1080 PHYSIOLOGY 



classified according as they produce extracellular or intracellular toxins. 

 We may deal first with the manner in which the body reacts to the toxins 

 excreted by the first class. If a culture of diphtheria or tetanus bacilli be 

 filtered, the clear filtrate free from bacilli is found to exercise as poisonous 

 results as if the culture itself of the living bacilli had been employed. The 

 toxins contained in these fluids are extremely potent. Thus five-millionths 

 of a gramme of tetanus toxin is a fatal dose for a mouse, and -00023 grm. 

 would kill a man. These weights apply to the mixture obtained by the 

 evaporation of the solution of toxin, so that the pure toxin must be even 

 more powerful than is represented in these figures. We have at present no 

 means of preparing a toxin in a pure condition, nor we do know to what class 

 of compounds it should be assigned. The toxin is an unstable body and is 

 destroyed by heating to 65 C. Similar toxins are widely distributed 

 throughout the vegetable and animal kingdoms. Thus they form the 

 active constituent of snake venom and of the poison of scorpions and spiders. 

 They also occur in the seeds of castor oil and of jequirity, the toxins of 

 which seem to be of protein character and are known as ricin and dbrin. 

 There is a great variability in the reaction of different animals to these 

 toxins. Thus to the poison of tetanus the rabbit is weight for weight two 

 thousand times and the hen twenty thousand times more resistant than 

 the guinea-pig. As in the case of infection by bacteria themselves, a certain 

 incubation time is necessary after the introduction of the toxin before its 

 effects are displayed. There is a striking difference in this respect between 

 the action of these complex bodies and the action of drugs, such as strychnine 

 or morphine. Thus by increasing the dose of strychnine it is possible to kill 

 an animal within half a minute. The period of survival after the injection 

 of a dose of toxin cannot be reduced beyond a certain limit, however much 

 toxin be injected. Thus a lethal dose of diphtheria toxin kills a guinea- 

 pig in fifteen hours. If ninety thousand such doses be injected into a 

 guinea-pig, it is not possible to reduce the time of survival below twelve 

 hours. Another characteristic of these toxins is the specificity of their 

 action. One kind of toxin may act chiefly on the central nervous system, 

 another on the peripheral nerves, another on the red blood corpuscles. 

 In this respect of course they resemble ordinary drugs. Associated with, 

 and apparently a necessary condition of, this specific action is the actual 

 combination which occurs between the toxin and the organ on which it 

 exerts its effect. Thus tetanus toxin has a specific affinity for the central 

 nervous system, and may be removed from a solution by shaking the latter 

 up with an emulsion of brain. In spite of the excessively fatal character of 

 these toxins it is possible to render an animal immune to their action. If 

 a dose of diphtheria or tetanus toxin which is smaller than the fatal dose 

 be injected into an animal, the latter may show signs of injury from which 

 it recovers. When recovery is complete, it is found that three or four times 

 the fatal dose may be injected without producing any evil effects ; and this 

 process of injection of toxin may be repeated in continually increasing doses 

 until the animal is able to withstand a dose one hundred thousand times 



