222 C. P. RHOADS 



The concept of governing factors in the cytoplasm, though almost as 

 old as cytology, has recently been supported by new and limited but con- 

 vincing evidence reviewed by Haddow ( i8). It is a subject of great im- 

 portance to the cancer problem because it provides a principle of mor- 

 phogenesis which has been involved to explain the transmission of some 

 unusual but actively studied examples of neoplastic disease by cell-free 

 agents (viruses) in part derived from avian tumors. Some have assumed 

 that these agents must be cytoplasmic entirely, and require little con- 

 sideration of a genie origin, though adequate justification or even need 

 for this assumption is hard to establish. 



Satisfactory data attest to the view, however, that a very considerable 

 and important part of the form and function of sexual cells, as well as 

 of vegetative forms, is controlled by genes without the participation of 

 any non-genic or cytoplasmic factor. Hence, since a normal adult cell 

 differs profoundly from its primitive undifferentiated precursor, the 

 genes of the two forms should differ also. In support of this possibility 

 is the fact that differentiated cells contrast sharply with their primitive 

 relatives in their susceptibility to injury by one agent, x-rays, known to 

 have a profound effect on genes (19). Similarly, since the form and 

 function of the cancer cell differ distinctly from those of the normal cell, 

 the genes of these two cell types also should be different. Morphological 

 grounds to support this view are at hand in a long series of studies, of 

 which the most recent are those of Biesele (20). Although obvious ab- 

 normalities of chromosomes are not present in every cell believed to be 

 neoplastic, they frequently can be demonstrated. Furthermore, it is clear 

 from the results of experiments to be discussed later (21) that genie 

 changes adequate to cause profound cellular alterations may exist with- 

 out any morphological evidence of their presence. 



As a basis for the concept that the progressive steps in cellular dif- 

 ferentiation, normal or abnormal, can be controlled by genes, proof must 

 be advanced that genes can mutate spontaneously in a regular fashion, 

 since only in this way could they control the changes in structure and 

 activity associated with orderly development. Demerec (22) has pre- 

 sented adequate evidence that genes vary greatly in their stability. Some 

 genes of Drosophila, for example, mutate rarely or not at all, whereas 

 others, and these are numerous, particularly in plants, mutate hundreds 

 of times in the development of a single individual. Plough (2T)) has 

 shown that the spontaneous lethal mutation rate in two of the three large 

 chromosomes of Drosophila is in direct proportion to temperature and 

 that the mutations so induced may subsequently disappear. Further- 



