TOXIN AND ANTITOXIN US 



noticed that, even after deterioration had occurred to a considerable 

 extent, and the amount necessary to kill a guinea pig had been much 

 increased (the number of fatal doses in L constantly decreasing as 

 toxoids replaced toxin), the L + nevertheless remained unchanged. 

 This, he held, could mean one thing only. The elements present in 

 toxic broth which possessed a weaker affinity for antitoxin than the 

 toxin itself, namely, the epitoxoids, were present from the very begin- 

 ning and were probably separate and primary secretion products of 

 the diphtheria bacilli, remaining relatively stable and constant as the 

 broth was preserved. In order to avoid confusion, therefore, he now 

 referred to the "epitoxoids" as "toxons" to preclude their confu- 

 sion with the other toxoids or true toxin deterioration products. 

 These toxons possess, according to Ehrlich, a "haptophore" group 

 identical with that of the toxin, but have a different toxophore group. 

 For there is reason to believe that the toxon, lacking the power of 

 causing acute death, gives rise to slow emaciation and paralysis, 

 finally killing after a subacute or chronic course. Thus, in the tab- 

 ulation just preceding, we have seen that the toxic broth added to 

 neutral mixtures of toxin and antitoxin (containing the L dose), 

 does not give rise to the acutely toxic effect of one M L D or T until 

 an amount has been added which considerably exceeds one toxin 

 unit. This, we explained, by Ehrlich's reasoning, on the supposi- 

 tion that "epitoxoids' 7 or "toxons" are displaced from their union 

 with antitoxin, giving place to toxin and becoming free. Such toxin- 

 antitoxin mixtures in which the amount of toxin broth ranges be- 

 tween the L and the L + doses therefore, contain no free toxin 

 units but contain varying amounts of free toxon. An ?*njection into 

 guinea pigs is not followed by acute death in these cases, but leads 

 with considerable regularity to emaciation, paralysis, and death 

 after a long incubation period. 



It has been objected to this, as we shall see, that the slow poison- 

 ing produced by such mixtures is due, not to a qualitatively differ- 

 ent poison but to the presence of minute qu ntities of free toxin too 

 small to produce acute death, yet sufficient to produce this gradual 

 injury. This Dreyer and Madsen 14 tried to disprove by experi- 

 ments in which they prepared antitoxin-toxin mixtures so bal- 

 anced that they possessed the toxon effect, and of these mixtures 

 injected increasing multiples. In no case did they succeed in pro- 

 ducing acute death even when the amount injected had been multi- 

 plied to such an extent that free toxin, if present, must have asserted 

 itself. The same workers were able to show that the injection of 

 these mixtures, in which free toxons were assumed to be present, 

 produced immunity against toxin, thus indicating the similarity of 

 the haptophore group of toxin and toxon a conception which will 

 14 Dreyer and Madsen. Zeitschr. f. Hyg., Vol. 37, 1901. 



