508 GENETICS OF SOMATIC CELLS 



appears to be a popular route. In addition to numerical changes, structural alterations 

 of chromosomes also enter the picture to increase variability. To students of classical 

 genetics, great variability in chromosomal constitution is unthinkable. In Drosophila, 

 for example, a deletion of a small segment of a chromosome will result in death of the 

 organism. Then how could mammalian cells, with the chromosomal constitution so 

 far away from normalcy, live and thrive in vitro? The answer probably lies in the 

 difference between intact organisms and cellular culture. The situation mentioned in 

 Drosophila is analogous to mongolism in man, in which the trisomic condition for a 

 very small chromosome leads to serious damage of normal form and function in the 

 individual. It must be borne in mind that development of an organism requires both 

 growth and differentiation, whereas in cultures of cells growth is the main concern. 

 Thus a few missing genes or duplicated genes which affect embryonic development 

 with great impact may exert little influence in cultures. The well-known Griineberg 

 disease of the mouse, the result of a gene mutation which affects proper cartilage 

 formation, is lethal. Conceivably this gene, whether in its normal form, mutant form, 

 deleted or duplicated, should not have severe influence on the growth and reproduc- 

 tion of cultures of epithelial cells or fibroblast cells. By the same token, numerous 

 genes essential to a normal organism may be useless or even detrimental to the growth 

 of cells in culture. The concept of genie balance must be discarded when we talk 

 about cells in vitro. In a way we must regard the cells in vitro as artificial species which 

 start their evolutionary course the moment they are placed in a culture vessel. They 

 will have to forget the functions they are supposed to perform and live like bacteria. 

 It is, therefore, rather surprising to see that diploid human cells can maintain diploidy 

 for as long as a year in vitro. 



Extending the above-mentioned concept to explain why aneuploidy is prevailing 

 in neoplasms, cancer cells, although growing in vivo, tend to forget what they are 

 supposed to do and regard the body as a giant culture vessel. 



Cells in normal tissues are not always diploid. Occasional aneuploid cells can be 

 found if large samples of mitotic cells are analyzed. The frequency of aneuploid cells 

 in situ may even be higher than recorded, for aneuploid elements may be handicapped 

 in normal organisms so that they do not divide as often as diploids. In the case of 

 cellular cultures, the situation is different. Here the normal functions of the cells are 

 not required. In fact the cells are required to grow, a function normally demanded 

 only under special circumstances such as during wound healing. Mitotic anomalies, 

 in an astronomical number of divisions, are bound to happen. Cells lose and gain 

 chromosomes or change parts. Some of them may happen to lose genes that are 

 detrimental to perpetual growth. Some of them may happen to gain genes that aid 

 perpetual growth. Thus they may become selected by the artificial environment and 

 emerge as the stemline. The fact that populations of cells in vitro are full of chromo- 

 somal variation strongly indicates that a large number of genes are not necessary. 



Variation in karyotype also offers an excellent tool to study many problems in 

 cellular biology. Many populations of cells contain special karyotypes with marker 



