LEUKAEMOGENESIS — VIRAL AND CYTOLOGICAL ASPECTS 81 



berenblum: Why is it, both in Gross's experience, and I believe in others, that when you 

 try to demonstrate a leukaemia virus — when you inject newborn C3H mice, it depends on 

 the sub-hne of C3H whether the experiments will be successful or not? I don't know 

 whether anyone has any evidence why there should be this extraordinary specificity in 

 the recipient, except that after you've transmitted the virus many times, this peculiar 

 specificity seems to disappear. Have you any information on this subject? 

 UPTON: The question of host range is a very important one. Furthermore, as concerns 

 viral potency — what do you mean by a potent virus? Do you mean large numbers of 

 particles per unit weight or volume of extract, or do you mean a type of particle that's 

 more potent than another type of particle. Such quantitative aspects are still to be 

 elucidated. 



BiNGELLi: Did you find that some cells of the tumour had a large number of virus 

 particles and if so were other cytoplasmic or nuclear changes noticeable within those 

 cells? 



UPTON: It is my impression that Dr. Parsons found only one inclusion body of viral type. 

 In most instances, isolated viral particles were found just outside cells or at the cell 

 membrane. This was particularly true in vitro. 



BERENBLUM: The question of multiple viruses, of course, is another bugbear. For 

 leukaemia virology we took a few years to be certain that the polyoma virus and the 

 leukaemia virus were separate entities that might exist together. It took a long time even 

 to demonstrate that, although the manifestations of these two were so very striking. 

 What is the situation with myeloid versus lymphomatous virus in a line like RF? Is there 

 one virus or two? 



UPTON: This is a question to which we are addressing ourselves now. We don't know. 

 You may recall, however, that Gross in passaging his so-called A virus found that 

 thymectomized recipients would occasionally develop myeloid leukaemias. When he 

 passaged the virus from these myeloid leukaemias in thymectomized recipients back into 

 intact recipients, he got thymic lymphomas (see Gross, 1961). Moloney also found with 

 his virus, which characteristically induces a lymphoid tumour, that splenectomized 

 recipients occasionally develop myeloid leukaemias; again, passage back to an intact 

 host elicits lymphoid tumours. I beheve Graffi et al. also noticed, on serial passage of their 

 mouse leukaemia virus, that the characteristics of the disease would vary from one 

 passage generation to another, i.e. they would get myeloid leukaemias interspersed with 

 lymphomas. Wliether we have two agents or one agent that can induce either kind of 

 disease, I don't know. Certainly, however, experience with the polyoma agent would 

 indicate that a single tumour virus need not attack a single target- ceU. There can be a 

 broad spectrum of host cell sensitivities. 



DRASiL: Do you think that these leukaemogenic agents are always highly organized 

 particles or could small pieces of changed DNA play a role. DNA was shown last year to 

 be taken up by some haematopoietic ceUs. 



UPTON: There is ample evidence in the literature that virus nucleic acids are infective 

 per se. Hence, I would venture to suggest that, in time, there wiH be evidence for 

 leukaemogenesis by nucleic acid preparations. Preliminary data have been reported by 

 Hays et al. {Nature, Land., 1957, 180, 1419) and by Latarjet (1959). It is perhaps just a 

 question of time. We have not attempted to test nucleic acid extracts systematically in 

 our laboratory. We have made one or two experiments with Dr. E. Volkin; in one of these 

 we had what seemed to be enhancing effects on radiation leukaemogenesis, and in another 

 no effect at all. I think, to reiterate, we need better assay systems than we have now. 

 Currently, these experiments are terribly time-consuming. We don't get many myeloid 

 leukaemias until after several months. Hence, it is very hard to make headway. 



