NATUKE OF ANTITOXIC ACTION 567 



namely: (1) Does the "toxin" in any particular case represent 

 a single substance or several 1 (2) What is the nature of the 

 combination of any one constituent substance and its anti-sub- 

 stance — is it reversible or is it not? It seems impossible to 

 explain the facts with regard to diphtheria toxin on the hypo- 

 thesis t>f a single substance, even if this should have its combin- 

 ing and toxic actions equally weakened ; " toxoids " in Ehrlich's 

 sense must in our opinion be supposed. Then there is an im- 

 portant fact established by Danysz and by v. Dungern, namely, 

 that the amount of toxin neutralisable by a given amount of 

 antitoxin is different according as the toxin is added in several 

 moieties or all at once — in the latter case the amount of toxin 

 neutralisable is greater. There seems no explanation of this 

 according to the view of Madsen and Arrhenius, as the same state 

 of equilibrium ought to be reached in the two cases — that is, the 

 amounts of toxin neutralised should be the same. 



An important factor in the union of toxin and antitoxin is 

 the time necessary for the union to be complete. Morgenroth 

 has shown that in the case of diphtheria toxin this is considerable, 

 — about twenty-four hours. Up to this time, mixtures of toxin 

 and antitoxin, when injected intravenously, show decreasing 

 degrees of toxicity according to the time they have been kept. 

 On the other hand, when the subcutaneous method of injection is 

 used the time interval has no effect, and this he considers to be 

 due to a catalytic action of the tissues which accelerates the 

 union of the two substances. A striking phenomenon, which 

 apparently points to the reversibility of the combination, was 

 noted by Behring in the case of diphtheria toxin, and afterwards 

 studied by Madsen and by Otto and Sachs in the case of 

 botulismus toxin, namely, that when a certain amount of a 

 mixture of toxin and antitoxin was found to be neutral on 

 injection, a fraction of this amount might produce toxic 

 phenomena or even death. This was apparently due to dissocia- 

 tion of the toxin in the greater dilution, and in favour of this 

 being the case Otto and Sachs found that when the mixture was 

 allowed to stand for twenty-four hours, so that combination was 

 complete, the phenomenon no longer occurred. Other facts 

 might be brought forward which show that the firmness of union 

 of toxin and antitoxin increases with time, or in other words, that 

 dissociation becomes more difficult. It was shown by Morgenroth, 

 and by Muir independently, that the union of a hsemolytic 

 immune-body with the corresponding red corpuscle was of 

 reversible nature, and the latter observer found that in this case 

 the union was not increased in firmness after twenty-four hours. 



