64 TOXINES AND ANTITOX1NES. 



micro-organisms that which we see exerting its activity in the 

 pathology of these infectious diseases in man. An extraction 

 process, such as occurs spontaneously in old cultivations, is by no 

 means one that has little effect upon the constitution of these 

 unstable bodies. In such old cultivations great changes of re- 

 action from acid to strongly alkaline occur abruptly ; ammonium 

 compounds and other chemical substances are produced, which 

 we know tend to change and destroy bacterial poisons. Hence 

 we must assume that even these traces of cholera virus, &c., that 

 pass into solution, and to which an antitoxine can be prepared, do 

 not represent the primary poisons of these micro-organisms, the 

 poisons that they undoubtedly produce in the human organism, 

 but are rather a secondary and more stable modification ; and 

 this conclusion is based on the fact that while, as WASSERMANN 

 found in the case of the poison of B. pyocyaneus, we are certainly 

 able to prepare an antitoxine to this dissolved poison, yet this 

 antitoxine behaves quite differently to the antitoxines in diph- 

 theria. For the latter neutralise the corresponding quantities 

 of toxine in any given multiples of the dose, provided that their 

 own quantities are increased in the same proportion. Thus, if 

 10 doses of diphtheria antitoxine neutralise 10 doses of toxine, 

 1,000 doses will neutralise 1,000 doses of toxine. But in the 

 case of pyocyaneus poison this " law of multiples " only holds 

 good within very narrow limits up to about eight or ten times 

 the lethal dose. Beyond that there is no neutralisation, and 

 animals die in spite of large doses of antitoxine. 



We must, therefore, conclude that it is altogether doubtful 

 whether we have ever had the primary true toxine of cholera, 

 &c., in our hands when using the culture media at our present 

 disposal. It may be a question of suitable nutrient media, and 

 further systematic research may be required before we get nearer 

 to this important goal. The great influence of a suitable culture 

 fluid upon the production of the true poison in artificial nutrient 

 media is shown by the case of diphtheria virus, of which in the 

 earlier experiments of Boux and YERSIN from 30 to 36 c.c. were 

 required to kill an animal with the typical acute symptoms, 

 whereas a close systematic study of culture media and the choice 

 of suitable cultivations have had the result of reducing the 

 amount now required to 1 to 2 mgrms. Hence we must regard 

 the question of cholera virus and similar poisons as still unsettled 

 in many respects. 



At the same time, we must not omit to call attention to the 

 fact that so experienced a worker in practical research into the 

 nature of cholera infection as B. PFEIFFER holds the view that 



