HAROLD P. RUSCH 



3. "The inherited state is an unstable or poorly balanced 

 system confined to an organ or tissue in which the specific cells 

 tend to become malignant either from functional strain or from 

 unfavorable environmental conditions." 



4. "Almost all, if not all, classes of cells may be rendered 

 malignant under the influence of one or more agents." 



Although no recent discoveries have invalidated the 

 general conclusions reached almost 20 years ago, research 

 during the intervening years has advanced at an ever-increasing 

 tempo, and it is only natural that some of the older beliefs 

 would be clarified, others modified, and that sufficient evidence 

 would be available for additional concepts. Progress during 

 the past few years in areas such as cellular physiology, genetics, 

 and biochemistry has provided the framework for some 

 new conclusions and interpretations, which form the basis of 

 this paper. Some of the mechanisms by which metabolic 

 patterns can be altered will be considered first. 



Inherited Cellular Changes 



To keep pace with the rapid advances in cellular inheritance 

 it is necessary to turn to fundamental experiments that were 

 carried out with various forms of life without reference to the 

 cancer problem. The geneticist, for example, has found that 

 metabolic pathways are genetically determined. Although it is 

 impossible to cite all the references that support such conclu- 

 sions, the line of research on mutations in Neurospora carried out 

 by Beadle (6) and by Beadle and Tatum (7) illustrates this type 

 of study. The finding that the mutant strains have their 

 counterparts in many naturally occurring forms of life suggests 

 the generality of the conclusions. From this work have come 

 stimulating concepts of the origin of life and the idea that life 

 is continually evolving (32,46,51). 



It is a tempting leap to the assumption that each type of 

 cell within the body of a higher animal represents a sort of 

 mutant from some predecessor. With such an assumption the 



676 



