232 ANNUAL REPORT SMITHSONIAN INSTITUTION, 195 



palsies, raw eyes, dirt-rotten livers, wheezing lungs, bladders full of 

 imposthume, sciaticas, lime-kilns i' the palm, incurable bone-ache, and 

 the riveled fee-simple of the tetter." Most of these diseases are no 

 longer important: there are now no serious cases, so far as I know, 

 of riveled fee-simple of the tetter, but "incurable bone-ache," under 

 which we might include arthritis, is a very serious disease, of which 

 little control has been obtained. There are still virus diseases that 

 are very troublesome — poliomyelitis, influenza, the common cold. 

 Then there remains the problem of the degenerative diseases — cancer, 

 heart disease, cerebral disease, nephritis — which, as control of other 

 diseases is obtained, are becoming increasingly important. To attack 

 these great medical problems new basic knowledge is needed about 

 the nature of cells and of physiological processes, and about the 

 chemotherapeutic action, as well as the normal physiological action, 

 of chemical substances. 



STRUCTURAL BASIS OF PHYSIOLOGICAL ACTIVITY 



The greatest problem that remains to be solved is that of the struc- 

 tural basis of the physiological activity of chemical substances. "Wlien 

 once this problem has been solved, and when it has become possible to 

 determine in detail the molecular structure of the vectors of disease 

 and of the constituents of the cells of the human body, we shall be 

 able to draw up the specifications of the specific therapeutic agent to 

 protect the body against a specific danger, and then to proceed to 

 synthesize the agent according to the specifications. So far, we have 

 only the hint that chemotherapeutic agents may act through competi- 

 tion with essential metabolites, as in the competition, pointed out by 

 Woods and Fildes, of the sulfa drugs with p-aminobenzoic acid. 



I believe that this problem — that of the nature of the competition 

 of two substances presumably for specific combination with some part 

 of a living cell — is very closely related to the general problem of the 

 nature of the forces that lead to the striking specificity of properties 

 shown by many biological substances, especially the native proteins 

 and polysaccharides. I believe that these forces are also operative in 

 the phenomenon of self -duplication shown by viruses, genes, and other 

 biological entities. I myself have been especially interested in the 

 specific forces operating between an antibody molecule and the mole- 

 cules of antigens or haptens with which it has the power of specific 

 combination. My interest in this problem was developed over 10 

 years ago in conversations with Dr. Karl Landsteiner, and the work 

 that my collaborators and I have done has consisted largely in the 

 extension and refinement of investigations initiated by Dr. Landsteiner. 



Let us review briefly the basic phenomena of immunochemistry. 

 When a foreign material of large molecular weight — a protein or 



