GENETICS OF INFECTIOUS DISEASES 



393 



ROUTE OF INFECTION AND SEVERITY OF DISEASE 



Between 1920 and 1940 great emphasis was laid on studying disease through 

 utilizing only natural routes of infection. The advocates produced little evidence for 

 their contention that use of other routes could not lead to comparable resistances in the 

 hosts. Attempts to cause natural infections often produced trauma as great as that of 

 experimenters who openly avowed that the routes of infection they were using were not 

 natural. Further difficulties arose in that attempts to introduce the pathogens by 

 natural routes also introduced dosage variations to increase variance in the results. 

 However, the real problems involved, while often overlooked, were of interest and have 

 been pursued by several investigators. 



The methodologic problem really turns on whether natural resistance or suscepti- 

 bility to a disease is dependent on localized differences in resistance of tissue at some 

 customary portal of entry for the disease organism, or is a property of all cells of the 

 body. Roberts and Card, 1059 Irwin, 642 Lambert and Knox, 746 Schott, 1167 Gowen 

 and Schott, 467 Hetzer, 573 and others collected data showing that the normal portal 

 of entry could be bypassed and genetic resistance to any one of several diseases could 

 be established in the host. Webster 1363 collected data for different routes of entry on 

 mice which he had previously selected for resistance and susceptibility to Salmonella 

 enteritidis introduced through the so-called natural route, the stomach. The selections 

 were based on intrastomachal instillation of 5,000,000 organisms through a silver tube 

 inserted into the stomach. The relative resistances of these susceptible and resistant 

 strains of mice are indicated in figure 52. 



The most striking result of these tests is that each route of instillation of the S. 



Fig. 52. Relationship between route of entry and mortality of selected mice 



DUE TO BACTERIAL INFECTION. 



Intrastomachal intravenous Subcutaneous Intraperitoneal 

 Dose 5,000,000 Dose 50,000 Dose 50,000 Dose 50,000 



Relative resistance of mice selected for susceptibility (Sus) and resistance (Res) to 

 Salmonella enteritidis when the bacteria are introduced into the stomach through the esophagus 

 by silver tube (dose of 5,000,000 organisms), or injected intraperitoneally, subcutaneously, 

 or intravenously (dose of 50,000 organisms). 



