’s Introduction to the Study of Bacteriology, widely read both in the original and in translations. In the first edition published in 1890[916] the theory of phagocytosis is curtly dismissed as “being incapable of withstanding criticism.” In the fifth edition of the same work, however[917], published in 1898, this theory is no longer treated thus summarily. It is given a place amongst the theories of immunity and an attempt, similar to that made by Buchner, is made to reconcile it with the humoral theory.
A change in the same direction may also be observed in Charrin’s view. In the first edition of his Pathologie générale infectieuse, this observer[918] had already taken an eclectic view on this question of the theories of immunity. But the function which he assigns to the phagocytes is subsidiary and secondary, whilst to that of the humoral properties is assigned a position of primary importance. In the second edition of the same work, which appeared seven years later[919], the importance of phagocytosis is recognised in a much larger measure, as may be gathered from the following passages: “For my part, I have always accepted phagocytosis: at the same time I have always accepted the existence of special humoral properties. As early as 1888 I showed, in vivo, that the germs are modified outside the cells; but I did not know from what groups of anatomical elements these properties were derived, I exaggerated their importance and it is the decision of this origin and this importance that renders it possible to reconcile the two theories” (p. 250). “After all, the defence rests upon these two great processes or cellular activities, phagocytosis in the first line, and then humoral influences, some of them bactericidal and injurious to the living germ, others antitoxic and injurious to their secretions” (p. 253).
Whilst the theory of phagocytosis has been consolidated by the demonstration: (1) that the phagocytes, in cases of immunity, ingest and destroy the living and virulent micro-organisms without the latter needing to be previously deprived of their toxins; (2) that the phagocytes absorb toxic substances; (3) that the phagocytes contain bactericidal cytases and produce fixatives; the humoral theories, in spite of all the efforts made to defend them, could never be developed as theories that were in the slightest degree of general application. Certain observers who from the first were very sympathetic to the humoral theories have attempted to give a complete summary of these properties. Thus, Stern[920] and later Frank[921] have published reports drawn up with great care and in a very impartial spirit on the works treating of the properties of the body fluids and the part they play in immunity. This is how they sum up the question. Stern came to the conclusion that it is impossible “to demonstrate at all regularly the existence of relations between the bactericidal action of the blood and immunity in all the infective diseases. In some cases, however, these relations are so marked that, for these examples, a causal bond between the two factors is extremely probable.” Frank expresses himself in the following manner: “It follows most clearly that the immunity of an animal—immunity innate or acquired—corresponds with the bactericidal property of the blood in certain exceptional cases only. The only animal, absolutely susceptible to anthrax and whose blood is entirely without any bactericidal power, that it is at present possible to cite, is the mouse.” “The bactericidal action of the blood serum is undoubtedly a fact of great biological importance; but equally certainly it cannot be the general cause of immunity, whether innate or acquired.”
An attempt was made to give fresh life to the humoral theory, either by assuming that the bactericidal substance is nothing but the eosinophile or pseudo-eosinophile secretion of the leucocytes (Kanthack), or by supposing that for the destruction of micro-organisms in the animal body the intervention of the agglutinative substance dissolved and distributed in the body fluids is essential (Max Gruber). These two views were put forward in a tentative form and as preliminary communications only; there is no possibility of raising them to the dignity of theories, and of late years they have not been upheld.
It cannot be denied that not one of the humoral theories has been able to retain its position or to stand against the numerous facts that have been accumulated during recent years.
This extraordinary discrepancy between the bactericidal power of the body fluids and immunity is explained by the circumstance that the microbicidal substances exist in the living animal within phagocytes and only escape from them when these cells have been injured. The fact, so well demonstrated by Gengou, that the blood plasma is without any bactericidal power has given the final blow to the microbicidal theory of the body fluids and it can no longer be maintained.
The humoral theories, based on the antitoxic and protective power of the body fluids, can claim only a very restricted application. These properties are met with in acquired immunity only, and even there are not constant. Many cases of acquired immunity against micro-organisms are unaccompanied by any antitoxic power, and in several examples of this immunity the body fluids do not exhibit any protective power.
There is only one constant element in immunity, whether innate or acquired, and that is phagocytosis. The extension and importance of this factor can no longer be denied.
It is clearly proved that phagocytes are susceptible cells which react against morbific agents, whether organised or not. These cells ingest micro-organisms and absorb soluble substances. They seize microbes whilst these are still living and capable of exercising their noxious effect and bring them under the action of their cellular contents, which are capable of killing and digesting the micro-organisms or of inhibiting their pathogenic action. Phagocytes act because they possess vital properties and a faculty of exerting a fermentative action on morbific agents. The mechanism of this action is not yet definitely settled, and we can foresee that for future researches there will be a vast and fertile field to be reached by pursuing this path.
The present phase of the question of immunity constitutes one stage only in the development of biological science and one which is capable of many improvements.