CHEMICAL ACHIEVEMENT — PAULING 235 



My collaborators^ and I have outlined and extended this work, 

 primarily by developing and using quantitative methods, permitting 

 the determination of approximate values for the equilibrium constant 

 of the reaction of combination of hapten and antibody. We have 

 also made use of a simplification in the experiments, involving the 

 elimination of one protein from the precipitation test. Inasmuch 

 as the structure of no protein is as yet known, a precipitation reaction 

 involving two proteins, the antibody and the azoprotein, is an espe- 

 cially complicated reaction to study, and the possibility of obtaining 

 information about the antibody might well become greater if the other 

 protein could be eliminated. Landsteiner and van der Scheer ob- 

 served that certain simple substances that they had prepared for use 

 as hapten inhibitors themselves gave a precipitate with the hapten- 

 homologous antiserums. These substances were dyes obtained by 

 coupling two or more haptenic gi^oups together; an example is re- 

 sorcinol with two or three azobenzenearsonic acid groups attached 

 to it. Many of our hapten-inhibition experiments have been per- 

 formed with use of precipitating polyhaptenic antigens of this type, 

 the system under study then containing only one substance of un- 

 known structure, the antibody itself. 



COMPLEMENTARINESS IN STRUCTURE 



Landsteiner's results could be interpreted in terms of our modern 

 knowledge of atomic and molecular structure to permit a definite 

 conclusion to be reached regarding the nature of the specific forces 

 between antibody and antigen and the structure of antibody molecules, 

 and this conclusion has been strengthened by the additional informa- 

 tion given by the experiments that my collaborators and I have per- 

 formed in Pasadena. The conclusion is that the specificity of inter- 

 action of antibody and homologous antigen results from a detailed 

 complementariness in structure, as was first suggested by Haurowitz 

 and Breinl and by Jerome Alexander, and later emphasized by Stuart 

 Mudd. 



The complementariness in structure must be such as to permit a 

 large portion of the surface of the antigen to be brought into juxta- 

 position with a corresponding portion of the surface of the antibody 

 molecule. The weak forces that operate between any atom or small 

 atomic group and adjacent atoms would then come into operation be- 

 tween each surface atom of the antigen and the immediately adjacent 

 atoms of the antibody; these weak forces, integi-ated over the juxta- 

 posed surfaces, would produce a resultant force strong enough to lead 

 to the formation of an effective bond. Inasmuch as most of the weak 



» Prof. Dan H. Campbell, David Pr&'sman, Carol Ikeda, Miyoshi Ikawa, David H. Brown, John T. 

 Maynard, Allan L. Grossberg, Stanley M. Swingle, John H. Bryden, Leland H. Pence, and Frank Lanni, 



