Interviewer: Maggie Sui
Professor Frances Arnold is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at Caltech and a 2018 Nobel Laureate in Chemistry. Her research focuses on using directed evolution to create new enzyme function. Prof. Arnold received a B.S. in Mechanical and Aerospace Engineering from Princeton University and received a Ph.D. in Chemical Engineering from the University of Berkeley.
Favorite book: Too many to choose from. I am now enjoying Ai Wei Wei’s memoir
Favorite Place: Planet Earth
Favorite Food: oysters
Favorite Protein molecule: cytochrome P450 BM3
What type of research does your lab focus on?
We breed molecules like you can breed cats and dogs, selecting for the traits that are useful to us in a process that mimics evolution by artificial selection. The ‘directed evolution’ methods we pioneered to engineer better enzymes are now used all over the world for everything from laundry detergents, cosmetics, treating disease to making jet fuel from renewable resources. I envision a world where nature’s clean and efficient chemistry replaces dirty human manufacturing processes. Wouldn’t it be wonderful to make our pharmaceuticals, cosmetics, fuels and chemicals like we make beer? Wouldn’t it be wonderful to have microbes eat our plastic wastes and convert them to valuable new materials? That’s all possible with enzymes. But someone has to make them do what humans want rather than what they do in nature. That’s what we do.
What aspects of research do you most enjoy?
I love discovering new things that enzymes can do. Sharing the joy of discovery with others is almost as much fun. And since my students are always discovering new things, it’s a blast to go to work.
What influenced you to pursue science? Did you have any role models growing up?
My father was a nuclear physicist and also did a lot of engineering design. I wanted to be like him when I grew up, but I didn’t love nuclear physics. I tried a few things before I found protein engineering, at the beginning of the DNA revolution.
What was the origin for your directed evolution idea? When did you first think of it?
When no existing design approaches worked to make better enzymes, I was getting a bit desperate. I decided to try lots of mutations, easily done randomly using error-prone polymerase chain reaction (PCR) and testing by screening in plates. I was thrilled when we found beneficial mutations in surprising places, where no one would have predicted. We accumulated those mutations in sequential rounds, and sometimes recombined them, just like breeding cats or dogs over multiple generations. That worked beautifully, and evolution became the only reliable method for generating better enzymes. It was an instant ‘hit’ with people in industry, but took much longer to gain the respect of scientists, who always want to understand why. To understand why, however, it’s much nicer to start with the correct answer and work backwards. Directed evolution gave the correct answer.
How did you become the Nobel-prize winning scientist you are today?
I don’t really know for sure, but it probably has something to do with Caltech. I came here naïve and with limited training, but a good idea. I was able to implement my ideas here, and formulate even better ones with the help of critical colleagues and brilliant students and postdocs. I never stopped to worry whether it would be possible to make better enzymes or whether I would be able to do it. Nor did my students.
What is your work in Washington like?
Nobel Laureates are always warned not to get involved in things we know nothing about. I threw that advice to the wind when I took on co-chairing the President’s Council of Advisors on Science and Technology (PCAST) in January, 2021. I find it fascinating. And I have already learned that science is easy compared to dealing with…people. People are really complicated. We can have all the right science, but if people don’t trust it or won’t use it for other reasons, it goes nowhere. In this job, I am also seeing many fascinating new science problems and solutions.
I see this work (which is unpaid and takes a lot of time, by the way) as a way to pay back, to make sure that future scientists will have the same wonderful opportunities that I enjoyed.
What are some of the challenges you’ve recently faced? How do you overcome them?
We all face challenges: loss of loved ones, illness, failure. If you have lived as long as I have, you will experience all of those, perhaps multiple times. I find that the best way to face life is to be grateful for what I have, which is so much. I try not to dwell on what I have lost, nor do I feel sorry for myself. I am grateful to still be healthy and able to do something useful.
What are your interests outside of science?
I love music, gardening, hiking, meals and conversation with friends. I used to love travel, but I haven’t been many places lately…
What advice would you give to Caltech students and other young students interested in research?
Do it because you love it. All else will follow.