304 F. M. BURNET 



being Andrewes' (1936) inflammatory 1A variant, which produces only a 

 mild inflammatory lesion in the rabbit (Andrewes and Shope, 1936). 



Smith finds that transforming agents TA (i.e., heated extracts of infected 

 tissues) prepared from strains of any type will (with some irregularity) allow 

 transformation of strains lower in the series up to a level not higher than that 

 of the virus from which the agent was prepared. If a low grade fibroma 

 approaching 1A in character is used with myxoma TA, the usual result is not 

 the production of myxoma but of a more active fibroma resembling the 

 Boerlage type (Shope, 1950). Similarly, the inflammatory variant can be 

 converted to standard fibroma by treatment with Boerlage fibroma TA. The 

 transformed strains breed true on passage. Even where typical myxoma is 

 produced the usual finding is that the rabbit inoculated with the primary 

 mixture produces a large tumor which eventually regresses. Rabbits sub- 

 inoculated from this lesion develop typical lethal myxomatosis. 



The transformation has not been produced in experiments using the 

 chorioallantois (Hoffstadt and Pilcher, 1941; Smith 1952), but Killiam (1956, 

 1957) has recently described successful transformations in experiments with 

 tissue culture growth of the viruses. 



In discussing the conditions under which successful transformation can be 

 obtained, Smith (1952) notes individual variability in rabbits but could not 

 relate this to such factors as age, breed, and sex. The transforming agent 

 seemed to be the least variable component of the system. This can be prepared 

 from any tissue containing adequate amounts of myxoma virus. The tem- 

 perature of inactivation is not critical and may be as high as 85°C. and still 

 give active material (Berry, 1937). As would be expected, it remains active in 

 sealed ampules indefinitely at refrigerator temperature. The only evidence as 

 to its chemical nature is found in the fact that active solutions can be de- 

 proteinized by repeated treatment with chloroform without loss of activity 

 (Smith, 1952). This, plus resistance to treatment with alcohol, is at least 

 consistent with the assumption that the agent is a nucleic acid, but does not 

 exclude other possibilities, e.g., mucopolysaccharide. 



It is to be hoped that a full analysis of this phenomenon will be forthcoming 

 in the near future. Present evidence does not seem adequate to accept it as a 

 transformation analogous to the pneumococcal transformation although, of 

 course, this interpretation is not excluded. If nucleic acid is concerned it is 

 most desirable that it should be identified as DNA or RNA. 



Perhaps the most interesting feature is the observed capacity of storage in 

 glycerol to "enforce" an inheritable change to a lower level of activity. This 

 change can only be reversed by the use of transforming agent from a form 

 higher in the series. There is a suggestion here that something other than a 

 straightforward survival of a glycerol-resistant mutant is taking place. The 

 evidence does not allow any specific suggestions, but one would feel that it is 



