ON THE NATURE OF TOXINS 57 



observers is very contradictory and difficult to understand, the 

 difficulty being increased by the fact that in the earlier researches 

 the distinction between antitoxic and bacterial immunity was not 

 understood. As a result of this we have to be careful in in- 

 terpreting these early results, so as to make sure that when the 

 author speaks of a serum as containing antitoxin he does not 

 really mean that it contains a protective substance which may 

 not be an antitoxin at all. In many cases the data are not 

 sufficient for us to discover its actual nature. 



The organisms on which the chief amount of experimental 

 work has been done are those of cholera, typhoid, tubercle, 

 anthrax, and the pneumococcus, and it is these which we shall 

 discuss in chief, excluding, however, the consideration of the 

 toxins of the tubercle bacillus for separate consideration in a 

 subsequent chapter. 



The general facts brought out by experiments with organisms 

 such as those of typhoid and cholera are these : The germ-free 

 filtrate of a young and actively growing culture is very slightly 

 toxic, if at all. The nitrate of an older culture is usually feebly 

 toxic, but to a degree which can hardly be compared with that of 

 diphtheria or tetanus ; it may take several cubic centimetres to 

 kill a rabbit or guinea-pig. And even this feeble toxicity is 

 largely discounted by the fact that the nitrate may contain acids, 

 nitrites, etc., which are poisonous, but in no way related to true 

 toxins. Yet in some cases exotoxins do exist in the filtrate, 

 since it is possible to obtain an antitoxin for them. The re- 

 actions of these antitoxins, however, are peculiar, in that the law 

 of multiples does not seem to apply beyond a certain figure. This 

 is well seen in the case of B. pyocyaneus, which forms a sort of 

 connecting-link between cholera and diphtheria, in that it forms 

 a definite though feeble exotoxin, whilst the immunity to it is 

 bactericidal. Wassermann showed that it is possible to produce 

 a true antitoxin against this toxin, and to determine the amount 

 which will just neutralize one lethal dose. He found, however, 

 that a multiple of this amount of antitoxin beyond ten would not 

 protect an animal against a corresponding dose of toxin, With 

 larger doses of toxin even a great excess of antitoxin was power- 

 less to prevent a lethal issue. Similar results have been obtained 

 in the case of cholera. These and other results have led some 

 authorities to consider that these exotoxins are not the specific 

 toxins which the pathogenic action of the bacillus defends, but 



