PROTEIN SENSITIZATION OR ANAPHYLAXIS 273 



carrying out this work, even with the guinea-pig, the 

 results are not constant, and variations in the quantitative 

 relations of the solutions concerned in the reaction may 

 lead to failure. An excess of the anaphylactogen prevents, 

 apparently at least, the action of the ferment, and no 

 poison is formed. Here lies an important question which 

 we will briefly discuss. Some years ago when we were 

 testing the lethal doses of certain bacterial cellular pro- 

 teins, 1 we frequently observed that a small dose killed, 

 while two or three or more times this amount did not; or 

 the smaller dose killed within a shorter time than the 

 larger. The proteins were administered intra-abdominally, 

 and in suspension. Finally, we demonstrated that the more 

 finely powdered cell substance was ground the more poisonous 

 it became. By this we mean that smaller doses killed. 

 Later we found, much to our surprise, that high tempera- 

 tures increased the toxicity of the suspensions of cellular 

 proteins. We came to the following conclusions: (1) The 

 toxicity of the bacterial suspensions is determined by the 

 rapidity and completeness with which the cells are split 

 up by the ferments of the body. (2) Other things being 

 equal, the rapidity and completeness with which the cells 

 are digested depend upon the proportion of surface exposed 

 to the action of the ferment. (3) Grinding the powder more 

 finely increases the surface exposure of a given weight, and 

 therefore leads to the liberation of a larger amount of the 

 poison in a given unit of time. (4) When the bacterial 

 suspensions are heated the proteins contained in the cells 

 are partly dissolved, or at least the molecular surface is 

 extended, digestion is more rapid and complete, and the 

 substance becomes more efficient as a poison, not because 

 more poison is generated, but because that contained in 

 the cell is made more available. Later in our work on 

 protein fever 2 we came upon the same thing in a new guise. 

 W r e found that intra-abdominal and intravenous injections, 

 single or repeated, of egg-white in large doses in rabbits 



1 Trans. Assoc. Amer. Phys., 1902. 



2 Zeitsch. f. Immunitiitsforschung, ix, 458. 

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