NEOPLASTIC ABNORMAL GROWTH 23 1 



has been exposed to all the derivatives of the carcinogen to which 

 mammalian cells are exposed in the course of carcinogenesis. 



Pure Speculation Concerning Normal 

 AND Abnormal Mutations 



From the data it is clear that certain correlations exist between the 

 production of mutations and the production of cancer. In general these 

 correlations concern the ability of some agents to do both things, and 

 the fact that the agents afifect, in doing both, those constituents of cells 

 which are composed of a material, nucleic acid, which is known to be 

 involved in genes and in self -perpetuating alterations of vegetative 

 bacterial material. Opposed to this concept of cancer as due to a dis- 

 continuous variation (mutation) are two considerations: first, the so- 

 called "virus theory" by which the neoplasm is held to be due to an 

 infection of the cell by a foreign parasite; and second, the fact that the 

 cancer cell clearly is at a competitive advantage as compared to the 

 normal cell, apparently able to carry out a vast number of processes not 

 available to its more dififerentiated normal associate. Were the cancer 

 cell a mutation in the accepted sense in which the term is used in describ- 

 ing the experiments on Neurospora, it should be less rather than more 

 competent, since most mutations studied precisely have been shown to 

 involve a loss rather than a gain of function. This fact requires a fur- 

 ther consideration of development and of the possibility of back 

 mutation. 



Perhaps normal differentiation of cells is, after all, simply the result 

 of mutations occurring normally at a predictable rate in an organized 

 fashion with the continued growth only of those forms which have a 

 superior adaptation to their environment. The word "mutation" as 

 applied commonly to cancer should by this concept be "abnormal muta- 

 tion," defined more precisely as an abnormal change occurring at an 

 unpredictable rate and in a specific fashion. This is productive in large 

 part of lethal effects or of pathological conditions including cells which 

 are out of environmental control and so can compete to great advantage 

 with their associates. Beadle (71) states, ". . . in present-day cellular 

 organisms there exists a possible mechanism for acquiring totally new 

 reactions. Occasionally through accident, one or more genes become 

 duplicated, i.e., a small segment of a chromosome occurs twice in every 

 set. But such a duplicate gene may undergo mutation in such a way that 

 it directs the formation of an entirely new enzyme. If this new enzyme 



