GENETICS OF INFECTIOUS DISEASES 403 



and maintained in such hosts indefinitely. At the present time we have seen no adverse 

 effect on these hosts, and the demonstration of the virus is by subinoculation into mice. 



We have discussed these findings among ourselves as a method for investigating 

 genetic factors in the ability of arthropods to propagate or transmit the viruses that 

 infect vertebrates. With the system Dr. Hurlbut has used, the amount of virus going 

 into the arthropod can be accurately controlled, and the amount present after a suitable 

 incubation period can be satisfactorily measured. By choosing insect species in which 

 genetic studies have already been made and in which various genetically described 

 strains are available, suitable combinations of insect and virus could probably be found 

 for a fruitful attack on this problem. 



Dr. Roderick: Dr. Gowen, did you find any difference between the selected and 

 unselected lines with reference to qualitative manifestations of the diseases ? Differences 

 in the symptoms between the lines might indicate that the selected lines were resistant 

 because they had in some way changed their mode of reaction to certain specifications 

 of the pathogen. 



Dr. Gowen : Symbiotic relations of an organism to one host, for which this host 

 may supply a reservoir for nutrients, maturation, or multiplication, as well as acting 

 as a vector for transmission of the organism and pathogenic relations of the same 

 organism to a later ultimate host, constitute real challenges to genetic research. The 

 two-step relations hold through a range of pathogenic organisms — viruses, bacteria, 

 protozoa, helminths, fungi, and the like. The genetic controls for these diverse cases 

 would seem to have been developed independently. Damage to the vector host may 

 range from none observable, through moderate, to that which acts relatively slowly 

 compared with the time necessary for infecting the ultimate host. The specificity of 

 the host-parasite relations is so exact that basically the relations must be largely under 

 genie control. For instance, some malarias and viruses seem to damage the mosquito 

 but little, yet the mosquitoes offer conditions suitable for their multiplication. In 

 retrospect it seems not unlikely that this long-standing relationship has an evolutionary 

 history such that the virus or protozoan was initially pathogenic but that, with time and 

 possibly through genetic modifications of both pathogen and host, they were able to 

 live together in a symbiotic relationship. That genie changes are basic to this pattern 

 is evident from studies on a number of related species displaying differences in reaction 

 patterns. Huff 608 some years ago found that Culex pipiens, to become a carrier of avian 

 malaria, required the presence of the dominant gene of a pair of alleles, resistance being 

 recessive. 



The second question concerns changes in virulence within particular lines of the 

 pathogen. In our work Salmonella typhimurium 11C rarely changed its virulence. 

 Zelle, 1467 in a series of experiments covering three years, obtained convincing mutants 

 in virulence only four times. The parental organisms were passed through successive 

 transfer in mice of a resistant line or mice of a susceptible line. The mutants were 

 always directional to greater virulence. Very rarely an avirulent mutant may also 

 occur when planted on culture media. Salmonella gallinarum, on the other hand, 



