74 M. DEMEREC [VOL. 56 



The increase in resistance to streptomycin also can be explained by the as- 

 sumption that several genes are instrumental in the process. These genes vary 

 greatly in their potency, however, and consequently a mutation in a highly potent 

 gene will be responsible for a high degree of resistance, a mutation in a less potent 

 gene for a low degree of resistance. 



From the knowledge gained concerning the mechanism of origin of resistance, 

 it is concluded that in treatment with penicillin the development of highly re- 

 sistant strains can be avoided by application of the penicillin in doses sufficiently 

 large to prevent survival of first-step resistant mutants. In treatment with 

 streptomycin, however, the development of highly resistant strains cannot be 

 prevented; effective treatment does not eliminate all bacteria, but it probably 

 reduces their number to a level at which the organism is able to eliminate them. 



REFERENCES 



Demerec, M. 1945a Production of Staphylococcus strains resistant to various concen- 

 trations of penicillin. Proc. Natl. Acad. Sci. U. S., 31, 16-24. 



Demerec, M. 19456 Genetic aspects of changes in Staphylococcus aureus producing 

 strains resistant to various concentrations of penicillin. Ann. Missouri Botan. Garden, 

 32, 131-138. 



Demerec, M., and Fano, U. 1945 Bacteriophage-resistant mutants in Escherichia coli. 

 Genetics, 30, 119-136. 



Luria, S. E., and Delbruck, M. 1943 Mutations in bacteria from virus sensitivity to 

 virus resistance. Genetics, 28, 491-511. 



Meads, M., Ory, E. M., Wilcox, C., and Finland, M. 1945 Penicillin sensitivity of 

 strains of six common pathogens and of Hemophilus hemolyticus. J. Lab. Clin. Med., 

 30, 725-729. 



North, E. A., and Christie, R. 1945 Observations on sensitivity of staphylococci to 

 penicillin. Med. J. Australia, 2, 44-45. 



Oakberq, E. F., and Luria, S. E. 1947 Mutations to sulfonamide resistance in Staphy- 

 lococcus aureus. Genetics, 32, 249-261. 



90 



