We must not forget that in this same period much of the immortal work of Pasteur on hydrophobia, of Behring and Roux on diphtheria, and of Ehrlich and many others to whom the eternal gratitude of mankind is due, has been going on. It is only some fifteen years since Calmette showed that if cobra poison were introduced into the blood of a horse in less quantity than would cause death, the horse would tolerate with little disturbance after ten days a full dose, and then day after day an increasing dose, until the horse without any inconvenience received an injection of cobra poison large enough to kill thirty horses of its size. Some of the horse’s blood being now withdrawn was found to contain a very active antidote to cobra poison—what is called an antitoxin. The procedure in the preparation of the antitoxin is practically the same as that previously adopted by Behring in the preparation of the antitoxin of diphtheria poison. Animals treated with injections of these antitoxins are immune to the poison itself when subsequently injected with it, or, if already suffering from the poison (as, for instance, by snake-bite), are readily shown by experiment to be rapidly cured by the injection of the appropriate antitoxin. This is, as all will admit, an intensely interesting bit of biology. The explanation of the formation of the antitoxin in the blood and its mode of antagonising the poison is not easy. It seems that the antitoxin is undoubtedly formed from the corresponding toxin or poison, and that the antagonism can be best understood as a chemical reaction by which the complex molecule of the poison is upset, or effectively modified.
The remarkable development of Metschnikoff’s doctrine of phagocytosis during the past quarter of a century is certainly one of the characteristic features of the activity of biological science in that period. At first ridiculed as ‘Metschnikoffism,’ it has now won the support of its former adversaries.
For a long time the ideal of hygienists has been to preserve man from all contact with the germs of infection, to destroy them and destroy the animals conveying them, such as rats, mosquitoes, and other flies. But it has now been borne in upon us that, useful as such attempts are, and great as is the improvement in human conditions which can thus be effected, yet we cannot hope for any really complete or satisfactory realisation of the ideal of escape from contact with infective germs. The task is beyond human powers. The conviction has now been arrived at that, whilst we must take every precaution to diminish infection, yet our ultimate safety must come from within—namely, from the activity, the trained, stimulated, and carefully guarded activity, of those wonderful colourless amœba-like corpuscles whose use was so long unrecognized, but has now been made clear by the patiently continued experiments and arguments of Metschnikoff, who has named them ‘phagocytes.’ The doctrine of the activity and immense importance of these corpuscles of the living body which form part of the all-pervading connective tissues and float also in the blood, is in its nature and inception opposed to what are called the ‘humoral’ and ‘vitalistic’ theories of resistance to infection. Of this kind were the beliefs that the liquids of the living body have an inherent and somewhat vague power of resisting infective germs, and even that the mere living quality of the tissues was in some unknown way antagonistic to foreign intrusive disease-germs.
Fig. 37. Fig. 38. Fig. 39.
Fig. 37.—Phagocyte or colourless corpuscle of a guinea-pig in the act of engulphing two Spirilla or parasitic vegetable microbes of a spiral shape. Fig. 38.—The same half an hour later, one of the Spirilla is nearly completely engulphed. Fig. 39.—The same ten minutes later still, one of the Spirilla is completely absorbed into the substance (protoplasm) of the phagocyte. (From Metschnikoff’s book, “Immunity,” kindly supplied by the Cambridge University Press.)
The first eighteen years of Metschnikoff’s career, after his undergraduate course, were devoted to zoological and embryological investigations. He discovered many important facts, such as the alternation of generations in the parasitic worm of the frog’s lung—Ascaris nigrovenosa—and the history of the growth from the egg of sponges and medusæ. In these latter researches he came into contact with the wonderfully active cells, or living corpuscles, which in many low forms of life can be seen by transparency in the living animal. He saw that these corpuscles (as was indeed already known) resemble the well-known amœba, and can take into their soft substance (protoplasm) at all parts of their surface any minute particles and digest them, thus destroying them. In a transparent water-flea Metschnikoff saw these amœba-like, colourless, floating blood-corpuscles swallowing and digesting the spores of a parasitic fungus which had attacked the water-fleas and was causing their death. He came to the conclusion that this is the chief, if not the whole, value of these corpuscles in higher as well as lower animals, in all of which they are very abundant. It was known that when a wound bringing in foreign matter is inflicted on a vertebrate animal the blood-vessels became gorged in the neighbourhood and the colourless corpuscles escape through the walls of the vessels in crowds. Their business in so doing, Metschnikoff showed, is to eat up the foreign matter, and also to eat up and remove the dead, wounded tissue. He therefore called these white or colourless corpuscles ‘phagocytes,’ the eater-cells, and in his beautiful book on Inflammation, published twenty years ago, proved the extreme importance of their activity. At the same time he had shown that they eat up intrusive bacteria and other germs (see figs. 37 to 43); and his work for the last twenty years has mainly consisted in demonstrating that they are the chief, and probably the only, agents at work in either ridding the human body of an attack of disease-causing germs or in warding off even the commencement of an attack, so that the man or animal in which they are fully efficient is ‘immune’—that is to say, cannot be effectively attacked by disease-germs.