ANAPHYLATOXIN (PROTEIN POISON) 585 



Weichardt also produced it by digesting placental protein with the 

 serum of rabbits immunized with placental cells. Friedberger 1 studied 

 the subject more extensively by observing the action of normal guinea- 

 pig serum upon serum precipitates, and was first to apply the term 

 "anaphylatoxin" to the poison. At the time he regarded it as a true 

 toxin, similar to diphtheria and tetanus toxins, but at present we know 

 that this poison is not a true toxin, because it cannot produce an anti- 

 toxin, is thermostabile in acid solution, and is not a single specific 

 substance, but a mixture of more or less closely related substances 

 in the nature of protein cleavage products, as first shown by Vaughan 

 and Wheeler, and since accepted by Friedberger himself and a number 

 of other investigators. In a strict sense, therefore, this term is a mis- 

 nomer, but it is in such general use that it need not be discarded if 

 we have a clear understanding that the sum total of independent re- 

 searches by numerous investigators shows that it is not a true toxin, 

 as tetanus toxin, for instance, but a protein poison. 



As the symptoms of anaphylaxis are always the same in the same 

 animal, no matter what protein is used, it would appear that the protein 

 poison is either always the same or composed of a group of very closely 

 allied products, and, indeed, this seems to have been proved by an 

 extended series of researches with the most diverse proteins of animal, 

 bacterial, and vegetable origin. 



It may be stated, therefore, that anaphylatoxins may be regarded as 

 protein poisons composed of protein cleavage products, and that these are 

 responsible for the lesions and symptoms of anaphylaxis. There is some 

 difference of opinion regarding the source of the protein matrix and the 

 mechanism of its cleavage with the production of the poison in anaphy- 

 laxis, and I shall consider this phase of the subject later. There is, 

 however, a striking uniformity of experimental evidence and opinion 

 regarding the role and primary importance of the protein cleavage 

 poisons in the anaphylactic process. Briefly summarized, the evidence 

 on this point is as follows: 



1. As was just stated, the first to advance the theory regarding the 

 role of protein-split products in anaphylaxis, as well as in infection and 

 immunity in general, were Vaughan and Wheeler. In 1907 these 

 observers showed that proteins may be split by boiling with alcoholic 

 sodium hydroxid solution into two fractions one non-toxic and alcohol 

 soluble and the other toxic and alcohol insoluble. The toxic fraction, 

 when injected into normal guinea-pigs in doses of from 8 to 100 mg., 

 1 Zeitschr. f. Immunitatsf., 1910, 4, 636. 



