By Liu Jiajia and Wang Zhaoyu
She stands as the fifth woman ever to receive the Nobel Prize in Chemistry, honored in 2018 for her remarkable contributions to the field of "directed evolution of enzymes." Frances H. Arnold's groundbreaking work in the 1990s on "directed evolution" has brought about revolutionary changes in the realm of biology.
However, behind her professional success lies a life fraught with challenges and hardships. Frances battled breast cancer and underwent 18 months of treatment. Moreover, she endured the pain of losing both her husband and her son in two separate marriages.
This is the dual life of a legendary woman—Frances H. Arnold.
Francis Arnold Interview: Engineering Life at Its Best
In a recent interview with Chinese Science Daily, the vibrant 67-year-old Francis Arnold sat at her computer, freshly returned from the gym, looking as youthful as ever. Currently serving as a professor at the California Institute of Technology and a board member of various tech companies, Arnold's days are a whirlwind of Zoom meetings – six with the White House alone on the day of the interview – interspersed with laboratory experiments, workouts, and evening engagements.
In just 25 short minutes, we caught a glimpse into the life of this legendary figure, who approaches every challenge with an open mind and boundless enthusiasm.
Her life has always been one of exploration.
Becoming an Engineer of the Protein World
"Directed evolution" is a process that mimics natural selection, used to enhance the performance of biological molecules and organisms such as enzymes, proteins, and microbes in laboratory settings. The core idea of "directed evolution" is to generate a large number of variants through random mutations and then select those with desired properties, simulating the "mutation-natural selection" mechanism of natural evolution.
Recently, Francis Arnold's team collaborated with Dow Corning to publish their findings in Science, where they expanded enzyme activity using directed evolution to break carbon-silicon bonds, opening up possibilities for the degradation of methylsiloxanes, a type of synthetic compound.
Chinese Science Daily: Could you please introduce your latest findings?
Francis Arnold:
Over the past decade, I've been determined to prove that nature can learn to do anything a chemist can do, and sometimes even better, including manufacturing and breaking chemical bonds not found in the biological realm.
In this breakthrough, we've created the first enzyme capable of breaking carbon-silicon bonds, something unprecedented in nature. There are around 50 epoxy enzymes in the room you're sitting in right now, products of synthetic chemistry that cannot be degraded by natural organisms. But we've evolved this capability in enzymes, demonstrating its chemical feasibility as enzymes can now degrade silicon.
Francis Arnold Team Recent Achievement Image Source: Science Website
China Science News: Did you use "directed evolution" method for this?
Francis Arnold:
Yes, indeed. "Directed evolution" has shown us many things. Evolution is a very powerful engineering process that applies to all scales from molecules to ecosystems. We can guide evolution to create new enzymes, which are excellent chemists and catalysts.
The real trick of "directed evolution" is finding better things in the vast space of possibilities and accomplishing it within a defined time frame.
China Science News: Where did you get the inspiration for pioneering "directed evolution"?
Francis Arnold:
I have a background in engineering (Note: Arnold majored in Mechanical and Aerospace Engineering at Princeton University in the United States) and have always wanted to create new things.
I fell in love with proteins when I first cut and pasted DNA, and I wanted to become an engineer of the protein world. However, no one knew how to do it, how proteins worked, how the minimal sequence determined their function, or how to design subtle differences. I had to figure it out myself. Good engineers must rely on proven theories, so I turned to evolutionary theory. Evolution is the way to make humans better.
2018 Nobel Prize in Chemistry Winners: Francis H. Arnold, George P. Smith, and Sir Gregory P. Winter. Source: Nobel Prize Official Website
"Can Ordinary People Benefit from Directed Evolution?" - Interview with Francis H. Arnold
Interviewer (from Chinese Science Report): Can ordinary people benefit from "directed evolution"?
Francis H. Arnold:
Take, for example, laundry detergents. All of them contain enzymes, but which naturally occurring enzyme would willingly work in a washing machine? All the enzymes used in laundry detergents are optimized through directed evolution to function in the presence of bleach and surfactants.
There are thousands of examples like this. All reagents and DNA sequencing have been optimized through directed evolution, as have enzymes used in manufacturing drugs, fragrances, textile dyeing, and food production.
Interviewer: What do you consider your main contribution to science?
Francis H. Arnold:
I am the first person to use evolution to create new enzymes—I demonstrated an evolutionary process in the 1990s that is now used in labs and products worldwide.
Since then, I have continued to use directed evolution to create a variety of interesting enzymes and proteins, making things that people thought were impossible, like carbon neurons or carbon-silicon bonds, as well as very useful things.
"Science Isn't Just for Men"
Interviewer: Do you think gender affects scientific work?
Francis H. Arnold:
For women, pursuing a career in science has always been a challenge because we have many other interests. Women are interested in people, children, family, colleagues, teaching, and caring for others, but that's a good thing for me.
There were few female engineers in the 1970s, so I received a lot of attention. I told myself that when I spoke up about something, it had to be substantive—I had to talk about things that would really get attention. If you want to do science, you want your research to be noticed, right? We want people to read our papers, listen to our presentations, and buy into our ideas. So, I used my unique position as a rare woman to make sure that when I had the chance to speak, I could tell people something they wouldn't forget.
