TOXIN AND ANTITOXIN. 521 



on the most susceptible animals. Let us imagine, for example, a 

 mixture of sulphuric and acetic acids, neutralized by the gradual 

 addition of baryta water. Once all the sulphuric acid is neutralized, 

 even the most sensitive reagent to free strong mineral acids will be 

 unable to detect any trace of it." 



Let us see just what Gruber means by this comparison. The 

 sulphuric acid corresponds to the toxin ; the antitoxin is represented 

 by the alkali. In accordance with the comparison the receptors of 

 the cells are represented in the animal body by the alkali of the 

 tissues. If now we inject an animal with sulphuric acid previously 

 neutralized with ammonia, i.e., a solution of ammonium sulphate, 

 it will depend mainly on the affinity of the tissue alkali, whether or 

 not the neutral ammonium sulphate will be decomposed and sul- 

 phuric acid allowed to enter the tissues, ammonia being set free. 

 If we assume, for instance, that the tissue alkali is comparable to 

 a strong base like sodium hydroxid or barium oxid, the ammonia 

 introduced in combination with the sulphuric acid will be absolutely 

 unable to prevent the poisoning; the weak base will be forced out 

 of the salt and replaced by the stronger base. In general we must 

 assume that the antitoxin possesses a higher affinity to the toxin 

 than do the tissue receptors, for only on this assumption can we 

 explain the protective action of the antitoxin. Numerous phenomena, 

 however, indicate that the affinity of the tissue receptors can become 

 increased. I had reached these conclusions long before the pub- 

 lication of my theory, which as many know I formulated years before 

 it was published. The cause of this long delay was the phenomenon 

 of hypersusceptibility, i.e., the peculiar fact that immunized ani- 

 mals, despite a colossal excess of antitoxin, succumb to the action 

 of the poison. The first light on this subject was the study of Donitz, 

 in which it was shown that the poison shortly after its union with 

 the tissues is but loosely bound. In the course of a few hours the 

 union becomes firmer and firmer so that after a certain time, which 

 may vary from a few minutes to six hours, according to the dose, 

 the poison can no longer be abstracted from the tissues by the anti- 

 toxin. This fact seemed to indicate that under the influence of 

 the poisoning the affinity of the tissue receptors gradually becomes 

 Increased and that when a certain point is reached a cure by means 

 of antitoxin is impossible. This, however, furnished me with an 

 explanation of hypersusceptibility and removed the obstacle which 

 had kept me from publishing my theory. 



