408 GENETICS OF SOMATIC CELLS 



the heredity of higher forms, perhaps because of the lack of an insulated germ line, 

 and Lamarckism found its last stronghold in microbiology. 



This situation has radically changed since 1940. A closer scrutiny of bacterial 

 variation and, in particular, the analysis of clonal variance of mutations to phage 

 resistance by Luria and Delbruck 812 have led to the understanding that most cases of 

 adaptation find their explanation in the differential selection of spontaneous mutants. 

 It has been increasingly realized that bacterial cultures must be regarded as populations 

 which may have genotypically diverse components. The analogy between mutations 

 in higher organisms and bacterial variation has been clearly emphasized by Luria. 809 

 He pointed out, as common features, the random, apparently spontaneous occurrence 

 of variation at specific, generally low rates and its independence of physiologic condi- 

 tions. The same agents were found capable of inducing mutation in higher and lower 

 forms, for example, radiation and nitrogen mustards. Mutations affecting different 

 characters occurred, as a rule, independently of one another. Often the same type of 

 function, such as enzymatic specificity, was affected. The specific induction of muta- 

 tions by environmentally induced adaptation and inheritance of acquired characters 

 could be disproved in almost every case. The crucial proof, watertight even for the 

 most critical, came with the achievement of indirect selection of drug-resistant bacteria 

 by replica plating 776 or by other indirect means, 186 that is, without ever exposing the 

 cell population to the drug. 



The most important developments in the study of bacterial heredity that have led 

 to its spectacular ascendance and present outstanding position in contemporary genetics, 

 where it influences almost every major aspect of genetic thinking, have been undoubtedly 

 the discoveries of various methods permitting the intercellular transfer of genetic in- 

 formation, such as DNA-mediated transformation, sexual recombination, and phage- 

 mediated transduction. They have proved beyond doubt that bacteria contain linearly 

 organized genetic material, quite analogous to the chromosomal genes of higher organ- 

 isms with regard to chemical composition, structure, mutability, and function, and 

 advanced far beyond this demonstration, revealing a wealth of new facts and principles 

 concerning the fine structure and action of the genes. 



The recently reawakened interest in somatic-cell genetics is based on the belief 

 that genetic concepts may be helpful for the understanding of such somatic phenomena 

 in higher organisms as differentiation, enzymatic adaptation, antibody formation, neo- 

 plasia, and some forms of viral infection. In a way, the prospects for the study of gene- 

 tic phenomena in somatic cells are very similar to the situation in bacterial genetics 

 some twenty years ago, prior to the discovery of methods for genetic transfer. This 

 leads us immediately to the recurrent theme of this paper : although it is not certain 

 a priori that analogous methods of transfer can be worked out for somatic cells, there 

 is no more urgent need in this field than the exploration of all possibilities in this 

 direction. Meanwhile, the genetic approach will have to remain indirect and restricted 

 to the analysis of variation in populations of somatic cells, without any possibility 

 of proving its intrachromosomal or extrachromosomal nature. Although even such 