Arnold at the University of California, Berkeley's College of Chemistry, circa 1984. Image source: Nobel Prize website
China Science Daily: What advice do you have for female scientists?
Frances Arnold: Don't let science be a boys' club because science is just too fascinating. I've been at it for 40 years and never once felt bored or out of ideas. There's always something new to try, and my work is constantly evolving. My advice is to stick with it and enjoy the journey.
China Science Daily: How has winning the Nobel Prize impacted your work and life?
Frances Arnold: I've received significant awards before, but nothing on the scale of the Nobel Prize. So, the "impact" has elevated me to another level altogether.
Enzymes are nature's best chemists. After winning the prize, more attention was drawn to enzymes, and people began exploring new chemistry with them. Some exceptional young chemists decided to try their hand at "cooking" with enzymes and joined my lab, contributing to our chemical research.
China Science Daily: We heard you were quite mischievous as a child. Could you share some of your growing-up experiences?
Frances Arnold: I grew up in the 1970s, a time that was really interesting globally, including in the United States. It was an era of protests against the Vietnam War. Young people were discontent with their parents and the government. So, I was rebellious from an early age and brought that spirit into the realm of science.
I never hesitated to question authority. Being the only girl among four brothers at home, I wasn't afraid of men. I always found myself leading and organizing those around me. I often argued with my father, but we had a very close relationship, and he was proud of me.
It was also the beginning of the women's movement, where women felt empowered to do things beyond just getting married. I used to tell my father back then that I would never get married, never have children, and instead, I would travel the world. Although I did eventually get married and have children, those aspirations were always a part of me.
In 1961, a photo was taken of a young Arnold (center) playing "war games" with his brothers. Image source: Nobel Prize official website.
Freedom and openness are the essence of life.
Chinese Science Daily: How did your childhood influence your scientific career?
Frances Arnold: It was a very interesting time that shaped my personality significantly.
The most important aspect was the sense of freedom. I could freely read books, play outdoors with friends; I lived in a safe community. So, I felt free and confident to do whatever I wanted. I enjoyed exploring new things in various places, which became a part of my personality.
Chinese Science Daily: Do you think this freedom is the key to success in research?
Frances Arnold: Absolutely! The freedom to question authority, to challenge what people say is correct because sometimes they are not.
Moreover, the key to science is to work hard to learn as much as possible, then pivot to new fields. In a new field, you're not an expert, but you bring experiences from other fields that you can apply to new problems.
For me, with a strong background in mathematics and engineering, I entered the field of proteins. Biochemists would say, "You know nothing about proteins." And I would counter, "Excuse me? Who are you to question me?" It's because I didn't come from biochemistry that I could think about problems in biochemistry in a very different way. Sometimes knowing too much can limit your thinking.
Chinese Science Daily: Can you talk about your daily life now?
Frances Arnold: My daily life is quite fulfilling. Today, I had six different Zoom meetings with the White House, as I work for Biden and sit on corporate boards. I just came back from the gym, now having this interview with you, and later I have a dinner to attend. As you see, it's a long day starting at 6 a.m. and ending late at night. But I love this busy life, doing different things excites me.
I also travel frequently, visiting Washington every two months for meetings and other events. At Caltech, I work in the lab or meet my students.
Chinese Science Daily: How did you overcome challenges in life? Did research give you a lot of strength?
Frances Arnold:
Yes, research has given me tremendous strength. I have amazing colleagues! Caltech, where I work, is very special with only 900 undergraduates, smaller than most high schools, meaning my students are the best in the world. We have 1,000 graduate students, still quite small; it's like a family. I always knew Caltech was my pillar in difficult times. Of course, my family is a rock too. I have three sons who are all my pillars.
In the fall of 2018, Arnold and her sons James Bailey (left) and Joseph Lang (right) are pictured at the California Institute of Technology. Another son, William Lang, passed away in 2016 due to an accident. Image source: Official website of the College of Chemistry, University of California, Berkeley.
China Science Daily: You had the first Chinese Ph.D. student in the field of "directed evolution," Zhao Huimin, and have since interacted with many Chinese scholars and students. What has it been like collaborating with them?
Frances Arnold:
I've thoroughly enjoyed working with Chinese scholars. Over the years, I've had many students from China, and they have been exceptionally talented. Some have returned to China, some have stayed in the U.S., and some have even gone on to mentor their own students and become professors themselves. Chinese students bring creativity, diligence, and a competitive spirit to the table, which makes collaborating with them fantastic.
China Science Daily: How do you view the increasing issue of academic misconduct worldwide?
Frances Arnold:
Everyone makes mistakes, whether they're students or professors. When errors or falsehoods are identified, it's crucial to acknowledge and correct them in the literature. I've experienced this firsthand; in 2019, I had to retract a paper, and I did so promptly. I admitted my mistake and the world responded positively.
Conversely, when you try to cover up your mistakes, that's when trouble arises, and you jeopardize the careers of young researchers. For instance, I'm aware that some students might rely on my papers, and if those papers contain errors, it wastes their time. So, correcting mistakes is vital to ensure others don't squander their valuable time.
China Science Daily: What advice do you have for scientists today?
Frances Arnold:
Science is our common language—it's the same in China, Russia, the U.S., Egypt, and Africa. We all face challenges like climate change, water, and food security. I hope we can use this common language of science to come together and address these issues collaboratively.
