Metabolic Products 461 



hind quarters. The effect of the poison was slow and death 

 took place days or weeks after injection, sometimes being 

 preceded by marked emaciation. Temperatures of 58 C. 

 lessened the activity of the toxin and temperatures of 100 

 C. destroyed it. It was precipitated by absolute alcohol 

 and mechanically carried down by calcium chlorid. Brieger 

 and Frankel * confirmed the work of Roux and Yersin, and 

 concluded that the poison was a toxalbumin. Tangl f 

 was able to extract the toxin from a fragment of diphtheria 

 pseudo-membrane macerated in water. 



The nature of the diphtheria toxin has been studied by 

 Khrlich { and found to be extremely complex. As it 

 exists in cultures it is composed of equal parts of toxin and 

 toxoid. Of these, the former is poisonous, the latter harm- 

 less for animals or at least not fatal to them. The toxoids 

 have equal or greater affinity for combining with antitoxin 

 than the toxin and cause confusion in testing the unit value 

 or strength of the antitoxin. In old or heated toxin all 

 of the toxin molecules become changed into toxons or tox- 

 oids and the poisonous quality is lost though the power of 

 combining with antitoxin remains. 



The toxin is intensely poisonous, and a filtered bouillon 

 containing it may be fatal to a 3oo-gram guinea-pig in doses 

 of only 0.0005 c - c - It is thought not to be an albuminous 

 substance, as it can be elaborated by the bacilli when 

 grown in non-albuminous urine, or, as suggested by Uschin- 

 sky, in non-albuminous solutions whose principal ingredient 

 is asparagin. The toxic value of the cultures is greatest 

 in the second week. 



This soluble toxin so well known in bouillon cultures is 

 probably only one of the poisonous substances produced by 

 the bacillus. An intracellular, insoluble toxic product 

 seems to have been discovered by Rist, who found it in 

 the bodies of dried bacilli, and observed that it was not 

 neutralized by the antitoxin. 



Palmirski and Orlowski|| assert that the bacillus pro- 

 duces indol, but only after the third week. Smith,** how- 



*" Berliner klin. Wochenschrift," 1890, 11-12. 

 f "Centralbl. f. Bakt.," etc., Bd. xi, p. 379. 

 J "Klinisches Jahrbuch," 1897. 

 "Soc. de Biol. Paris," 1903, No. 25. 

 || "Centralbl. f. Bakt. u. Parasitenk.," March, 1895. 

 ** "Jour. Exp. Med.," Sept., 1897, vol. n, No. 5, p. 546. 



