GENETICS OF SOMATIC CELLS 409 



an approach may lead to the discovery of many valuable facts, interpretation of the 

 phenomena in terms of cellular mechanisms by analogies will be difficult, more so than 

 during the corresponding stage of bacterial genetics, since it has to be recognized that 

 somatic cells of higher organisms are subject to developmental processes, the cellular 

 mechanisms of which still represent some of the most formidable unknown territories of 

 biology. Many attractive models are available, borrowed from various fields of 

 genetics, 133, 417 ' 821 - 1173 ' 1257 and the method of nuclear transplantation opens 

 fascinating possibilities for direct studies on embryos, 131 but information presently 

 available on the relationships between genotype and cellular differentiation does not 

 offer a firm foundation on which to build the delicate superstructure of somatic-cell 

 genetics. The classical notion of genotypic equality in all somatic cells, based essentially 

 on the nature of the mitotic process, has not been confirmed experimentally. On the 

 one hand, it is quite true that phenotypic diversity does not exclude genetic identity. 

 That can often be proved with differentiated microorganisms with cells that can be 

 subjected to breeding analysis and may turn out to be genetically identical, in spite of 

 profound, permanent, and stable phenotypic differences. 935 These differences are 

 believed to be epigenetic 325, 934 due to mechanisms that regulate the expression of 

 genetic potentialities, rather than truly genetic mechanisms regulating the maintenance 

 of structural information. On the other hand, the doctrine of genotypic identity of 

 somatic cells is being viewed with increasing caution, 1257 particularly in the light of the 

 nuclear transplanation experiments of Briggs and King, 131 pointing toward the existence 

 of a true nuclear and probably chromosomal 1257 differentiation. On the one hand, 

 there are many workers who believe that development and differentiation are much 

 too orderly and predetermined processes to be akin to the random changes at the genetic 

 level known under the category of mutations, even if the term is used in a broad sense. 

 On the other hand, there are others who disagree on this point, and genetic models of 

 differentiation have been constructed, based on the phenomena of gene activation and 

 the concept of controlling elements, such as dissociators, activators, and modula- 

 tors 133, 821, 1173 



Under these cirumstances, the study of somatic-cell genetics will have to be limited 

 at the present time to the thorough experimental study of comparatively simple situa- 

 tions, without too many theoretical preconceptions. Generalizations will seldom be 

 justified, except in the form of working hypotheses. The possible approaches can be 

 classified as the study of appropriate phenotypic marker characteristics, detectable 

 at the cellular level, and the direct examination of chromosomal morphology. Since 

 the latter subject will be discussed in the next chapter, this discussion will be mainly 

 limited to the former type of approach and chromosomal studies will only be considered 

 if they have direct bearing on the topic discussed. Subsequently, an attempt will be 

 made to review briefly various approaches toward the possible development of methods 

 that might permit the accomplishment of genetic transfer between somatic cells. 

 Microbial genetics will be regarded as the master discipline as far as methods and 

 approach are concerned, while interpretations based on analogies will be viewed with 



