THE CONSTITUENTS OF DIPHTHERIA TOXIN, 497 



This behavior shows that on standing there is not, for example, 

 a marked destruction of the poison, but merely a slight chemical 

 change affecting only the toxophore and not the haptophore group. 

 It would be improper, therefore, to speak of the poison "spoiling." 



The observations on the origin in the various forms of toxoid are 

 particularly important. 



In the first phase of toxin formation, there was a development 

 of toxoids of weaker affinity for the antitoxin, while during the second 

 stage, toxoids of greater affinity developed. Occupying a position 

 between these two opposing poison modifications is the hemitoxin 

 fraction, and this has remained intact. We are thus really forced to 

 arrange these three poison constituents, according to their affinity, 

 as prototoxoid, deutero toxoid, and tri to toxoid. This brings me to 

 the crux of my views concerning the constitution of diphtheria poison. 



In titrating and evaluating the diphtheria antitoxic' serum I began 

 with the simplest assumption, namely, that the poison was a simple 

 uniform substance. In the formation of toxoids, therefore, I con- 

 sidered three possibilities: 



1. That the affinity of the haptophore becomes increased; 



2. That it remains the same, and 



3. That it decreases. 



Which of these possibilities will apply in any given case will, of 

 course, depend upon the stereochemical circumstances, especially 

 upon how far one functionating group is removed from the other. 

 If, in what we must conceive to be a very large molecule, these groups 

 are quite far apart, it may be assumed a priori that the destruction of 

 the toxophore group will probably not exert a marked influence on 

 the haptophore group. In other words, syn toxoids will be formed. 

 If the two groups are nearer together a change in the affinities, either 

 positively or negatively, can readily occur. As a matter of fact, 

 the possibility of an increase or decrease of affinity as a result of this 

 transformation into inert modifications has also been observed in con- 

 nection with related subjects. Researches conducted by myself and 

 Sachs have shown that in the formation cf complementoid the hap- 



was the expression of a certain loss of combining groups. This, however, is 

 merely apparent; in the second phase a greater excess of the poison (containing, 

 as it does, more toxoid) is required to produce death than is the case with 

 the haemitoxin. Bearing this consideration in mind it is easy to convince 

 one's self that not a single one of the combining groups present has been lost 

 and that the change which the poison has undergone was a quantitative one. 



