458 HOWARD B. NEW COM BE 



the argument, and the results can be considered as critical evidence that there 

 are no appreciable differentials favoring the mutants during the latter part 

 of the growth of a culture. 



The conclusions from the experiments discussed above are applicable to 

 differentials, both of division and of survival, and eliminate all possibility 

 that the widely different estimates of mutation rate obtained using method 1 



Table 4 



Mutation rates of B/r to resistance to phage Tl, calculated from the increase in the proportions of 

 resistant bacteria in cultures grown from large inocula {method 3 of this paper). Entire growth under 

 conditions approaching saturation. 



on the one hand, and methods 2 and 3 on the other, are due to such differen- 

 tials. 



Method 3 thus provides critical confirmation of the estimates obtained by 

 method 2. 



VARIATIONS IN MUTATION RATE WHICH WOULD BE REQUIRED TO EXPLAIN 

 THE DISCREPANT ESTIMATES FROM METHODS 1 AND 2 



It thus seems certain that the high estimates of mutation rate from the 

 numbers of resistant individuals are not the product of an upward bias, and 

 we may now turn to the possibility that the low estimates from the numbers 

 of resistant clones are due to a downward bias. Two alternative possibilities 

 have been suggested which would account for these lower values: (1) a change 

 to a low rate of mutation during the later part of growth, and (2) a delay in the 

 phenotypic expression of a mutation. 



The problem of distinguishing between these will be simplified if we con- 

 sider the first and determine the time at which the supposed transition 

 would have to occur, and whether this time is related to the number of genera- 

 tions from resting stage or to the approach to saturation. 



To determine whether the supposed transition would be a function of the 

 number of generations from resting stage the data of table 1 may be used. 

 Half the cultures were inoculated with 10 and half with 10,000 bacteria, and 



6o 



