REFLECTIONS
Musings

F. H. Westheimer

From the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138

    ARTICLE
TOP
ARTICLE

My experience goes back to the time when chemistry and biochemistry were entirely separate disciplines. Actually, chemistry itself was an entirely different discipline from what it is today. I joined the American Chemical Society in 1933, some 70 years ago. The science has undergone several revolutions since then.

The first revolution was instrumental. I used to joke that the only difference between the Harvard chemistry laboratories when I was a graduate student and Emil Fischer's laboratories in Berlin at the turn of the century (the 20th century, that is) was that we had Pyrex glass and he did not. Electronic UV was not available and neither was IR. Neither paper chromatography nor column chromatography had been developed. Of course there was no NMR, which, all by itself, has revolutionized chemistry. (Edward Purcell, the inventor of NMR, visited the chemistry laboratories at Harvard after we had bought a 100-megacycle machine from Varian and remarked that, for the first time, he knew what a chemist was. A chemist was a scientist who did physics with good equipment.) Soon after, we joined the computer age and went on to practice x-ray crystallography as well as NMR.

The next revolution in organic chemistry was intellectual. The British and the Americans developed physical-organic chemistry, and this subdiscipline (which explained how reactions occur) had a practical side effect; it enabled organic chemists to design and perform original syntheses with perhaps only one-tenth the man years required before. A modification of a popular aphorism reads that nothing fails like success. The German synthetic organic chemists and their disciples in the United States were so proud of their achievements, where they relied on prodigious memories and hard work in the laboratory (trial and error) that they ignored new developments. No, that's not right. They scorned these developments. One prominent United States chemist claimed that, except for Morris Kharasch, there were no organic chemists at the University of Chicago. I was one of several physical-organic chemists there, but apparently we didn't count. Robert Woodward, at Harvard, taught everyone by example that synthetic organic chemists could intellectualize their work and could not safely ignore physical-organic chemistry.

Then there was a third revolution in chemistry involving biochemistry. A German dogma stated that tierchemie ist schmierchemie (biochemistry is sloppy chemistry). This was at the same time that Otto Warburg in Germany was opening the chemistry of co-enzymes and that Otto Myerhof and others were illuminating the pathway for glycolysis. It is hard to understand the tightly compartmentalized minds of the chemists of that day. (An extreme example of compartmentalization: at the chemistry library at Cambridge University, an imaginary line divided the room into two parts, one for physical chemists and one for organic. The library had two sets of the Journal of The Chemical Society, since an organic chemist was not supposed to cross that imaginary line to use the volumes on the physical chemistry side of the library, and vice versa.) Organic chemists did not read the biochemical literature either or attend biochemical seminars. A colloquium set up many years later for my students and those of another professor in the chemistry department at Harvard quickly divided along an imaginary line between chemists and biochemists.

Let me return to my own career and discuss how I became interested in biochemistry. When I was a postdoctoral student at Columbia, I did not know about compartments and so starting reading a biochemical textbook and some of Myerhof's papers. Then I was lost to old fashioned organic chemistry forever. When I got my toehold job at the University of Chicago in 1936, I knew I would try to combine physical-organic chemistry and biochemistry. Because enzymes are proteins and proteins are made of amino acids, I thought that the amino acids themselves might have special catalytic properties. I set up a study of the mutarotation of glucose catalyzed by amino acids to find out if this was so. Of course, there was no special catalysis by amino acids per se; enzymic catalysis is not so simple, but I am not ashamed of that failure.

I did better with the application of physical-organic chemistry to biochemistry with a study of the metal-ion catalysis of the decarboxylation of beta -ketodicarboxylic acids and much better with a study of the direct and stereospecific transfer of hydrogen in reactions catalyzed by NAD. I am also proud of demonstrating the need for pseudorotation in the hydrolysis of cyclic phosphate esters and of photoaffinity labeling of enzymes. At any rate, I had a wonderful time because I saw the essential unity of chemistry and biochemistry---not a great feat, really, but astonishingly difficult for some chemists at that time.

I was privileged to chair The National Academy of Sciences Committee for the Survey of Chemistry and asked Arthur Kornberg and Dan Koshland to introduce some biochemistry into the mix. When I had completed a rough draft of the report, I sent it to a respected professor at Columbia and asked him for his opinion and suggestions. He wrote back that he did not like the report at all; to begin with, just the summary contained a large number of references to proteins and nucleic acids, work by people who did not even call themselves chemists. So the aspect of the report of which I was most proud, the unification of chemistry and biochemistry, was subject to severe criticism. And this was in 1965. I took this criticism as a badge of honor then and assume that this particular type of criticism has long since vanished.

I wonder what our blind spots are now.

    FOOTNOTES

Published, JBC Papers in Press, January 29, 2003, DOI 10.1074/jbc.X300001200


Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.



This Article
Full Text (PDF)
All Versions of this Article:
278/14/11729    most recent
X300001200v1
Purchase Article
View Shopping Cart
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in PubMed
Alert me to new issues of the journal
Download to citation manager
Copyright Permissions
Google Scholar
Articles by Westheimer, F. H.
Articles citing this Article
PubMed
PubMed Citation
Articles by Westheimer, F. H.


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   Biochemistry and Molecular Biology Education 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.