46-4 GENETICS OF SOMATIC CELLS 



Dr. Kaliss: Dr. Klein's article contains an excellent review of the literature, and 

 the most rewarding thing that comes out of my having to discuss it is that I was able to 

 read it and learn from it. I think it is an excellent contribution, and certainly there 

 would not be any point in my trying to add anything more to specific topics covered. 

 I will, therefore, confine myself to some more general comments. 



The motivating force in the study of somatic-cell genetics is the problem of the 

 differentiation of cellular function, whether it be in the single-cell or multicellular 

 organism. This symposium is concerned with the genetics of the mammalian organism 

 and, thereby, with the problem of functional differentiation as expressed in the specific 

 assignment of functions to the various cells, tissues, organs, and organ systems. Paren- 

 thetically, the so-called gap between genetics and embryology, about which there is 

 often complaint, is, of course, a conceptual gap between the geneticist and the embryo- 

 logist. The fertilized ovum apparently has no difficulty in knowing in which direction 

 it should develop. Perhaps the original stumbling block between the two disciplines 

 has been the controversy in genetics as to whether or not the organization of the 

 nuclear apparatus, specifically the chromosomes, remains unaltered from generation 

 to generation of cell division. The prime argument offered in support of the in- 

 violability of the chromosomes from generation to generation of the somatic cells has 

 been the stability of the transfer of genetic information by the germ cells (barring 

 mutation). The point at issue is amenable to experimental investigation with nuclear 

 transplantation into foreign cytoplasmic environments, as is being done in amphibian 

 embryos. 130 - 131, 365 



Danielli and co-workers 238 have made nuclear transfers between two species of 

 Amoeba and have demonstrated that the cytoplasm of the heterospecific host left its 

 imprint in the form of permanent and characteristic alterations in the transplanted 

 nucleus after 500 generations of cellular division, as determined by retransfer of the 

 nucleus to the cell of its native species. These changes are expressed in some 10 

 characteristics that were studied, such as shape and locomotion of the amoebae and the 

 rate of cellular division of a derived clone. On the other hand, those antigenic 

 properties presumably located in the cellular membrane were characteristic of the 

 nuclear species, as determined by the specificities of cytotoxic antiserum. 



One could postulate a number of models for organic differentiation, and I suppose 

 it would be possible eventually to devise feedback systems picturing the way in which 

 the DNA-RNA-protein-enzyme systems and other cellular constituents are interrelated 

 in time and space to carry on the multitudinous functions of the whole cell. The 

 division of the cellular domains into nucleus and cytoplasm, in our thinking, is, of 

 course, one of convenience ; it seems to me that we should not preclude the possibility 

 of nuclear alterations (reversible or irreversible) that constitute interlocking events in 

 the process of differentiation. 



A few words are in order as to what we may consider somatic-cell characters. 

 Dr. Klein has covered this point in detail in his article with respect to the histocompati- 

 bility antigens, and I only wish to reemphasize some of its aspects. It is not clear what 



