PROTEIN SENSIT1ZATION OR ANAPHYLAXIS 313 



when suspensions were injected into the abdominal cavity 

 we found that large doses often failed to kill, or killed 

 slowly, while smaller doses killed more certainly and more 

 promptly; then we found that grinding our cellular sub- 

 stances more finely increased their toxicity; later we found 

 that the introduction of large quantities of egg-white into 

 fresh animals was without visible effect, while the repeated 

 injection of very small doses produced prompt effects and 

 speedily killed. Later still we ascertained that when a 

 small amount of the blood serum of a guinea-pig sensitized 

 to egg-white was incubated with from 1 to 5 mg. of egg-white 

 in vitro we obtained an active poison, but when the amount 

 of egg-white present was greatly increased there was no 

 evidence of the production of a poison. Friedberger has 

 repeatedly met with the same thing in preparing his ana- 

 phylatoxin. With a small amount of ferment and an 

 excessive amount of substrate the reaction is impeded. 

 Then the presence and accumulation of the products of 

 fermentation retard the fermentative process. The con- 

 centration of the ferment, the substrate, and the products 

 of fermentation all influence the rapidity w T ith which the 

 fermentative process proceeds, and all of these are altered 

 when a few cubic centimeters of the blood serum of an 

 animal in the anti-anaphylactic state is transferred to a 

 fresh animal and the latter receives an injection of the 

 proper protein. Besides, it is possible that in the prepara- 

 tion of the serum the amount of available ferment is increased 

 by disruption of the leukocytes. 



Friedberger at first stated that his anaphylatoxin is 

 thermolabile. If this be true it cannot be identical with or 

 very closely related to our protein poison, which is ther- 

 mostabile. Later, Friedberger found that in acid solution 

 anaphylatoxin is thermostabile. It is well to see how these 

 differences can be reconciled. It must be understood that 

 anaphylatoxin has never been isolated, not even partially, 

 from the serum in which it is formed, and of course the 

 serum is alkaline. Years ago we showed that our poison 

 in alkaline solution decreases in toxicity, and that this 



