398 BACTERIOPHAGES 



tions in earlier days. Adaptation in phages, which will be dis- 

 cussed later, is of two types, host-induced or phenotypic modi- 

 fication, and host-range mutation. It can be accepted that 

 adaptation has occurred if the newly propagated phage is in- 

 distinguishable from its unadapted parent in all respects other 

 than host range, and if a phage that has undergone host-induced 

 as opposed to mutational modification of host range can be shown 

 to revert in one growth cycle to the host range of the unadapted 

 phage when propagated on a suitable bacterial strain. There is 

 no evidence that such tests were applied in the earlier work to 

 establish that true phage adaptation had taken place, and claims 

 that phages had been adapted must therefore be treated with 

 caution. 



Marcuse (1925) and Hadley (1926) were perhaps the first to 

 point out the relationship between phage specificity and the 

 heat-stable surface antigens of Enterobacteriaceae. The most 

 important early work in this respect, however, was that of Burnet 

 and his colleagues (see Burnet, 1927, 1929b, 1930, 1934b; 

 Burnet and McKie, 1930; Gough and Burnet, 1934). These 

 workers showed that, in the phage-host cell systems they studied, 

 there was a close correspondence between the somatic antigens 

 and phage sensitivity. Mutation of the organisms from the 

 smooth to the rough state, which involved loss of the characteris- 

 tic somatic antigen, brought about resistance to phage. Thus, 

 it was possible to select rough variants of salmonellas with phages 

 specific for smooth strains. On the other hand, phages were 

 found that lysed only rough variants. Organisms surviving the 

 attack of "rough-specific" phages were often found to be in the 

 original smooth state of the host strain. Burnet (1930) recog- 

 nized, however, that mutation of bacteria to phage resistance 

 was possible without demonstrable antigenic change, and he sug- 

 gested that distinct bacterial agglutinogenic and phage-adsorbing 

 receptors were carried by a single unit. Levine and Frisch (1 933a, 

 b, 1934) observed that aqueous extracts of Shigella shigae and 

 Salmonella paratyphi B specifically neutralized the phages to which 

 these organisms were susceptible, but were virtually without ef- 



