312 PROTEIN POISONS 



poison is a toxin, in the sense of diphtheria or tetanus 

 toxin, though both continue to call it a toxin. The work of 

 Bessau and Friedberger confirms ours and establishes 

 beyond any doubt that the increased tolerance brought 

 about by repeated administrations of the protein poison 

 by direct injection or by recovery from anaphylactic shock 

 is not of the nature of a toxin-antitoxin immunity. 



It seems to us that there is one point about anti-anaphyl- 

 axis which both Bessau and Friedberger fail to see. When 

 a sensitized animal is reinjected with the homologous 

 protein and recovers, it immediately loses, for a time at 

 least, its responsiveness to the same protein. As Fried- 

 berger has shown, injections of two hundred times the 

 amount necessary to kill the sensitized animal is without 

 effect. Indeed, the animal seems to be returned suddenly 

 to the condition of a fresh animal, one which has never 

 received a protein injection. The usual explanation is 

 that all the specific ferment in the sensitized animal has 

 been exhausted by the non-fatal reinjection. Bessau 

 thinks it due, as we have seen, to a decreased susceptibility 

 to the poison, or, as we say, to an increased tolerance of 

 the poison. Both of these are undoubtedly factors, and 

 they may be the most important factors in the sudden 

 development of the anti-anaphylactic state, but they are 

 not the only factors, and we are inclined to the opinion 

 that they are not the most important. That the specific 

 ferment (the antibody of other writers) is not wholly 

 exhausted is shown by the fact that the blood serum of 

 an animal in the anti-anaphylactic state, when transferred 

 to a fresh animal, sensitizes the recipient. This could not 

 be if the ferment had been wholly used up. There must 

 still be active ferment in the portion of blood serum trans- 

 ferred. The factor which we suspect of being of greatest 

 importance in the production of the anti-anaphylactic 

 state is the changed relation between the amount of ferment 

 and the substrate. This is one of the most important and 

 interesting problems connected with protein sensitization. 

 In our earliest work with the cellular bacterial poisons, 



