548 COLLECTED STUDIES IN IMMUNITY 



animal experiments, furnished a more exact basis, so that the mathe- 

 matical harmony of toxin-antitoxin experiments in vivo and in vitro 

 became very convincing. At the present time, therefore, we may 

 regard it as almost axiomatic that toxin and antitoxin act on each 

 other chemically and without the intervention ot vital forces. 



These quantitative biological studies, however, have not merely 

 thrown light on the relations existing between toxin and antitoxin t 

 but have also given us valuable intormation concerning the constitu- 

 tion of the poisons themselves. Almost at the outset it was found 

 that the two properties of toxins which could be analyzed, namely, 

 poisonous action and the property to bind antitoxin, do not at all 

 go hand in hand. In this connection the continuous study of toxin 

 solutions which are allowed to stand for some time proved particu- 

 larly instructive, for it was found that while the power to bind anti- 

 toxin remained constant, the toxicity gradually dminished. This 

 study gave us one of the fundamental conceptions underlying the 

 modern view of toxins, namely, that toxicity and combining power 

 are two distinct and independent properties of the toxin molecule. 

 As is well known, this fact is expressed by the side-chain theory by 

 assuming that the toxin molecule possesses two specific atomic groups, 

 one of which is toxophore, the other haptophore. Destruction or 

 loss of the toxophore group gives rise to the non-toxic toxoids which 

 are still capable of binding antitoxin. As a result of the high degree 

 of lability of the toxophore group, this transformation into toxoid is 

 a spontaneous process. And since the production of effective bacterial 

 toxin solutions takes a certain time, it is obvious that we can practi- 

 cally never obtain a pure toxin consisting entirely of similar molecules. 

 All our work must be done with toxic solutions which, even if we 

 assume that the bacteria have produced only a single primary toxin, 

 represent a "mixture of toxin and toxoid. 



But do the bacilli secrete only a single, homogeneous poison? 

 This question has come more and more to be the subject of an ani- 

 mated discussion. Closely associated with it is the further question 

 as to the nature of the reaction which occurs when toxin and anti- 

 toxin unite. The study of these problems was made possible by 

 an important extension of quantitative toxin analysis, namely, 

 Ehrlich's method of partial neutralization. This consists essentially 

 in mixing a constant amount ot poison with varying amounts of anti- 

 toxin and then determining the toxicity of the various mixtures, 

 i.e., the decrease in toxicity brought about by each successive addi- 



