Nichols Medal Address

Pennsylvania Hotel, March 7, 1941

Mr. Chairman, Professor Hixon, Ladies and Gentlemen: I do not know how to express my pleasure and my thanks to the members of the New York Section and to the Committees of Award for having selected me to be the recipient of this beautiful and highly esteemed medal. I can only say sincerely that I do thank you that I am glad that you could see me as far away as California and that I hope it was not too much a case of distance lending enchantment - of the grass on the other side of the continent appearing greener than that nearby.

I am happy also that this occasion has brought me in touch with many old friends - with Paul Emmett and Joe Mayer and many others. Several of them said to me tonight that I appeared to be getting fat. This is not so. You know, when I was a boy in Oregon I used to go around a great deal in the green, damp Oregon woods, and I always came into contact with poison oak, which caused my face to swell and my eyes to swell shut, and me to apply so much lead acetate solution that it is a wonder that I didn't die of lead poisoning. Yesterday I must have bumped into something similar, for my face began to swell, and I began to be afraid that I would have to speak here tonight with my eyes swollen shut - which I could have done, with the practice I have had speaking in the dark. Well, while I was wondering what the responsible protein could have been, I decided that it was a visitation - that I was being punished for thinking wicked thoughts. The other day I said "It is too bad that something doesn't happen to Senator Wheeler - nothing serious, just something that would lay him up with his eyes shut for two or three weeks" and my wife said "No what you want is something that would keep his mouth shut - his eyes are closed already."

But now I must take up the topic of my address. When I got a telegram from Mrs. Snell asking why I didn't send her a title, I sent to her "The Structural Chemistry of the Future," and since then I have been trying to find an address to fit it. When I think of the chemistry of the future I have a vision, pruned [?] from the early novels of H. G. Wells, of a man in a synthetic suit swallowing a pill instead of eating his dinner. We are almost there now, thanks to the energy and ability of R. R. Williams of this Section in flooding the market with thiamine chloride. You no doubt all know about the girl who took her vitamin B1 pill, and then, seeing that she had got the wrong bottle, read the label, which said "Plantabs the perfect plant food - each tablet is the equivalent of one shovelful of fresh manure."

President Conant said once that stories are the tools of the trade of the college president, bearing to him the same relation that facts bear to the scientist. He received the Wm H. Nichols Medal in 1932, not long before he became President of Harvard; Joel Hildebrand, Medalist two years ago, became Dean of the College of Arts and Sciences at U. C. I think that I shall now get busy on some facts, so as not to tempt fate in this direction any father.

Modern structural chemistry involves the detailed discussion of the structure of molecules - interatomic distances, bond angles, electronic structures, etc. The tools are many - x-rays, spectra, electron diffraction, magnetic measurements, quantum mechanical theory. It is new, mainly developed in the last twenty years. Consider the determination of the structure of gas molecules by the diffraction of electron waves. This was started about 1929 by Professor H. Mark, then at Ludwigshafen, now at Brooklyn Polytechnic, and Wierl, a young fellow who died in 1931 or 2. When I saw Mark and Wierl's apparatus in 1930 I was enthusiastic, and asked if they would object to my building a similar apparatus in Pasadena. They said no, and the apparatus was built by Dr. L. O. Brockway, then a young graduate student working with me. At the same time Debye and his collaborators were trying x-ray diffraction by gas molecules. One important difference between the two methods is exposure time - seconds vs. days. At first there was 4% disagreement in results - I remember that in 1932 on a tour of this country Debye told everyone that electron diffraction was not good because it gave results disagreeing with the x-ray gas results. It took a year or two of work to prove that it was the x-ray values which were wrong, and the electron diffraction right.

Now the structures are known of hundreds of molecules, with an accuracy of 1% about. We might ask what the value of this information is. I think that it is largely pedagogical - in addition, of course, to its pure-scientific value. When Frankland, Kekulé and Couper developed valence theory it could not be used directly as the basis of an industrial process - but every student of chemistry, every chemist owes these men a debt of gratitude for having made it easier, far easier, for them to learn the facts of chemistry, to tie them together, to suggest worth-while new experiments. I believe that before long, as the new knowledge becomes incorporated into the methods of teaching, it will become easier and easier for chemistry to be taught and learned, despite the ever-increasing body of chemical knowledge. Let me give a simple example of this. This year I have taken over the burden - or, rather, grasped the opportunity - of teaching the course in Freshman chemistry at CIT. I have not tried to teach any more than the elements of electronic theory, but, week before last, I told the boys how to remember the strengths of acids. The formulas (HNO₃, H₃PO₄; HClO₄, HSIO₆) of course, are related to atomic sizes in a way which the Freshmen easily grasp. The rules for strengths are the following:

1. K₁:K₂:K₃ = L:LΘ^-5:LΘ^-10

[Additional series of compounds that comprise the rules of strength]

[List of slides]

The great problem of the future is the explanation of physiological activity in terms of structure. We don't know how vitamins work, how hormones work, how a local (or general) anesthetic works; it can almost be said that we don't know how any substance with physiological activity works (exception: CO on Hb). I think that we may hope that the structural chemistry of the future will play its part in the solution of this great problem - not a more important part than that of the biologist, the immunologist, the physiologist, the biochemist - but nevertheless and important part. We have already some hints that it is by the action of steric factors, van der Waals forces, hydrogen-bond formation, that some important physiological processes occur. The experiments of Dr. Karl Landsteiner with azoproteins and inhibition by haptens show that this is the case - that a part of an antigen or haptene combines with a complimentary structure in the antibody or antitoxin, which fits it tightly. Woods and Fildes found that p-aminobenzoic acid inhibits the growth-inhibitory activity of sulfanilamide on hemolytic streptococci - this is not doubt a case of the p-aminobenzoic acid molecule hooking onto the streptococci and preventing the sulfanilamide molecule from hooking on. Dr. Buchman and his collaborators in our laboratory have shown that thiazole pyrophosphate competes with cocarboxylase (thiamin pyrophosphate) in hooking onto the protein to make carboxylase, and that the pyrimidine part of thiamine shows a similar (though weaker) action. Also analogs are effective, though to a smaller extent? These effects are just what would be expected from the view described above.

I think that as our knowledge of structural chemistry becomes more and more precise and more and more extensive we shall ultimately obtain the solution to this great problem of the basis of the physiological activity of substances, as well as of physiological action in general, and that this will be accompanied by unbelievable progress in chemotherapy and in medicine. This, I believe, is the main goal of the structural chemistry of the future.