THE BACILLUS AND THE BACTERIOLOGY OF TETANUS 227 



epileptiform convulsions. The tetanus toxins undoubtedly combine 

 readily with the cells of the central nervous system. They also com- 

 bine with other tissue cells with less apparent effects. The symptoms 

 in tetanus depend upon an increased reflex excitability of the motor 

 cells of the spinal cord, the medulla, and pons. 



Presence of Tetanus Toxin in the Blood of Infected Animals. The blood 

 usually contains the poison, as has been proved experimentally on animal. 

 Neisser showed that the blood of a tetanic patient was capable of inducing 

 tetanus in animals when injected subcutaneously. In St. Louis the serum 

 of a horse dying of tetanus was given by accident in doses of 5 to 10 c.c. to 

 a number of children, with the development of fatal tetanus. In this 

 connection Bolton and Fisch showed by a series of experiments that 

 much toxin might accumulate in the serum before symptoms became 

 marked. Kitasato also found the serous exudates of the pleural and 

 pericardial cavities as well as the blood of tetanic animals would cause 

 tetanus when transferred to other animals. Ehrlich has shown that 

 besides the predominant poison which gives rise to spasm (tetano- 

 spasmin) there exists a poison capable of producing solution of certain 

 red blood corpuscles. This he calls tetanolysin. It was not found in 

 all culture fluids and does not pass through in the first portion of the 

 filtrate from a porcelain filter. Whether in actual disease this poison is 

 ever in sufficient amount to cause appreciable harm is not known. 



Tetanus Antitoxin. Behring and Kitasato were the first to show 

 the possibility of immunizing animals against tetanus infection. The 

 entire procedure is analogous to immunization against diphtheria. The 

 treatment of tetanus is directed against the action of the toxin and this 

 is accomplished by the neutralization of the toxin by antitoxin in the 

 body. 



The immunizing experiments in tetanus have borne practical fruit, 

 for it was through them that the principle of serum therapeutics first 

 became known the protective and curative effects of the blood serum 

 of immunized animals. It was found that animals could be pro- 

 tected from tetanus infection by the previous or simultaneous injection 

 of tetanus antitoxin, provided that such antitoxic serum was obtained 

 from a thoroughly immunized animal. From this it was assumed 

 that the same result could be produced in natural tetanus in man. 

 Unfortunately, however, the conditions in the natural disease are very 

 much less favorable, inasmuch as treatment is usually commenced not 

 shortly after the infection has taken place, but only on the appearance 

 of tetanic symptoms, when the poison has already attacked the cells of 

 the central nervous system. 



The tetanus antitoxin is developed in the same manner as the diph- 

 theria antitoxin by inoculating the tetanus toxin in increasing doses 

 into horses. The toxin is produced in bouillon cultures grown anae'ro- 

 birally. After six to fifteen days the culture fluid is filtered through 

 porcelain, and the germ-free filtrate is used for the inoculations. The 

 horses receive \ c.c. as the initial dose of a toxin of which 1 c.c. kills 

 250,000 grams of guinea-pig, and along with this a sufficient amount 



