THE CONSTITUENTS OF DIPHTHERIA TOXIN. 487 



attenuation of the toxins, which occurs at room temperature and 

 without any further chemical manipulation. 1 



It has been found that the bouillon on standing can preserve its neutral- 

 izing property intact, and often actually does so, irhile the toxicity is 

 considerably decreased. Observations of this kind have been made 

 by myself and Madsen for diphtheria poison, by Jacoby for ricin, 

 by Myers for snake venorn, and recently by Arrhenius and Madsen 

 for tetanus poison. This phenomenon, which in many cases is quanti- 

 tative, is most readily explained by assuming that the poison molecule 

 contains two functionating groups. One, the "haptophore group," 

 combines with the antitoxin and in the animal body effects the com- 

 bination with the tissues; this group is quite stable. The other, 

 the "toxophore group/' effects the true poisonous action; it is com- 

 paratively readily destroyed. In my opinion the transformation of 

 toxin into toxoids by the destruction of the toxophore group is the 

 key to a correct understanding of my conception of antitoxic im- 

 munity and the subject of toxins. 2 



If we see, for example, that in spite of decreased toxicity the 

 constants of neutralization L t and L remain entirely unchanged, 

 it follows, in my opinion, that two important deductions can be made. 

 The first is one which I have always drawn, namely, that in normal 

 toxoid formation not brought about by chemical additions, the num- 

 ber of haptophore groups suffers no loss. This behavior, however, 

 also seems to indicate that in toxoid formation the affinity of the hapto- 

 phore groups for the antitoxin is in no way changed. I may be per- 

 mitted to elucidate this by means of a chemical example. Tetra- 

 methylammoniumhydroxid is a very strong base (like KOH) which 

 through suitable procedures (heating, etc.) is transformed into the 



1 Obviously these poisons can also be attenuated through chemic or thermic 

 influences, but the decomposition in that case takes place rapidly and with 

 destruction. In my investigations, therefore, I have never made use of these 

 methods, but have kept to the moderate changes which occur spontaneously 

 in the toxic bouillon on standing. 



2 At the outset of the modern study of immunity, von Behring, Aronson, 

 and others had observed that an active immunity could be brought about 

 particularly through attenuated, modified poisons. At that time, however, 

 it was very difficult to appreciate these relations, and so in the year 1894 we 

 find a high authority, as a result of his investigations, denying the existence 

 of modified poisons, although he had previously assumed their existence. The 

 results, which had been obtained with immunization, he ascribed, not to the 

 presence of modified poisons, but exclusively to a dilution of the poison. 



