536 COLLECTED STUDIES IN IMMUNITY. 



disappear from the circulation in a few minutes. It is therefore 

 idle to talk of a slow union such as would correspond to weak affini- 

 ties. But, says Gruber, "it is impossible to understand why the 

 toxophore groups, after they have been brought into proximity to 

 the protoplasm, do not at once commence their activity, but always 

 stop to consider the matter for several hours." One cannot seriously 

 discuss the subject with such a questioner. Gruber might just as well 

 ask that all chemical reactions proceed rapidly, and deny the possi- 

 bility of a slow reaction. 



The slow action of the toxophore group is not at all remarkable, 

 especially in the domain of toxins. This is particularly true if we 

 remember that with certain poisons (e.g. botulism toxin), one part 

 of toxin to 500 million parts of body weight suffices to cause death, 

 and that the rapidity of action is dependent to a high degree on 

 the amount of the active substance. 



Is Gruber possibly of the 'opinion that in the paralysis of diph- 

 theria, which as is well known usually develops after the lapse of 

 weeks, the toxon courses about free for twenty days or more before 

 entering the tissues and then suddenly exerts its action? To the 

 unprejudiced critic the importance of the separation of toxin bind- 

 ing and toxin action for the proper understanding of the period of 

 incubation, is conclusively demonstrated by Morgenroth's l experi- 

 ments with .tetanus in frogs. Courmont and Doyon, as is well known, 

 discovered that the frog is susceptible to tetanus poison only at 

 higher temperatures, and not when the animal is kept cold. Mor- 

 genroth was able to show that at low temperatures the tetanus poison 

 is bound, but exerts no toxic action. Frogs are injected with tetanus 

 toxin and then kept on ice for days. If then they are subjected 

 to higher temperatures, it will be found that they behave exactly 

 as if they had just been inoculated. And yet the toxin has been 

 bound by the central nervous system even at the low temperature; 

 for if after several days at low temperature the animal be injected 

 with an amount of antitoxin, even much more than sufficient to 

 neutralize the poison, tetanus will still develop if the frog is subjected 

 to a higher temperature. But this is not all. If frogs, after being 

 injected with tetanus, are subjected to a high temperature for one 

 day, and then placed in the refrigerator, they will not become sick. 

 But on bringing the animals back into higher temperatures after 



1 Arch. Internat. de Pharmacodynam., Vol. 7, 1900. 



