Frank Westheimer was an influential and versatile chemist whose activities cut through the traditional borders of different branches of chemistry. He did his studies in the 1930s, receiving his Ph.D. at Harvard University in 1935. He started his academic career at the University of Chicago and continued it at Harvard University. During World War II, he worked at the Explosives Research Laboratory of the National Defense Research Committee (NDRC) in Bruceton, Pennsylvania. He chaired the Committee of the National Academy of Sciences of the U.S.A. in 1964–1966 that surveyed chemistry and produced the famous Westheimer Report.

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Frank Westheimer at Owl’s Head on Squam Lake in Center Harbor, New Hampshire, 1995 (photograph by I. Hargittai)

Westheimer’s father was a stockbroker and he was expected to go into his father’s business. During his college years, however, he fell in love with chemistry, and he never left it for the rest of his life. Few structural chemists are aware of the fact that Westheimer was a pioneer of what we today call “molecular mechanics.” It happened after the war when he returned to the University of Chicago. He had no ongoing research and no students and he stumbled upon the idea of calculating the steric effects from first principles and classical physics, relying on known values of force constants and van der Waals constants. In his energy minimization calculations he asked for advice from Joseph Mayer and molecular mechanics got started from their interaction. There were similar attempts by others, but Westheimer provided a “reduction to practice” as he called it and therefore it had considerable impact.

His interest in the steric effects manifested itself in biochemical studies, such as his work on direct and stereospecific transfer of hydrogen in the enzymatic oxidation of ethanol. There, alcohol dehydrogenase could distinguish between the two hydrogen atoms on the methylene group. Although Westheimer was generally counted as an organic chemist, at one time he served on the Editorial Board of the Journal of Chemical Physics. In fact, he started out as a physical chemist, became a physical-organic chemist, and, finally, a biochemist.

He had many achievements in various branches of chemistry and was richly decorated by important awards, including the Willard Gibbs Medal (1970), the Robert A, Welch Award (1982), the Cope Award (1982), the National Medal of Science (1986), the Priestley Medal (1988), and others. In the 1960s, the National Academy of Sciences of the U.S.A. set up a series of committees to survey the state of the various sciences. One of the purposes was to advise the government about financing pure research. Westheimer was selected as chairman of the committee for chemistry. The title of their report was Chemistry: Opportunities and Needs. He solved his task splendidly although it was a great challenge. As he said, preparing a report about physical science is not itself physical science; it is social science. Among others, they pointed out the importance of pure research as being the roots of important chemical inventions. They selected 20 of the most important industrial and 20 of the most important pharmaceutical inventions, and studied the first papers where the inventions were reported. Judging by the references in those papers they could see what the inventors themselves considered to be the important underpinnings of their own inventions. They determined that the vast majority of the references came from academic, fundamental research.

I recorded a long conversation with Frank Westheimer during my wife’s and my visit with him and his wife in their summer house at Owl’s Head on Squam Lake in Center Harbor, New Hampshire, on July 23, 1995. At that time his main interest was in RNA catalysis. He was fascinated by the notion that the first living organisms on earth may have used RNA rather than DNA and from this followed that evolution would progress from RNA to DNA. He was telling about his research, again, describing the fundamentals and the potential applications.

In 1995, I was at the beginning of my interviewing project, so I did not realize it then that my Westheimer interview would remain one of my most memorable interviews ever. At some point, I asked him about people who had the strongest influence on his career. He singled out James Bryant Conant. Westheimer had originally wanted to be Conant’s doctoral student, but by the time he had arrived at Harvard, Conant had become Harvard’s president. So he did his work with someone else. When he was finishing, he won a prestigious fellowship for postdoctoral work. From this point I let Westheimer take over the narrative:

About that time, Conant called me into his office. He said that he knew I was getting my doctorate and was interested in my career. What was I going to do? I told him I’d won this fellowship and explained with great pride the problem I’d submitted and was going to work on. Conant had the habit of putting the tips of his fingers together and rocking back and forth while he thought, and he put the tips of his fingers together and rocked back and forth, and then he said, “Well, if you are successful with that project, it will be a footnote to a footnote in the history of chemistry”. As I walked out of his office, I realized what he had told me.

Really, it was two things. One was, of course, that my project wasn’t very important. The other was—and it may have been pretty stupid that I had never thought this until that moment—that I was supposed to do important things. Chemistry was a lot of fun; it was great entertainment, and I was going to be paid—or at least so I hoped—for entertaining myself with it. Yet Conant had essentially told me that I was expected to do things that were scientifically important. The interview with Conant provided a vital kick in the pants for me. It changed the way I thought about my future. At Columbia, I did the project that I had proposed, and it worked out beautifully. But it was exactly what Conant had said it was, a footnote to a footnote in the history of chemistry.

Then I set my sights higher—much too high, as a matter of fact. As a physical-organic chemist I was concerned with general acid—general base catalysis and had decided that enzyme catalysis was probably caused by simultaneous general acid—general base catalysis. I was going to demonstrate this in my next piece of research. Amino acids, with their combination of acid and base in the same molecule, should prove especially active catalysts themselves. So I tried their catalysis of the mutarotation of glucose, but it turned out that there was nothing special about them. The project was obviously enormously ambitious, and although I was fundamentally correct about enzymes, demonstrating it was much too big a project for me at the time. That attempt came to nothing, but at least Conant wouldn’t have been able to object that the attempt was directed at a footnote to a footnote. Eventually I settled down to things that were more important than footnotes to footnotes, but not as grandiose as the youthful project that I just mentioned. I never discussed my research with Conant again, but I did restrict myself to things that he might have approved of.

Many years later, after I was a Professor at Harvard, and after Conant had retired from his many careers, I was working in my office one Saturday when someone knocked on my door. I opened it, and there he stood. He looked at me and said, “Do you remember me?” Needless to say, I did.

When Westheimer quoted the sentence, “Do you remember me?” he was so moved that we could not continue the recording. He added the last sentence in our subsequent correspondence. His story about Conant was an example that even a “kick in the pants” can serve as a life-time mentor. Sometimes I repeat what Westheimer told me about his experience with Conant in my talks about my interviews. When I reach the point of Conant standing in the doorway to Westheimer’s office I am much moved, too.