48 M. Demerec 



mechanism is vested in genes, which are component parts of 

 threadhke structures known as chromosomes. 



Since it is now a well established fact that in every organism 

 genes carry the primary responsibility for transmission of 

 all biological properties whose mode of inheritance has been 

 investigated, and since bacterial resistance to drugs has all 

 the characteristics of such properties, it is to be expected 

 a priori that a genetic mechanism is responsible for the origin 

 and transmission of resistance. It would be remarkable 

 indeed if bacterial resistance did not conform with what 

 appears to be a general biological rule. And the experimental 

 evidence obtained by direct studies of resistance fully confirms 

 the a priori expectation. Geneticists have directed a greater 

 than ordinary eff^ort towards this analysis, not only because 

 in the beginning very few of the methods now available were 

 at their disposal, but also because the problem was of con- 

 siderable practical importance for purposes of regulating the 

 clinical use of antibiotics, and therefore evidence adequate to 

 convince non-geneticists as well as geneticists was called for. 

 The results of their work fully support the conclusions reached, 

 namely, that as a rule genes determine bacterial resistance to 

 drugs, and that mutations in certain genes are responsible for 

 its origin. Comprehensive reviews of the literature on micro- 

 bial drug resistance have been published by Cavalli-Sforza 

 and Lederberg (1953) and by Bryson and Szybalski (1955). 



The most conclusive evidence of genie determination of 

 resistance to drugs is the fact that in all genetic tests bacterial 

 resistance has shown the same patterns of inheritance as 

 other gene-determined characters studied. The tests have 

 involved three diff*erent approaches: studies of the origin of 

 resistant variants ; studies of frequencies of spontaneous and 

 induced mutations; and studies of transmission of resistance 

 by crossing, by transformation and by transduction. 



Origin of resistant variants 



Much of the work has been directed toward distinguishing 

 between two possible modes of origin of bacterial resistance : 



