510 S. E. LURIA AND M. DELBRtJCK 



inocula of about 100,000 bacteria. In some of her cases this number was suffi- 

 ciently high to result in numerous mutations during the first division cycle 

 of the bacteria. In other cases the number was apparently not high enough, 

 since the author reports troublesome variations of the fractions of variants in 

 successive subcultures. In those cases where the size of the inocula was high 

 enough, the author succeeded in deriving reproducible values for the mutation 

 rates from the study of single cultures, followed through numerous subcultures. 

 In these cases it is sufficient to apply the equations of the theory referring to 

 the average numbers of mutants as a function of time. It is clear, however, 

 that this method is applicable only in cases of mutation rates of at least io~ 4 

 per bacterium per division cycle. 



In our case, as in many others, the virus resistant variants do not exhibit 

 any striking correlated physiological changes. There is therefore little oppor- 

 tunity for an inquiry into the nature of the physiological changes responsible 

 for the resistance to virus. Since the offspring of the mutant bacteria, when iso- 

 lated after the test, are unable to synthesize the surface elements to which the 

 virus is specifically adsorbed in the sensitive strain, one might suppose that 

 this loss is a direct effect of the mutation. However, it is also conceivable that 

 the loss occurs upon contact with virus, since it is detected only after such 

 contact (hypothesis bi). In some of the cases studied by Burnet (1929), 

 where the mutational change to resistance is correlated with a change of phase, 

 from smooth to rough or vice versa, the change of the surface structure must 

 be a direct result of the mutation, since the mutant colonies may be picked up 

 prior to the resistance test and, when tested, exhibit the typical change of 

 affinity of the surface structure. These findings make it more probable that 

 the loss of surface affinity to virus is a direct effect of the mutation. 



The alteration of specific surface structures due to genetic change is a phe- 

 nomenon of the widest occurrence. The genetic factors determining the anti- 

 genic properties of erythrocytes are well known. There is evidence (Webster 

 1937; Holmes 1938; Stevenson, Schultz, and Clark 1939) that resistance 

 or sensitivity to virus in plants and animals is correlated with, or even de- 

 pendent on, genetic changes, possibly affecting the antigenic make-up of the 

 cellular surface. The proof that resistance to a bacterial virus may be traced 

 to a specific genetic change may assume importance, therefore, with regard to 

 the general problems of virus sensitivity and virus resistance. 



summary 



The distribution of the numbers of virus resistant bacteria in series of similar 

 cultures of a virus-sensitive strain has been analyzed theoretically on the basis 

 of two current hypotheses concerning the origin of the resistant bacteria. 



The distribution has been studied experimentally and has been found to 

 conform with the conclusions drawn from the hypothesis that the resistant 

 bacteria arise by mutations of sensitive cells independently of the action of 

 virus. 



The mutation rate has been determined experimentally. 



