The concepts of biochemical genetics have already been, and will un- 

 doubtedly continue to be, significant in broader areas of biology. Let me 

 cite a few examples in microbiology and medicine. 



In microbiology the roles of mutation and selection in evolution are coming 

 to be better understood through the use of bacterial cultures of mutant strains. 

 In more immediately practical ways, mutation has proven of primary impor- 

 tance in the improvement of yields of important antibiotics — such as in the 

 classic example of penicillin, the yield of which has gone up from around 40 

 units per ml. of culture shortly after its discovery by Fleming to approximately 

 4 000, as the result of a long series of successive experimentally produced 

 mutational steps. On the other side of the coin, the mutational origin of an- 

 tibiotic resistant microorganisms is of definite medical significance. The 

 therapeutic use of massive doses of antibiotics to reduce the numbers of bac- 

 teria which by mutation could develop resistance, is a direct consequence of 

 the application of genetic concepts. Similarly, so is the increasing use of com- 

 bined antibiotic therapy, resistance to both of which would require the si- 

 multaneous mutation of two independent characters. 



As an important example of the application of these same concepts of 

 microbial genetics to mammalian cells, we may cite the probable mutational 

 origin of resistance to chemotherapeutic agents in leukemic cells (44), and the 

 increasing and effective simultaneous use of two or more chemotherapeutic 

 agents in the treatment of this disease. In this connection it should be pointed 

 out that the most effective cancer chemotherapeutic agents so far found are 

 those which interfere with DNA synthesis, and that more detailed information 

 on the biochemical steps involved in this synthesis is making possible a more 

 rational design of such agents. Parenthetically, I want to emphasize the 

 analogy between the situation in a bacterial culture consisting of two or more 

 cell types, and that involved in the competition and survival of a malignant 

 cell, regardless of its origin, in a population of normal cells. Changes in the 

 cellular environment, such as involved in chemotherapy, would be expected 

 to affect the metabolic efficiency of an altered cell, and hence its growth 

 characteristics. However, as in the operation of selection pressures in bacterial 

 populations, based on the interaction between cell types, it would seem that 

 the effects of chemotherapeutic agents on the efficiency of selective pressures 

 among mammalian cell populations can be examined nxusL effectively only in 

 controlled mixed populations of the ceU types concerned. 



In other areas in cancer, the concepts of genetics are becoming increasingly 

 important, both theoretically and practically. It seems probable that neoplastic 



s-46 



