362 Chapter XII 



nation. Lowering the temperature retards, whilst raising it accelerates 

 the neutralisation of the toxins by the antitoxins. Insisting on the 

 purely chemical character of the combination between these two 

 substances, Ehrlich and Knorr adduce the fact that this combination, 

 in cases where we have a complete neutralisation of the toxin, follows, 

 most rigorously, the law of multiple doses, that is to say, in order to 

 render innocuous a hundred doses of toxin we have only to take a 

 hundred times the quantity of antitoxin. 



The series of facts summarised above demonstrate distinctly that 

 antitoxins act directly on toxins. But how can this result be recon- 

 ciled with the observations given above according to which must be 

 admitted the no less real influence of the organism of the living 

 animal on intoxication by mixtures of antitoxin with toxin ? Knorr 1 

 sought at first to minimise the importance of the facts brought for- 

 ward by Buchner and Roux. He failed to corroborate Buchner's 

 results and found that the injection of mixtures, made with very 

 large doses of tetanus toxin (20,000 times the minimal lethal dose) 

 and corresponding quantities of antitetanus serum, brought about 

 the same effect in guinea-pigs and mice. By modifying the quantity 

 of antitoxin, he rendered the mixture equally innocuous or equally 

 toxic for these two species. But the data given by Knorr are quite 

 sufficient to prevent us from accepting his conclusion. In his experi- 

 ments, as in those of Buchner, the guinea-pigs manifested a greater 

 susceptibility and died from mixtures which, in mice, caused merely a 

 tetanus of medium intensity. 



Some have sought to explain Buchner's experiment by assuming 

 that the mixtures, lethal for the guinea-pig and innocuous for the 

 mouse, owed their toxic action to the presence of the tetanus toxone 

 and not of the true tetanus poison, the tetanospasmin. This hypo- 

 thesis of toxones, as stated above, was put forward by Ehrlich as the 

 [381] outcome of his ingenious researches on the constitution of the diph- 

 theria poison. As, however, the toxones must act differently from the 

 toxins, we can only attribute to their action the results in those cases 

 where the guinea-pigs die without presenting typical symptoms of 

 true tetanus, that is to say without spasms. Now, in Buchner's 

 experiments, a much larger proportion of these animals, injected 

 with the same mixtures as the mice, succumbed and exhibited the 

 characteristic tetanic convulsions. Even in those cases, however, 



1 " Experimentelle Untersuchungen iiber die Grenzen der Heilungsmoglichkeit 

 des Tetanus," Marburg, 1895, SS. 14, 21. 



