ON THE NATURE OF TOXINS 45 



saline solution to remove all traces of free haemolysin, are dissolved 

 when raised to the body temperature. In other words, the 

 specific haemolysin of tetanus can form a combination with the 

 structures on which they act. Numerous similar examples will 

 be met with. 



(c) In some of the specific exotoxins, notably that of tetanus, we 

 meet with a similar dependence on a suitable temperature for the 

 development of their toxic action, a property in which again 

 they resemble the soluble enzymes. The most striking example 

 is obtained by a study of the action of tetanus toxin on the frog, 

 which, in common with all cold-blooded animals, is but slightly 

 susceptible to its action. If, however, the frogs be kept in an 

 elevated temperature 30 C. or higher they develop the typical 

 symptoms of the disease after five days or thereabouts. Now 

 Morgenroth has shown that the toxin unites with the central 

 nervous system at a low temperature (8 C.), but without the de- 

 velopment of symptoms. For the production of these a high tem- 

 perature is necessary, exactly as in the case of the combination 

 of tetanolysin with red blood-corpuscles and the solution of the 

 latter. 



(d) These and similar researches lead us to distinguish between 

 two faculties of a toxin that of combining and that of injuring ; 

 and the fact that in some instances these processes can take place 

 at different temperatures leads us to the belief that they are quite 

 different properties of the toxin. In other words, the mere union 

 of a toxin with a cell is not sufficient to cause injury to the latter. 

 This is susceptible of proof. In Ehrlich's elaborate studies on the 

 standardization of diphtheria antitoxin he first obtained a speci- 

 men of diphtheria antitoxin, and determined its minimum lethal 

 dose for test guinea-pigs. For the sake of simplicity we will 

 suppose that for a given sample of toxin this was T ^ c.c. i.e. 9 

 that amount of the filtered broth culture of the diphtheria bacillus 

 would just kill a guinea-pig weighing 250 grammes in four days. 

 Further, let us suppose that we have a standard sample of anti- 

 toxin of which i c.c. just neutralizes i c.c. of toxin (100 lethal 

 doses), so that the mixture of the two causes no symptoms when 

 injected into a test animal. Diphtheria antitoxin is a relatively 

 stable substance, and can be preserved in a dry state, at a low 

 temperature, for long periods if light and air are excluded. It is 

 thus possible to re-test the sample of toxin with a precisely similar 

 solution of antitoxin after some months. When this is done, it is 



