228 F. FENNER AND J. CAIRNS 



the line is, as we shall see in the last example of variation in virulence, not 

 assisted by exceptionally great lethality; if the host is rapidly killed, the 

 chance of successful transplantation of the virus to another host may not be 

 high (Burnet, 1945). 



Throughout this chapter we are dealing with the variation of virulence and 

 the way in which discernibly new varieties of virus arise. Occasionally, 

 evidence is mentioned which indicates that, during the change in character of 

 a virus, one population of virus particles is being replaced by another. But 

 the process of natural selection must be read into everything that follows. At 

 all levels of complexity, the adaptation of a virus to a new situation must 

 be pictured as the product of a single change or succession of changes, 

 augmented by intense selection pressure. What is known of the manner in 

 which these primary changes occur will now be discussed briefly, taking first 

 of all evidence from the field of bacteriophage to provide a basis for what little 

 is known in the case of the animal viruses. 



A. In Bacterial Viruses 



First, and simplest, variants may arise by a process of random mutation 

 occurring during virus replication; in this case, variant clones are found in 

 the virus populations yielded by individual cells (Luria, 1945, 1951). The 

 distribution of such clone sizes among the yields of individual cells shows that 

 the change is random rather than directed by the host cell. 



The second process operates primarily on the host cell; variant clones are 

 distributed randomly among virus populations yielded by large groups of 

 host cells, but these clones arise from particular cells which themselves are 

 variants in that they give rise (uniformly or not) to virus variants (Fredericq, 

 1950a,b). Although such host-induced changes are usually only phenotypic 

 (Luria and Human, 1952; Bertani and Weigle, 1953), there is apparently one 

 instance of the change being ultimately genotypic (Fredericq, 1950a,b). In 

 many instances, this distinction between primarily virus and primarily host- 

 induced variation disappears, for there is increasing evidence of genetic 

 homogeny between certain bacterial viruses and their hosts (Stent, 1958). 



Thirdly, genetic recombination may provide a mechanism whereby changes 

 resulting from the operation of the first two mechanisms may be transferred 

 from one virus to another differing in many aspects of its genetic constitution. 

 It is conceivable that genetic recombination may play an important part in 

 the ecology of bacterial viruses. 



B. In Animal Viruses 



Adequately documented examples from the field of animal viruses of the 

 three processes described in the previous section are so rare as to be almost 

 unique. 



