Frances H. Arnold poses outdoors.
Credit: Lauren Justice
In brief
Frances H. Arnold has spent her career creating enzymes that can accomplish chemistry that nature never intended. C&EN spoke with the busy Nobel laureate and Priestley Medalist about her days as a rebellious teenager, her life as a leader in biochemical engineering, and her time serving her country.
In celebrity-filled Los Angeles, Frances H. Arnold can walk down the street in relative anonymity. That’s not to say she’s not famous. Fans of the popular TV show The Big Bang Theory might recognize her from one episode (in which she played herself), and art lovers might have seen her photo in the collection of the Smithsonian Institution’s National Portrait Gallery. But in Tinseltown, she can go about her daily routine in relative peace.
That changes when Arnold—the Linus Pauling Professor of Chemical Engineering, Bioengineering, and Biochemistry at the California Institute of Technology—is among scientists and engineers. When she attends meetings and conferences, strangers will stop her to talk. Students commonly ask her to pose with them for selfies.
Arnold is “chemistry famous.” Her many accolades include a Nobel Prize in Chemistry and the Charles Stark Draper Prize, the engineering profession’s highest honor. She is a member of all three National Academies—Engineering, Medicine, and Science—and the National Inventors Hall of Fame. This year, Arnold will add the Priestley Medal, the American Chemical Society’s highest honor, to her collection of prizes.
Arnold takes this specialized fame in stride, and she makes it known that her success also belongs to those who work with her. “These medals go to one person, which doesn’t make any sense at all,” she says. “We tend to put somebody on a pedestal for the work of so many. So I just want to point out that the future belongs to them. The science belongs to them, and it’s been a huge privilege to be able to take the ride with them.”
The directed evolution revolution
Arnold earned her chemical renown for her groundbreaking development of the directed evolution of enzymes, a method that uses evolution to create enzymes that accomplish tasks no one has found them to do in nature. Enzymes are nature’s chemical reactors. They transform one molecule into another, making and breaking bonds through a delicate dance of amino acids. Unlike plenty of benchtop chemistry, enzymes don’t require harsh conditions or caustic reagents. They accomplish complex chemistry even in water. Arnold has long admired their versatility and chemical acumen.
Before Arnold’s groundbreaking work, some scientists thought you couldn’t make enzymes that can perform useful tasks unheard of in natural systems. An enzyme might comprise hundreds, thousands, or even tens of thousands of amino acids, folded into a complex structure. Figuring out how to change them so the enzyme did your bidding was just too daunting.
A crowd wearing formal attire looks on as a woman in a blue dress shakes hands with a man in a tuxedo.
Credit: Associated Press
Frances H. Arnold (left) receives her Nobel Prize from King Carl XVI Gustaf of Sweden in 2018.
But Arnold decided to use nature’s own process for improving enzymes: evolution. She and her lab directed this evolution by iteratively making random changes—mutations, in biochemical terms—to an enzyme and then screening for ones that improved the enzyme in the way they wanted.
“I proposed that we could take this evolutionary walk and not just find neutral mutations like evolution does but find adaptive mutations,” Arnold says. The researchers began with an enzyme called subtilisin, which breaks down the milk protein casein. Using directed evolution, Arnold and her team created a version of subtilisin that works in the organic solvent dimethylformamide, demonstrating that they could create an evolved enzyme that did something no natural enzyme had been shown to do. It contains 10 mutations that would have been impossible to logically think up in advance.
To screen for subtle improvements in an enzyme’s ability to do a certain job, “you have to have good analytical chemistry, and you have to measure small changes,” Arnold says. She knew she had hit upon something good, she says, because no one could explain or predict her evolved enzymes, but she could find them. “That’s where I got the confidence to really forget the naysayers.”
And there were plenty of naysayers. “A lot of people told me that proteins couldn’t do nonnatural things because nature doesn’t do it,” she says. Also, “a lot of people felt it wasn’t science—that anyone could do random mutagenesis—and if you couldn’t get it from your big brain, it wasn’t worth doing,” she says. But, Arnold says, “I knew I had something powerful from the beginning.”
We tend to put somebody on a pedestal for the work of so many.
Frances Arnold, 2025 Priestley Medalist
In the intervening decades, directed evolution’s skeptics have been proved wrong time and time again. Arnold’s lab has produced a dazzling array of enzymes that can catalyze chemistry that has yet to be observed in nature. Her enzymes have been used to make drugs, build biofuels from sugar, and make and break carbon-silicon bonds.
Evolved enzymes even clean your clothes. “I think it’s pretty safe to say that all the enzymes in laundry detergent applications are optimized by directed evolution, because what self-respecting natural enzyme wants to work in your laundry machine?” Arnold quips.
