changes are dir2ctly correlated with changes in the biochemistry of the cell. 

 The relationships between DNA, RNA, and enzymes which have evolved 

 during the last few decades, lead one to look for the basic neoplastic change in 

 one of these intimately interrelated hierarchies of cellular materials. 



In relation to DNA hereditary changes are now known to take place as a 

 consequence of mutation, or of the introduction of new genetic material through 

 virus infection (as in transduction) or directly (as in transformation). Although 

 each of these related hereditary changes may theoretically be involved in can- 

 cer, definite evidence is available only for the role of viruses, stemming from 

 the classic investigations of ROUS on fowl sarcoma (45). At the RNA 

 level of genetic determination, any one of these classes of change might take 

 place, as in the RNA containing viruses, and result in an heritable change, 

 perhaps of the cytoplasmic type, semi-autonomous with respect to the gene. 

 At the protein level, regulatory mechanisms determining gene activity and 

 enzyme synthesis as mentioned earlier, likewise provide promising areas for 

 exploration. 



Among the many exciting applications of microbial-genetic concepts and 

 techniques to the problems of cancer, may I mention in addition the explora- 

 tion by Klein (46) of the genetic basis of the immunological changes which 

 distinguish the cancer cell from the normal, and the studies on the culture, 

 nutrition, morphology and mutation of isolated normal and malignant mam- 

 malian cells of Puck (47) and of Eagle (48). Such studies are basic to our 

 exploration and to our eventual understanding of the origin and nature of the 

 change to malignancy. 



Regardless of the origin of a cancer cell, however, and of the precise genetic 

 level at which the primary change takes place, it is not too much to hope and 

 expect eventually to be able to correct or alleviate the consequences of the 

 metabolic defect, just as a closer understanding of a heritable metabolic 

 defect in man permits its correction or alleviation. In terms of biochemical 

 genetics, the consequences of a metabolic block may be rectified by dietary 

 limitation of the precursor of an injurious accumulation product, aromatic 

 amino acids in phenylketonuria; or by supplying the essential end-product 

 from without the cell, the specific blood protein in hemophilia, or a specific 

 essential nutrient molecule such as a vitamin. 



Time does not permit the continuation of these examples. Perhaps, however, 

 I will be pardoned if I venture briefly on a few more predictions and hopes 

 for the future. 



It does not seem unrealistic to expect that as more is learned about control 



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