At Caltech
[Curator’s note: The following material quotes and paraphrases extensively from articles posted by the Nobel Prize Committee and The Princeton Alumni Weekly.]
The Nobel Prize in Chemistry: 2018
The Nobel Prize in Chemistry 2018 was divided, one half awarded to Frances H. Arnold "for the directed evolution of enzymes", the other half jointly to George P. Smith and Sir Gregory P. Winter "for the phage display of peptides and antibodies."
Evolution – the adaption of species to different environments – created an enormous diversity of life. Frances Arnold used the same principles – genetic change and selection – to develop proteins that solved humankind’s chemical problems. In 1993, Arnold conducted the first directed evolution of enzymes, which are proteins that catalyze chemical reactions. The uses of her results included more environmentally friendly manufacturing of chemical substances, such as pharmaceuticals, and the production of renewable fuels.
Academic career and Princeton University
Frances Arnold was born and raised in Pittsburgh, Pennsylvania on July 25, 1956. She studied mechanical and aerospace engineering at Princeton University. She then continued her studies at the University of California, Berkeley, where she earned a doctorate in chemical engineering in 1985. She has subsequently worked at the California Institute of Technology. She became interested in energy technology early and formed a company in 2005 to produce renewable fuels.
Arnold ‘79, who received her bachelor’s degree in mechanical and aerospace engineering, is the first female Princeton alum to win a Nobel. In 1993, Arnold — the fifth woman to win the Nobel in chemistry — conducted the first directed evolution of enzymes; since then she refined methods that are now used routinely in biochemistry. Arnold’s enzymes led to more environmentally friendly manufacturing of chemical substances, including pharmaceuticals, and the production of renewable fuels. As Princeton chemistry professor David MacMillan told PAW in 2014, Arnold “hijacks biological enzymes and makes them do her bidding.”
During her junior year at Princeton, she spent time studying at the Center for Energy and Environmental Studies with a young group of engineers and scientists who were trying to solve the riddle of sustainable energy. Robert Socolow, now professor emeritus but then the center’s director, describes the group in its early days as “bold” and “driven” in its determination to work out complicated problems, qualities he says Arnold has exhibited throughout her career. Arnold remembers the researchers as being “activists who really cared about where our energy was going to come from and at what cost.” She became interested in that, too.
Inspired by her undergraduate work at Princeton, Arnold devoted much of her career to finding alternative sources of energy. She had, for example, developed an enzyme that could thrive in airless environments, enabling Gevo Inc., a company she co-founded, to produce biofuels without air-circulating equipment. Gevo also used fermented plant materials to produce fuels that one day might replace petroleum-based gasoline and jet fuel. Directed evolution also contributed to a new field called “bioremediation,” which used mutated organisms to eat oil spills or toxic waste at Superfund sites (Arnold had not worked in this area herself).
Arnold’s Contributions
Still another promising application was in a field called optogenetics: using light to control nerve cells. Shining light on certain microbial proteins found in the ocean, for example, could open channels in their cell membranes. Arnold’s lab took those ocean-microbe proteins and bred them into versions that could be activated inside the human brain, which could lead to the development of new treatments for Parkinson’s disease, schizophrenia, autism, and other neurological disorders.
Early in her career, Arnold recalled, her methodology was viewed skeptically by “gentleman scientists” who thought that proteins should be designed rationally rather than built scattershot and looked askance at her focus on manipulating the outcomes before she fully understood the processes that drove them. But, she told herself, “I’m not a gentleman and I’m not a scientist” — Arnold defined herself first and foremost as an engineer — “so I didn’t mind.”
Saying she was not a scientist is debatable, as directed evolution draws upon chemistry, molecular biology, chemical engineering, and physics. Says Princeton chemistry professor Michael Hecht, a longtime friend, “She combined the kind of thinking that an evolutionary biologist would do with real engineering thinking and real chemistry thinking. That’s unusual. She does basic science but thinks like an engineer, focused on real-world applications.”
In her conversation with PAW in 2014, she addressed two challenges inherent in directed evolution. One was a question of capacity: Reviewing the results of experiments and using them to devise mutation takes time. The larger challenge is conceptual, she said: “Directed evolution requires great human imagination.”
“We only have the sequence nature gives us to start with,” she explained. “Instead of studying what biology has already made, we have to imagine what biology could make. You can say, ‘Oh, I want a cure for cancer,’ but that doesn’t tell you what evolutionary pathway will take you from here to there. What are the intermediate steps?”
One could call this trying to improve on nature, but Arnold believes the relationship works both ways. “I see a future in which nature gives us a helping hand,” she said in a recent video for the BBC. “Instead of destroying the natural world, why can’t we use it to solve the kinds of problems that we are facing?”
Additional honors
Honored by President Obama
In 2014 President Barack Obama presented the National Medal of Science and National Medal of Technology and Innovation to 20 honorees, including alumni Frances Arnold ’79, Sidney Drell ’47, and Barry Mazur *59, as well as Anne Treisman, the James S. McDonnell Distinguished University Professor of Psychology Emeritus.
Arnold, who received the technology and innovation medal, is a professor of chemical engineering at Caltech. A leader in protein engineering, her work uses “methods of laboratory evolution to generate novel and useful enzymes and organisms for applications in medicine and in alternative energy,” according to her lab website.
Frances Arnold, PhD, numerous awards include: First woman to win the Millennium Technology Prize (2016) and the Charles Stark Draper Prize for Engineering (2011), National Medal of Technology and Innovation and National Inventors Hall of Fame, holds more than 60 U.S. patents. She is the co-founder of three companies in sustainable fuels, chemistry, and agriculture, member of U.S. National Academies of Sciences, Engineering, and Medicine; Foreign member of U.K. Royal Society and Royal Academy of Engineering.
President-elect Joe Biden tapped Eric Lander ’78, president and founding director of the Broad Institute of MIT and Harvard, to lead the White House Office of Science and Technology Policy, and Nobel chemistry laureate Frances Arnold ’79 to head the President’s Council of Advisors on Science and Technology.
SOURCES
• Source: Frances H. Arnold – Facts – 2018. NobelPrize.org. Nobel Prize Outreach AB 2022
• Source: The Nobel Prize in Chemistry 2018. NobelPrize.org. Nobel Prize Outreach AB 2022
• Source: The White House: President's Council of Advisors in Science and Technology
• Source: PAW: Biden taps scientists Lander and Arnold
OTHER RESOURCES
• PAW: Frances Arnold Ted Talk
• PAW: Tiger laureate Frances Arnold
• PAW: Evolution gets an assist
• LA Times: Cal Tech scientist among three to win Nobel Prize