David A. Tirrell, Arnold’s colleague at Caltech and the school’s provost, says, “When somebody wants to make an enzyme that does something that no enzyme does, evolution is almost certainly the strategy that they use. It is the way people do protein engineering these days.”
Tirrell says he judges the importance of a body of scientific work with two questions: “Does it change the way we think about things?” and “Does it change the way we do things?” To Tirrell, answering yes to either of those questions means the work is important. “One of the striking things about Frances’s work is that you can answer yes to both questions,” he says. “She’s changed how we think about things and the way we do things.”
As for the naysayers, Arnold says, “Luckily, I’m pretty good at letting criticism go in this ear and exit the other one, as I’ve done my whole life.”
From rebellious teen to enzyme engineer
Arnold grew up in the suburbs of Pittsburgh during the 1960s and ’70s. She was the second of five children and the only girl among her siblings. Her father was a nuclear physicist and captain in the US Army Reserve, and Arnold recalls that she and her brothers frequently played war as children. “I’m a seasoned warrior,” she jokes. In a photo of her taken when she was 5 years old, Arnold looks defiantly at the camera, a toy rifle slung over one shoulder.
A young girl wearing a hat and holding a toy rifle.
Credit: Courtesy of Frances H. Arnold
Frances H. Arnold in 1961. Arnold says she often captions this photo, "Please forgive my early attempts at forming an armed militia."
Her teenage years were restless and rebellious. Arnold remembers being bored, skipping school, and hitchhiking to Washington, DC, to protest the Vietnam War. “I had other things that I thought were worth doing. And sitting in class was not high on my list of things worth doing.”
Her parents, she says, thought she was setting a bad example for her brothers. Their disapproval escalated, and Arnold moved out of the family house at age 15 to live on her own.
“It was exhilarating in some ways, because back then in Pittsburgh, you could actually work at a pizza parlor and pay rent. I didn’t have any extra money, and I lived on leftovers from the pizza parlor, but I had a roof over my head,” she says. “I felt empowered that I could live on my own. But of course, I was lonely. I was scared.” During this time, in addition to working in a pizza parlor, Arnold held jobs as a department store clerk, receptionist, cocktail server, and taxi driver. “I learned a lot of things I didn’t want to do for my career,” she says.
After graduating from high school in 1974, she studied mechanical and aerospace engineering at Princeton University. She took a year off to work and travel in Spain and Italy and earned her undergraduate degree in 1979 magna cum laude. She spent a year working on passive solar heating and cooling technologies at a new national lab—known then as the Solar Energy Research Institute and now as the National Renewable Energy Laboratory—in Colorado.
Research funding for renewable energy took a hit when Ronald Reagan was elected US president in 1980. Arnold felt there was little future for work in passive solar heating and cooling, so she made the move to graduate school at the University of California, Berkeley, in early 1981. She shifted gears in her field of study, choosing to pursue her PhD in chemical engineering. Arnold was initially interested in biofuels, but she arrived at UC Berkeley during an exciting time for biotechnology, as companies like Amgen and Genentech were looking for engineers who could work on their processes for making protein therapies.
Harvey W. Blanch, who was Arnold’s doctoral mentor, recalls that it was unusual for someone with an undergraduate degree in mechanical engineering to jump into chemical engineering. He says UC Berkeley’s chemical engineering faculty insisted that Arnold complete the core undergraduate chemical engineering coursework, essentially cramming 3 years of classes into a single year. “She didn’t do well in one of the courses,” he says deadpan. “She only got an A. In all the others, she got A plus.”
Arnold recalls being intrigued by her classes in organic chemistry. “It was like putting together puzzle pieces. You had to see these molecules in 3D. You had to come up with strategies for making them,” she says. “I had a mechanical mind, so I think that made me good at it, and I really enjoyed it. Then I hit biochemistry, and that blew the top of my head off. I just thought that was amazing.” She was particularly fascinated by enzymes. “Humans think they’re pretty smart, but you take a look at enzymes, and it just puts human chemistry in a whole different light,” she says.
Unlike chemists, who might marvel at a fabulous lab-scale synthesis, chemical engineers appreciate seeing a full-scale process in operation, Blanch says. The challenge with enzymes, he says, is to translate them into industrial products. Arnold has done that by cofounding four companies.
Blanch says he’s not surprised at what Arnold has achieved. She was always an excellent problem solver. He recalls that on one occasion, the lab wanted to start cultivating hybridoma cells, which would require a clean room with control over the room’s air pressure and special air-lock doors. Arnold proposed using the men’s room, which was next to Blanch’s lab on the third floor of the building.
