CHAPTER LIV 

 THE PHYSICAL CHEMISTRY OF TOXIN AND ANTITOXIN 



MARY E. MAVER' 



University of Chicago 



The theory of Metchnikoff^ which postulated a physiological role for antitoxin 

 in stimulating the body to the attack upon toxin was no longer held valid after Ehrlich' 

 demonstrated that the toxin-antitoxin reaction could occur m vitro. Thereafter the 

 problems concerning the nature of toxin and of antitoxin and their reaction were ap- 

 proached by the application of current chemical theories. Since no one has ever 

 succeeded in establishing the chemical identity of either toxin or antitoxin, these 

 reagents have necessarily been studied in their native media. Considering the physical 

 and chemical complexity of the solutions studied, it is not surprising that no theory 

 has been advanced which can explain all of the phenomena exhibited by toxic and 

 antitoxic solutions. 



THE THEORIES OF EHRLICH AND ARRHENIUS 



The conception of the chemical nature of the neutralization of toxin by antitoxin 

 was apparently inherent in the discovery of this phenomenon as it was made by von 

 Behring and Kitasato in 1890. Ehrlich^ considered the reaction of toxin with anti- 

 toxin to be a simple chemical reaction similar to the practically irreversible reaction 

 of a strong acid with a strong base. However, when experiments were undertaken to 

 standardize toxin and antitoxin it was discovered that, on standing, toxin lost its 

 toxic power but not its ability to combine with antitoxin. To explain this, Ehrlich 

 found it necessary to postulate the presence of such a long series of substances possess- 

 ing varying degrees of toxic and combining powers that the theory of a simple 

 chemical reaction was lost in the confusion of explanatory details. 



At this time Arrhenius, as the leader of the modern ionization theory, undertook 

 to correlate the reaction of toxin and antitoxin with the new theory of solutions which 

 had recently been developed by van't Hoff. Arrhenius^ treated the complex toxic 

 and antitoxic solutions as homogeneous solutions of weak electrolytes and applied to 

 these solutions the laws of van't Hoff. He found that toxins and antitoxins, like 

 other substances, diffused with unequal rates into gelatin, and he therefore felt justi- 

 fied in concluding that they obeyed van't Hoff's law of osmotic pressure and conse- 

 quently the law of mass action. Calculations of velocity constants from reactions in 

 such complex heterogeneous solutions which would call for numerous assumptions 



' Fellow under the Douglas Smith Research Foundation. 



' Metchnikoff, E.: Immunity in Infective Diseases. Cambridge, 1905. 



3 Ehrhch, P.: Fortsckr. d. Med., 15, 41. 1897. 



^Ehrlich, P.: Deutsche med. Wchnschr., 24, 597. 1892. 



s Arrhenius, S. : Immunochemistry. Macmillan, 1907. 



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