$0 TOXlNfiS AND ANTITOXlNES. 



acute symptoms in the rabbit. On the other hand, most of 

 the animals experimented upon with such mixtures, which 

 undoubtedly contained nothing but toxones still in the free 

 state, perished later with secondary paralytic affections. One 

 animal, however, remained alive and was able to receive without 

 injury very large amounts of toxone, eventually even several 

 multiples of a lethal dose of the toxine ; but its serum never 

 showed even the slightest trace of an antitoxine constituent. 



No explanation of this remarkable phenomenon can yet be 

 given, unless we are willing to accept the view that although the 

 active immunisation had stimulated the formation of protective 

 substances, these had not been thrown off in a free state into 

 the circulation (" sessile receptors " in EHRLICH'S terminology). 



Owing to the weak affinity of diphtheria toxone it is fixed 

 much more slowly by the receptors of the organism i.e., it does 

 not disappear so rapidly from the circulatory system as the 

 toxine. We have shown above that even fifteen minutes after 

 the injection of seven times the lethal dose DONITZ was no 

 longer able to save the animal by means of a quantity of 

 antitoxine exactly neutralising the poison in vitro. 



DREYER 1 has made corresponding experiments with the 

 toxones. 



After two hours the equivalent amount of antitoxine was 

 invariably able to render completely harmless a dose of toxone 

 which would otherwise have been undoubtedly fatal after twelve 

 to eighteen days, both being introduced into the rabbits by 

 intravenous injection. With an interval of five hours between 

 the injections the first signs of paresis appeared ; with ten hours' 

 interval they invariably occurred, though not until after twenty 

 to twenty-two days ; with an interval of sixteen to twenty-four 

 hours the antitoxine was completely powerless. 



Similar results were obtained in the therapeutic experiments 

 made by DREYER with larger quantities of antitoxine, both 

 substances being subcutaneously injected into guinea-pigs. A 

 five-fold dose introduced twenty -four hours after the injection of 

 a dose of toxone which would be undoubtedly fatal after twelve 

 to eighteen days, was sufficient to prevent death, though not 

 invariably to prevent paresis. 



Of seven animals that received after forty-eight hours a dose 

 of antitoxine neutralising 5,000 to 10,000 times the amount of 

 toxone injected, one had no paresis, while the others had only 

 slight attacks ending in a cure after eighteen to twenty-five days. 



1 Dreyer, "Ueber die Grenzen d. Wirkung d. Diphtherieheilserums 

 gegeniiber d. Toxonen," Zeit.f. Hyg., xxxvii., 267, 1901. 



