Metabolic Products 345 



poisonous and productive of tonic convulsions. Later Brieger and 

 Frankel isolated an extremely poisonous toxalbumin from sugar- 

 bouillon cultures of the bacillus. Ehrlich* later discovered a new 

 poisonous element to which he applied the name tetanolysin. 



The purified toxin of Brieger and Cohn was fatal to mice in doses 

 of 0.00000005 gram. Lambertf considers the tetanus toxin to be 

 the most poisonous substance that has ever been discovered. 



Fermi and PernossJ found most toxin produced in agar-agar 

 cultures, less in gelatin cultures, and least in bouillon cultures. 



Ehrlich§ found two poisons in the tetanus toxin, one of which 

 was convulsive and was in consequence called tetanospasmin, the 

 other hemolytic and called tetanolysin. When tetanus toxin is 

 added to defibrinated blood, the tetanolysin is absorbed by the 

 corpuscles, many of which are dissolved, while the tetanospasmin 

 remains unchanged. 



Donitzjl and Wassermann and Takaki** have found that the 

 tetanus toxin has a specific affinity for the central nervous system, 

 with whose cells it combines in vitro and becomes inert. 



Roux and Borrelff have found that when tetanus toxin is injected 

 into the brain substance a very much smaller dose will cause death 

 than is necessary when the poison is absorbed from the subcutaneous 

 tissues. 



Like most of the bacterial toxins, the tetanus poison is only effect- 

 ive when produced in or injected into the tissues and absorbed into 

 the circulation. It is harmless when given by the digestive tract, 

 RamonlJ having administered by the mouth 300,000 times the fatal 

 hypodermic dose without producing any symptoms. 



One of the most interesting peculiarities about the toxin isthe com- 

 parative uniformity of the period intervening between its administra- 

 tion and the appearance of the symptoms — erroneously called the 

 incubation period. This varies within a narrow margin, inversely, 

 with the size of the dose. Thus, according to Behring, the effect of 

 varying doses of the toxin upon mice becomes evident according to 

 the size of the dose in from twelve to thirty-six hours, thus: 



13 lethal doses symptoms in 36 hours 



no lethal doses symptoms in 24 hours 



333 lethal doses symptoms in 20 hours 



1300 lethal doses symptoms in 14 hours 



3600 lethal doses symptoms in 1 2 hours 



The local action of the toxin is very painful and associated with 

 spasm of the muscular fibers with which it comes in contact. Pit- 



* (11 



'Berliner klin. Wochenschrift," 1898. 



t "New York Med. Jour.," June s, 1897. 



t "Centralbl. f. Bakt.," etc., xv, p. 303. 



§ "Berliner klin. Wochenschrift," 1898, No. 12, p. 273. 



II "Deutsche med. Wochenschrift," 1897, p. 428. 

 ** "Berliner klin. Wochenschrift," 1898, 35. 

 tt "Ann. de I'lnst. Pasteur," 1898 xii. 

 Jt "Deutsche med. Wochenschrift," Feb. 24, 1898. 



