56 M. Demerec 



the calculated values might be obtained if the formula for calcu- 

 lating probabilities could take into account the variability due 

 to several biological factors of which geneticists are well aware. 



As a logical consequence of the genetic concept of the origin 

 of bacterial resistance, multiple chemotherapy was suggested 

 by geneticists as the most effective means of preventing the 

 development of resistant pathogens. Its successful clinical 

 use provides good confirmation of the validity of the assump- 

 tion that gene mutations play the most important role in the 

 origin of resistant variants. 



Very little is known yet about the chemical structure of 

 genes, but it has been convincingly demonstrated that they 

 are not protein molecules and thus cannot be enzymes. 

 Evidence is rapidly accumulating, however, to indicate that 

 each gene controls one enzymic reaction — in other words, 

 that there is an intimate relationship between genes and 

 enzymes. This constitutes a common ground for agreement 

 between those geneticists who judge that change in a certain 

 gene is responsible for a particular resistance and those bio- 

 chemists who consider that resistance is the result of modifica- 

 tion in a certain enzymic reaction. The striking difference 

 between the two groups lies in their interpretation of the 

 nature of this change — the geneticists concluding that it is 

 brought about by gene mutation, independent of the presence 

 or absence of a drug, whereas the biochemists believe that it 

 develops gradually under the influence of the drug. Even here, 

 however, there is a certain degree of concurrence between 

 the two groups, since neither denies the possibility that both 

 kinds of mechanism may operate. Nevertheless, geneticists 

 have ample experimental evidence to justify the conclusion 

 that a mechanism involving gradual adaptation must play only 

 a minor role, if any, in the development of resistant strains. 



Summary 



During the past decade much time and effort have been 

 devoted to examination of the role played by genetic mechan- 

 isms in the origin of bacterial resistance to various drugs. 



