September 3, 1891] 



NATURE 



421 



became diseased or old. Hence these proteins were chiefly found 

 in old cultures, the filtered and sterilised extracts of which always 

 possessed a strong attracting influence on leucocytes. Hence it 

 followed that, "The more a given micro-organism is harmfully 

 influenced by the living fluids of a given species of animals, 

 the more proteins will be excreted. This, as a natural conse- 

 quence, is followed by a corresponding increase in the number of 

 cells which emigrate to the point of inoculation." In every case 

 the living fluids of the body exert a harmful influence on micro- 

 organisms, and then, when in consequence of this the excretion 

 of proteins takes place, the amoeboid cells emigrate to the spot. 



Turning now to the characteristics of this germicidal sub- 

 stance present in serum, he thought that this germicidal power 

 gradually disappeared, so that after a few days the serum had 

 no bactericidal power. This germicidal action was destroyed by 

 the micro-organisms themselves, for, unless the latter were com- 

 pletely destroyed, they soon began to grow freely in ?erum. This 

 germicidal substance was easily destroyed by heat. Serum 

 which had been maintained at 55° C. during half an hour, or at 

 52° C. during six hours, lost its bactericidal power completely. 

 A moderate degree of warmth (37° C.) intensified the germicidal 

 action of the blood or serum. 



Turning now to the queslion as to whether this bactericidal 

 action of the blood had any share in the production of immunity, 

 he gave the f 'llowlng facts as proving that there was some con- 

 nection between the immunity of a given animal against a given 

 infectious disease, and the bactericidal action of its blood on the 

 micro-organism producing the disease : — 



{a) The blood and serum of animals, such as mice and guinea- 

 pigs, which readily succumbed to anthrax had no bactericidal 

 power on anthrax-bacilli. 



(/') The serum of animals which took anthrax readily never 

 possessed such a strong bactericidal action as the serum of white 

 rats, which were immune against anthrax. 



{c) The blood and serum of animals rendered artificially 

 immune possessed stronger bactericidal powers than the blood 

 and serum of normal animals. 



((/) The blood and serum of animals rendered artificially 

 immune against a given micro-organism lessened the virulence of 

 the specific micro-organism causing the disease. 



{e) Whenever blood and serum possessed no bactericidal 

 action on microorganisms, this absence of bactericidal action 

 might be due to the fact that, owing to the necessary manipu- 

 lations, this bactericidal substance had been altered or even 

 destroyed. 



As further proving that the immunity of animals depended on 

 some substance present in the serum, he mentioned the facts 

 described by Behring, Kitasato, Ogata, and Emmerich, in which 

 the injection of blood or serum of an animal immune against 

 a given bacillu=, cured another animal afflicted with the same 

 disease. This curative power he attributed to the presence in 

 the blood of immune animals of a protective substance, probably 

 proteid in its nature, to which he gave the name of " alexine " 

 (from h.\i%f:l.v, to protect). These alexines were not ordinary 

 oxidation products of the tissues, as they were quite specific in 

 their action. They were not simply enzymes, as they had no 

 hydrolytic properties, but they were most probably proteid sub- 

 stances. These alexines were probably formed in the cells ; but, 

 when formed, their action was quite independent from that of 

 cells, and they were probably always present in immune animals. 



Mr. E. H. Hankin, of Cambridge, after giving a m«wi? of the 

 work done by various observers, said that theoretical considera- 

 tions led him to suspect that a particular ferment-like proteid, 

 known as cell globulin B, was a substance possessing bacteri- 

 cidal power. He tested its action on anthrax bacilli, and found 

 that it had the power of destroying these microbes. 



He further found that similar substances were present, not 

 only in animals that were naturally immune again>t anthrax, but 

 also in those that were susceptible to this disease. To these sub- 

 stances he had given the name of defensive proteids. In his pub- 

 lished papers on this subject he had noted various similarities in 

 the bactericidal action of these substances, and that possessed by 

 blood -serum, and these resemblances were such as to leave little 

 room for doubt that the bactericidal action of blood-serum was 

 due to the presence of these defensive proteids. 



