PROTEIN SENSITIZATION OR ANAPHYLAXIS 269 



Reference has already been made to the endotoxin theory 

 of Pfeiffer. This assumed the existence of a preformed 

 poisonous body in the cell, and cytolysis resulted in setting 

 it free. It was believed to be an intracellular toxin, an 

 independent and separate molecule, and not a group in a 

 more complex molecule. This theory was applicable only 

 to cellular proteins. An endotoxin, as understood by 

 Pfeiffer, could not exist in a soluble protein, and since soluble 

 proteins are most efficient as anaphylactogens, the theo- 

 retical endotoxin cannot be the anaphylactic poison. Indeed, 

 there is now no reason for believing in the existence of the 

 endotoxin. The brilliant work of Fried emann 1 has shown 

 that red blood corpuscles may be dissolved without setting 

 free any active poison, and, on the other hand, the poisonous 

 group from the hemoglobin molecule may be extracted 

 without dissolving the corpuscles. Hemoglobin is not an 

 active poison. 2 Animals are not affected by a large amount 

 of it given in a single dose, but it is an anaphylactogen 

 which means, according to our understanding at least, 

 that its molecule contains a poisonous group which is 

 liberated on rein ject ion through the cleavage action of the 

 toxogen. Fried emann showed that the poisonous group 

 can be extracted from the proteins of the red corpuscles 

 without dissolving them. He used 3 c.c. of a heavy sus- 

 pension of washed ox-corpuscles. To this he added an 

 equal volume of a highly active anaphylactic serum, and 

 after a time separated the corpuscles in the centrifuge. 

 The corpuscles were again washed and incubated for 

 a short time with fresh rabbit serum, then placed in an 

 ice-box, then centrifuged, and the colorless fluid injected 

 into fresh animals induced anaphylactic shock. By this 

 method Friedemann was the first to prepare the anaphyl- 

 actic poison in vitro. This work has been confirmed, and 

 it has been shown fully that the formation of the anaphyl- 

 actic poison is quite independent of hemolysis. Thomsen 3 



1 Zeitsch. f. Immunitatsforschung, ii. 



2 This is Friedemann's statement, not ours. We have found hemoglobin 

 quite poisonous, even to the species supplying it. 



3 Zeitsch. f. Immunitatsforschung, i, 741. 



