NATURE OF THE TOXIN-ANTITOXIN REACTION 225 



Antitoxin is protective and curative, in that it actually destroys the 

 toxin, in a manner similar to the dissolution of a bacterium caused by a 

 specific bacteriolysin: or it may influence the tissue-cells in some way and 

 render them more resistant to the toxins, a view that was held by 

 Roux, and particularly by Buchner; or the antitoxin may form a di- 

 rect chemical union with the toxin, similar to the chemical neutraliza- 

 tion of an acid by a base an opinion early held by Behring and elabora- 

 ted later by Ehrlich. 



Experimental data support the view of chemical union with the 

 toxin. In the test-tube some time is required for the union of toxin and 

 antitoxin to occur; this union is hastened by heat and retarded by cold; 

 it is more rapid in concentrated than in dilute solutions, and in general 

 takes place in accordance with the law of multiple proportions all 

 of which tends to show the close similarity of the toxin-antitoxin reaction 

 to a chemical process. 



It is generally conceded that antitoxin does not directly destroy the 

 toxin, for when neutral mixtures of toxin and antitoxin are injected into 

 animals, portions of toxin may become dissociated and unite with tissue- 

 cells possessing greater affinity for the toxin, and symptoms of infection 

 may result. It is probable that toxin and antitoxin form a distinct 

 compound, and this action requires time for its consummation. For 

 example, Martin and Cherry, by filtering mixtures of toxin and anti- 

 toxin through fine filters that would permit the toxin molecule to pass 

 through but restrain the larger antitoxin molecule, found that, if filtered 

 immediately, all the toxin in the mixtures was extruded, but that, as the 

 interval between mixing and filtration was prolonged, less and less toxin 

 appeared in the filtrate, until finally, two hours after mixing, no toxin 

 whatever passed through the filter. 



This element of time in support of the chemical nature of the reaction 

 is further strengthened by the experiments of Calmette with snake venom 

 and antivenin, and likewise serves to demonstrate that the antitoxin 

 apparently does not directly destroy the toxin. Although most toxins 

 are thermolabile, Calmette found that snake venom is rendered inert 

 by heating to 68 C., whereas the antivenin remains uninfluenced by a 

 temperature of 80 C. When neutral mixtures of venom-antivenin were 

 heated to 70 C., they were found to become toxic again, presumably 

 on account of the destruction of the antivenin, the venom itself not 

 being destroyed. Similar experiments were carried out by Wassermann 

 with mixtures of pyocyaneus toxin-antitoxin, with similar results. In 

 both instances, however, as developed later, if the mixtures had been 

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