The serum of white rats contained a proteid body possessing 

 a well-marked alkaline reaction, and a power of destroying an- 

 thrax bacilli. Further, when injected into mice along with fully 

 virulent anthrax spores, it would prevent the development of the 



NO. II 40, VOL. 44] 



disease. On the other hand, defensive proteids of animals sus- 

 ceptible to anthrax did not exert such protective power, and 

 consequently these experiments indicated a difference in the 

 mode of action of defensive proteids of immune and non-im- 

 mune animals respectively. Further, the amount of defensive 

 proteid present in a rat could be diminished by the causes which 

 were known to be capable of lowering the animal's power of 

 resisting anthrax. For instance, Feser stated that rats become 

 susceptible to anthrax when fed on a vegetarian diet. Mr. Hankin 

 obtained similar results with wild rats. The ordinary white 

 rat he found to be generally refractory to anthrax on any 

 diet, and the defensive proteid could always be obtained from 

 its spleen and blood -serum. This was not the case with wild 

 rats. In one experiment eight wild rats were used ; of these, four 

 vvere fed on bread and meat, the others on plain bread, for about 

 six weeks. Then one rat of each lot was inoculated with an- 

 thrax ; of these, the one that had been subjected to a bread diet 

 succumbed. The remaining rats were killed, and it was found 

 that while the spleens of the flesh-fed rats contained abundance 

 of the defensive proteid, only traces of this substance could be 

 obtained from the spleens of the rats that had been fed on bread 

 alone. A similar result was obtained in other experiments. 



Very young rats were known to be susceptible to anthrax, 

 and so far as could be judged from the litmus test (after dialysis 

 and addition of NaCl), their serum appeared to contain less of 

 the defensive proteid than did ihit of the adult rat. Further, 

 Mr. Hankin found that a young rat could be preserved from 

 anthrax by an injection of its parent's blood-serum. 



These facts appeared to prove that the defensive proteid of 

 the rat deserved its name, in that it preserves the animal from 

 the attack of the anthrax microbe ; in other words, that this 

 substance was at any rate a part cause of the rat's immunity 

 against anthrax. 



Defensive proteids appeared to be ferment like, albuminous 

 bodies, and it was extremely unlikely that we should for a con- 

 siderable time be able to classify them by any other than 

 physiological tests. From this point of view it was possible to 

 divide them into two classes ; first, those occurring naturally in 

 normal animals, and secondly, those occurring in animals that 

 have artificially been made immune. For these two classes Mr. 

 Hankin proposed the namesof sjzins2:ci& phylaxins. A '* sozin " 

 was a defensive proteid that occurred naturally in a normal 

 animal. They had been found in all animals yet examined, 

 and appear to act on numerous kinds of microbes or on their 

 products. A "phylaxin" was a defensive proteid which was 

 only found in an animal that had been artificially made immune 

 against a disease, and which (so far as is yet known) only acted 

 on one kind of microbe or on its products. 



Each of these classes of defensive proteids could obviously be 

 further subdivided into those that acted on the microbe itself, 

 and those that acted on the poisons it generated. These sub- 

 classes he proposed to denote by adding the prefixes myco- and 

 toxo- to the class name. Thus myco-sozins were defensive 

 proteids occurring in the normal animal, which had the power 

 of acting on various species of microbe. Toxo-sozins were 

 defensive proteids, also occurring in the normal animal, 

 having the power of destroying poisons produced by various 

 microbes. Myco-phylaxins and toxo-phylaxins similarly would 

 denote the two subclasses of the phylaxin group. 



The classification might be represented by the following 

 scheme : — 



, Myco-sozins : — 

 I Alkaline globulins from rat (Han- 

 kin), destroying anthrax bacil- 

 lus. 



lis 



, Sozins: — 

 Defensive proteids present in 

 the normal animal. 



Phylaxins ; — 

 Defensive proteids present in 



the animal after it has been 

 ^ made artificially immune. 



Toxo-s3zins: — 

 Of rabbit, destroying V. metchni- 

 \ kovi poison (Gamaleia). 



Myco-phylaxins: — 

 Of rabbit, destroying pig typhoid 

 bacillus (Emmerich). 



Toxo-phylaxins ; — 

 Of rabbit, &c., destroying diph- 

 theria and tetanus poisons 

 (Behring and Kitasato, anti- 

 toxin of TizzonI and Cattani). 



Prof. Emmerich, of Munich, read a paper on " The Artificial 

 Production of Immunity against Croupous Pneumonia and the 



