IMMUNOLOGICAL BEHAVIOR 111 



Somewhat similar results ^vere obtained ^vith active principles of 

 meningococcus (Chapter xni) . 



CONVERSION OF ACTIVE PRINCIPLES TO TOXOID 



The con\ersion of toxin into toxoid has been studied by Ehr- 

 lich (1898) and Ramon (1923, 1924) for diphtheria toxin, by 

 Behring and Ransom (1898) , Lowenstein (1909) , and Eisler and 

 Lo\venstein (1912) for tetanus toxin, and by Weinberg and Goy 

 (1924) for the toxins of the B. botulinus and of the gas gan- 

 grene anaerobes {i.e., B. oedematiens, etc.) . Ramon (1925) has 

 also con\'erted abrin and cobra venom into toxoids. The change 

 ^vas obserxed to occur spontaneously (Ehrlich, Behring and Ran- 

 som) , and also could l^e induced artificially by means of various 

 physical and chemical agents; namely, for tetanus toxin iodine 

 trichloride (Behring and Ransom), formalin (0.1 to 0.2 per 

 cent) and exposure to a Nernst lamp (Lowenstein) , formalin 

 (o.i to 0.2 per cent) and slight heat (30° c.) (Eisler and Lowen- 

 stein) ; and for diphtheria toxin formalin (0.3 to 0.4 per cent) 

 and heat (40-42° c.) (Ramon, 1924) . By similar procedures (for- 

 malin and heat) abrin, cobra venom (Ramon, 1925) , and toxins 

 of the B. botulinus and the gas gangrene anaerobes (Weinberg 

 and Goy) have also been converted into toxoid states. 



These studies elaborated the concept of a toxoid first an- 

 nounced by Ehrlich. In its completed form, the definition of a 

 toxoid is that it is a toxin so altered that the toxicity is decreased 

 whereas the antibody-combining capacity and the antigenicity are 

 essentially luidiminished. It has been observed (Low^enstein, 

 1909; Ramon, 1925) that the antigenicity of tetanus and diph- 

 theria toxoids varies with the potency of the mother filtrates. 

 It can be estimated by the antitoxin-combining capacity, to "which 

 it is directly proportional. 



Fluctuations in potency of filtrates employed in my studies 

 suggested toxoid formation and necessitated the development of a 

 standard procedure in Avhich the titer of the filtrates \\as calcu- 

 lated from the dilution neutralized by a given amount of neu- 

 tralizinoj serum selected as a standard. This Avas done as follow^s: 



An "agar Avashings" B. typhosus filtrate freshly made and highly 

 active was titrated for reacting potency (Method III) (600 re- 

 acting units per c.c.) . The neutralizing potency of an immune 

 antityphoid seriun \\as then titrated against this filtrate. In these 



