INFECTIOUS DISEASES OF MICE 453 



environment, and the host. The extensive work in experimental epidem- 

 iology (276, 74, 5, 6, 181, 313, 314, 320, 94, 279, 92) well demonstrates the 

 significance of these factors in natural diseases of the mouse, and numerous 

 other observations attest their importance in artificial infections. 



Microbic factors. — The type of disease resulting from the introduction 

 of an infective agent into the body of the host is dependent on dosage, route 

 of inoculation, and virulence of the agent. Thus, increase in dosage may 

 alter the course from a benign subclinical infection to a rapidly fatal, over- 

 whelming infection; or the subcutaneous route of inoculation may be 

 entirely ineffective, whereas intracerebral injection produces a striking 

 encephalitis. The role of virulence or pathogenicity is somewhat more 

 difficult to assess. Strains of an organism obtained from different sources 

 or in various stages of dissociation undoubtedly vary in their capacity to 

 produce disease. Whether or not it is possible to alter the inherent virulence 

 of a given strain by repeated animal passage is open to question, at least 

 in the case of certain organisms, when all other factors are kept as nearly 

 constant as possible (308. 192, 309, 310, 311, 312). 



Environmental factors. —Various features of the environment — tempera- 

 ture, diet, season, number of animals per cage, and cleaning routine — alter 

 the type of disease chiefly by their eft'cct on host factors, and, to a less 

 extent, on microbic factors. Thus, mice of the same stock reared on a 

 bread and milk diet without obvious dietary deficiency were found to be 

 more susceptible to mouse typhoid (329, 210) than those fed the more com- 

 plete McCollum diet. Crowding of animals in a cage may aft"ect the 

 microbic factors by increasing the dosage or altering the route of infection 

 if the organism is excreted by the inoculated animals. 



Host factors. — When a group of mice, maintained under controlled 

 environmental conditions, is given a standard dose of an infective agent, a 

 certain number of them become ill and die, others recover, and still others 

 may show no signs of infection. The relative proportion in each group will 

 depend on the specific and nonspecific resistance of the host — a complex 

 mechanism, the individual factors of which are not easily segregated and 

 subjected to quantitative analysis. Considerable progress has been made in 

 this direction, however, chiefly as a result of the stimulating investigations in 

 the field of experimental epidemiology. 



Specific resistance is considered to be an immunity acquired through 

 previous contact with the infectious agent. That such specific immunity 

 as a factor in resistance is operative in certain natural and experimental 

 infections is generally accepted, but in others its relative importance in 



