574 A THEORY OF MICROBIC VIRULENCE 



2. Assuming that the ordinary animal test for toxigenicity is a measure of toxin 

 excretion by toxin-producing bacteria; 



3. Assuming that the ratio of toxin concentration outside the cell to the toxin 

 concentration inside the cell is a measure of cell semi-permeability; 



It follows from the principle of the Donnan equilibrium that: 



4. The P.D. between the cell and the menstruum will be minimal when the toxin 



concentration outside approaches the toxin concentration inside, and will be maximal 



HT C 

 when the concentration outside is least (because' tt, — ti = ^ log -p^ where ttj and tti 



nt C2 



are the positive potentials of the solutions, Ci and C. the concentrations of the dif- 

 fusible ion on the two sides of the membrane, and R, T, n, and F have the usual 

 thermodynamic significance). 



5. And the large P.D. values are to be expected for strains which do not excrete 

 toxin and small P.D. values for strains which freely excrete toxin. 



Experimental verification of these expectations has been thoroughly established 

 by L. B. Jensen.^ It has even been possible to utilize a simple electrophoresis procedure 

 for the rapid determination of virulence (toxigenicity) in routine diphtheria control. 

 The indications are, further, that small- or large-scale toxin production may be 

 controlled by controlling P.D. 



It would appear, then, that even among toxigenic bacteria P.D. parallels virulence 

 (toxigenicity), although it may be for different reasons, and reciprocally from the 

 parallelism which obtains among non-toxigenic bacteria. 



ELECTROPHORETIC POTENTIAL AND HOST JiESISTANCE 



If it be true that P.D. is a measure of (or a determining factor in) virulence, it fol- 

 lows from the intimate relation between virulence and resistance that was empha- 

 sized earlier that certain mechanisms of resistance might be associated with en- 

 hanced properties of tissues or body fluids to affect the P.D. on invading organisms 

 or their toxins. And there is a substantial body of evidence in accord with this 

 expectation. 



Thus, it has been demonstrated that immune sera not only exceed normal sera 

 in the capacity to reduce P.D. on bacteria, but these enhanced capacities of immune 

 sera are specific. Within the pneumococcus group, the P.D.-reducing capacities of 

 antisera are even type specific.^ Furthermore, all of the recent work on specific 

 toxin-antitoxin flocculation^ indicates that antitoxin specifically modifies the P.D. on 

 toxin. This follows from the fact that the flocculation of a coUoid is intimately re- 

 lated to its P.D. The older notion that the reaction between toxin and antitoxin 

 does not fall into this category of colloid dynamics was based upon the conclusion of 

 Field and Teague (and of Bechhold) that both toxin and antitoxin are electropositive 



' Donnan, F. G., and Green, G. M.: Proc. Roy. Soc, A, 90, 450. 1914. 



2 Preliminary reports of this work have appeared in the Proc. Soc. E.xper. Biol. &• Med., 23, 783. 

 1Q26; and in the Am. J. Pub. Health, 17, 714. 1927. The detailed reports will appear shortly in the 

 J. Bad. 



3 Shibley, G. F.: J. Exper. Med., 40, 453. 1924; Falk, I. S., and Jacobson, M. A.: J. Infect. 

 Dis., 38, 182. 1926. 



4 Except that of Bronfenbrenner and Reichert. Cf. chap. Ivi by Dr. Baync- Jones in this volume. 