The men’s room was tiled and washable, and it wouldn’t cost too much to turn it into a clean room. It was the only restroom on the third floor, though. “We proposed this to the dean, and Frances was pretty persuasive. She almost got the dean to go along with this,” he says, but some of the male chemists who worked on the third floor did not like the idea of walking down a flight of stairs to use the restroom, so it never happened. Blanch notes that at this time, the women’s restroom was on the first floor, so Frances had to walk down two flights of stairs when she wanted to use it.
“In those days, the role of women in both chemistry and chemical engineering was not an easy one,” Blanch says. Reimagining the third-floor restroom was, in Blanch’s opinion, Arnold’s way of making a point.
An antifragile leader
In 1986, Arnold moved to Caltech, where she has spent the entirety of her independent career. Alongside her success, adversity and hardship have been constants, both professionally and personally. Arnold made her way in engineering and science at a time when there were few women. She survived cancer. She raised her three children—James, William, and Joseph—as a single mother during their teenage years. Her middle son, William, died in an accident in 2016, when he was 20 years old.
A blue T-shirt printed with the image of a creature that has a wolf's head and bird's body and the words "Arnold Lab Exploring the Non-natural World."
Credit: Courtesy of Frances H. Arnold
This T-shirt shows Wolfird, the Arnold Lab's official mascot.
“I continuously remind myself that no one is guaranteed an easy life, but we can make it easier for others,” she writes in her Nobel Prize biographical remarks, the best source to read about Arnold’s personal and scientific achievements and struggles.
Shortly after learning she’d won the Nobel Prize in Chemistry in 2018, Arnold told C&EN: “Life is a tornado, and I am a leaf.” But Arnold has shown more fortitude than that statement suggests. More than 6 years later, when asked about her 2018 choice of words, she concedes that “leaf” is probably not a fair characterization. “Maybe I’m a palm tree,” she says. “I think I’ve been gifted with a natural inability to focus on my woes.”
Although many would describe Arnold as resilient, Sabine Brinkmann-Chen, who came to Arnold’s lab as a postdoctoral fellow in 2006 and has been the lab’s manager since 2008, thinks that is the wrong word.
Brinkmann-Chen instead chooses the word antifragile. “Antifragile is more than resilient,” she says. A resilient person can withstand stress and adversity, she says, but an antifragile person thrives when faced with stressors. Brinkmann-Chen marvels at how Arnold has faced hardship repeatedly throughout her life yet has managed to overcome obstacles and excel. “She’s used work as her therapy,” Brinkmann-Chen says.
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Arnold’s students—past and present—as well as her colleagues all say that she has high standards, for herself and those under her aegis. “She’s leading by example,” Brinkmann-Chen says. “She outworks us all.”
Arnold admits that she’s not one to waste time. “I use every bit of time to get something done,” she says. During the working day, “I rarely just sit down and chill.” After 6:00 p.m., she says, it’s a different story.
Arnold’s ability to juggle her many responsibilities while still guiding her research team was evident when C&EN visited Arnold at Caltech in November 2024. During a group meeting, she encouraged her students to work smart instead of just hard. “What makes that interesting? How does it lead to some new information you can use?” she asked her students of a new result. This is the kind of thinking that has put Arnold at the top of her field.
Huimin Zhao, a chemistry professor at the University of Illinois Urbana-Champaign who earned his PhD with Arnold in the 1990s, remembers her as a mentor who gave him a lot of autonomy. “What I appreciate the most, in retrospect, is that Frances gave me—and not just me, all the students—freedom to pursue new ideas,” he says.
He also remembers that she was professional, and a little intimidating, as a mentor. He says he got to see her more personal side only when he drove her from Pasadena, California, to a conference in San Diego in 1995. “Because she was 9 months pregnant, she didn’t want to drive,” he says. “I remember my car was old, and it didn’t have any air-conditioning.” Windows rolled down, Zhao and Arnold chatted amiably during the drive.
Touring Arnold’s lab at Caltech, one gets a sense that while her students work hard, they also have fun. Small rubber duckies can be found in unusual places throughout the laboratories. Googly eyes give one of the lab’s microwaves a goofy look.
“This is where the magic happens,” Brinkmann-Chen says as she shows C&EN the room that houses the lab’s liquid chromatography/mass spectrometry instruments. Brinkmann-Chen says the room is called Wolfird’s Den, a nod to the lab’s official mascot, Wolfird, a wolf-bird hybrid meant to evoke exploration of the nonnatural world.
