566 A THEORY OF MICROBIC VIRULENCE 



constant and invariate such experimental conditions as affect virulence. The special 

 interest which attaches to spontaneous or induced variations in virulence is the al- 

 leged cyclical character of the variation — as in the case of certain examples in epi- 

 demiological literature — or, more particularly, the permanence of the variation under 

 laboratory conditions. Insufficient attention has been accorded the general, biological 

 significance of this type of inheritance and persistence of acquired characteristics in 

 such unisexual forms as the bacteria. For the purposes of this analysis I wish to direct 

 attention not merely to the relative permanence of modifications in virulence, but to 

 the experimental and theoretical opportunities associated with the fact that the 

 modifications in virulence are generally, if not invariably, associated with concurrent 

 variations in other characteristics of the parasite. In the study of the simultaneously 

 varying characteristics lies the opportunity to integrate a large number of observa- 

 tions into a general theory of the mechanism of virulence. 



In epidemiological studies attention has been frequently directed to the probkm 

 of variations in the virulence of communicable disease. The cyclical recurrences of 

 epidemic influenza and of other diseases have been explained as easily on the assump- 

 tion of cyclical changes in the virulence of the etiological agent as in the resistance of 

 the host. Why frank cases of poliomyelitis or of plague show high, and of chicken 

 pox or measles low, fatality rates find no ready answer.' There is little doubt that 

 in scarlet fever and in smallpox — to mention only two diseases of man — there have 

 occurred fairly sharp and perhaps discontinuous variations in epidemicity and in 

 fatality, so far as these characteristics of an infectious disease can be determined by 

 statistical methods. It is only necessary to consult two recent, competent writers on 

 this subject, however, to discover the absence of unanimity of opinion concerning the 

 factors that have caused the changes.- Contrariwise, there are indications in the vital 

 statistics of typhoid fever^ and of other diseases, as well as in certain experimental 

 epidemiological investigations, that there are a variety of conditions which tend to 

 make for a constancy of virulence in disease of man and other animals.'' Discussions 

 of the problem of the disease carrier which revolve primarily about considerations of 

 microbic virulence or of host resistance are futile. There is not available here or else- 

 where any device by which a separation can be made between the two groups of 

 interdependent variables. 



Typhoid and yellow fever are primarily diseases of man ; mosaic disease is similar- 

 ly a disease of the tobacco plant. In each case the specificity of microbic virulence is 

 neither greater nor lesser than the specificity of host resistance or immunity. I stress 

 these facts here, as I shall again later, for two reasons: First, the trend of research is 

 to indicate that parasite virulence and host resistance are related and not independent 

 variables. Second, the characteristic of a microbe (P.D.)^ which is associated with or 

 determines virulence appears to be identical with that property of antibodies (P.D.) 

 by which the resistance of the host is determined. 



' Falk, I. S.: Scient. Monlli., 20, 3S3. 1925. 



= Chapin, C. V.: J. Frev. Med., i, i. 1926; Hoist, P. M.: //'/(/., ji. 279. 1927. 



'3 Falk, I. S.: ibid., p. s,v ii)2(). " Cf. Webster, L. '!'.: J .. /■'..vpcr. Med., 45, 911- 1927. 



s"lM)." is used In refer to the electrical potential (iilTereiue l)et\veen a particle and its men- 

 slruum, as postulatetl in the llemholt/. double-layer theory. "C'harf;;'" may l)eused instead, on the 

 j,M(.unds {)resented in chapters x and Iviii of thi.s volume. 



