TOXIN AND ANTITOXIN 517 



Guinea-pig III receives 0.8 cc. poison, otherwise same as I. It 

 dies in three and one-half days. 



Guinea-pig IV receives 0.8 cc. poison, otherwise same as II. It 

 dies in three and one-half days. 



Another thing which is entirely irreconcilable with Gruber's 

 assumption is the fact that there exist prototoxoids, i.e., toxoids 

 which possess a higher affinity for the antitoxin than the toxin itself 

 does. The existence of these was first pointed out by me and has 

 since been confirmed by Madsen and also by Arrhenius. The exist- 

 ence of the prototoxoids becomes clearly manifest by the fact that 

 one can add a certain quantity of antitoxin to the toxin solution 

 without affecting the toxicity in the slightest degree. 



Mention must also be made of the fact that similar phenomena 

 have been observed in a large number of other poisons. It will 

 suffice here if I remind the reader that toxoid changes have been 

 observed in ricin (Jacoby), abrin (Romer), staphylotoxin (Wechs- 

 berg, Neisser), cobra venom (Meyers, Flexner). Furthermore Mor- 

 genroth and I showed that in complement also there is a destruction 

 of the real active portion, the zymotoxic group, while the hapto- 

 phore group remains intact. The existence of complementoids 

 has been demonstrated decisively by Sachs and myself, 1 although 

 Gruber had termed them " merely fervent wishes floating about 

 in the serum." 



Furthermore it will be remembered that similar phenomena 

 are observed in the agglutinins and coagulins (precipitins), the hap- 

 tophore group of the agglutinin or the precipitin remaining intact, 

 while the agglutinophore group is destroyed. This phenomenon 

 was first pointed out in the excellent study made by Eisenberg and 

 Vblk in Paltauf s laboratory. Since that time a large mass of liter- 

 ature has grown up around this subject so that now there is not 

 the least doubt concerning the existence of these substances, which 

 normally occur in the form of proagglutinoids. A recent study 

 by Korschun 2 makes it probable that something similar to this 

 occurs in ferments, particularly in rennin. In all these various 

 cases it seems to be the rule that the real functionating group is far 

 more labile than the one which effects combination, namely, the 

 haptophore group. Hence I believe that the formation of such 



1 See page 209. 



2 Zeitsch. f. physiol. Chemie, Bd. 37, 1903. 



