TOXIN AND ANTITOXIN: METHODS OF THEIR STUDY 549 



tion of antitoxin. By means of a graphic representation ot the 

 figures thus obtained, we can get a deeper insight into the details 

 of the combining phenomena. Even now, after physical chemistry 

 has taken such great interest in the reactions between toxin and 

 antitoxin, all the various statements concerning the subject are 

 finally based on the method of partial neutralization. 



From the outset Ehrlich felt sure that toxin and antitoxin could 

 not be simple substances of strong affinities which combined, for 

 instance, like caustic soda and hydrochloric acid. This was evi- 

 denced particularly by the phenomenon which has often been termed 

 the "inequality" of serum experiments. Thus if varying amounts 

 of toxin are added to a constant amount of antitoxin (an immune 

 unit), two distinct limits will be obtained: L ( = Limit zero) is the 

 quantity of toxin in which the mixture is just completely non-toxic, 

 i.e., physiologically neutral. Lf ( = Limit death) is the quantity of 

 toxin in which the mixture is still just able to exert all its character- 

 istic toxin action, i.e., in the case of diphtheria poison to just kill 

 the guinea-pig acutely. Now if toxin and antitoxin behaved like 

 caustic soda and hydrochloric acid, the difference between L^ and LQ, 

 which we shall term D, should correspond to one lethal dose (L D .). 

 As a matter of fact, however, D is usually considerably larger, so that 

 our first inequality becomes L|-Lo>L. D. 



Hence only two possibilities exist. Either toxin and antitoxin 

 react with one another like a weak base and a weak acid (e.g., am- 

 monia and boric acid), in which case the high value of D is the expres- 

 sion of an incomplete neutralization, or else the poison solution, 

 besides the real toxin, contains a second substance of less affinity. 

 This substance, while unable to produce the characteristic toxin 

 effects, gives rise to certain mild toxic phenomena. In the case of 

 diphtheria poison (owing to the practical importance of diphtheria 

 antitoxin, the discussion has usually centered around this poison) 

 human pathology had long taught that acute diphtheria infection 

 is often followed by a second set of intoxication phenomena, namely, 

 the peculiar paralyses which develop after the acute disease has dis- 

 appeared. A priori, therefore, the assumption was highly probable 

 that the high value of D was due to different components of the poison 

 And when the results of clinical experience and animal experiments 

 harmonized so perfectly, the probability became almost a certainty. 

 It has been found that the toxicity of mixtures whose toxin content 

 lies between L and L t is not quantitatively diminished, but is actually 



