BACILLUS TETANI 515 
that mixtures of tetanus toxin with small amounts of tyrosin are non- 
toxic upon subcutaneous injection into guinea-pigs and mice, but such 
mixtures result in the development of immunity after a period of about 
two months. 
Types of Tetanus Bacilli. Tulioch^ has immunized experimental 
animals with various tetanus bacilli obtained from infected wounds, 
and has found four types which appear to be serological entities, as 
shown by agglutination tests with sera of high potency. Of these 
types. Type I, which corresponds to the type more commonly used in 
the past for the preparation of antitoxin, is the one more frequently 
encountered by Tulloch in a study of organisms from 100 wounds. It 
was found that the antitoxin for one type was qualitatively, and, for 
all practical purposes, quantitatively a specific neutralizing agent for 
the toxin of the other three types. 
Action of Tetanus Toxin.— Even when massive doses of toxin are 
injected into suscejjtible animals, a latent period exists between the 
time of inocidation and the appearance of symptoms, which cannot be 
reduced below eight hours.- The incubation period increases when 
smaller amounts of toxin are used; symptoms may not appear until 
two or three days, or even a week after inoculation. Subfatal doses 
of tetanus toxin administered to experimental animals give rise to 
local symptoms which are frequently the only signs observed. The 
incubation periofl of the natural infection in man is usually about 
fourteen to sixteen days. It may be stated as a general rule that the 
shorter the incubation period, the higher the mortality. The site of 
inoculation of the tetanus toxin influences the character of the symp- 
toms and the incubation period quite materially. Subcutaneous 
injections are usually followed by symptoms (spasms) which affect 
the muscles nearest the site of inoculation as a rule. Intravenous 
injections usually cause a generalized spasm.'' When toxin is intro- 
duced directly into the central nervous system smaller doses cause 
death and the symptoms develop much more rapidly. There is great 
restlessness in these cases before the characteristic spasms occur, and 
the spasms are epileptiform in character. The toxin is supposed to 
exert a harmful effect on the central nervous system, which it reaches 
by way of the nerve trunks. Donitz,'* and Wassermann and Takaki-^ 
have shown that mixtures of brain tissue (especially the gray sub- 
stance) and tetanus toxin are practically without effect when they are 
injected into susceptible animals, indicating that a firm union has 
taken place between the tissue and the toxin. This union will take 
1 Jour. Hyg., 1919, 18, 10.3. 
2 Courmont and Doyen (Arch, de Phys., 1893) and Goldscheider and Flatau (Kong. f. 
inn. Med., Berlin. .June 11, 1897; Deutsch. med. Wchnschr., 1897, 23, 278; Fort. d. Med., 
1897, 15, 609) have noticed, however, that changes in the anterior horn ganglion cells 
of the spinal cords of rabbits are demonstrable two hours after injection of tetanus toxin. 
' Ransom: Deutsch. med. Wchnschr., 1898, 24, 117. Marie and Morax: Ann. 
Inst. Pasteur, 1902, 16, 418. 
« Deutsch. med. Wchnschr., 1897, 23, 428. 
s Berl. klin. Wchnschr.. 1898. 25, 5. 
