420 



NATURE 



[September 3, 1891 



into sensitive animals, the greater the degree of refractoriness 

 shown by the animal, the more rapidly the microbes were con- 

 sumed by the leucocytes. In a non-resistant animal the microbes 

 remained free ; no such phenomenon as phagocytosis could be ob- 

 served. It seemed, therefore, that the phagocytes were charged 

 with the defence of the human organism, and entered into con- 

 flict with the parasites which infected the human frame. It 

 might be said that there were diseases in which the microbes 

 were to be met with in the cells specially, and that these microbes 

 nevertheless proved fatal to the animal. In tuberculosis and in 

 leprosy the bacilli were to be found in the cells, and the results 

 were of the most serious kind, in spite of the intense phagocytosis 

 induced by the microbes of these diseases. This fact proved that 

 the phagocytes and all the other means of defence were, under 

 certain conditions, and at certain times, powerless to effect any 

 good results ; they had done their best to take up the microbes, 

 but these had adapted themselves to the interior of the cells, and 

 had conquered. It was not sufficient that the microbes should 

 be eaten up, it was essential that they should also be digested 

 by the phagocytes. Even in those cases where the struggle was 

 going against the human organism, these cells still were the 

 aggressors. It had been frequently observed in tuberculosis 

 and leprosy that the bacilli had been killed in the interior of 

 certain of these cells. The theory asserted that a struggle oc- 

 curred between the microbes and the cells, but it did not imply 

 that the bacilli always won the day. Phagocytosis only occurred 

 in immune animals ; in animals susceptible to the disease it was 

 either not to be observed, or it was incomplete. 



He then proceeded to discuss the questions whether immunity 

 was the consequence of this power of the cells to digest the 

 virulent microbes. As had been said, the cells of a refractory 

 animal took up the microbes, which, it would appear, under 

 favourable circumstances remained inert in the interior of the cells. 



Numerous facts had been alleged to show that the microbes 

 at the time they were taken up by the phagocytes were 

 not degenerated, but were, on the contrary, in a condition of 

 full activity. Thu?, to take only one example, it had been 

 found that in frogs the bacilli which had been taken up by the 

 lecocytes remained alive within the protoplasm of the cell ; this 

 was apparent from their movements. In lymph taken from the 

 body of a pigeon, numerous bacilli were to be seen imprisoned 

 in the leucocytes, and these bacilli could be watched growing, 

 actually under the eye of the observer, within the interior of 

 dead phagocytes ; they could be seen to elongate, to push out 

 the protoplasm, distort the form of the cell, and finally to make 

 their escape. Another demonstration of the importance of the 

 action of the phagocytes was afforded by the fact that even in 

 immune animals the microbes were found to increase when 

 kept out of the reach of the leucocytes ; thus, if a rabbit were 

 inoculated in the anterior chamber of the eye, where there were 

 no cells, the bacteria grew freely, and their development was only 

 checked when the leucocytes had after a time migrated in large, 

 numbers, and began to take the microbes into their interior. It 

 thus appeared that phagocytosis was a very general pheno- 

 menon, and one which was very efficacious in checking the 

 advance of the organisms ; when it failed, the individual 

 succumbed to the virulence of the bacteria. The question 

 remained, What was the mysterious force which attracted the 

 cells towards the microbes ? Why were the leucocytes, which 

 in immune animals destroyed the microbes, incapable of seizing 

 upon them in non-immune animals ? 



In 1883, Metchnikoff propounded his theory of phagocytosis. 

 This theory rested on two assumptions : first, that the cells were 

 attracted to the microbes in virtue of a special sensibility 

 manifested towards all foreign bodies introduced into the 

 tissues ; the second was that this power of seizing upon 

 the virulent microbes in immune animals originated in a habit 

 formed during the earlier struggle with the attenuated virus with 

 which the animal had been previously inoculated. The be- 

 haviour of the leucocytes might be more readily explained by 

 assuming that leucocytes had the property, analogous to that 

 possessed by the zoosperms of the myxomycetes — namely, that 

 of being attracted by certain bodies and repelled by others. 

