Nobel Special: Frances H. Arnold – Better than Nature herself

Read Chris Tachibana's exclusive interview with Frances H. Arnold, a Nobel Laureate in Chemistry 2018, and learn more about her bold approaches to optimizing enzymes for society’s benefit. “I’m interested in big questions,” says Frances Arnold. And nothing stops the 2018 Chemistry Nobel Laureate from answering them. Arnold, the California Institute of Technology Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry, received half the 2018 award, with half to Gregory Winter, University of Cambridge and George P. Smith, University of Missouri. The honor was for directed evolution of enzymes, which Arnold alters to have science-fiction abilities. She gets proteins to work at temperatures or in solvents that kill ordinary enzymes. She directs them to bond carbon to silicon for compounds never found in cells. “How do you compose new DNA to solve problems for humans?” Her methods – creatively applying mutation, selection, and recombination to alter a protein’s substrates, products, or activities – combines what she calls “the simple algorithm of evolution” with selective breeding principles. She describes her work as: “How do you compose new DNA to solve problems for humans?”   Toward sustainability The problems Arnold solves center on sustainability. “It will take a lot of creativity to figure out how to make materials, food, chemicals, and fuel to sustain our daily lives without destroying our natural world,” she says. “I’d like to see the most creative scientists working on these problems.” “When I set out to do protein engineering, I wanted to make proteins that people will use.” Arnold’s research is pragmatic and multidisciplinary, simultaneously basic and applied. She was inspired by biotech companies such as Genentech that launched early in her career. “When I set out to do protein engineering,” she says, “I wanted to make proteins that people will use.” Jeffrey Moore, principal scientist at Merck, has worked with Arnold since earning a PhD in her lab in the 1990s. He was part of groundbreaking studies showing that mutations that alter protein activity can occur outside the active site. These changes are hard to predict but revealed by directed evolution, say proponents of the method. “Frances has amazing insights into what industry, academia, and the world need,” Moore says. “She’s able to rapidly drill down to core issues and she’s always ‘scientifically on,’ challenging and pushing ideas.”     Arnold partners with industry on projects that meet her criteria: “They have to advance our methods, be challenging intellectually and show how protein engineering can solve a range of problems.” Her work is vital for the life sci