DISSOCIATION AND TRANSFORMATION 145 



In Amzel's 15 next paper it was reported that pneumococci iso- 

 lated from pneumonia patients before optochin injections were of 

 the smooth type, while the organisms cultivated after injection 

 grew as rough colonies. Untreated cases yielded only smooth colo- 

 nies and, in two cases repeatedly treated with optochin, the iso- 

 lated culture was persistently composed of both smooth and rough 

 forms. Amzel attempted to convert the rough into smooth strains 

 by mouse passage but was able to effect this reversion in only one 

 of three trials. 



During the 1920's there came abundant confirmation and expan- 

 sion of the earlier observations on pneumococcal dissociation. Ja- 

 cobson and Falk ( 1926-1927 ), 674 " 5 continuing their earlier studies, 

 were able to degrade smooth strains of Blake and Trask's A, B, 

 and C modifications into rough strains by growing the organisms 

 in broth containing specific immune serum, although after twenty- 

 three transfers the conversion was incomplete. The cultures were 

 still mixtures of S and R varieties. The former continued to have 

 the same virulence and electrophoretic potential, but the latter 

 were reduced in both virulence and potential. Rough variants of 

 the B and C strains reverted after twelve transfers in homologous 

 immune serum broth, and showed the same virulence and potential 

 as the original smooth organisms. In all the strains studied there 

 were alterations in virulence accompanied by parallel alterations 

 in electrophoretic potential and by reciprocal changes in agglu- 

 tinability. Levinthal 800 also observed changes in virulence and in 

 the cultural and serological behavior of a highly virulent Type I 

 pneumococcus after cultivation in serum broth. He was able to 

 effect the transformation of R to S forms by growth in broth at 

 25° and by subsequent mouse passage. 



IN VIVO VARIATION 



Similar variations apparently taking place in vivo were de- 

 scribed by Wadsworth and Sickles. 1474 Cultures isolated directly 

 from the blood stream of horses undergoing immunization, or at 



