CHEMICAL ACHIEVEMENT — PAULING 239 



This picture of the nature of enzymes may well make us optimistic 

 about the future of chemotherapeutics, for it predicts that for every 

 enzyme, and in particular for the enzymes that are essential for bac- 

 terial growth, it would be possible to find an inhibiting molecule which 

 is more closely complementary in structure to the enzyme than is the 

 substrate itself, and which would accordingly be an effective inhibitor. 

 The picture even presents us with an idea as to the nature of substances 

 which would be effective inliibitors, namely, that these substances 

 should closely resemble the activated complex, intermediate in con- 

 figuration between the reactants and the products of the catalyzed 

 reaction. A possible practical application of this concept is in rela- 

 tion to penicillin and its destruction by the enzyme penicillinase. 

 Some of the organisms that resist the bacteriostatic action of penicillin 

 may achieve their resistance through the manufacture of penicillinase, 

 which destroys the penicillin as it approaches the organism. If it 

 were possible to synthesize or to obtain by the degradation of penicillin 

 il self a substance with molecular configuration such that it would com- 

 bine with penicillinase more strongly than does penicillin, and thus 

 would inhibit the action of the penicillinase, this specific inhibitor 

 might be injected (or even taken by mouth) along with the penicillin, 

 which might in this way increase its bacteriostatic action. 



FORMATION OF SPECIFIC ANTIBODIES 



We have far less evidence bearing in a detailed way on the problem 

 of the process of formation of complex biological molecules than on 

 the problem of the nature of specific biological forces. Nevertheless, 

 a reasonable proposal can be made as to the process of formation of 

 these molecules, on the basis of the information available on the nature 

 of the forces themeslves, and the assumption that the known laws of 

 molecular physics are applicable to biological systems. I shall illus- 

 trate this proposal by discussing a possible mechanism of formation 

 of specific antibodies.* 



The problem that we pose is the following : How is it possible for 

 a cell to manufacture an antibody molecule with the power of specific 

 combination with an arbitrarily chosen antigen? It might be that 

 the difference in structure of the antibody molecule and a normal 

 molecule of y-globulin or an antibody molecule homologous to an- 

 other antigen would result from a difference in the ordering of the 

 amino acid residues in the polypeptide chains, as was suggested by 

 Breinl and Haurowitz, and by Mudd.^ However, a simpler assump- 

 tion is that all antibody molecules produced by the same protective 



« Pauling, L., Journ. Amer. Chem. Soc, vol. 62. p. 2G43, 1940. 



• Breinl, F., and Haurowitz, F., Zeitschr. Physiol. Chem., vol. 192, p. 45, 1930; Mudd, D., Journ. Im 

 munol., vol. 23, p. 423, 1932 



