132 INFECTION AND RESISTANCE 



can be rendered tetanic if they are warmed to 25 to 30 C. Further 

 work, however, by these authors as well as by Morgenroth 40 has 

 satisfactorily cleared up this difficulty. As a matter of fact, tetanus 

 poison disappears more rapidly (that is, is bound by the cells more 

 rapidly) from the circulation of frogs, if the frogs are warmed to 

 30 C. or more. Furthermore, if the toxin is injected into these 

 animals, and they are kept at low temperatures, no disease results, 

 but if they are then warmed up to the temperature stated, they grad- 

 ually succumb to the disease. Morgenroth has shown that the ap- 

 parently anomalous behavior of frogs in this respect is actually a 

 question of temperature. At low temperatures the poison is bound, 

 though with extreme slowness, but the toxophore group of the toxin 

 does not functionate. When the animals are warmed, not only does 

 the binding proceed more rapidly, but the toxophore group becomes 

 active. He thus not only has answered Metchnikoff's objections to 

 Ehrlich's theory on this ground, but has furnished an additional in- 

 direct confirmation of the dual constitution of toxin, that is, its 

 constitution of a haptophore and a toxophore atom group, suggested 

 by Ehrlich in his diphtheria-toxin analysis. 



There is apparently, then, a strong absorption of tetanus toxin 

 by the brain and nervous tissue of all animals which are susceptible 

 to the poison, an absorption which amounts, as we have seen, to neu- 

 tralization, the brain emulsion acting like antitoxin when mixed 

 with the toxin before injection, as in Wassermann's and Takaki's 

 experiments. 



A serious objection has been brought, however, to the assumption 

 that this binding can be identified in its nature with the similar bind- 

 ing of toxin by antitoxin, and a number of authors have claimed that 

 the binding by the brain is not a binding by specific receptors, but 

 an accidental property due to the presence of some fortuitous fixing 

 substance in the central nervous system. Besredka 41 showed, for 

 instance, that the brain of susceptible animals could bind much more 

 toxin than it could actually neutralize, and that, if antitoxin was 

 added to a brain emulsion previously saturated with the toxin, the 

 toxin is removed from its combination with the brain cells and these 

 again regain their original absorbing property. These experiments 

 would seem to point to a difference, especially in regard to affinity 

 and firmness of union between the nature of the combination between 

 toxin and brain emulsion on the one hand, and toxin and antitoxin 

 on the other. This, of course, would prove a serious obstacle to the 

 interpretation of the binding of toxin by susceptible cells in the sense 

 of Ehrlich, as depending as it were upon union with specific recep- 

 tors, or, as they might be termed, "sessile" antitoxin. Moreover, to 

 strengthen such objections to this point of view, the work of Land- 



40 Morgenroth. Arch, internat. de Pharm., Vol. 7, 1900, pp. 265-272. 



41 Besredka. Ann. de VInst. Past., Vol. 17, 1903, p. 138. 



