GENETICS OF SOMATIC CELLS 455 



from the biochemical or cytomorphologic and chromosomal points of view. Frozen 

 storage may be an invaluable help in preserving initial and intermediate stages for 

 critical replicate experiments. 



Malignization of cultured cells has been achieved unequivocally and within 

 surprisingly short intervals by the use of certain oncogenic viruses in vitro, as discussed 

 in the previous section. This is a highly promising field which, again, may be advan- 

 tageously combined with the use of genetically known material from inbred animals 

 so as to permit a rigorous correlation between the morphologic changes observed 

 in vitro and the malignant behavior that must be proven by retransplantation experiments 

 to appropriate hosts. 



Even the possibility of populations of malignant cells turning nonmalignant during 

 prolonged cultivation has been indicated by a number of experiments. The significance 

 of these findings is not clear, however, since the selection on nonmalignant cells present 

 from the beginning or the development of histoincompatibility between the cells and the 

 strain of the recipient mouse have not been excluded. 



Relationships between cells in vivo and in vitro. — The greatest problem of the field of 

 tissue culture as related to somatic-cell genetics is the question of representativeness. 

 Obviously, if all types of cells could be grown in vitro with unchanged characteristics 

 and without limitations, nearly exclusive use of methods of tissue culture could be 

 wholeheartedly advocated for the study of somatic-cell variation. Unfortunately, 

 this is by no means the case. In the words of Eagle: 314 "Most of these dispersed cell 

 cultures fail to carry out specialized functions. Fibroblast cultures do not usually 

 make collagen ; melanoblast cultures do not make melanin ; liver cultures are so called 

 only because they originally derived from a bit of liver, and not because they carry 

 out the specific metabolic activities generally associated with that organ. The signifi- 

 cant biochemical differences between normal and malignant tissues which are implicit 

 in the very fact of malignancy may similarly fail to be expressed in cell culture ; at 

 least, they have not been recognized to date. " It may be added that some organ-specific 

 and blood-group antigens disappear within surprisingly short periods of time during 

 cultivation in vitro; 590, 1371 bone-marrow cells lose their ability to differentiate 

 and to repopulate the marrow and function in lethally irradiated mice although they 

 are perfectly capable of doing so if grown in diffusion chambers in vivo. 81, 82 Many 

 similar examples could be cited. Since cloning techniques fail to give more than about 

 1 per cent clones with tissue taken directly from the body, 1024 it cannot be decided 

 whether the few and surprisingly similar cellular phenotypes obtained from different 

 tissues in vitro are due to the selection from large heterogeneous populations of certain 

 cells preadapted for growth under the artificial conditions of modern tissue culture or 

 to a tendency of all kinds of cells to convert to a fairly uniform common type under the 

 pressure of the environment. The low cloning efficiency of tissues taken directly 

 from the organism is undoubtedly partly due to technical difficulties, but this does not 

 have to be the whole story and it is quite conceivable that most cells are not capable of 

 growing under the conditions of tissue culture. The critical period of adaptation of 



