ANTI-ENZYME IMMUNITY 205 



attraction between a positive charge in the antibody and negative 

 charge of the carboxyl of a haptene, presumably forming a hydrogen 

 bond, are responsible for their union. In his discussion on the denatura- 

 tion and properties of various protein groups, Anson (1945) considers 

 the hydrogen bond theory plausible on general chemical grounds, but 

 it has not as yet any direct experimental basis. 



It is evident also in these reactions between the positively charged 

 ammonium groups of antibodies and negatively charged carboxyl 

 groups of antigens, with or without the formation of hydrogen bonds, 

 that these side groupings do not themselves carry the specificity of the 

 reactions of the complex reactants to which these side groupings are 

 attached. There is no specific information as to what properties of the 

 configuration of an antigen enable its carboxyl groups to react specifi- 

 cally with the ammonium or imino groups of the homologous anti- 

 body, and do not permit them to react with the same groups in heterol- 

 ogous antibodies. 



The question of whether an antibody which specifically inhibits 

 the biological activity of an antigen contains specific configuration 

 evolved in response to the stimulus by the active groups of the specific 

 protein molecule, or whether the observed inhibition is the result of 

 a secondary reaction associated with the union of antigen and antibody 

 may now be considered. It is a known fact that the toxicities of anti- 

 gens can be eliminated with non-specific agents without loss of their 

 ability to produce antibodies possessing the ability of combining with 

 both the inactive and active forms of the antigen. The unanswered 

 question is the mechanism by which inactivated antigen is capable of 

 producing an antibody which neutralizes the toxicity or the enzyme 

 activity of the antigen. Ramon (1943) inquiring into this question 

 experimented with papain. As Achalme (1901) had previously re- 

 ported, Ramon observed that papain acts like certain bacterial toxins 

 and venoms. The papain solutions filtered through porcelain and in- 

 jected subcutaneously into guinea pigs, rabbits, or a horse produced 

 local disorders. Oedema and inflammation were followed by the forma- 

 tion of a scar. Papain in large amounts caused the death of animals. 

 Treated with formaldehyde at 45 °C. papain lost its in vitro enzyme 

 activity and in vivo toxicity. Detoxified papain produced antibody 

 which flocculated and neutralized the toxicity and the known activity 

 of the enzyme, in a manner comparable to the properties of diphtheria 



