DIPHTHERIA. 311 



infect everything on which it is allowed to act. In the case 

 of the cholera bacillus we have already pointed out that 

 under certain conditions it is capable of producing a much 

 more violent form of disease than in others. 



Roux and Yersin have been able to demonstrate that the virulence of the 

 bacillus of diphtheria undergoes marked modifications even during the 

 progress of an attack of diphtheria in the same individual, and they believe 

 that the condition of the patient is modified not only by the alterations in 

 the number of the bacilli, but also by their virulence at different stages. 

 They find, for example, that in the early stages of the disease (except in 

 very rare cases) the number of bacilli is comparatively small, but that as 

 the disease advances the number of virulent bacilli present also increases 

 rapidly, this being tested both by microscopic examination and by cultiva- 

 tion and inoculation experiments ; whilst, on the other hand, as the case 

 approaches cure the bacilli that can be isolated are not only fewer in 

 number, but those that are cultivated are not nearly so active, for when 

 inoculated into animals they produce neither such marked constitutional 

 symptoms nor such severe local reactions. It is indeed believed that 

 the virulent and non-virulent bacilli represent a difference in degree of 

 virulence only, and not a morphological or specific difference, that the 

 difference is one of degree and not one of kind, and that the pseudo- 

 diphtheritic bacillus described by Loffler and Hoffman is really only the 

 organism undergoing a kind of saprophytic phase which is interpolated in 

 the life of the parasitic bacillus. 



Roux and Yersin obtained an imperfectly attenuated virus first by 

 keeping the dried membrane for a considerable time, when they found 

 that cultivations from them of bacilli, in which were present all the typical 

 appearances and morphological characteristics, when inoculated into 

 animals had lost their virulence. They found that they were able to 

 diminish the virulence of the diphtheritic organisms growing in broth 

 by passing currents of air at 39.5 C. through this medium, and that if 

 the process was continued too long the bacilli were completely deprived 

 of life. It would appear that this was simply an interference with the 

 vitality of the organism which was deprived of one function after another 

 until it was killed altogether. They found it impossible, however, by 

 these methods to graduate the attenuation, and although they proved 

 that the virulent bacillus alone could elaborate the toxic material, and then 

 only under favourable conditions, the virulence became modified as the 

 conditions were altered, the activity of the toxine being also modified ; 

 these conditions could not be controlled except in a very rough and in- 

 adequate fashion. 



Recently Fraenkel has found that by heating cultures of 

 the diphtheria bacillus to a temperature of 65 or 70 C. and 

 injecting from 10 to 20 cc. of such cultures into guinea-pigs, 

 after an interval of fourteen days subcutaneous injections of 

 even the most virulent diphtheria poison had no effect. If 

 however, the animals were again injected within the 

 prescribed period of fourteen days they succumbed to the 



