384 HOST-PARASITE RELATIONSHIPS 



Because of the multifactorial nature of the causation of infectious disease, investi- 

 gators without exception have limited their quantitative studies to specific pathogens 

 in fixed amounts and under pre-established environmental conditions. For new 

 diseases the limits within which these variables were controlled have been determined 

 by trial and error. Search then has been made for ways and means by which the geno- 

 typic variability of the host could be broken up into pure breeding strains so that the 

 factors could be studied within a more limited range. Most workers have limited their 

 attention to one or two of these strains generally derived by repeated inbreeding. 

 Such limitations seriously restrict the generality of any disease studies as they may be 

 applied to the species or to the more important transfer of the information gained to 

 man. Our own viewpoint has been that the host strains for study should be specific 

 samples, each covering a limited range of the whole species' susceptibility to the disease 

 but that when all inbred strains are considered they should cover the full range of 

 susceptibility or resistance to the disease as represented by the species genotypes. The 

 same considerations have been given to the genotypes of the lines which may be developed 

 from the pathogenic species, although in much of the work herein reported only one 

 line of the organism (one that is remarkably consistent so far as virulence is concerned) 

 has been utilized. Other observations have not been reported since this program is 

 designed to cover methodology within mammalian hosts. 



Initial attention may be turned to the variations in resistance to murine typhoid 

 due to Salmonella typhimurium 1 1 C that may be established for mice as a whole and fixed 

 in inbred lines. The procedures by which these strains were established were diverse, 

 but all have been inbred brother x sister over many generations with selection for the 

 desired disease resistance in fixing the levels of mortality. The results are shown in 

 table 61. 



Table 61 



Resistance of inbred strains of mice to murine typhoid 

 Salmonella typhimurium, 200,000 11C 



These strains have characteristic reactions to this disease. They range from the 

 most resistant to the most susceptible. Binomial standard deviations of the means are 



