NEOPLASTIC ABNORMAL GROWTH 255 



tain agents to cause (a) gene mutations in sexual forms, (b) changes 

 with similar results in vegetative forms or bacteria, not susceptible to 

 study by the conventional methods of the geneticists, and (c) cancer in 

 avian and in mammalian tissue. Whereas this correlation may of course 

 be pure coincidence, it would be surprising if the basic mechanisms in 

 the three types of cells were not similar or perhaps identical. 



The induction of certain forms of neoplastic abnormal growth by 

 filtrates of the affected cells, free of the whole cells as such, poses a par- 

 ticularly nice problem to the investigator. In some instances, such as that 

 of the Rous agent, the active material, proven conclusively to be related 

 closely to constituents of the normal cells which it affects, can be recov- 

 ered regularly from the resultant neoplasm. In other cases, as for ex- 

 ample with the cancer which arises on the Shope virus-induced papil- 

 loma, this is not true. Here the virus, though etiologically related to the 

 neoplasm, disappears, conceivably incorporated into the affected cells, 

 and a new protein constituent arises, immunologically quite distinct 

 from the inoculated material and from any substance present in the host 

 before inoculation. 



Whereas self -perpetuating cytoplasmic entities are well-known in 

 lower forms, and some of these, as the Kappa factor of Paramecia and 

 perhaps certain plant constituents, can be passed from the cytoplasm of 

 one cell to that of another, they tend to be dependent to some extent 

 upon the genes of the host. It would be of great interest if a protein sub- 

 stance could be isolated which, when taken in by the cytoplasm of a cell, 

 could be proved to substitute either for a normal substrate or for a nor- 

 mal enzyme, and as a result would alter the gene to produce a wholly 

 new constituent. Such a compound might disappear and so not be re- 

 coverable, but it would have exerted its effect in causing a mutation. 

 There seems to be no fundamental reason why such a mechanism should 

 not exist, and indeed it is wholly possible that this may be one route 

 operative in the production of cancer by physical agents. Dale has shown 

 that x-rays need not affect the gene directly, but may do so indirectly 

 through their effects on enzyme systems. Kensler and Rhoads have 

 proven that the naturally occurring metabolites of one carcinogen af- 

 fect profoundly certain enzymes of the target tissue. 



The studies on the Brown-Pearce tumor have been referred to as pro- 

 viding new evidence for the presence of antigenic constituents in a 

 transplantable neoplasm. The principle is extended by the preparation 

 of specific antibodies against the milk factor in mice and in the V2 carci- 

 noma of rabbits. There has been little doubt for many years that anti- 



