332 



NA TURE 



[August 2, 1906 



thnt the mere living quality of the issues was in some 

 unknown way antagonistic to foreign intrusive disease- 

 germs. 



The first eighteen years of Metschnikoff's career, after 

 his undergraduate course, were devoted to zoological and 

 embryological investigations. He discovered many import- 

 ant facts, such as the alternation of generations in the 

 parasitic worm of the frog's lung — Ascaiis nigroveiiosa — 

 and the history of the growth from the egg of sponges and 

 medusjE. 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 amoeba, 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 Metsch- 

 nikoff saw these amceba-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 become 

 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 ; 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 lo say, cannot be effectively 

 attacked by disease-germs. 



Disease-germs, bacteria, or protozoa produce poisons 

 which sometimes are too much for the phagocytes, poison- 

 ing them and so getting the upper hand. But, as 

 Metschnikoff showed, the training of the phagocytes by 

 weak doses of the poison of the disease-germ, or by weak- 

 ened cultures of the disease-germ itself, brings about a 

 power of resistance in the phagocytes to the germ's poison, 

 and thus makes them capable of attacking the germs 

 and keeping them at bay. Hence the value of inocula- 

 tions. 



The discussion and experiments arising from Metsch- 

 nikoff's demonstrations have led to the discovery of the 

 production by the phagocytes of certain exudations from 

 their substance which have a most important effect in 

 weakening the resistance of the intrusive bacteria and 

 rendering them easy prey for the phagocyte. These are 

 called "sensitisers," and have been largely studied. They 

 may be introduced artificiallv into the blood and tissues so 

 as to facilitate the work of the phagocytes, and no doubt it 

 is a valuable remedial measure to make use of such sensi- 

 tisers as a treatment. Sir A. E. Wright considers that such 

 sensitisers are formed in the blood and tissues independ- 

 ently of the phagocytes, and has called them "opsonins," 

 under which name he has made most valuable application 

 of the method of injecting them into the body so as to 

 facilitate the work of the phagocytes in devouring the 

 hostile bacteria of various diseases. Each kind of disease- 

 producing microbe has its own sensitiser or opsonin ; hence 

 there has been much careful research and experiment re- 

 quired in order to bring the discovery to practical use. 

 Metschnikoff himself holds and quotes experiments to show 

 that the "opsonins" are actuallv produced by the pha- 

 gocytes themselves. That this should be so is in accord- 

 ance with some striking zoological facts, as I pointed out 

 nearly twenty years ago. For the lowest multicellular 

 animals provided with a digestive sac or gut, such as the 



NO. I 91 8, VOL. 74] 



polyps, have that sac lined by digestive cells which have 

 the same amoeboid character as " phagocytes," and actually 

 digest to a large extent by swallowing or taking into their 

 individual protoplasm raw particles of food. Such particles 

 are enclosed in a temporary cavity, or vacvole, into which 

 the cell-protoplasm secretes digestive ferment and other 

 chemical agents. Now there is no doubt that such digestive 

 vacuoles may burst and so pour out into the polyp's stomach 

 a digestive juice which will act on food particles outside 

 the substance of the cells, and thus by the substitution of 

 this process of outpouring of the secretion for that of in- 

 gestion of food particles into the cells we get the usual 

 form of digestion by juices secreted into a digestive cavity. 

 Now this being certainly the case in regard to the history 

 of the original phagocytes lining the polyp's gut, it does 

 not seem at all unlikely, but on the contrary in a higher 

 degree probable, that the phagocytes of the blood and 

 tissues should behave in the same way and pour out 

 sensitisers and opsonins to paralyse and prepare their bac- 

 terial food. And the experiments of Metschnikoff's pupils 

 and followers show that this is undoubtedly the case- 

 Whether there is any great variety of and difference be- 

 tween "sensitisers" and "opsonins" is a matter which is 

 still the subject of active experiment. Metschnikoff's con- 

 clusion, as recently stated in regard to the whole progress 

 of this subject, is that the phagocytes in our bodies should 

 be stimulated in their activity in order successfully to fight 

 the germs of infection. Alcohol, opium, and even quinine, 

 hinder the phagocytic action ; they should therefore be 

 entirely eschewed or used only with great caution where 

 their other and valuable properties are urgently needed. 

 It appears that the injection of blood-serum into the tissues 

 of animals causes an increase in the number and activity of 

 the phagocytes, and thus an increase in their resistance 

 towards pathogenic germs. Thus Durham (who was a 

 pioneer in his observations on the curious phenomena of 

 the " agglutination " of blood corpuscles in relation to 

 disease) was led to suggest the injection of sera during 

 surgical operations, and experiments recently quoted by 

 Metschnikoff seem to show that the suggestion was well 

 founded. After years of opposition bravely met in the pure 

 scientific spirit of renewed experiment and demonstration, 

 Metschnikoff is at last able to say that the foundation- 

 stone of the hygiene of the tissues — the thesis that our 

 phagocytes are our arms of defence against infective germs 

 • — has been generally accepted. 



Another feature of the progress of our knowledge of 

 disease — as a scientific problem — is the recent recognition 

 that minute animal parasites of that low degree of unicellu- 

 lar structure to which the name "Protozoa" is given, are 

 the causes of serious and ravaging diseases, and that the 

 minute algoid plants, the bacteria, are not alone in posses- 

 sion of this field of activity. It was I^averan — a French 

 medical man — who, just about twenty-five years ago, dis- 

 covered the minute animal organism in the red blood-cor- 

 puscles, which is the cause of malaria. Year by year ever 

 since our knowledge of this terrible little parasite has 

 increased. We now know many similar to, but not identical 

 with it, living in the blood of birds, reptiles, and frogs. 



It is the great merit of Major Ross, formerly of the Indian 

 Army Medical Staff, to have discovered, by most patient 

 and persevering experiment, that the malaria parasite passes 

 a part of its life in the spot-winged gnat or mosquito 

 (Anopheles), not, as he had at first supposed, in the 

 common gnat or mosquito (Culex), and that if we can get 

 rid of spot-winged mosquitoes or avoid their attentions, or 

 even only prevent them from sucking the blood of malarial 

 patients, we can lessen, or even abolish, malaria. 



This great discovery was followed by another as to the 

 production of the deadly " Nagana " horse and cattle disease 

 in South Africa by a screw-like, minute animal parasite, the 

 Trypanosoma Brucci. The Tsetze fly, which was already 

 known in some way to produce this disease, was found by 

 Colonel David Bruce to do so by conveying by its bite the 

 Trypanosoma from wild big-game animals, to the domesti- 

 cated horses and cattle of the colonists. The discovery of 

 the parasite and its relation to the fly and the disease was 

 as beautiful a piece of scientific investigation as biologists, 

 have ever seen. A curious and very important fact was 



