I. S. FALK 571 



been modified by the demonstration of intermediate "O" forms. Except for this com- 

 plication, the variation between "S" and "R" colony form has generally been con- 

 sidered to be qualitative and discontinuous.' Comparisons of virulence between "S" 

 and "R" forms are, of necessity, similarly qualitative and discontinuous. It is usually 

 impossible to discover whether or not there occur intermediate gradations in virulence 

 between the extreme "S" and "R" forms because (when "S" is being converted to 

 "R" or vice versa) the intermediate cultures are unstable and injections of such cul- 

 tures into animals to test virulence usually result in reversions to the virulent "S" 

 variety. But by studying in vitro the electrophoretic potentials (P.D.) on "S" and 

 "R" forms of pneumococci and on all the intermediate cultures, Jacobson and I found-" 

 that the progressive conversion of "S" to "R" is accompanied by apparently gradual 

 (and not discontinuous) changes in P.D. Furthermore, "S" cultures which have been 

 changed with respect to the magnitude of P.D. have not necessarily been sufficiently 

 altered to show "R" colonies, nor have those which have been changed to the "R" 

 forms been, of necessity, sufficiently changed in virulence or P.D. to give sensibly 

 different measurements. I am led to conclude tentatively that: 



1. In all the cases which we studied, alterations in the virulence of pneumococci 

 for white mice were accompanied by parallel alterations in P.D., inagglutinability, 

 and in other characteristics; and such alterations occurred in a continuous and not 

 in a discontinuous manner. 



2. It is probable that the variations between virulent "S" and avirulent "R" 

 forms represent the fixed extremes of continuous variations in virulence; and that 

 with respect to colony form, as with other characteristics, the variations are con- 

 tinuous. 



WHY IS P.D. CORRELATED WITH NON-TOXIGENIC VIRULENCE? 



From evidence of the type which has been briefly summarized, it has appeared 

 that there are parallelisms between virulence and the electrophoretic potential differ- 

 ence (P.D.) on non-toxigenic bacteria which are not merely accidental or occasional. 

 Every device used by which P.D. is changed (without destruction of viability) has 

 resulted in a parallel change in virulence ; and every change in virulence studied was 

 accompanied by similar alterations in P.D. Inasmuch as the resistance of the host 

 against the non-toxigenic bacteria studied is principally associated with a phagocytic 

 mechanism of immunity, we turned to a study of the relations between P.D. and 

 phagocytosis for an explanation of the findings. The analysis is still in progress, but 

 enough has already been done to indicate that the phagocytosis of live or dead organ- 

 isms bears a definite relation to the charges on the bacteria and on the phagocyte. 

 Falk and Matsuda have reported: 



1. For the A, B, and C strains of pneumococci, the sequence for P.D. and for 

 virulence to mice is A>B>C. 



2. In the presence of normal rabbit serum or of immune horse serum, the sequence 

 of the phagocytic index is C>B>A. 



' Observations in my laboratory are not in accord with this view. We have generally found that 

 the "S" and "R" colonies vary in "smoothness" and "roughness" and grade from one form to the 

 other. 



' Loc. cit. 



