PROSPECTS FOR A GENETICS OF SOMATIC AND TUMOR CELLS

Since I have had no experience a t all with ascites tumors, Doctor Theodore S. Hauschka’s suggestion that I discuss Doctor Klein’s paper had to be construed as an invitation to review the potential impact of microbial genetics on tumor studies. In fact, most of the hypothetical notions that will be summarized are the result of informal discussions with Doctor Hauschka, Doctor Klein, and others. The analogy between the ascites tumor cell and an infectious microorganism hardly needs to be stressed, and something may be gained by pursuing the analogy both in method and in concept. Bacteria have been the subject of investigation of several types of genetic change and exchange: M u t a t i o n and selection. Klein’s paper illustrates one of the most disputed problems of bacterial genetics, the origin of adaptive mutations, usually involving resistance to drugs but also including nutritional or other biochemical modifications. By ever more precise methods, it has become possible to prove that such adaptive mutations occur “spontaneously,” that is, independently of the environmental stress to which they confer improved fitness.’, By indirect election,^ for example, drug-resistant bacteria can be isolated without exposing them to the drug. It would be possible, if tedious, to extend this technique to tumor cells, but I doubt whether such an extension beyond these already impressive demonstrations4 would be worth the effort that might be expended on more informative experiments. Once given reliable procedures for the detection and estimation of mutations, we may then anticipate a more systematic application of mutagenic agents, both radiations and chemicals: a t first, to facilitate the isolation of mutants that might be useful as genetic markers and, later, for the elucidation of radiobiological effects on tumor cells -the role of genetic damage in radiation injury5, and the mechanism of radioresistance, be it polyploidy‘j or an adaptive mutation i t ~ e l f . ~ The role of selection in the determination of cell populations is obvious in some of Klein’s and Hauschka’s studies.8 Bacteriological studiesg have also drawn attention to the sampling effect of adaptive mutations: their origin, usually from a single cell, means that genotypes in mixed populations can become randomly fixed as effectively as by the purposeful technique of single cell isolation. The impact of selective forces should not be deduced solely on hypothct id grounds, as many examples of anomalous sele~tion in mixed cultures are not readily predictable from the behavior of the isolated components.1° The availability of a variety of genetic markers ha5 led to Transducti0n.l’