PROBLEMS CONCERNING THE TUMOR VIRUSES 333 



for their ultimate reactions to a virus capable of initiating cellular prolifera- 

 tion. The virus plays an important role in the cancer process because it is 

 responsible for the first step in the papilloma-to-carcinoma sequence. 



Various chemical carcinogens produce papillomas in the rabbit and in 

 other rodents and, if applications of the carcinogen are continued, some of the 

 papillomas become malignant. This is relevant to the present discussion 

 because the necessity of an enduring relationship between the cell and 

 carcinogen is not essential for the propagation of these cancers in new hosts. 

 The supposition that some tumor viruses, and the papilloma virus could be 

 one, are responsible only for the initiation and not the completion of the 

 cancer process is attractive because it implies that ordinary viruses may be 

 implicated in the origins of tumors. This idea may have led Duran-Reynals 

 (1952, 1957a,b) to investigate the neoplastic properties of the viruses of fowl- 

 pox and vaccinia. In the final analysis, a cancer cell is a modified cell and it is 

 becoming increasingly clear that this modification is dependent upon the 

 interplay of various influences. Hence, one of the major problems of the 

 tumor viruses is to ascertain their roles in relation to other known influences 

 which bear upon the cancer process. 



One experimental finding in support of the concept that virus must be 

 present to assure continuous propagation of a virus-induced tumor was the 

 demonstration of antibodies in rabbits bearing transplants of the V 2 car- 

 cinoma (Kidd, 1942). This tumor was induced in a domestic rabbit with the 

 papilloma virus and throughout a series of transfer generations all efforts to 

 expose the infectious virus were unsuccessful, but antibodies to the virus 

 were detectable in the sera of the hosts. This was interpreted as evidence 

 that the virus was present in the tumor but in a noninfectious, or vegetative, 

 form, until it was found (Rous et ah, 1952), during subsequent generations, 

 that antibodies to the virus were no longer present and the tumor remained 

 propagable. Perhaps the simplest explanation for the findings in earlier 

 transfer generations would be that the virus was a "passenger" in the 

 tumor instead of an essential "masked virus." 



Beard (1956) has assembled impressive evidence against the theory of the 

 masking phenomenon in virus-induced tumors and used the rabbit papilloma 

 virus as the test virus for his viewpoint. His discussion was based upon the 

 acquisition of highly purified preparations of the virus (Beard et at., 1955) 

 and known host- virus relationships. Use of purified virus in quantitative 

 studies of the host response permitted an estimation of the number of virus 

 particles obtained from papillomas and the number necessary to induce 

 papillomas. The yield of virus from cottontails varied 1000-fold and from 

 some no measurable amounts of virus were recoverable. The maximum 

 computed yield from domestic rabbits was much less; the best from their 

 lesions was only 0.48 % of the best from cottontail papillomas. Calculations 



