Frances Arnold's Directed Evolution

The Proteins Evolve, and So Does She
Photograph by Kyle Johnson for Bloomberg Businessweek

For a person who invented something called directed evolution, Frances Arnold has followed quite a meandering career path. As the highly intelligent daughter of a nuclear physicist, she seemed destined to become a scientist. In her teens she instead became an activist and hitchhiked from her Pittsburgh home to Washington, D.C., to protest the war in Vietnam. In her 20s, she worked on a solar project in South America and learned to get by on about $1 a day and tolerate flea-ridden beds before heading to the University of California-Berkeley for her PhD. “In the ’70s it was the thing to do,” she laughs. “I was looking for what I was and who I was.”

That’s an indulgence she doesn’t allow the proteins in her lab. Arnold, 56, is a professor of chemical engineering, bioengineering, and biochemistry at the California Institute of Technology. In the early 1990s, she pioneered a method to evolve proteins not found in nature. She starts by mutating DNA, the genetic blueprints for building proteins, by mixing it with molecules that cause it to copy itself with mistakes. The DNA with the mutations that seem most promising are inserted into living organisms, which translate the genes into proteins. This process is repeated over and over—sometimes up to 50 times—to get the desired characteristics.

A few years ago Arnold’s work led to a new kind of enzyme (a type of protein that helps speed chemical reactions) that can function in airless environments. It meant millions in savings for the biofuel company Gevo, which she co-founded in 2005, since its factory was able to make do without expensive air-circulation equipment. “She’s super-pragmatic in understanding what we need as a business,” says Patrick Gruber, chief executive officer of Gevo, which went public last year. Her techniques also helped Merck develop the diabetes drug Januvia. The mutated proteins can help factories be more environmentally friendly by reducing their reliance on toxic chemicals.

Arnold is working on proteins that could revolutionize brain imaging. Today researchers rely on MRIs to monitor brain activity. But MRIs only show changes in blood flow, an imperfect proxy for what’s actually happening in the brain. Arnold and her collaborators have developed proteins that bind to neurotransmitters and can be detected by MRIs. When injected into a patient, they reveal a map of the chemistry inside the brain. The technique is being tested on lab rats and could eventually help researchers study and create drugs for Alzheimer’s, Parkinson’s, and depression. “The real frontier is making these hybrid systems where you expand the capabilities of biology with chemistry,” Arnold says.

Arnold still travels frequently. Her office in Pasadena features large framed photos by the French photographer Yann Arthus-Bertrand, who specializes in aerial shots of diverse locales and environmentally sensitive areas around the globe. The photos “remind me why I am doing what I am doing,” she says.

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