GENETICS OF SOMATIC CELLS 465 



role these antigens, which are revealed by the technique of tissue transplantation, play 

 in the economy of the cell. Kandutsch's work 682 in this laboratory indicates that they 

 are located in the cellular membrane. It is possible that they may be involved in fetal- 

 maternal isoimmunization, but aside from this they are antigens only because the 

 experimenter uses immunologic methods for their detection; their usefulness as a 

 genetic tool is fully documented in Dr. Klein's paper. There are, of course, many 

 other cellular characteristics that might be exploited. The uniqueness of the histo- 

 compatibility antigens is that they are amenable to study both in vivo and in vitro. The 

 importance of being able to utilize the two approaches is emphasized by the apparent 

 loss of physiologic specialization, for example, by hepatic cells or hematopoietic tissue in 

 tissue culture. On the other hand, this very loss of function, if it is indeed a true 

 phenomenon and does not represent selective survival of more generalized cells, such as 

 fibroblasts, only serves to reemphasize in another form the problems of what constitutes 

 functional differentiation at the level of tissues and organs. 



A final word on the question of neoplasia as a possible example of somatic mutation 

 at the nuclear level; Dr. Klein discusses this in detail in his article. It has been 

 mentioned to some extent in the other discussions. It has been repeatedly emphasized, 

 as Dr. Andervont pointed out, that cancer is most probably not a single disease but a 

 number of different diseases. I have heard the analogy made between the entity, 

 cancer, and the designation of fever as a disease entity during the last century, with 

 the eventual understanding that rising temperature reflected a general physiologic 

 expression of a large variety of infections. If we attempt to homologize bacterial 

 transduction with a viral etiology of cancer, we are confronted with such phenomena 

 in the cancer process as the very long latent period between the carcinogenic stimulus 

 and the first overt sign of the cancerous process or the progression from dependence to 

 auton6my in the cancerous growth, as Dr. Klein mentioned. (Incidentally, autonomy 

 should be looked upon in broad terms, beyond those which we derive from hormone- 

 dependent tumors alone. Dr. Harry Greene, 495 for example, has drawn a parallel 

 between the degree of malignancy of a given tumor, as manifested by the formation of 

 metastases, and the ability of the tumor to survive as an heterograft.) 



One could evoke genie activation to account for the latent period, but it is not 

 clear to me what is meant by genie activation by those who use the term. It is difficult 

 for me to conceive how a part of a chromosome or of other constituents of the nucleus 

 and the cytoplasm can be inactive at one time and come to life, so to speak, at another 

 time. I suppose one could postulate an induced alteration at some point in the 

 cellular apparatus, perhaps the chromosome, which can be expressed as a malignancy 

 only under certain conditions of differentiation in the animal possessing the affected 

 cells. The correlation between age and the increase of the incidence of cancer may 

 depend upon continued differentiation of the host, differentiation, progressive and 

 retrogressive, being considered the essence of life from the time of conception of the 

 individual until death. 



Dr. Snell: Dr. Klein used the H-2 locus in a very fascinating fashion to shed some 



