162 A MANUAL OF BACTERIOLOGY 



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 on subcutaneous inoculation is lethal to rabbits 

 on intra- 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 equilibrium 

 is reached (see also p. 163). When a recently prepared 

 mixture of toxin and antitoxin is injected subcutaneously, 

 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, intravenous 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 (toxoids and toxones), 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 considered 

 to be between two substances only, toxin and antitoxin, 

 that it is reversible, and that when the system has reached 



