RELATION OF TOXINES AND ANTITOXINES. 61 



thoroughly the question has been studied the more it has been found that 

 ARRHENIUS and MADSEN considerably over -rated the influence of mass 

 action. 



It was shown by VON DUNGERN in the case of diphtheria toxine and by 

 HANS SACHS in that of tetanolysine that the fundamental condition 

 theoretically essential for the view of ARRHENIUS and MADSEN viz., the 

 combination between the toxine and antitoxine should be reversible was 

 lacking, and that on the contrary the combination gradually became firm 

 and irreversible. At the same time VON DUNGERN brought direct proof 

 of the plurality of diphtheria poison by showing that a mixture of anti- 

 toxine and toxine could be non-poisonous after a single addition of the 

 exactly sufficient quantity of toxine, but that when the same amount was 

 added in two portions with an interval of twenty-four hours between them 

 it was poisonous. In the latter case the antitoxine being present in excess 

 is distributed between the toxine and the toxone, and when the second 

 portion is added after twenty-four hours the combination between the 

 toxone and antitoxine has become so stable that the toxine can no longer 

 find sufficient free antitoxine. 



The stability of the combination between toxine and antitoxine was 

 shown by WASSERMANN and BRUCK in another way. They found that 

 when .they injected a physiologically neutral mixture of tetanus toxine 

 and antitoxine, together with some adrenaline into an animal, the contrac- 

 tion of the vessels caused by the alkaloid led to a delay in the resorption 

 of the antitoxine, whereas the toxine which is resorted by the nerves 

 (vide Tetanus) was immediately taken up, and poisoning resulted. But 

 if they allowed the mixture to stand for two hours before the injection, 

 the toxine had combined so firmly with the antitoxine that no resorption 

 of the former took place and the animal remained well. 



Lastly, it was found by MADSEN himself that it was only possible in the 

 case of absolutely fresh mixtures of diphtheria toxine and antitoxine to 

 effect a separation of the two components by means of their different rates 

 of diffusion through gelatin, and that after the lapse of even a short 

 time such separation could no longer be effected. This was also proved 

 indirectly by an experiment of MORGENROTH, who found that fresh 

 mixtures of diphtheria toxine and antitoxine were poisonous when injected 

 intravenously into rabbits, but that after some time they were inert. 



However, even if the complicated relationships that exist in the case of 

 bacterial poisons cause the curve of saturation to take such a form that it 

 can be shown to have some resemblance, externally at least, to the curve 

 of equilibrium between substances of weak affinity, yet in the case _ of 

 Cobra venom the conditions are such that there is apparently a pure toxine 

 there. At all events, according to KYES, the curve of saturation between 

 the toxine and antitoxine here forms a straight line, like that formed 

 between a strong acid and a strong base. 



The discussion has had the further very important result of raising the 

 fundamental question whether there is any justification at all for applying 

 the law of mass action to the reactions between colloidal substances. 

 NERNST and others have given a vigorous denial to this. This has led in 

 turn to a closer investigation of the properties of colloids, which has 

 already established many important ratios between the reactions of toxine 

 and antitoxine and those of the colloids, the consideration of which here 

 would lead too far. 



L. Michaelis, " tJb. die Giiltigkeit des Massenwirkungsgesetzes bei der 

 Reaction zwischen T. u. A.," Biochem. CentralbL, iii. [1], 1904. 



