NATURE OF ANTITOXIC ACTION 565 



that a definite period of time elapses before the neutralisation 

 of the toxin is complete, that neutralisation takes place more 

 rapidly in strong solutions than in weak, and that it is hastened 

 by warmth and delayed by cold. C. J. Martin and Cherry, and 

 also Brodie, showed that in the case of diphtheria toxin and 

 in that of an Australian snake poison, the toxin molecules will 

 pass through a colloid membrane (p, 191), whilst those of the 

 corresponding antitoxin will not. Now, if a mixture of equivalent 

 parts of toxin and antitoxin is freshly prepared and at once 

 filtered, a certain amount of toxin will pass through, but the 

 longer such a mixture is allowed to stand before filtration the 

 less toxin passes, till a time is reached when no toxin is found 

 in the filtrate. Further, if the portion of fluid which at this 

 stage has not passed through the filter be injected into an animal 

 no symptoms take place ; this shows that after a time neutral- 

 isation is complete. Again, in cases where the toxin has some 

 definite physical effect, demonstrable in vitro, e.g., lysis, aggluti- 

 nation, coagulation, or the prevention of coagulation, its action 

 can be annulled by the antitoxin ; in such circumstances 

 manifestly no physiological action of antitoxin through the 

 medium of the cells of the body can come into play. These 

 facts are practically conclusive in favour of antitoxin action 

 depending upon a direct union of the two substances concerned, ' 

 and Morgenroth has shown that the combination toxin-antitoxin 

 can be broken up by the action of hydrochloric acid and the 

 two constituents recovered. 



Although authorities are now agreed as to the direct combination of 

 toxin and antitoxin, there is still much uncertainty as to the exact nature 

 of this union. Regarding this subject there may be said to be three chief 

 views — (a) that of Ehrlich, according to which there is a firm chemical 

 union of toxin and antitoxin, and the former is not homogeneous but has 

 a complex structure ; (6) that of Arrhenius and Madsen, who consider 

 that the phenomena correspond to the behaviour of two substances in 

 weak chemical union ; and (c) that of Bordet, who regards the combina- 

 tion to be not of chemical, but of physical nature, corresponding to a 

 process of adsorption. Controversy on this question may be said to date 

 from the important work of Ehrlich on the neutralisation of diphtheria 

 toxin. Using an immunity unit of antitoxin (the equivalent of 100 doses 

 of toxin) he determined with any example of crude toxin the largest 

 amount of toxin which could be neutralised completely, so that no 

 symptoms resulted from an injection of the mixture. This amount he, 

 called the limes null dose, expressed as L . He then investigated the 

 effects of adding further amounts of toxin to the immunity unit and 

 observed the quantity which was first sufficient to produce a fatal result, 

 that is, which contained one M.L.D. of free toxin ; this amount he called 

 the limes todtlich, fatal limit, expressed as Lt. Now if, as he supposed, 

 the union of toxin and antitoxin resembled that of a strong acid and 



