BIOCHEMICAL FEATURES 93 



been described in some detail as representing one of the recent 

 trends in the investigation of Pneumococcus and to draw attention 

 to still unstudied possibilities of this remarkable cell and its prop- 

 erties. 



So-Called Toxins 



The severe intoxication that so frequently accompanies pneumo- 

 coccal disease naturally led early investigators to search for a 

 soluble toxin. Profoundly impressed, as they must have been, by 

 the discoveries by von Behring and Kitasato and by Roux of 

 diphtheria and tetanus toxins and of the dramatic efficacy of the 

 corresponding antitoxins, there came a vision of a new and similar 

 agent for the treatment of pneumonia. 



Foa, 458 in 1890, thought that he had found a poison in pneumo- 

 coccal cultures. He isolated the supposed principle by precipita- 

 tion with ammonium sulfate, dialysis, and subsequent concentra- 

 tion. The extract thus prepared produced marked biological 

 changes in rabbits, but failed to kill the animals. Repeated injec- 

 tions raised the resistance of the test animals to later inoculation 

 with a virulent culture, but it seems safe to infer that Foa was 

 merely dealing with the deleterious degradation or lytic products 

 of Pneumococcus. In the next year, Bonome 137 succeeded in pre- 

 paring filtrates that were lethal for rabbits. The toxicity was 

 directly related to the virulence of the culture, and the more poi- 

 sonous extracts, after repeated doses given subcutaneously, intra- 

 venously, and intraperitoneally, rendered rabbits resistant to in- 

 fection. But the subsequent effects were neither toxic nor antitoxic 

 in the true sense of the terms. Issaeff, 673 at the Pasteur Institute, 

 reported similar experiments with comparable results. The serum 

 of rabbits treated with broth cultures of low toxicity possessed 

 therapeutic but no antitoxic power. Issaeff, therefore, had not dem- 

 onstrated the existence of a toxin. Bunzl-Federn 186 also tested in a 

 similar way heated broth cultures but found that their toxicity 

 and antigenicity were feeble. Cole 250 was able to elicit more severe 



