PROBLEMS CONCERNING THE TUMOR VIRUSES 331 



These results were selected from others obtained by Greene because they 

 best serve the purpose of this discussion. Apparently, the virus from lesions 

 of cottontail rabbits was changed sufficiently to produce papillomas through 

 serial transfer in domestic rabbits. Greene mentioned that this "infectious 

 virus" may have differed from the original virus from cottontails because the 

 latter induced multiple and confluent lesions of the skin of domestic rabbits 

 within 2 weeks, whereas the "infectious virus" produced a few discrete 

 lesions and usually required at least 6 weeks to do so. He looked upon the 

 "infectious virus" as a variant form of the original virus, and in his discussion 

 stated: "The infectiousness of Selbie's virus for domestic rabbits was lost 

 after passage in a cottontail, while, in the present instance, the infectiousness 

 of the virus was not altered by such procedure. Despite their apparent 

 differences, the variant viruses possess the significant common property of 

 resistance to the masking effect of adult domestic skin and, as such, offer 

 material for studies of possible pertinence in a clarification of the operation of 

 of the so-called masking process." 



Greene's efforts have done more than procure a variant which can be 

 used for the purpose he described. The acquisition of this virus is a very 

 practical achievement, because it established a ready supply of papilloma 

 virus and frees investigators from dependence upon the naturally occurring 

 papillomas which, in the past, have been the only source of virus. 



2. The Pa'pilloma-to-Carcinoma Sequence 



The occurrence of malignant epidermoid cancers at the base of induced 

 papillomas is, through its implications to the cancer process, the major 

 problem associated with this tumor virus. At first the transfor- 

 mation was thought to be limited to the induced lesions of domestic 

 rabbits, but Syverton (1952) found: (1) it was not uncommon in 

 Western cottontails carrying naturally occurring papillomas; (2) the rate 

 of transformation in these rabbits was similar to the rate displayed 

 by Eastern cottontails bearing induced papillomas; (3) the tendency toward 

 the development of malignancy was most pronounced in domestic rabbits. 

 It will be recalled that in these three groups of rabbits Syverton found a 

 similarity in the persistence of papillomas in Eastern cottontails and domestic 

 rabbits, whereas the papillomas of Western cottontails showed a greater 

 tendency to regress. The fact that the Eastern cottontails resembled domestic 

 rabbits in the persistence of their papillomas, but resembled Western cotton- 

 tails in the ability of their papillomas to undergo the change to malignancy, 

 suggests the importance of genetic factors in the reactions between host and 

 virus. 



Efforts to incriminate the virus in the change to malignancy were difficult 

 for the simple reason that it was not detectable in the cancer. Rous (1936) 



