THE TRANSMUTATION OF ANTIGENIC TYPES 305 



stimuli. It seems probable that bacteria afford particularly favourable material 

 for this field of biological study. 



Although the colonial changes associated with the S — > R variation have been 

 described in particular detail, it must not be supposed that they constitute the only 

 variations in colony form to which bacteria are subject. Such is far from the case. 

 We have already noted D variants, and, in the coli-typhoid group of bacilli, the 

 occurrence of mucoid variants that clearly do not conform with the M forms in 

 the M — > S — > R series observed in pneumococci, streptococci and the influenza 

 bacillus. This type of variation is not infrequently stimulated when a non-mucoid 

 bacterium is submitted to the action of a bacteriophage to which it is sensitive. 

 It seems likely that most variations associated with a change in colony form will 

 be found to be associated also with a change in the antigenic components at the 

 bacterial surface, but not necessarily with that particular change on which the 

 S — > R variation depends. 



The Transmutation of Antigenic Types. 



The loss of a specific antigenic component in the S — >- R variation and its re- 

 appearance when, as occasionally happens, the rough variant again gives rise to 

 the normal smooth form, naturally raises the question as to whether it is possible 

 for a rough strain to acquire the power of synthesizing, not the specific antigen that 

 characterized the smooth strain from which it was derived, but some different 

 antigen that is characteristic of another serological type belonging to the same 

 species. Is it possible, for instance, to transmute a smooth Type I pneumococcus, 

 via the non-capsulated rough variant, into a smooth Type II or Type III pneumo- 

 coccus % The problem is so important, in its biological interest and implications, 

 that the evidence must be considered in some detail. 



The pioneer experiments in this field were those of Griffith (1928). He injected 

 mice subcutaneously with living cultures of rough avirulent pneumococci, mixed 

 with large amounts of heat-killed smooth pneumococci belonging to the same or 

 another type. From the animals so inoculated smooth virulent pneumococci were 

 frequently recovered ; not only was a rough strain induced to revert to the smooth 

 type from which it was derived, but a rough variant from a Type II strain was 

 changed to a smooth Type I strain, a rough variant from a Type I strain to a smooth 

 Type II strain, rough variants of Type I or Type II strains to a smooth Type III 

 strain, and so on. 



These results were confirmed by Neufeld and Levinthal (1928), by Reimann 

 (1929) and by Dawson (1930a, 6). The study of this phenomenon was considerably 

 advanced by the experiments of Dawson and Sia (1931), who were able to bring 

 about a similar change in vitro by growing rough variants in a medium containing 

 a heavy suspension of heat-killed smooth pneumococci of the type it was desired 

 to produce. The addition of an anti-rough serum greatly assisted the transmuta- 

 tion, but was not an essential factor. In further experiments (Sia and Dawson 

 1931) it was found that the transmutation could not be induced by growing rough 

 pneumococci in the presence of purified pneumococcal polysaccharide, and that 

 heat-killed smooth pneumococci obtained from old autolysed cultures, or from 

 suspensions that had been subjected to repeated freezing and thawing, were unsuit- 

 able for this purpose. These results clearly demonstrated that the presence of the 

 polysaccharide antigen belonging to a given type could not induce a rough variant 

 to manufacture that particular antigenic component, and pass on the capacity 



