328 H. B. ANDERVONT 



lesions in hosts carrying natural and artificially produced papillomas. Of 

 those occurring naturally in cottontails, 21 % regressed within 6 months and 

 36 % within the following 18 months; of those induced in cottontails, only 

 6 % regressed during the first 6 months and none did so thereafter; of those 

 induced in domestic rabbits, 9 % regressed within 6 months and none 

 regressed within the next 6 to 24 months. Thus, the rate in domestic rabbits 

 was similar to that in artificially infected cottontails, but the highest 

 incidence occurred in the naturally infected cottontails. Considerable work 

 has been done to ascertain the reasons for these regressions and the findings 

 were summarized by Ginder (1952). The presence of antibodies in infected 

 rabbits was not responsible because papillomas persisted in animals containing 

 potent neutralizing antibodies in their blood, and the disappearance of the 

 virus from the papillomas was ruled out when highly active virus was found 

 in receding papillomas. Ginder mentioned another finding of interest, namely, 

 that multiple growths on individual rabbits receded at the same time, and 

 concluded: "Some little understood host factor is of great importance." 

 That this factor could be the genetic constitution of the host will be empha- 

 sized throughout this discussion. 



When the virus was introduced into the traumatized skin of cottontails, 

 papillomas were detectable within 8 or more days and the lesions usually 

 contained the virus in variable quantities, but in some papillomas the virus 

 could not be detected and, on the average, less virus was present in the 

 induced lesions of cottontails than in those of the natural disease. This wide 

 range of virus content between papillomas from different cottontails could 

 reflect the mixed genetic composition of the hosts. 



Transfer of the virus from cottontail papillomas to the scarified skin of 

 domestic rabbits resulted in the occurrence of papillomas and disclosed a 

 problem of major importance when it was learned that the lesions often 

 failed to contain detectable virus. This discovery sparked a long series of 

 experiments and a controversy concerning "masked" viruses which is one 

 of the most interesting unresolved problems of the tumor viruses. Syverton 

 (1952), in a discussion of this feature of the disease in domestic rabbits, 

 states: "If cottontail papilloma virus were not available as a reagent to 

 establish immunologic evidence for the presence of virus, the growth would 

 inevitably fall into the category of a nonviral mammalian tumor, even 

 though its viral etiology might be suspect." His statement defines the problem 

 and its implications and indicates the desirability of further study to achieve 

 a solution. 



Ginder (1952) has summarized the results of the experimental approach to 

 the problem. The fact that infected domestic rabbits developed antibodies to 

 the virus received much attention and efforts were made to reveal the virus 

 through the application of immunological procedures. Extracts of the 



