PROBLEMS CONCERNING THE TUMOR VIRUSES 359 



leukemia in the Bittner substrain of C3H mice. In over 300 of these mice used 

 as test animals, 28 % developed leukemia, and extracts from these leukemias 

 resulted in the appearance of the disease in 37 % of 175 mice. It is regrettable 

 that the only available incidence of spontaneous leukemia for this substrain 

 comes from the colony maintained by Gross, but it is very doubtful that the 

 normal incidence approaches 28-37 %. Gross' evidence, supported by the 

 findings of Woolley and Small (1957), indicates that their procedures did 

 elicit leukemia in the C3H mice. Oncologists familiar with inbred mice strains 

 used in cancer research are not too much concerned over the conflicting 

 results obtained when the NCI and Bittner substrains were used to investigate 

 the leukemia virus It has been known for many years that these substrains 

 differ in their tumor responses as well as in other ways. Further evidence of a 

 leukemia virus was presented by Gross when he showed that, in his hands, 

 cell-free extracts of AK/n leukemic tissues produced the disease in C57BR/cd 

 mice and similar extracts from strain C58 leukemic tissues did so in strains 

 C3H and C57BR/cd. Finally, his recent efforts to acquire a transmissible 

 strain of the virus are most encouraging, for it may now be possible to 

 characterize its physical, chemical, and biological properties and thus compare 

 it with other known tumor viruses. 



Much remains to be done. The activity of the virus in newborn mice of 

 other strains and, of more importance, further studies of the age factor in 

 resistance to it must be pursued. Serological and tissue culture studies are 

 essential to keep apace with modern techniques for investigation of a virus. 



Perhaps one of the major handicaps investigators of this problem have 

 imposed upon themselves is their tendency to focus attention upon their 

 immediate problems and their failure to interpret their efforts in relation to 

 the broad problem of mouse leukemia. Dunn (1954) has written an excellent 

 review of the disease in mice and has presented a classification of its numerous 

 forms which should serve as a meeting ground for those working in the field 

 to assure themselves that they are working with the same type of lesion. 

 Gross' (1957b) review, for example, contains no reference to Dunn's paper or 

 to those of other pathologists who have studied the morphological forms of 

 the disease. It should also be kept in mind that it has also received attention 

 from excellent investigators who have done much to establish the importance 

 of hereditary factors, chemical and physical carcinogenic agents, hormones, 

 and the role of the thymus in the occurrence of the disease. Law (1957) has 

 written a concise review of these efforts which contains most of the pertinent 

 references. The lack of effort on the part of recent workers to discuss the 

 applicability of their findings to the known factors involved in the occurrence 

 of mouse leukemia is disappointing. The thymus gland is recognized as the 

 primary site of origin of the disease in the AKR and C58 mouse strains; if the 

 thymus is removed from these mice, their tendency to develop spontaneous 



