TOXINS OF THE TETANUS BACILLUS 381 



of the filtered culture be left in contact with equal portions of 

 gelatin for various lengths of time, there is no increase of toxicity 

 in those kept longest. There is thus no fresh development of 

 toxin during the advancing liquefaction of the gelatin. Thus 

 peptic digestion and toxin formation are apparently due to 

 different vital processes on the part of the tetanus bacillus. 



Whatever the nature of the toxin is, it is undoubtedly one 

 of the most powerful poisons known. Even with a probably 

 impure toxalbumin Brieger found that the fatal dose for a 

 mouse was '0005 of a milligramme. If the susceptibility of 

 man be the same as that of a mouse, the fatal dose for an average 

 adult would have been '23 of a milligramme, or about ^^^ths 

 of a grain. Animals differ very much in their susceptibilities 

 to the action of tetanus toxin. According to v. Lingelsheim, if 

 the minimal lethal dose per gramme weight for a horse be taken 

 as unity, that for the guinea-pig would be 6 times the amount, 

 the mouse 12, the goat 24, the dog about 500, the rabbit 1800, 

 the cat 6000, the goose 12,000, the pigeon 48,000, and the 

 hen 360,000. 



A striking feature of the action of tetanus toxin is the 

 occurrence of a definite incubation period between the introduc- 

 tion of the toxin into an animal's body and the appearance of 

 symptoms. The incubation period varies according to the species 

 of animal employed, and the path of infection. In the guinea- 

 pig it is from thirteen to eighteen hours, in the horse five days, 

 and the incubation is shorter when the poison is introduced into 

 a vein than when injected subcutaneously. In man the period 

 between the receiving of an injury and the appearance of tetanic 

 symptoms is from two to fourteen days. 



With regard to the action of the toxin, it has been shown to 

 have no effect on the sensory or motor endings of the nerves. 

 It acts solely as an exciter of the reflex excitability of the motor 

 cells in the spinal cord. The motor cells in the pons and 

 medulla are also affected, and to a much greater degree than 

 those in the cerebral cortex. When injected subcutaneously 

 the toxin is absorbed into the nerves, and thence finds its way 

 to that part of the spinal cord from which these nerves spring. 

 This explains the fact that in some animals the tetanic spasms 

 appear first in the muscles of the part in which the inoculation 

 has taken place. This is not the case with man, in whom usually 

 the first symptoms appear in the neck. In artificial injection of 

 toxin part finds its way into the blood stream, and if infected 

 animals be killed during the incubation period there is often 

 evidence of toxin in the blood and solid organs. In the guinea- 



