524 BIOLOGY OF PNEUMOCOCCUS 



along with a host of modifications in the preparation of each anti- 

 gen have been considered in attempts to increase the therapeutic 

 potency of antipneumococcic serum. 



Virulence. The virulence of strains of pneumococci used for im- 

 munization was recognized as an important factor soon after im- 

 munological studies were begun. Emmerich and Fowitzky (1891) 357 

 found that rabbits injected subcutaneously with attenuated cul- 

 tures became only partly immune, but after the intravenous admin- 

 istration of fully virulent cultures a "complete" immunity resulted. 

 It should be borne in mind, however, that while the difference in the 

 routes of injection may have played a part in the outcome of the 

 experiments, the conclusions reached are in accord with present 

 conceptions. A year later, Mosny 932 stated that cultures used for 

 immunization should be virulent, and added the requirement that 

 cultures should be heated for three hours at 60°. Emmerich, 356 and 

 Romer 1155 both subscribed to the idea of using only virulent strains 

 for immunization, and Landmann, 779 who worked under Romer, 

 found that more uniform and potent serums were obtained when 

 only highly virulent strains of pneumococci were employed. Neu- 

 feld and Haendel 989 also used only strains of exalted virulence. 

 Wadsworth, 1458 in determining the curative and protective activity 

 of immune serum in infected rabbits, reported that while immune 

 serum might be protective, only after immunization of animals 

 with living, virulent cultures did the serum acquire marked cura- 

 tive properties. In the same year, Dochez 316 reported the develop- 

 ment of highly potent protective serum by immunization of the 

 horse with large doses of virulent organisms in the living state. 



In the well-known Rockefeller Monograph No. 7, Avery and his 

 colleagues 36 emphasized the importance of using virulent strains 

 for immunization. So, too, Raphael 1121 declared that the degree of 

 immunizing action is dependent upon virulence, and advocated a 

 study of the antigenicity of only virulent strains in rabbits before 

 attempting the hyperimmunization of larger animals. In studying 

 the response of mice and rabbits to immunization with living or 



