226 BACTERIA PATHOGENIC TO MAN 



tiplication at this point that they exert their action through the produc- 

 tion of powerful toxins. These toxins are named, according to their 

 action, the tetanospasmin and the tetanolysin. One one-hundredth of 

 a milligram of the filtrate of an eight-day glucose bouillon culture of 

 a fully virulent bacillus is sufficient to kill a mouse. From this filtrate, 

 however, the active toxic substance has been obtained in a much more 

 concentrated form. The purified and dried tetanus toxin prepared by 

 Brieger and Cohn was surely fatal to a 15-gram mouse in a dose of 

 0.00000005 gram. Reckoning according to the body- weight of 75 kilo- 

 grams, or 175 pounds, it would require but 0.00023 gram, or 0.23 

 milligram, of this toxin to prove fatal to a man. The appalling strength 

 of tetanus toxin may readily be appreciated. By comparing it with 

 snake poison and strychnine, Calmette has found that dried cobra venom 

 would require 4.375 milligrams to kill a man of 70 kilograms. A fatal 

 dose of strychnine is from 30 to 100 milligrams. 



The quantity of the toxin produced in nutrient media varies accord- 

 ing to the age of the culture, the composition of the culture fluid, reac- 

 tion, completeness of the exclusion of oxygen, etc. The variation in 

 strength is partly due to the extreme sensitiveness of the toxin, which 

 deteriorates on keeping or on exposure to light, being also sensibly 

 affected by most chemical reagents and destroyed by heating to 55 to 

 60 C. for any length of time. It retains its strength best when protected 

 from heat, light, oxygen, and moisture. Under the best conditions the 

 amount of toxin produced in cultures by the fifth day is such that 

 0.000005 c.c. is the fatal dose for a 15-gram mouse. 



The tetanus cultures retain their ability to produce toxins unaltered 

 when kept under suitable conditions ; but when subjected to deleterious 

 influences they may entirely lose it. The usual medium for the develop- 

 ment of the toxin is a slightly alkaline bouillon containing 1 per cent, of 

 peptone and 0.5 per cent. salt. The addition of more than a trace of 

 sugar or glycerin is to be avoided, as the acid produced injures the toxin. 



Action of Tetanus Toxin in the Body. After the absorption of the 

 poison there is a lapse of time before any effects are noticed. With 

 an enormous amount, such as 30,000 fatal doses, this is about twelve 

 hours; with ten fatal doses, thirty-six to forty-eight hours; with two fatal 

 doses, two to three days. Less than a fatal dose will produce local 

 symptoms. The parts first to be affected with tetanus are, in about 

 one-third of the cases in man and usually in animals, the muscles 

 lying in the vicinity of the inoculation for instance, the hind foot of 

 a mouse inoculated on that leg is first affected, then the tail, the other 

 foot, the back and chest muscles on both sides, and the forelegs, until 

 finally there is a general tetanus of the entire body. In mild cases, or 

 when a dose too small to be fatal has been received, the tetanic spasm 

 may remain confined to the muscles adjacent to the point of inoculation 

 or infection. The symptoms following a fatal dose of toxin vary greatly 

 with the method of injection. Intraperitoneal injection is followed by 

 symptoms which can hardly be distinguished from those due to many 

 other poisons. Injection into the brain is followed by restlessness and 



