160 M. J. Thornley, J. Sinai and J. Yudkin 



inhibit DNAse; it seems therefore that it might act by pre- 

 venting the destruction of transforming DNA by the enzyme 

 of the recipient cells. 



Conclusion 



We have demonstrated, in the one system Esch. coli-pro- 

 flavine, the origin of resistance through: (1) mutation and 

 selection, (2) phenotypic adaptation to a low level of resist- 

 ance at some stages in the division cycle, (3) Lamarckian 

 inheritance and (4) transformation. We have not been able 

 to exclude the possibility that clonal variation also occurs. 

 We believe that in natural situations, the environments and 

 micro-environments to which the cells are exposed are so 

 complex that it is profitless to attempt an assessment of the 

 relative importance of these mechanisms in determining the 

 emergence of a resistant population. Nevertheless, in the 

 simpler conditions existing in laboratory experiments, we can 

 readily visualize the ways in which such a population may 

 emerge by the simultaneous or sequential occurrence of these 

 different modes of origin. We believe also that it is possible, 

 through an extension of the unitary theory of enzyme induc- 

 tion (Cohn and Monod, 1953; Pollock, 1953), to bring together 

 these various mechanisms into a unitary theory of the origin 

 of drug resistance. 



REFERENCES 



Akiba, T. (1954). In Origins of Resistance to Toxic Agents, p. 82. 



New York: Academic Press. 

 Baskett, a. C. (1952). Proc. roy. Soc. B, 139, 251. 

 BoiviN, A. (1947). Cold Spr. Harb. Symp. quant. Biol, 12, 7. 

 Cohn, M., and Monod, J. (1953). Symp. Soc. gen. Microbiol., 3, 182. 

 Lederberg, J., and Lederberg, E. M. (1952). J. Bad., 63, 399. 

 LuRiA, S. E., and Delbruck, M. (1943). Genetics, 28, 491. 

 McCarty, M., and Avery, O. T. (1946). J. exp. Med., 83, 89, 97. 

 Myers, V. L., and Spizizen, J. (1954). J. biol. Chem., 210, 876. 

 Pollock, M. R. (1953). Symp. Soc. gen. Microbiol, 3, 150. 

 SzYBALSKi, W. (1955). Antibiotics Annual 1954-1955, p. 576, New 



York: Med. Encycl. Inc. 



