NEOPLASTIC ABNORMAL GROWTH 223 



more, the existence of genes which affect in turn the spontaneous muta- 

 bility of other genes has been proven by Rhoades (24). 



Once the fundamental instability of genes has been established, if we 

 are to invoke them as regulators of differentiation, it is necessary to 

 specify what changes of cells are involved in that process and to estab- 

 lish that they are alterations of constituents which are dependent upon 

 specific genes for their existence. If this can be done, and if we are satis- 

 fied that those particular genes exist in mammalian cells, then, pending 

 the submission of strong evidence concerning the regulatory function of 

 cytoplasmic factors, it is not unreasonable to consider the possibility 

 that orderly, genie controlled variation is adequate to provide a basis for 

 development, either orderly or disorderly. Beadle states : "Cells of iden- 

 tical genotypes travel many divergent paths in the process of differentia- 

 tion of the individual organism" (25). The different paths involve the 

 acquisition of structural and functional characteristics which concern, 

 particularly, the protein components of the cell. Satisfactory proof is 

 available that organs of special function are constructed of different and 

 characteristic proteins ; the composition of the skin, for example, is 

 demonstrably quite different from that of other tissues. Functional dif- 

 ferences between cells depend upon kinetically active protein enzymes, 

 and examples of their specificities in differentiated tissues are almost 

 numberless. With the special proteins and enzymes established as charac- 

 teristic of cellular differentiation, proof is required that the production 

 of these constituents is controlled by genes. 



Ample demonstration that genes control the constitution of tissue 

 proteins is found in the antigenic specificities of tissues as compliant 

 with the principles of heredity. From Landsteiner's (26) contributions 

 concerning the blood groups of man, through the more recent studies of 

 Wiener (27) on the Rh factor, a mass of evidence is available. Particu- 

 larly striking is the fact that a i :i gene-to-antigen relationship has been 

 shown to exist in experimental material by Tatum (28), a fact which 

 suggests that the antigens are direct products of the genes, or even fur- 

 ther, that the antigen is "the copy of the gene." The thesis of the con- 

 trolled production of antigens by genes is further supported by immuno- 

 logical studies referred to later, in which genes apparently have been 

 altered by use of antisera specifically directed against the antigen, or 

 gene product. 



Striking evidence that enzyme production is also under the control of 

 genes is to be found in the experiments of Beadle and his associates, well 

 summarized in a recent publication (25). Elaborate studies of Neuro- 



