A scientist’s journey to the Nobel Prize

David MacMillan in the College of Chemistry library, 2022. Photo Brittany Hosea-Small

By Marge d’Wylde

The Nobel Prize is one of the most prestigious awards for the sciences in the world. Other notable international awards include the National Medal of Science (United States), the Wolf Prize (Israel), The Royal (Queen’s) Medal (England), and the Leibniz Prize (Germany) acknowledging many long research hours spent by scientists and their teams in labs around the world.

However, the Nobel Prize remains the most renowned. College of Chemistry faculty have been awarded the Prize five times. Most recently in 2020 when Professor Jennifer Doudna shared the prize with colleague Emmanuelle Charpentier for their groundbreaking work on CRISPR technology.

Members of the College of Chemistry were delighted when Professors David MacMillan of Princeton University and Benjamin List of the Max-Planck-Institut were awarded the 2021 Nobel Prize in Chemistry for their independent discovery in 2000 of asymmetric organocatalysis. Researchers had long believed that there were, in principle, just two types of catalysts available: metals and enzymes. Their research showed that small organic molecules could also be used to create catalyzing reactions. We were also very pleased because UC Berkeley and the College were part of Prof. MacMillan’s research journey to the Nobel Prize. In fact, his first appointment as an assistant professor in chemistry was at Berkeley in 1998 where he did his initial Nobel Prize winning research.

Prof. MacMillian was working with two co-researchers Kateri Ahrendt (Ph.D. ’03, Chem) and Christopher Borths (M.S. ’00, Chem) during the time he taught at Berkeley. Kateri was working on her Ph.D. in Chemistry in the lab of Jonathan. A. Ellman. Currently she is Associate Professor of Chemistry at Regis College, Weston, Massachusetts. Christopher received his M.S. in Chemistry at Berkeley and then went on to CalTech for his Ph.D. He has more than 17 years’ experience in the pharmaceutical industry as a synthetic organic chemist with Amgen.

“Dave started as an assistant professor the year after me at the College. It was amazing to see firsthand the fire and creativity he brought to his research. From day one, he thought beyond accepted dogma with a passion for impactful science that was inspirational to his students and colleagues,” stated Jeffrey Long, UC Berkeley Professor of Chemistry and Chemical Engineering.

Born in Bellshill, Scotland and armed with a B.Sc. in Chemistry from the University of Glasgow, he came to the United States to earn his Ph.D. at UC Irvine in 1996. He went on to postdoctoral research at UC Irvine and Harvard through 1998. In 1998 he joined UC Berkeley as an assistant professor in the College of Chemistry. He moved to Caltech in 2000 and ultimately settled in as a professor of chemistry at Princeton University in 2006.

Prof. MacMillan had been pursuing early research into organocatalysis during his postdoc at Harvard when he came to Berkeley. At Berkeley, he developed a more durable catalyst from organic molecules that, like metals, could temporarily accommodate or provide electrons. He tested the organic molecule’s ability to drive a Diels-Alder reaction, which can build rings of carbon atoms.

His reaction worked perfectly. He states, “I remember jumping up and down and telling myself, I think I’m going to get tenure.”

The most important thing about their discovery was that now scientists could make medicines faster with less dire consequences. Chemists and pharmaceutical researchers often only want one version of a molecule, and typically in a catalytic reaction they will produce two (a left and right mirror version of the same molecule). Having both can lead to disastrous results. A tragic example was in the 1950s and 1960s, when a mirror image of the molecule thalidomide caused severe birth defects in thousands of babies in a treatment for morning sickness in women.

But asymmetric catalysis has the ability to produce just one asymmetric molecule, the left or the right, a boon for safety and for reducing chemical waste moving toward more green chemical processing in pharmaceuticals.