ANTIGENICITY OF PNEUMOCOCCUS 327 



dependent upon the maximal amount of unaltered protein and car- 

 bohydrate in the cell. 



All through the literature on pneumococcal immunity, from the 

 time of Denys and of Washbourn, there are repeated statements to 

 the effect that virulent pneumococci are more active immunizing 

 agents than are attenuated strains. The study of the antigenic ac- 

 tion, especially in regard to type-specificity, of variant forms of 

 pneumococci substantiates this fact. Neufeld, Cole, Wadsworth, 

 and others, have always advocated the use of cultures in a virulent 

 state for the production of immune serums. Barach 75 has shown 

 that a highly virulent pneumococcus provokes a more marked im- 

 munity than an organism of low virulence — an observation cor- 

 roborated by Meyer and Sukneff, 898 Day, 308 and many others. 

 Therefore, whether the immunizing antigen is to be the living or 

 killed organism or any of the separate substances isolated or de- 

 rived from the cell, the evidence is wholly in favor of selecting a 

 culture in vigorous condition and of exalted virulence. 



Dead Cultures 



HEAT-KILLED ANTIGENS 



For a long time living pneumococci, usually after a preliminary 

 course of injections of heat-killed cultures, were used for the vac- 

 cination of horses in the production of curative serums. The prac- 

 tice, however, caused a grave mortality among the animals under 

 treatment. In 1917, the senior author of this volume, among 

 others, desiring to prevent the depletion of his stables, substituted 

 for living cocci, heat-killed organisms from broth cultures, and al- 

 though the agglutinin titer of the horses was low, the content of 

 the serum in mouse-protective antibodies was more than sufficient 

 to meet standard requirements of that time. 



Using cultures devitalized by heat, formaldehyde, soaps, or 

 other means became the practice in many serum-producing labora- 

 tories, although the literature contains relatively few detailed ob- 



