TOXIN-ANTITOXIN REACTION 191 



toxin, and Buchner performed experiments showing that 

 while mice are more susceptible than guinea-pigs to 

 tetanus toxin, a tetanus toxin-antitoxin mixture which 

 is just neutral for mice is distinctly toxic for guinea-pigs. 



To explain this Ehrlich suggested that there may be 

 present in a toxin solution several toxic substances, some 

 of which exert a toxic action on the guinea-pig but not 

 on the mouse. Madsen and Dreyer showed that a mixture 

 of diphtheria toxin and antitoxin which is innocuous to 

 guinea-pigs by subcutaneous inoculation is lethal to rabbits 

 by in tra- venous injection, and in order to explain this 

 Ehrlich made a similar assumption. Morgenroth, how- 

 ever, found that the difference in the latter case depends 

 on the mode of injection. The reaction between the 

 toxin and antitoxin takes time to complete : there is an 

 interval probably of some hours at 20 C. before equili- 

 brium is reached (see also next page). When a recently 

 prepared mixture of toxin and antitoxin is injected sub- 

 cutaneously, absorption is slow, and in the meanwhile 

 the toxin and antitoxin combine, but when the mixture 

 is injected into the veins, the toxin is fixed by the tissues 

 before it has had time to combine with the antitoxin, and 

 poisoning ensues. If the mixture be kept for some hours 

 before injection, intra- venous injection is then innocuous. 



Ehrlich concluded that diphtheria toxin is neutralised 

 by diphtheria antitoxin much in the same way as a strong 

 base is neutralised by a strong acid, and that the course of 

 neutralisation suggests the presence in the toxin of several 

 toxic and atoxic substances (toxin, toxone and toxoid), all 

 of which combine with, though they have different 

 affinities for, the antitoxin. 



Arrhenius and Madsen, however, believe that the toxin- 

 antitoxin reaction is analogous to the action of an acid 

 on an alcohol, and that the chemical laws of mass action 

 apply equally to the two. The chief reaction is con- 



