502 COLLECTED STUDIES IN IMMUNITY. 



Certain other considerations have convinced me of the plurality 

 of the toxins. Chief of these is the behavior of the poisons on long 

 standing. As is well known, poisons freshly produced rapidly deterio- 

 rate in toxicity until a point is reached beyond which the constants 

 of titration, especially Lj, remain unchanged. Such " ripened " poisons 

 are made use of in the official testing of diphtheria antitoxin, and we 

 have therefore had abundant opportunity to convince ourselves that 

 they remain constant. 



From the standpoint of physical chemistry this fact (that the 

 toxicity after a time becomes constant) could perhaps be ascribed 

 to an equilibrium between toxin and toxoid. Such an equilibrium, 

 however, is found only in reversible reactions, i.e., in chemical proc- 

 esses, which also proceed in the reverse direction. Toxoid formation, 

 however, is not a reversible reaction ; no one has yet discovered even 

 a suggestion of a toxoid passing over into toxin. Another point which 

 speaks against a condition of equilibrium is the fact that through 

 artificial influences heat, chemicals any desired proportion of toxin 

 and toxoid can be produced. Only one other explanation therefore 

 remains, namely, that various toxins are present, of which some are 

 more resistant, others less so. 



I have thus presented in detail the reasons which led me to assume 

 the existence of preformed varieties of toxins. As a result of my ex- 

 periments I must emphatically deny the assumption that the phe- 

 nomena observed by me in diphtheria poison are only the expression 

 of a weak affinity between diphtheria toxin and antitoxin. I have 

 demonstrated that the observed deviations can only be due to the 

 admixture of toxoids with different affinity, and have further made 

 it probable that these different degrees of affinity exist preformed 

 in the toxin and do not arise with the formation of toxoid. It must, 

 however, be distinctly understood that the points of view here laid 

 down are not applicable to the relations between toxins and antitoxins 

 in general. They apply only to diphtheria toxin and its antitoxin. 

 The important researches of Arrhenius and Madsen on tetanolysin 

 show that neutralization proceeds in an entirely different fashion 

 when the two components possess a weak affinity for one another. 

 The studies of these authors clearly indicate the errors in the interpre- 

 tation of neutralization phenomena when dissociation is disregarded. 



My results were obtained by the long and tedious experimental 

 method. I can assure the reader that the experiments upon which 

 all this is based, experiments carried out by my fellow workers (espe- 



