Months after the death of Spain’s dictator Francisco Franco, a 19-year-old American woman landed in Madrid for a summer internship at Westinghouse, the manufacturer of the first nuclear reactors in Spain. The engineering student moved into a shared apartment on Ibiza street, next to the city’s Retiro park. “I spent a wonderful summer in Madrid in 1976,” recalls Frances Arnold, now 64. “I was young, Spain’s new democracy was young... It was a constant party.”
Born in Pittsburgh, Arnold had by then already worked as a waitress in a pizza restaurant and jazz club, as a receptionist and a taxi driver. In Madrid, she began to devour the works of Argentine writer Jorge Luis Borges, dictionary in hand. She even compliments Borges with helping her win the Nobel Prize in Chemistry in 2018.
Arnold’s work focuses on directed evolution, which means she breeds proteins the way others breed dogs. she provokes mutations in proteins and selects the ones that interest her the most. The resulting molecules, according to the Nobel Prize award statement, “solve mankind’s chemical problems,” such as the production of renewable energy. Arnold, a chemical engineer at the California Institute of Technology (Caltech), has just returned to Spain to participate in the Princess of Girona Foundation Awards ceremony in Barcelona.
Question. The Frances Arnold living in Madrid in 1976... what was she like?
Answer. Curious. She wanted to learn about everything. the Spanish language, Spanish culture, Spanish cuisine, tapas, music, literature. She read all the time. She absorbed a lot of information.
Q. You had previously worked in Pittsburgh as a cab driver.
A. Yes, I was one of very few women taxi drivers. There were these huge yellow cabs and the streets of Pittsburgh are very narrow. I learned my way around and how to maneuver in tight circumstances.
Q. You were only 18 years old, wasn’t that quite tough?
A. I didn’t even think about it, I thought I could do anything, like all 18-year-olds. Only later do we learn our limitations.
Q. Being a taxi driver isn’t typically on the résumé of Nobel laureates. Do you know if there are any other former cab drivers who have won this prize?
A. I doubt I’m the only one, because most of us had to work our way through college. It was not uncommon for young people to work. In a pizza parlor you got paid 75 cents an hour, but as a cab driver I made two or three dollars an hour. It was much easier to make money. I also worked as a cab driver for two years while at Princeton.
“I thought I could do anything, like all 18-year-olds. Only later do we learn our limitations”
Q. You also worked as a house cleaner for the philosopher of science Thomas Kuhn.
A. Yes, Thomas Kuhn had a piece of embroidery hanging on the wall that said, “Bless this paradigm.” He was never home, because I went to clean during the day.
Q. You couldn’t learn philosophy from Thomas Kuhn, then.
A. No, I only learned that he smoked too many pipes. [Laughs]
Q. You said in your Nobel speech that Jorge Luis Borges had a great influence on your work. In what way?
A. One of Borges’ stories, The Library of Babel, is the best description I know of a universe of possibilities. If you pick letters of the alphabet at random and put them together in a book, what you usually get is gibberish. The same is true of DNA – our book of life. This frustrated the librarians in The Library of Babel, because they could never find a specific book. If you have a library with every book possible in it, you can’t find anything that makes sense. On the other hand, if you think of all the possible books of life, you can find the meaningful ones just by scraping the bottom of your shoe. The library of the books of life is as big as Jorge Luis Borges’ but books with meaning are everywhere, thanks to evolution. Evolution has already gone through all the possibilities and found the ones that encode life, so we can find these beautiful books everywhere. Jorge Luis Borges described the dimension of possibilities and [Charles] Darwin figured out how to navigate that library.
Q. The story of The Library of Babel is required reading in your molecular engineering classes at the California Institute of Technology.
A. Yes, the students love it. If you read The Library of Babel you understand what the word big means.
Q. When you were young, you were not interested in chemistry at all yet you ended up winning the Nobel Prize in Chemistry. Do you have a message for young people who are not drawn to chemistry?
A. Life is long, and you can have many different lives. You can learn many different things, and you never know when they will be useful, so learn as much as you can and combine your knowledge in new ways. Adapt, be flexible and never stop learning.
Q. What are the uses of directed evolution that we can see in everyday life?
A. Almost everyone uses the products of directed evolution. For example, when you wash your clothes, there are enzymes in the detergent, and they are all made by directed evolution, and optimized to work in a washing machine. And there are many, many other examples. Many drugs are produced by enzymes made by directed evolution. And these enzymes are also used to diagnose and treat diseases.
Q. You never patented the technology for directed evolution. Why?
A. I wanted the world to use it. I also didn’t think I had the right to own evolution. You can patent very specific methods, but you can’t patent a general idea, and I felt that the general idea was so obvious and important that the world should take advantage of it.
Q. Do you regret it? You could be swimming in money now.
A. I have no regrets. I’m not interested in swimming in money. I’m much more interested in the world making use of this very powerful process.
Q. You said in your Nobel speech that the code of life is like a symphony. Do you think there is a Beethoven, a God, who wrote that code?
A. I think evolution wrote the code.
Q. How do you imagine the future with directed evolution?
A. My dream is to stop using dirty human chemistry for our daily needs. What we wear, where we sit, what we burn in our cars.... All are products of human chemistry. If we could transition to clean, efficient, circular, sustainable, biological chemistry.... Encode in bacteria the ability to do whatever you want. I dream of moving away from polluting methods and adopting really clean alternatives.
Q. Do you think chemistry is dirty today?
Q. The chemical industry tries to project a clean image.
A. It is much cleaner than it used to be, but a good part of that is still inefficient and its byproducts continue to pollute the planet. It is much better than before, because manufacturers have to pay for polluting, and when they have to pay the price of pollution, they clean themselves up. But there is still a lot of room for improvement.
Q. What are you working on now?
A. Evolution, for about four billion years, has done everything in the biological world, but this is now in the past. Chemists can now explore completely new things using evolution. I’m not talking about optimization, which is what we did in the past. taking something that already exists and improving it, like with laundry detergent. I’m talking about making something completely new, a new chemistry, with chemical bonds that nature has never made. Carbon and silicon bonds, for example. Here [gesturing to the rooftop of a Barcelona hotel] there must be around 50 products with carbon and silicon bonds, all made with dirty human chemistry. If we could encode that into DNA, we could achieve the same thing with clean chemistry, but no one has found an enzyme in nature that makes that bond of carbon and silicon. So I made it thanks to evolution.
Q. Last year you had to retract a study published in the journal Science because your results were not reproducible [the work contained errors meaning the results could not be recreated]. You tweeted: “It is painful to admit, but important to do so. I apologize to all. I was a bit busy when this was submitted, and did not do my job well.” What happened in that study – did the first author make up the data?
A. I don’t want to talk about that. I made it very clear that I take the blame. It’s my responsibility.
Q. Your apology was celebrated. Why did people have that reaction?
A. The first reaction was: ”Take the Nobel Prize away from her.” That lasted about six hours, because after that everybody said, “Wait a minute, it’s great to admit a mistake and correct it.” I didn’t want students wasting their time trying to reproduce what I had published. It wasn’t fair. It was much easier to admit it publicly so no one would waste their time. People forgive you if you are honest, because they know that people make mistakes.