NEOPLASTIC ABNORMAL GROWTH 221 



The fact is remarkable that, to date, in spite of the enormously ex- 

 tensive studies which have been made of neoplastic tissue and the obvi- 

 ous morphological contrasts between normal and cancer cells, no quali- 

 tative chemical differences have been established conclusively. A 

 considerable series of studies culminating in the recent work of Friede- 

 wald (8), of Kidd (9, 10, 11), and of Green (12, 13) provide certain 

 immunologic evidence for the presence of abnormal constituent proteins 

 in the cancer tissue of animals. Very great extension of the work is re- 

 quired, since in few instances described did the tumor studied arise in 

 animals homozygous with the ones in which antibodies were induced. 

 The measurements of the enzymatic activities of neoplastic tissue insti- 

 tuted by the Warburg school (14) and so effectively continued by the 

 investigators of the National Cancer Institute (15), the McArdle labo- 

 ratory (16), by Salter (17) and others have not revealed completely 

 uniform qualitative differences between normal and neoplastic enzyme 

 function. Can it be that new enzymes have not been found because of 

 the tendency of investigators to examine cancer tissue for the activity 

 of normal systems against normal substrates, rather than to search em- 

 pirically for new metabolic pathways ? Differences of structure and func- 

 tion must exist, however, between normal and cancer cells, even though 

 they have not been satisfactorily defined. Perhaps a new approach can 

 be developed from a consideration of the possible origins of differences 

 between cells. 



Cfxl Characteristics as a Function of Genes 



The induction of changes in cells is frequently susceptible to analysis 

 in accord with the recognized principles of morphogenesis, under which 

 differentiation and growth are governed by genes. Whereas this con- 

 trol of the patterns of living organisms is well established, it is not en- 

 tirely clear how tissues and organs become differentiated into forms 

 which are completely distinct one from the other, when supposedly all 

 the component cells, being derived by mitotic divisions from a single 

 fertilized egg, have identical sets of genes. If genes are the sole regu- 

 lating agents, when a cell changes as it does in differentiating, the altera- 

 tion should follow and be the result of a mutation of the genes. It is 

 likely, however, that there exists in the cytoplasm of some cells a second 

 group of controlling factors which are distinct from the genes of the 

 chromosome thread, but which may depend on the genes for their origin 

 and to some extent for their continued growth. Conceivably both genie 

 and extragenic regulatory mechanisms operate coincidcntally. 



