ANTIGENICITY OF PNEUMOCOCCUS 325 



develop the subject by showing the manner in which our present 

 knowledge has been acquired. Although it was Fraenkel 468 who first 

 observed that rabbits surviving a subcutaneous injection of pneu- 

 mococci became resistant to subsequent inoculation with the same 

 organism, it was Foa and Bordoni-Uffreduzzi 461 who established 

 the fact in an experimental way. By injecting rabbits subcutane- 

 ously at three or four-day intervals, beginning with attenuated 

 cultures and then giving cultures of increasing virulence, the ani- 

 mals became insusceptible to inoculation with virulent cultures or 

 infected blood. The authors applied the method to man but with 

 no success. Then Foa 458 turned to the soluble products of Pneumo- 

 coccus, and attempted the chemical isolation of the immunizing 

 principle from broth cultures, but the experiments were inconclu- 

 sive. 



A great debt is owing the Klemperers, 723 ' 5 who laid the founda- 

 tion for the active immunization of animals against pneumococcal 

 infection. As has already been told, the Klemperers used the spu- 

 tum of convalescent pneumonia patients, bacteria-free pleural 

 exudates, heated glycerol extracts, and heat-killed cultures as an- 

 tigens and hence became the first to demonstrate that dead pneu- 

 mococci and some of their derivatives, quite as well as the living 

 cells, can render an animal immune. They also introduced the in- 

 travenous route for the administration of antigenic materials and 

 proved that the serum of the immunized rabbits carried substances 

 antagonistic to Pneumococcus. Like Foa, the Klemperers believed 

 incorrectly that the immunizing principle in Pneumococcus was a 

 toxin. 



There then began a succession of publications dealing with the 

 action of various pneumococcal materials in inducing immunity. 

 There were the successful results of Emmerich and Fowitzky 357 

 with cultures of attenuated and then of diluted, virulent strains, 

 and those of Bonome, 137 and of Kruse and Pansini, 763 with sterile 

 culture filtrates, injected intravenously, subcutaneously, and in- 

 traperitoneally. Mosny 932 was another to employ sterile culture fil- 



