GENETIC INTERACTIONS BETWEEN ANIMAL VIRUSES 281 



using Dulbecco's monolayer culture techniques with viruses like poliovirus. 

 It has not yet been reported that differences in plaque structures can be used 

 as genetic markers but it seems highly probable that systems of this type will 

 be found. It should then be possible to use the refined quantitative methods 

 that have been used in phage genetics. At present, the necessity to isolate 

 every clone to be characterized is a serious hindrance to satisfactory quanti- 

 tative study. Whatever the technique of providing the conditions for inter- 

 action of two strains of virus, analysis of the results requires the isolation 

 from the progeny of clones of virus among which recombinant characters can 

 be detected. Ideally we should hope that, as is the case with most of the 

 examples of genetic recombination that have been studied with bacterial 

 viruses, the proportion of recombinants will be of the same order as of the 

 parent types. This will allow isolation of recombinants without the necessity 

 of providing a selective environment. There are, however, many examples 

 where the yield of recombinants is much smaller, perhaps because recombina- 

 tion is only stable when one or other of the parents differs somewhat from the 

 dominant form. In such circumstances, it will always be difficult to exclude 

 the possibility that what is regarded as the recombinant is in fact a mutant. 

 In most cases, a consideration of the characters of the new form against those 

 of the two presumed parents will allow a tentative decision. Most such 

 experiments will automatically include controls in which both parent types 

 are also exposed alone to the selective environment. 



Where experimentation is designed to elucidate the conditions under which 

 recombination occurs, rather than to study the characters of the recombinant, 

 it is desirable to use two parent strains which give rise to an easily recognized 

 type of recombinant. The simplest such procedure, first demonstrated by 

 Burnet and Lind (1954a), and also used by Baron and Jensen (1955), and by 

 Hirst and Gotlieb (1956), is to use one inactivated parent with a serologically 

 distinct active parent. After interaction the yield is subcultured in the 

 presence of antiserum corresponding to the active parent. Any virus growing 

 up and having the serological character of the inactivated parent is a 

 recombinant. 



Another method we have frequently used is to choose a pair Ab/aB which 

 gives one recombinant AB which, when present in mixed culture, will over- 

 grow ab, Ab, or aB. This allows recognition of the fact of recombination 

 without the necessity of isolating and characterizing the recombinants. 



In most situations of potential practical importance, the most important 

 quality to be studied will be the virulence of strains and their mutants and 

 recombinants. Virulence is notoriously labile when a virus is undergoing 

 transfer from one type of host organism to another and some special require- 

 ments emerge in work on changes in virulence. In general the objective will 

 be to allow a strain with a high virulence V for some defined host H to interact 



