308 INFECTION AND RESISTANCE 



From the discovery of antibacterial properties in the extracts 

 of leukocytes it is but a logical step to the attempt to utilize these 

 substances therapeutically. Petterson 48 was probably the first to 

 study this phase of the problem systematically in connection with 

 anthrax infection in dogs and rabbits. In preliminary studies he 

 claimed to have determined that when leukocytes are left in con- 

 tact with serum for four hours or longer there develops in the mix- 

 ture a bactericidal power far superior to that which is possessed 

 by these elements when separately kept in salt solution and mixed 

 only just before the bactericidal tests. He attributes this to the 

 fact that in dogs, at least, the leukocytes furnish bactericidal sub- 

 stances to the serum an assumption which is entirely in accord 

 with the earlier opinion of Denys and Kaisin, 49 which we have men- 

 tioned in another place. In direct continuance of these experiments 

 he injected leukocytes into dogs at the same time at which he in- 

 fected them with anthrax and observed a moderately protective in- 

 fluence, which, however, he admits was not very great. He followed 

 this work in 1906 with similar observations on the protective influ- 

 ence of leukocytes in intraperitoneal infections of guinea pigs with 

 typhoid bacilli. In these experiments 50 he made the curious ob- 

 servation that, although such protective influence was unquestionable, 

 the guinea pig leukocytes contained no bactericidal substances active 

 against typhoid bacilli. In consequence he concluded that the de- 

 struction of these bacteria in the guinea pig was due entirely to the 

 serum-antibodies absorbed by the microorganisms before phago- 

 cytosis, even when the actual destructive process took place intra- 

 cellularly. The protective effect following on the injection of the 

 leukocytes he attributed to an indirect influence of the leukocytic 

 substances in stimulating the more rapid accumulation of alexin or 

 complement in the peritoneum, with consequently more powerful 

 phagocytosis. Following this, in 1908, Opie 51 carried out experi- 

 ments in which he observed that leukocytes injected intrapleurally 

 into dogs, together with tubercle bacilli, exerted a distinct protec- 

 tion. 



In the same year extensive observations on the protective prop- 

 erties of leukocyte extracts were published by Hiss. 



Hiss 52 worked at first with extracts of dog, rabbit, and guinea 

 pig leukocytes; later he confined himself entirely to rabbit leuko- 

 cytes. He extracted the leukocytes at first by repeated freezing and 

 thawing in physiological salt solution, but the technique of his sub- 

 sequent W 7 ork was uniformly as follows: Intrapleural injections of 



48 Petterson. Centralbl f. Bakt., Vol. 36, 1904. 



49 Denys and Kaisin. "La Cellule," Vol. 9, 1893. 



50 Petterson. Centralbl. f. Bakt., Vols. 40 and 42, 1906. 



51 Opie. Jour. Exp. Med.., 1908. 



52 Hiss. Jour, of Med. Ees., new series, Vol. 14, 1908. 



