TOXIN- ANTITOXIN REACTION 195 



mena can be calculated according to the law of "mass action," 

 there being an equilibrium between 



Free NH 3 . v Free H 3 Q 3 B2 ^ (NH 4 H 2 8 B). 



A - = JV ; 



vol. vol. vol. 



where K is the constant of dissociation. The curve of the neutra- 

 lisation of tetanolysin by anti-tetanolysin corresponds almost 

 exactly to the ammonia-boric-acid curve. 



Whereas on Ehrlich's views the combination of toxin and anti- 

 toxin would be represented by a straight line, and the crude toxin 

 seems to be composed of a whole series of different toxins and 

 substances having an avidity for antitoxin, on this hypothesis, 

 although the greater part of the toxicity of toxin is removed by 

 the antitoxin, the latter must be added in large excess before the 

 toxicity completely disappears, and the course of neutralisation 

 would be represented by a hyperbolic curve. In fact, as the 

 antitoxin is added, the amount of free toxin diminishes but never 

 completely disappears. There comes a point, of course, when the 

 amount of free toxin is so small as to be negligible and cannot be 

 recognised by the ordinary indicators (blood-corpuscles, animal 

 tests, etc.). This hypothesis would explain the fact that while a 

 certain amount, V, of a mixture of toxin and antitoxin is innocu- 

 ous to an animal, a multiple of the dose, n V, of the same mixture 

 may be toxic ; it would also explain Buchner's experiments 

 alluded to above (p. 191), and Roux's experiments in which a 

 toxin-antitoxin mixture innocuous to normal guinea-pigs was 

 toxic to guinea-pigs whose resistance had been reduced by injec- 

 tions of the Massowah vibrio. 



Nernst questioned from the mathematical standpoint the 

 validity of the views of Arrhenius, and so did Craw from much 

 experimental work on agglutination and on the interaction 

 between megateriolysin and anti-megateriolysin ; Craw also con- 

 sidered that there is some doubt attaching to Arrhenius' s calcula- 

 tions. According to Craw, the two substances most thoroughly 

 investigated by Arrhenius and Madsen, diphtheria toxin and 

 tetanolysin, do not admit of sufficiently exact determination, the 

 former because of the uncertainty attaching to animal experi- 

 ments, the latter because tetanolysin is a most unstable body. 

 Working with a more stable substance, megateriolysin, he held 

 that the Arrhenius and Madsen equation does not apply. Again, 



132 



