554 



COLLECTED STUDIES IN IMMUNITY. 



45 



40 



35 



25 



g 



20 



15 



10 



poison can thus be arranged as proto-, deutero-, - , tritotoxin, etc., 

 after which finally comes the constituent possessing the weakest 

 affinity, namely, the toxon. That this varied affinity does not arise 

 when the toxoids are formed, but differentiates the undecomposed 

 constituents of the poison from the outset, is demonstrated by 

 the genesis of toxoid formation. Thus if one is in a position to 

 study a very pure poison in its various stages of decomposition, it will 

 be found that there is a first phase which leads to the formation of 

 hemitoxin, and that a later phase changes this into prototoxoid. 

 If there were a change in affinity, 

 however, we should have had a 

 pure toxoid zone from the start. 



The prototoxoids proved a 

 serious obstacle to Arrhenius and 

 Madsen in the logical develop- 

 ment of their views. According to 

 their theory just the first amounts 

 of antitoxin added should de- g 30 

 crease the toxicity the most. 

 Nevertheless a number of experi- 2 

 ments were published by these 5 

 authors (Madsen, with diphtheria 

 poison, and Madsen and Wal- 

 baum, for ricin) in which the proto- 

 toxoids and their development were 

 only too apparent. And Arrhenius 

 and Madsen seem to appreciate 

 that they can no longer explain this 

 contradiction by assuming that the 



prototoxoid zone is due to "change- FIG. 2. Neutralization curve accord- 

 ments minimes dans le milieu am- ing to Arrhenius and Madsen. 

 biant," or by saying that the proto- 

 toxoid zone is "of little interest." In order, therefore, to eliminate 

 these prototoxoids, so annoying for their formula, they have discarded 

 the well-tried criterion for a fatal dose of diphtheria poison (death 

 of the guinea-pig in 3 to 4 days), and now attempt to calculate the 

 fatal dose in a new way. Their procedure is as follows: Retaining 

 the definition of a fatal dose, they believe it possible to calculate the 

 fraction or multiple of the fatal dose employed, from the time of 

 the animal's death or even from the resulting loss of weight. Such 



\ 



0.05 0.1 0.15 0.2 0.25 0.3 0.35 O.i 0.45 

 ANTITOXIN 



