524 COLLECTED STUDIES IN IMMUNITY 



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tralized doses, which I like the mixture ^r 1 possess a considerable 



excess of antitoxin, are absolutely innocuous for guinea-pigs and 

 can be injected in any desired quantity. In fact, owing to the excess 

 of antitoxin, such mixtures furnish the animal with passive immunity 

 and protect it, provided suitable amounts have been injected, against 

 diphtheria poison and diphtheria bacilli. If such mixtures, how- 

 ever, are still toxic for rabbits, only one possibility remains, namely, 

 that the diphtheria poison in question contains a substance which 

 is non-toxic for guinea-pigs, but still toxic for rabbits. This is my 

 toxonoid. 1 



So far as the behavior of partially neutralized mixtures is con- 

 cerned, the investigations of the two authors show that mixtures 

 which exert only toxon effects on guinea-pigs cause death and symp- 

 toms of diphtheria poisoning in rabbits. In my opinion the phe- 

 nomenon described can best be explained by the assumption that 

 at least three varieties of poison are to be distinguished, possessing 

 different affinities and different actions. Such an assumption, I 

 believe, will best harmonize the actual facts. These poisons are: 



1. Toxin, possessing the greatest affinity, kills rabbits and guinea- 

 pigs acutely, but is much more toxic for the former. 



2. Toxon, killing rabbits acutely and guinea-pigs with paralytic 

 symptoms. 



3. Toxonoids, producing paralyses in rabbits but innocuous for 

 guinea-pigs. 



That all these poisons act more powerfully on rabbits than on 

 guinea-pigs is explained by the absolute higher susceptibility of 

 these animals. So far as the behavior of the toxonoids is concerned, 

 in which enormous differences in rabbits and guinea-pigs are mani- 

 fested, such behavior finds numerous analogies in toxicology, espe- 

 cially in the study of toxins. Thus heroin, an acetyl derivative 



1 Almost at the outset of my investigations and long prior to Madsen and 

 Dreyer I obtained results entirely similar to these. My unpublished but very 

 extensive studies showed that this property is not possessed by all diphtheria 

 poisons, for I also encountered poisons in which the L dose was exactly the 

 same in guinea-pigs and rabbits. This fact controverts the assumption that 

 perhaps the described phenomenon is due to an incomplete neutralization, 

 such as Arrhenius and Madsen have demonstrated in the union of boric acid 

 and ammonia, and in that of tetanolysin and antilysin. If this were the case 

 one would expect the phenomenon to be present in all diphtheria poisons to 

 the same extent, and this is not the case. 



