GENETICS OF INFECTIOUS DISEASES 385 



calculated for each strain. These data are for the period 1944 to 1956. The repre- 

 sentation of the expected performance of each strain is on the whole good, but the data 

 themselves do not tell the full story. The S mice are now more resistant to the invasion 

 and growth of this pathogen than the figures show. For this strain there is a pronounced 

 difference in the reaction of the sexes, the males having less resistance than the females, 

 74 to 95 per cent, respectively. No other strain shows such a difference between the 

 sexes. Tests on the males show a much higher frequency of deaths, 1 to 4 days following 

 inoculation, than those for any other strain or even for the females of the S strain. 

 It is further found that the males are quite susceptible to large doses of killed S. 

 typhimurium 11C. The deaths also occur within the period of 1 to 4 days following 

 inoculation. These facts are interpreted as pointing to two causes of deaths for the 

 males of this particular strain. The deaths which come early in the disease are attri- 

 buted to rapid release of endotoxin from the digested bacteria. The deaths which 

 occur later are attributed to the common cause of death for all strains, the growth of 

 the organisms in the host. 



The genetic techniques which have been used to separate the differences in 

 resistance to disease have varied, but in each case have included inbreeding to fix the 

 particular genetic resistance observed within the strain. Throughout, the breeding 

 stock which has been the source of animals for test has been free from S. typhimurium 

 for a period of more than twenty years. Tests for resistance of some twenty different 

 strains (genotypes) have been made over this period. From the years 1944 to 1955, 

 21,669 mice were observed in these tests. These animals had their first contact with 

 the disease at ages from 45 to 700 days. All tests were made with a single line of 

 S. typhimurium 11C at a dose of 200,000 organisms injected intraperitoneally. This 

 line of the pathogen has shown a consistent virulence for over twenty-five years. In 

 tests with this organism, survival ratios include nearly completely resistant to nearly 

 completely susceptible, S and Ba strains respectively; the other strains show intermediate 

 values for resistance. Although these values have fluctuated during the 1 1 -year period 

 included in these data, they have kept their relative positions on the whole. The 

 observed stratifications may be interpreted on the basis of a number of genes affecting 

 different physiologic functions of the host responsible for the resistances or susceptibilities 

 to the bacteria. These resistances or susceptibilities could scarcely be analyzed in a 

 random-breeding population. In any such population, successive mice, when utilized 

 for disease tests, would show hit-or-miss resistance or susceptibility to the disease and 

 thus vitiate results coming from such experiments. 



Mortality represents the accumulated dysfunction of the various organ systems 

 which may be attacked by the invading organism. Different organs may be susceptible 

 in different strains. The temporal sequences in the progress of the disease may also 

 differ between inbred strains. The severity of the sickness (morbidity) expresses some 

 of the differences in the patterns of resistance. The S mice are so resistant that they 

 show almost no effects of the pathogenic organisms. The Ba mice are extremely 

 sick almost from the first contact with the disease. The other strains have characteristic 



