Toxins and antitoxins 247 



says that in this respect they "behave like peptids in which acids 

 transform cyclic groups to open chains and alkalies restore the 

 cyclic structure. ' ' 



Eaton (1938) says that toxins may be affected by physical and 

 chemical agents in three ways: (1) they may be denatured or 

 coagulated; (2) their toxic and biologic properties may be revers- 

 ibly masked by such agents as soaps and lipids; (3) aldehydes, 

 oxidizing agents and halogens may convert the toxin to toxoid. 



Toxoid or Anatoxin. — Pick (1908) has given an excellent re- 

 view of the early literature relative to the effect of physical and 

 chemical agents upon antigens including the toxins. It was recog- 

 nized quite early that iodine, formaldehyde and certain other 

 chemicals detoxify toxins without destroying their antigenic prop- 

 erty. Ehrlich (1903, 1910) noted that when diphtheria toxin is 

 allowed to age its toxic property is diminished although its 

 antigenic property is retained. He named the deteriorated toxin 

 thus produced toxoid. This latter term is now applied to toxin 

 that has been detoxified by formaldehyde or other chemicals that 

 do not destroy its antigenic property. Many unsuccessful attempts 

 were made to prepare a satisfactory diphtheria toxoid for use in 

 immunization before Ramon (1923, 1925) finally succeeded. He 

 suggested that toxin detoxified by adding formaldehyde and in- 

 cubating for a sufficient length of time at 37° C. be called 

 "anatoxin." Since the term "anatoxin" might be confused with 

 "antitoxin" his suggestion has not been adopted. To avoid 

 any confusion the term "toxoid" is now generally used to signify 

 a detoxified toxin intended for use in immunization. The observa- 

 tion that toxoid is antigenic but nontoxic led Ehrlich to conclude 

 that the toxic and antigenic fractions of the toxin molecule are not 

 identical. His conclusions are borne out by the more recent work 

 on toxoids formed by adding known chemical agents. An excellent 

 discussion of the mechanism of detoxification of diphtheria toxin 

 by formaldehyde is given by Eaton (1937, 1938). 



Method of Measuring Toxin and Antitoxin.— Ehrlich (1903, 

 1910) and his colleagues carried out an extensive investigation 



