PEOBLEMS CONCERNING THE TUMOR VIRUSES 327 



only in "the small, intimately related stock in which the growth occurred" 

 and, apparently, the virus was not detected until the sixth transplant 

 generation through susceptible hosts. One wonders whether tissue cultures of 

 the primary tumor would have exposed the agent. 



Before leaving the fowl tumor viruses, it is fitting to acknowledge that 

 investigations with these viruses have built a firm foundation for almost all 

 other work with tumor viruses and, after years of investigation, the two used 

 here as prototype viruses are probably the most useful in present-day research. 

 The Rous virus continues to be the most valuable for studies on cell-virus 

 relationships, while the virus of visceral lymphomatosis, because it is available 

 in the natural state, continues to be a test virus for the evaluation of concepts 

 concerning the origin, spread, and biological relationships between tumor 

 viruses. 



C. Papillomatosis of Rabbits 



Shope (1933) discovered that a virus was implicated in the origin of 

 cutaneous papillomas found in cottontail rabbits living in certain regions of 

 the United States. The benign lesions produced with the virus would probably 

 be of minor interest to oncologists if they had remained papillomatous, but 

 the discovery by Rous and Beard (1935) that they changed to malignant 

 epidermoid carcinomas focused attention upon them, and subsequent 

 investigations brought to light one of the most interesting and perplexing 

 problems of the tumor viruses. Adequate reviews of the early work with this 

 virus have been prepared by Rous (1936, 1943, 1946) and of later studies by 

 Ginder (1952), Syverton (1952), and Oberling and Guerin (1954). Hence, this 

 discussion includes few references to older work and deals with (1) transmis- 

 sion of the virus and, (2) the papilloma-to-carcinoma sequence. 



1 . Transmission of the Virus 



The disease is characterized by the occurrence of epithelial proliferations of 

 variable size and hornlike structure protruding above and loosely attached to 

 the skin. Syverton (1952) mentions one horn measuring 6 inches in length. 

 Histologically, the disease is limited to the epidermis and consists basically of 

 a multiplication of cells in the lower layers. Apparently the virus is infectious 

 only when brought into contact with the injured basal cell layer of the 

 epidermis. The natural routes of transmission of the virus are not known, but 

 available evidence suggests contact between virus and traumatized epithelium. 

 Dalmat (1958) has shown that, under laboratory conditions, the virus can be 

 transmitted by insect vectors. 



The papillomas, in common with those of other species, show a tendency to 

 regression. Syverton (1952) has summarized his observations of regressing 



