I. S. FALK 569 



NON-TOXIGENIC VIRULENCE AND ELECTROPHORETIC POTENTIALS 

 PARALLEL RELATIONS 



I have remarked upon the fact that the correlation between virulence and 

 morphological or biochemical characteristics is well established for certain groups of 

 non-toxigenic bacteria. In a search for the mechanism of virulence and an identifica- 

 tion of the properties which determine virulence and the correlated characteristics, 

 it seemed logical to start with the study of those phenomena whose operating mech- 

 anisms are best understood. For reasons which are presented elsewhere in this vol- 

 ume/ it has become apparent that under a wide variety of conditions of physio- 

 logical interest the agglutinability of bacteria is determined by the electrophoretic 

 charge or potential difference (P.D.). Hence, for some years my studies of virulence 

 have been focused upon the P.D. on organisms whose virulence and agglutinability 

 are correlated. 



There have been, from time to time, minor and incidental observations on the 

 parallel relations between P.D. and virulence.^ However, the first specific demonstra- 

 tions were made by Northrop and DeKruif-' who reported measurements of the higher 

 P.D. on a virulent and relatively inagglutinable strain (type D) of the rabbit sep- 

 ticemia organism and the lower P.D. on a non-virulent and spontaneously agglutin- 

 able strain (type G). But they considered that the P.D. -virulence relations might be 

 purely accidental. ^ With the co-operation of a number of colleagues, I have investi- 

 gated the relations between P.D. and virulence at some length. For our first series 

 of experiments we elected to work with pneumococci because there are available in 

 that group of organisms type and subtype varieties known to vary in virulence for 

 man and lower animals. After developing a technique to measure virulence for white 

 mice which gives reproducible results and after improving the precision of P.D. meas- 

 urements, we found particularly: 



1. From 76 strains of pneumococci of the three fixed types and of type IV which 

 were isolated from cases of lobar pneumonia, the P.D. and the virulence for white 

 mice were significantly difierent for the several types and the sequence for P.D. 

 (III>I>II>IV) was identical with the sequence for virulence to mice and the 

 probable sequence for virulence to man. 



2. For pneumococci of types II, III, and IV (and not for I), strains which had 

 been isolated from cases of pneumonia which terminated fatally showed higher P.D. 

 than strains isolated from cases that recovered. 



3. Variant strains of a tj^ae I pneumococcus prepared by Blake and Trask by 

 cultivation in the presence of specific antiserum showed differences in virulence for 

 mice, in agglutinability, antigenic properties, etc., and parallel dift'erences in P.D. 



4. The parallel relations between virulence, P.D., and other characteristics were 

 demonstrable on single-cell strains. 



' Cf. Northrop, J. H.: chap. Iviii of this volume. 



' Cf . Girard, P., and Audubert, R.: Compt. rend. Acad, de scL, 167, 351. 1918; Shearer, C: 

 Proc. Camh. Phil. Soc, 19, 263. 1919; /. Hyg., 21, 77. 1922. 



3 Northrop, J. H., and DeKruif, P. H.: /. General Physiol., 4, 639, 655. 1922. 

 -t Personal communication from J. H. Northrop. 



