From the Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138
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 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.
ARTICLE
TOP
ARTICLE
-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.
![]() |
FOOTNOTES |
---|
Published, JBC Papers in Press, January 29, 2003, DOI 10.1074/jbc.X300001200
|
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 |