Beyond the Nobel

LINDA HOSLER: It has taken millions and millions of years for evolution to shape the world around us. What if you could speed up that process to create new kinds of biology and chemistry?

This is Linda Hosler from the United States Patent and Trademark Office. Recently I interviewed Frances Arnold, who, in 2018, became the first American woman to win the Nobel Prize in chemistry.

She won it for her work in harnessing the power of evolution to create new proteins that have useful properties not found in nature. And she does it in days instead of millions of years. It’s similar to breeding domesticated animals or plants for a specific trait, except with microbes and done on an even shorter timeline.

Here is some of our phone conversation.

LINDA HOSLER: Congratulations on winning the Nobel Prize. We've worked together in the past because you've also won the National Medal of Technology and Innovation, and you've been inducted into the National Inventors Hall of Fame, which are two programs that I've worked on. So I was so thrilled to hear the news about your recognition. Could you describe for me what you won the Nobel Prize for?

FRANCES ARNOLD: The Nobel Prize came to me as a surprise, a wonderful surprise. As it is the Nobel Prize in chemistry, I won it for figuring out how to direct the evolution of enzymes, which are catalysts that do all the wonderful chemistry of the biological world. I'd figured out how to engineer new versions of these catalysts, bypassing our ignorance of how their sequence encodes their function, and how their sequence—the protein sequence—encodes new chemistry by using evolution to solve the problem for me.

LINDA HOSLER: And what motivated you to work on that?

FRANCES ARNOLD: Well, I was motivated many years ago, by the desire to do chemistry in a clean, green, and in an efficient way. I see that chemistry is so important to our daily lives. All the textiles, food, materials, housing, basically everything we use in our daily lives comes mostly from chemistry. We have to find a good way to do it better than what we've been doing, because we will soon have 10 billion people on the planet, and I happen to like the planet that we're on and all the natural world that we enjoy. So my feeling is that we have to be more efficient, less wasteful, remove toxic components, and biology, enzymes in particular, do that very well.

LINDA HOSLER: Could you tell me about a specific moment during your career where you felt that you failed or that you wanted to quit working on a problem?

FRANCES ARNOLD: Well, I've quit working on many problems over the years, but I haven't quit the basic goal, which is to understand how we can program the code of life—that wonderful, marvelous DNA code that tells us who we are and what our proteins do.

FRANCES ARNOLD: I've never let go of that goal of understanding how we can rewrite that, how we can compose new versions of that, to solve problems. Specific chemistries have eluded me, but there were many more that were successful. So if I fail at one thing, I'll either try again, or I'll move onto the next problem.

LINDA HOSLER: A lot of people talk about the role of mentors to help them get started or throughout their careers. Have you had any mentors that were pivotal in your career?

FRANCES ARNOLD: My first mentor was my father who told me I could do anything I put my mind to and to strive for excellence. My Ph.D. adviser, Harvey Blanch, took a risk on this mechanical engineer who wanted to learn a little bit of chemistry and become a chemical engineer. And he was supportive and also challenged me to do my own thing. I had a great postdoctoral adviser, Ignacio Tinoco at Berkeley, who taught me the scientific method in a way I had not seen before, and many colleagues and friends at the California Institute of Technology where I've been for the last 32 years.

FRANCES ARNOLD: I've had a number of mentors who've supported my ideas and who also criticized me. Mentors can be tough. Mentors can be supportive and nice. They come in all shapes and flavors, and the trick is to use what is beneficial, and disregard the parts that are not beneficial. So of course since I'm a woman in engineering, I had very few female mentors. Almost all my mentors were men, and I found it very challenging and helpful to work for them.

LINDA HOSLER: Do you have a moment in your childhood that you remember—was there a book or an activity or something that sort of encouraged you along the way?

FRANCES ARNOLD: Oh, there was so many. When I was 11 years old, I wanted to be a heart surgeon because I was inspired by the story of Dr. Christiaan Barnard, who carried out the first human heart transplant. And then I realized that the sight of blood made me sick, so I changed my career path and wanted to become something else, maybe a diplomat. Then I changed that idea because I realized I had no diplomatic skills, and I went through many different manifestations of careers.

My path has taken very different stages and steps. I started off as a mechanical engineer, became a chemical engineer, learned more chemistry. Now it's hard to define what I do. Maybe it's biochemistry or molecular biology, chemistry, chemical engineering. But, each of those stages there were inspirations that came from books, from people, from listening to what others were doing.

LINDA HOSLER: That's fantastic. Of course everyone, and you yourself speak of yourself as a scientist, and everyone knows you're a scientist, but you also hold 60 U.S. patents as well, and of course, as the USPTO, I have to ask, what has the role of patents and intellectual property played in your career?

FRANCES ARNOLD: I think the role of patents is... part is—is important on the process of getting technology into the hands of people. I like to say that your inventions, your creativity, your science, is not useful until someone uses it. How do you get people to use it? Well, it takes a lot of investment, of time, money and other resources on many people's parts to get product out into human hands. Therefore, I've been interested in this process of technology transfer since the beginning of my career, and I'm very proud when either a company takes my inventions and builds them into products, or when we start our own companies to do that. Patents play an important role because that investment that it takes won't come unless the reward can be visualized down the road.

LINDA HOSLER: Given your own experiences, what advice would you give to other innovators?

FRANCES ARNOLD: Linda, I don't like to give advice, because everyone's path is so different. My main advice is to enjoy the process, and I hope that creative people won't shy away from innovation. And also, it comes with experience; the more you do it, the better you get.

LINDA HOSLER: Looking back at the impact of your invention and your career, what are you most proud of?

FRANCES ARNOLD: Over my career, I'm most proud of having worked with over 200 of some of the smartest young people in the world, who have since gone on to have their own careers and collectively make [a] very big impact in the world of biological chemistry and the enzyme engineering. The community is one that I've watched grow and thrive over the years. And I'd love to see the people that I worked with do well.

LINDA HOSLER: And then of course I have to end this interview by asking about the Nobel ceremony. Can you tell me what it was like to be there?

FRANCES ARNOLD: The Nobel ceremony, the whole week, was an intense experience unlike any other I've had. It's beautifully organized. It's full of pomp and circumstance, but also science. It's a celebration of science, like we in this country celebrate entertainment.

And now I feel like Cinderella of course. I spend a week hobnobbing with royal families and being beautifully dressed and wined and dined. And then I came home to a very large pile of laundry, no more car and driver. My car turned into a pumpkin, and I'm back at my office. But it's a wonderful memory.

LINDA HOSLER: My next question was going to be, what's it like being back home afterwards?

FRANCES ARNOLD: [laughter] A lot of laundry!

LINDA HOSLER: [laughter] How does winning the Nobel Prize change things for you?

FRANCES ARNOLD: Well, winning the Nobel Prize changes a lot because my email box is exploding, and I am having a challenging time trying to organize my day. I probably do two interviews every day, and then I'm asked to do many other things for the organizations that I care about, and many that I don't care about. So I'm going to have to figure out how to organize my time.

Mainly I want to continue doing science. That's what I'm good at. All these other things are ancillary. They're important, I think, but I'd love to continue doing science somehow.

LINDA HOSLER: Many thanks to Frances Arnold for discussing her work, and for giving us a peek into what it’s like to win a Nobel Prize. From the USPTO, thanks for listening.