MECHANISM OF ANTIBODY FORMATION 87 



correspondence with the antigen for the reason that each structural 

 unit has been selected and oriented to fit the local configuration and 

 affinities of the antigen surface. Thus, an antibody "specific" for the 

 antigen, i.e., possessing specific stereochemical correspondence with it, 

 is supposed to have been formed. 



c. The Theory of Alexander. According to Hektoen the minimum 

 sensitizing dose of egg albumin is approximately 0.000,05 mg. It has 

 also been frequently shown that if an animal be bled, the temporary 

 drop in the titer of antibodies in the remaining blood is retrieved and 

 even surpassed. In view of this great disproportionality between the 

 antigen used and the antibody produced, Alexander points to a sim- 

 ilarity between these facts and the role of enzymes or catalysts. He 

 believes that the antigen forms within the (antibody forming) cells 

 themselves, new specific catalysts which are able to direct the forma- 

 tion of antibodies. In this connection three possibilities are considered : 

 (a) modification of a gene, (b) modification of a non-genic catalyst, 

 and (c) fixation of the antigen particle by a non-catalyst cytoplasmic 

 particle in such a manner that the combination functions as a specific 

 catalyst. Variations in the duration of immunity are assumed to cor- 

 respond to variations in the persistence of the antigen-catalyst complex, 

 while inability to establish immunity would indicate the non-formation 

 of such a complex. 



As will be discussed on pages 104-8 of this treatise we do not sub- 

 scribe to the idea of Alexander that an antigen produces a modification 

 of a gene. Our view concerning this question basically differs from that 

 of Alexander. 



d. The Theory of Pauling. In disagreement vdth Breinl and Hauro- 

 witz, and Mudd, Pauling does not believe that the effect of an antigen 

 in determining the structure of an antibody molecule is the ordering 

 of the amino-acid residues in the polypeptide chains in a way different 

 from that in the normal globulin. Hypothetically he assumes that all 

 antibody molecules contain the same 'polype-ptide chains as normal 

 globulin, and differ from, normal globulin only in the configuration of 

 the chain; that is, in the way that the chain is coiled in the molecule. 

 It is further stated that "the number of configurations accessible to the 

 polypeptide chain is so great as to provide an explanation for the 

 ability of an animal to form antibodies with considerable specificity 

 for an apparently unlimited number of different antigens, without the 



