B5 



are antigenically independent of each other. It also appears 

 that these differences are generally stable, tinder ordinary 

 laboratory conditions. Owing to the particular structure of the 

 " antigenic complex " in each strain, common properties seem 

 unable to find antigenic expression. 



But are any or all of these antigenic types equally " fixed " 

 in nature, and incapable of modification in the animal body ? 

 Since the biochemists have shown that a relatively slight chemical 

 or physical influence may profoundly alter antigenic characters, 

 it would seem probable that natural processes may accomplish 

 similar results. As the animal body is very commonly capable 

 of annihilating the whole antigenic complex of the pneumococcus, 

 it may, perhaps, be capable, either directly or indirectly, of 

 producing the less drastic changes required for transforming one 

 antigenic variant into another. At least, the balance of pro- 

 bability seems to be in favour of this view, although there 

 is an obvious difference between modification and destruction. 

 Attempts to decide the matter experimentally are confronted 

 with the familiar difficulty of discriminating between a modi- 

 fication and a mixture. As the pneumococcus is ubiquitous, the 

 demonstration that one variant has taken the place of another 

 in the body of an animal does not prove that the latter has been 

 modified into the former; the result may have been due to 

 selective action on a mixture. 



Perhaps some antigenic complexes are, in nature, more easily 

 modified (i.e., converted into different antigenic complexes) than 

 others, but there d.oes not seem to be any definite evidence that 

 this is the case with different strains of pneumococci. There is 

 some suggestion, however, that certain influences, e.g., those 

 which initiate disease, may tend to modify types in particular 

 directions, and that other influences, such as are prevalent in 

 recovery, may have a diverse tendency. This may be the reason 

 why certain types, such as I and II in some countries, are 

 relatively frequent in lobar pneumonia and usually disappear 

 ill convalescence. Of course, this view that types mutate in the 

 course of infection is only hypothetical; but the opposite view, 

 that types may be annihilated but cannot be modified, is at 

 least equally problematical. It seems to me to be begging the 

 question when one designates as " fixed " types those which are 

 found to be relatively more prevalent in pneumonia. 



In relation to the " mosaic pattern " conception of antigens, 

 discussed on pp. 51-54, it will be remembered (see pp. 16-18 

 of my preceding report) that French investigators who have 

 been working recently on pneumococci apparently accept this 

 theory as a satisfactory explanation of antigenic complexities, 

 and make it the basis of an elaborate and ingenious classification of 

 pneumococci by means of agglutination tests conducted according 

 to a special technique. And a similar explanation is offered for 

 antipneumococcal sera ; they are supposed to contain antibodies 

 corresponding to a large variety of constituents present in the 



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