388 HOST-PARASITE RELATIONSHIPS 



probably took place, several genes in different loci being important to resistance. 



The average mortalities for the crosses with L as the inbred parent were nearly 

 the same as those with Ba as the parent, 53 and 48 per cent, respectively. Survival 

 among the backcrosses ranged from 67 to 40 per cent. Examination of these crosses 

 showed no established reason for the variability. Higher susceptibility came in the 

 progeny of the F 1 (S$ x L^) for the L backcross, whereas the higher susceptibility was 

 evident in the offspring of the F x (L$ x S^) for the Ba backcross. The resistances of 

 these two crosses separately contradict hypotheses often used to explain resistance to 

 disease other than on inheritance grounds. In the first case the data paralleled those 

 of the two hybrid generations in suggesting differences in the reciprocal hybrids. 

 This hypothesis is refuted, however, by the second cross. The second cross suggested 

 that the Ba female parent was responsible for lowering the survival of her progeny, a 

 type of maternal effect ; but comparison with the other backcrosses and all the crosses 

 in general denies this conclusion. 



Tests on the inbred parents, hybrids between them, and backcrosses to the suscep- 

 tible strains consequently support the dependence of resistance to disease on genetic 

 factors transmitted along customary paths. The mode of action of this inheritance is 

 capable of wide modification through changes in numbers of the infecting organisms 

 of different lines of the bacterial species. Results of this type are generally sufficient 

 to establish the genetic dependence of disease susceptibility. However, there is another 

 hypothesis, contraindicated by many features of the above data, which often has been 

 cited in the past. Evidence on the validity of these hypotheses, consisting of even more 

 critical data on the problem, may be had by adopting the following approach. 



GENETIC ASPECTS OF DISEASE AS INDICATED BY PROGENY OF DOUBLE MATINGS 



The other hypothesis is that the progeny acquire an immunity either by active 

 contact with the low-grade disease or passive immunization and thus develop trans- 

 mitted resistance to the challenge tests. This hypothesis is based on the fact that ani- 

 mals which survive a disease develop an active immunity of irregular duration. Some 

 survivors retain a latent infection which is thought to protect them by keeping up an 

 active immunity. These carriers may spread subclinical infection to their progeny, 

 thereby inducing active immunity in them. Evidence indicates that passive transfer of 

 immunity from dam to progeny may take place, but males are not able to transmit 

 passive immunity to their offspring. A method for evaluating the weight to be given 

 the factors of genetic versus acquired immunity in resistance to disease was designed 

 by Gowen and Schott. 467 This was applied to studies on typhoid in the mouse 

 but has general applicability. The method consists in mating two males of different 

 strains to a single female in the same estrus period so that litters will contain young of 

 two known separable types. In our case S mice differ from L mice in their genetics of 

 coat color, so that it is possible to distinguish between S mice as albinos, L mice as silver 

 black, and hybrids as black mice. An L female mated in the same estrus period to 



