DISSOCIATION AND TRANSFORMATION 137 



Pneumococcus by cultivation in immune serum. When virulent 

 strains were grown in broth containing homologous immune serum, 

 there developed variations in agglutinability, decrease in virulence, 

 inhibition of capsule formation, increase in phagocytability with 

 normal serum, and a change in absorptive power and in antigenic 

 properties. Reversion of the changed forms to the original type 

 took place on animal passage, the number of such passages re- 

 quired usually varying with the number of previous serum treat- 

 ments. The immune response, as measured by agglutinins, was 

 slower in rabbits injected with strains grown in immune serum 

 than with those cultivated in normal serum. A spread of aggluti- 

 native action was evident in the ability of the serum of immune 

 rabbits injected with a serum-treated Type II culture to aggluti- 

 nate pneumococci belonging to both Types I and II. Type-speci- 

 ficity was being lost and replaced by species-specificity. Cultures 

 grown in normal serum formed capsules upon injection into mice, 

 whereas those grown in homologous immune serum under similar 

 conditions showed no demonstrable capsules. This loss of the abil- 

 ity of Pneumococcus to synthesize the capsular substance was 

 later to assume a new and broader significance. 



Later Observations of Dissociation 



SMOOTH AND ROUGH FORMS OF PNEUMOCOCCUS 



Arkwright (1921 ), 18 in studying the colony appearance of dys- 

 entery bacilli grown on media containing immune serum, gave the 

 designations S and R — smooth and rough — to the dissociants be- 

 cause of the corresponding differences in colony topography of 

 each form. Griffith, 560 in 1923, extended Stryker's observations and 

 applied the letters S and R to the two forms of colonies he ob- 

 served when pneumococci were grown in media containing homolo- 

 gous immune serum. The S colonies have a smooth surface, and 

 the cocci forming them produce the soluble specific substance in 

 broth culture, agglutinate with specific serum of the homologous 