“My feeling is that the people here are really happy, and that doesn’t come by itself. That takes real work,” Arnold says. “I credit Sabine with a lot of that.”
Tina Boville, CEO of Aralez Bio, a company she cofounded with Arnold and fellow Arnold lab alumnus David Romney in 2019, says her time as a postdoctoral fellow in Arnold’s lab was a great experience. Arnold “takes pains to make sure it is a good community, where you have everything you need and everybody’s kind of helping each other out,” she says.
Boville says she admires Arnold’s focus and drive. “She wants to build new technologies that are useful, are solving real problems, and she wants to work with the best people that she can that share that vision to see it done.”
One thing that might surprise people, Boville says, is that “Frances actually has a pretty wicked sense of humor.” Boville says Arnold enjoys a good-humored prank, like the time Boville created a fake award—a trophy topped with a gold-painted poop emoji—and, with the help of Arnold’s assistant, Cheryl Nakashima, hid it in Arnold’s office on a table that is covered with her many awards. Boville thought it would be months before Arnold found the fake prize, but she discovered it right away and had a good laugh. Arnold “doesn’t take herself too seriously, which I very much appreciate,” Boville says.
Serving her country
The year 2020 brought two big changes to Arnold’s life. The first was in August, when her grandson, James, was born. Many people were facing COVID-19-related lockdowns, but Arnold’s son and daughter-in-law were essential workers, so Arnold took over baby care for about 6 months. Being a grandmother, she says, “is the best thing that ever happened to me.”
A woman speaks at a podium in front of the US presidential seal. People wearing face masks are seated beside her.
Credit: Angela Weiss/AFP via Getty Images
Frances H. Arnold speaks on Jan. 16, 2021, after being nominated to the President's Council of Advisors on Science and Technology by US president-elect Joe Biden.
2020 was also the year that Joe Biden was elected US president. He made the presidential science adviser a cabinet-level position and named Eric Lander, a mathematician and geneticist at the Broad Institute of MIT and Harvard, to that role. In December that year, Lander asked Arnold to cochair the President’s Council of Advisors on Science and Technology (PCAST)—a presidential appointment.
“I just didn’t feel I could say no,” Arnold says. And so began 4 years of public service in which Arnold—as an unpaid volunteer—selected and regularly met with a council of scientific experts who advised Biden on science and technology issues and developed reports on topics that he deemed important. Arnold devoted herself to the work, attending virtual meetings, often early in the morning in her time zone and sometimes several times a day.
Maria T. Zuber, a geophysicist who was then vice president for research at the Massachusetts Institute of Technology, was Arnold’s PCAST cochair for the duration of Biden’s presidency. Zuber says they learned early on that it was important to show Biden how PCAST’s recommendations were going to help Americans. This is an area where Arnold excelled, Zuber says. “Frances has a really great sense of what was really important and how it could help people,” she says. “One of the things that Frances would say all the time is, ‘I want to write reports that could be actionable. I don’t want to write a report that goes into the circular file and is never seen again.’ ”
One influential report Zuber cites made recommendations for modernizing wildland firefighting to protect the country’s firefighters. The report identifies ways that science and technology can make wildland firefighting safer and more effective.
Arnold’s ability to talk to all kinds of people may be one of her most useful assets. “Frances has created a whole new field,” Zuber says. “But she’s very unassuming. If you didn’t know that about her, she wouldn’t let on. I think that that says something really important about her.”
What’s next?
Outside her office at Caltech sits a globe that’s so large, Arnold would struggle to wrap her arms around its equator. It was a gift, she says, and an appropriate one for a seasoned world traveler like herself.
Frances has created a whole new field. But she’s very unassuming. If you didn’t know that about her, she wouldn’t let on. I think that that says something really important about her.
Maria T. Zuber, E. A. Griswold Professor of Geophysics, Massachusetts Institute of Technology
In the past 6 months, Arnold has traveled across the country to finish up her PCAST duties and given talks and attended scientific meetings in Europe, Asia, and Africa. She also traveled with her family to Taiwan for the end-of-year holidays.
Before leaving on her trip to Africa and Asia, Arnold wrote her Priestley Medal address, which gave her an opportunity to reflect on her life, her career, and the impact she’s made. The award also comes at a time of change. With her PCAST responsibilities over, Arnold is keen to concentrate on making enzymes that can change the world. “I still love enzymes. There’s so much discovery that remains to be done,” she says.
But when pressed with the question “What’s next for Frances Arnold?,” her answer is plain: “Hell if I know. Life is next.”
Chemical & Engineering News
ISSN 0009-2347
Copyright © 2025 American Chemical Society
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