Metabolic Products 357 



the toxin from the bouillon by supersaturation with ammonium sul-. 

 phate, which causes it to float upon the liquid in the form of a sticky 

 brown scum that caji be skimmed off and dried. Such dry precipi- 

 tate retains its activity for months. 



From cultures of tetanus bacilli grown in various media, and from 

 the blood and tissues of animals affected with the disease, Brieger 

 succeeded in separating "tetanin," " tetanotoxin," tetanospasmin," 

 and a fourth substance to which no name is given. All were very 

 poisonous and productive of tonic convulsions. Later Brieger and 

 Frankel isolated an extremely poisonous toxalbumin from sugar- 

 bouillon cultures of the bacillus. 



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

 of 0.00000005 gram. Lambert* considers the tetanus toxin to be 

 the most poisonous substance that has ever been discovered. 



Fermi and Pernossif found most toxin produced in agar-agar 

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



EhrlichJ 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 

 coipuscles, many of which are dissolved, while the tetanospasmin 

 remains unchanged. 



D6nitz§ and Wassermann and Takakijl 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 Borrel** 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, 

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

 hypodermic dose without producing any symptoms. 



One of the most interesting pecuUarities about the toxin is the 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, 

 vsith 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: 



* "New York Med. Jour.," June 5, 1897. 



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



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



§' "Deutsche med. Wochenschrift," 1897, p. 428. 



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

 ** "Ann. de I'lnst. Pasteur," r898, xn. 

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



