572 A THEORY OF MICROBIC VIRULENCE 



3. It had l^een established that when suspensions of these organisms are washed 

 with water or dilute salt solutions, the P.D. sequence is inverted from A>B>C to 

 C>B>A. It was found correspondingly that washing resulted in an inversion of the 

 sequence for the phagocytic indices. 



4. If the P.D. on pneumococci be reduced by such a salt as lanthanum nitrate, 

 the phagocytosis of the organisms is increased proportionally. If the P.D. be in- 

 creased by treatment with sodium oleate, the phagocytosis is proportionately reduced. 



5. The phagocytic indices were modified successively when suspensions of 

 pneumococci were treated with lanthanum nitrate, were washed and then treated 

 with sodium oleate; and, reciprocally, when the procedure was reversed.' 



It is apparent that the organisms are more readily and more extensively phago- 

 cyted the lower the P.D., and vice versa. Hence, it is not surprising that virulence 

 and P.D. are parallel characteristics. 



The precise mechanism by which electrical charges (electrophoretic potential 

 differences) on phagocyte and bacterium affect phagocytosis is still unsolved. It 

 might be considered that the like charges on both phagocyte and bacterium provide 

 merely a repelling force, and the smaller the charges (on either or both), the less the 

 interference with engulfment of the particle by the phagocyte. Or — as Ponder- has 

 indicated recently — bodies with like charges may be attracted to each other when 

 brought close together, if the ratio between their diameters is large, by the attrac- 

 tive effect between original and induced charges. We are investigating this problem 

 further. 3 Abramson'' has shown recently that powerful electrophoretic fields may be 

 set up in vivo following tissue injury. 



SPECIFIC SOLUBLE SUBSTANCES, VIRULENCE, AND P.D. 



Assuming the validity of the analysis which reduces the parallelism of non- 

 toxigenic virulence, relative inagglutinability, etc., to P.D. and insusceptibihty to 

 phagocytosis, the question might be raised: By what constituents or properties of 

 the cell is the P.D. determined? The search for an answer at present lies with per- 

 meability phenomena, if the origin of the P.D. is explained on the basis of a Donnan 

 equilibrium ;5 or with the phenomena associated with the production and behavior of 

 specific soluble substances.^ 



I have already remarked that differences in the production of specific soluble sub- 

 stances parallel differences in P.D. among "S" and "R" variants. Cole^ reported that 

 infected exudates and sera which contain the specific, reactive substances of pneumo- 

 cocci possessed the property of neutralizing pneumococcus antibodies. Sia^ has pre- 

 sented some evidence to show that the inhibitory action of sera from naturally re- 



' Falk, I. S., and Malsuda, T.: Proc. Soc. Exper. Biol. &= Afed., 23, 781. 1926. 

 ' Ponder, E.: J. General Physiol., 9, 827. 1926. 



3 For a discussion of the mechanism of phagocytosis, see chap. Ixv by Dr. Fenn in this volume. 



4 Abramson, H. A.: /. Expcr. Med. 46, 987. 1927. 



s Winslow, C.-E. A., Falk, I. S., and Caulfeild, M. F.: J. General Physiol., 6, 177. 1923. 

 ^ Cf. Heidelberger, M.: Ghent. Rev., 3, 403. 1927. Also chap. Hi by Drs. Zinsser and Mueller in 

 this volume. 



7 Cole, R.: /. Exper. Med., 26, 453. 1917. * Sia, R. H. P.: ibid., 43, 633. 1926. 