 MM. Massart and Bordet had proved that the products of the 

 microbes exerted a very marked chemical action on the phago- 

 cytes. When a virus was introduced into the body, it pro- 

 liferated, and secreted a substance which attracted the leuco- 

 cytes ; the more active the virus, the more energetic were the 

 poisons elaborated by it, and the cells which penetrated to the 

 point of inoculation were paralyzed in their action, and rendered 



NO. I 140, VOL. 44] 



incapable of taking up the microbes, which therefore proliferated 

 without hindrance. Further, in certain diseases the virus pro- 

 duced a substance which was still more poisonous. In chicken 

 cholera, for instance, the poison secreted by the microbes 

 repelled the leucocytes from the point of inoculation ; it 

 thus came about that phagocytes were never found in this 

 particular affection. This, however, was not the case with 

 animals which had been rendered immune either by inoculation 

 of the attenuated virus, or by the injection of a suitable dose of 

 bacterial products. If the animal were given a strong virus, 

 phagocytes were attracted to the point of inoculation, and 

 these possessed the power of taking up the microbes before they 

 had time to elaborate effective doses of their toxic material. 

 It was, therefore, at the commencement of the disease that 

 the critical struggle took place. If the leucocytes could not 

 accomplish this at the beginning of the malady, their action 

 at a later period would be useless, since the microbes would 

 have produced enough poison to paralyze their activity. Every 

 cause, therefore, that prevented the access of leucocytes to the 

 point of iaoculation facilitated infection. The theory of im- 

 munity propounded by M. Metchnikoff" did not exclude the 

 possibility of there being other means of protecting the organ- 

 ism, but it simply proved that phagocytosis had a wider sphere 

 of action, and was more efficacious, than any other means of 

 protecting the organism. It seemed to explain all the facts, 

 and was, moreover, eminently suggestive. It was in this way 

 that the knowledge of microbic poisons and chemical inoculation 

 had thrown light on what would otherwise have been obscure. 

 Far from being shaken by the theories which were opposed 

 to it, this theory of Metchnikoff 's had gained by the opposition 

 which it has met, and that was a guarantee of its soundness. 



Dr. Buchner, of Munich, al'ter giving a general account of 

 the various theories of immunity, criticized freely Metchnikoff''s 

 views. The main objections he brought forward were as 

 follows : — 



(i) Many observers failed to notice any destruction of bacilli 

 by phagocytes, when naturally immune animals, such as white 

 rats or pigeons, were inoculated with anthrax. 



(2) In dis ases ending fatally, such as tuberculosis, mice- 

 septicaemia, &c., the micro-organisms were frequently found in 

 the interior of phagocytes. 



(3) The experiments of Petruchky, Baumgarten, Pekelharing, 

 and others seemed to show that the bacilli of anthrax perished 

 in the living fluids of immune animals even when the bacilli 

 were protected against the attacks of white corpuscles. 



Metchnikoff", however, denied this, and proved that the 

 living fluids of immune white rats form a most excellent cultivat- 

 ing medium for the bacilli of anthrax. These observations of 

 Metchnikoff', according to Buchner, might be explained by the 

 fact that Metchnikoff in his experiments introduced more 

 bacilli than could be destroyed by the living fluids of white rats, 

 as a certain quantity of serum was able to destroy only a very 

 small quantity of micro-organisms. Speaking of the experiments 

 made by his pupils Ibener and Roeder, he stated that, when a 

 certain kind of micro-organisms were placed into a given quan- 

 tity of serum, the micro-organisms might either be destroyed in 

 toto, or reproduce themselves in large numbers according to the 

 number of micro-organisms introduced in the first place into the 

 serum. When, instead of placing the micro-organisms directly 

 in contact with the serum, the micro-organisms were wrapped 

 up in sterilised cotton -wool, it was found that the bacilli, so 

 protected against the temporary harmful influence of serum, 

 began to grow luxuriantly at the end of twenty-four hours. The 

 bactericidal power of serum disappeared, therefore, shortly after 

 death. 



Massart, Bordet, and Gabritchewsky had previously proved 

 that the emigration of leucocytes to the spot where the virus was 

 introduced was due to the attracting influence (positive chemo- 

 taxis) of the chemical poisons secreted by micro-organisms, but 

 he (Buchner) was of opinion that the substances dissolved in the 

 cultures have hardly any action on leucocytes, but that this 

 attracting influence on leucocytes was due to the protein 

 present in bacterial cells themselves. Whereas the products of 

 the metabolism of micro-organisms had little or no attracting in- 

 fluence on the leucocytes, the proteins themselves attracted the 

 cells most powerfully. 



As long as the bacterial cells were active and capable of repro- 

 ducing themselves actively, the proteins were contained in the 

 cells, and these poisons only left the cells when the latter 



