Discoveries in bacterial nucleotide metabolism.

Mydecision to become a biochemist has its roots in youthful indecision. I grew up on a dairy farm in northwestern Illinois surrounded by domestic and wild animal and plant life and came to love the world of biology. This interest was strongly encouraged by my mother, who had been an excellent student of biology in college but was thwarted by the Great Depression and her family’s poverty from pursuing an opportunity for graduate study. Her books, preserved specimens, and microscope slides became my playthings. I set up a home “lab” using commercial chemistry sets from Gilbert and ChemCraft, items that are regrettably deemed unsafe for sale today, but I did not gain a good understanding of chemical principles until high school. There I became enamored of the ability of chemistry to explain the properties of matter, including living matter, in rigorous and elegant atomic andmolecular terms. How to compromise between these two fascinating fields of science? I decided in high school to seek a mixture, biochemistry, even though I had no real understanding of what that discipline involved. It proved to be an excellent decision! As the state’s land grant university, the University of Illinois at Urbana was a natural (and the only affordable) choice for my undergraduate education, especially after I won a scholarship by competitive examination that paid tuition and fees for all four years (1957–1961). Only gradually did I discover my good fortune: the University of Illinois had one of the most distinguished chemistry departments in the United States, and I received an excellent, intensive education. Biochemistry was deemed a graduate specialty at the time, so I majored in chemistry but took biochemistry and microbiology lecture and lab courses as soon as I could. Senior research under the direction of Carl Vestling, who leftme largely onmy own, introducedme to the confusions and ultimate satisfactions of research. I had the good fortune to win a National Science Foundation fellowship for graduate study, and I enrolled at the University of California at Berkeley, which was recognized as having one of the nation’s finest departments of biochemistry. I had no idea of the specialty I wished to pursue, so I was attracted to the breadth and depth of research topics pursued by Berkeley’s outstanding faculty. My graduate school years from 1961 to 1966 were wonderfully exciting years for a young biochemist! The genetic codewas being cracked. The groundbreaking papers by Jacob andMonod on regulatory genes were the subject of intense discussion: could such powerful biochemical conclusions be based on genetics alone?The concept of the subunit structure of proteinswas being clarified, and the first high-resolution x-ray structures of proteinswere emerging. I chose to pursue Ph.D. thesis research under H. A. Barker because I was fascinated with his recent discovery of the coenzyme form of vitamin B12 and the fact that no one understood the chemical basis for its role in catalysis. Barker was a modest, gentle man who emphasized the importance of rigorous, critical experimentation. Initially, he observedmywork carefully, but gradually he grantedme freedom to design and interpret experiments quite independently. We were able to make substantial contributions to the enzymology of the coenzyme B12-dependent glutamate mutase system (1), but the most important contemporary contribution to the mechanism of action of the coenzyme came from thework of Perry Frey and Robert Abeles, who demonstrated the transfer of hydrogen atoms THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 284, NO. 11, pp. 6585–6594, March 13, 2009 © 2009 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A.