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In Conversation with Nobel Laureate Frances Arnold

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November 26, 2018 19:31 EDT

In this edition of The Interview, Fair Observer talks to Frances Arnold, the 2018 Nobel Prize laureate in chemistry.

The Nobel Prize is arguably the most prestigious award a scientist can win. Established in memory of the late Swedish chemist, engineer and philanthropist Alfred Nobel in 1895, the prizes were first awarded in 1901 in five categories: chemistry, physics, medicine, peace and literature. In 1968, Sweden’s central bank established the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, which came to be known informally as the Nobel Prize in Economics.

Nobel Prize laureates are selected through a rigorous process that starts in September each year, when the Nobel Committee sends out confidential nomination forms to persons who are qualified to nominate individuals or organizations for a prize. These nominators include tenured professors, holders of corresponding chairs in at least six universities or university colleges, and the previous Nobel laureates. Every year, there is speculation and conjecture about the possible winners of the prize, but they rarely turn out to be accurate and the Swedish Academy usually surprises the world with its selections.

In 2018, the Nobel Prize for chemistry went to one British and two American scientists. Professor Frances Arnold is an American chemical engineer who won half of the Nobel Prize in Chemistry this year. Arnold was awarded the prize for her pioneering work on the “directed evolution of enzymes.”

In this edition of The Interview, Fair Observer talks to Arnold about her scholarly work, her path to success and her life after being awarded the 2018 Nobel Prize in Chemistry.

The transcript has been edited for clarity.

Kourosh Ziabari: Let’s start with a general question. It hasn’t been long since you were awarded the Nobel Prize in Chemistry, but I’m confident you have been showered with congratulatory messages, interview and speaking requests, and kind notes from across the world. How do you think the Nobel Prize has changed your career and will impact your life and work in the future?

Frances Arnold: On October 3, I woke up to a hurricane whose intensity has only grown over the weeks. I am hoping things will settle into a lower level of chaos after I go to Stockholm with more than 50 friends, colleagues and family in December.

I am still contemplating how I can and should manage the inevitable change in career. I have officially moved into senior scientist, sage category, before I was quite ready to do so. I suddenly have to be careful about dishing out criticism, jokes, etc. Before October 3, few people cared what I thought, and now I am asked to opine on all manner of things I am not necessarily knowledgeable about or even interested in. I have to manage the changes, because I do not want to lose what I value most: working with students, taking time to think, having relaxed time with family and friends.

Ziabari: When did you develop an interest in chemistry and biology, and sciences in general? Your father was a nuclear physicist. Were you motivated by his work and decided to pursue the path of sciences?

Arnold: My interest in chemistry and biology did not come until I went to graduate school, at UC Berkeley, when I was 25. I had to grow up a bit before I appreciated chemistry. But I admired my father and was always interested in and encouraged by him to pursue math, science and engineering. I also enjoyed competing with my four brothers.

Ziabari: You have had experiences with an array of majors and fields of study. You did your bachelor’s in mechanical and aerospace engineering, and at points even fancied becoming a diplomat or CEO or even making a turnaround from sciences to study international relations. Do you still maintain your interest in political affairs and diplomacy?

Arnold: I am interested in how the world works, and how humans manage their affairs. But I realized quite early on that I had no diplomatic skills and that I might contribute more as an engineer and inventor. I loved to travel and spent years living in Italy, Spain and South America in the 1970s. When I realized that academic scientists can combine research, travel, entrepreneurship, working with young people and that I would not have to choose one over the other, I chose an academic career. I was 29 and wanted it all. 

Ziabari: What do you do at your company, Provivi, which you have started recently? It’s quite uncommon for scientists deeply involved in scholarly and laboratory work to establish such enterprises. What was the motivation behind the founding of Provivi? How does it benefit from your research work at Caltech?

Arnold: I am very proud of Provivi, which is a wonderful example of how basic research and encouraging brilliant young people can translate into solutions to real-world problems. Provivi is developing non-toxic modes of agricultural pest control in order to replace pesticides in major food crops, including rice and corn.

The Provivi team has discovered and developed new, low-cost routes to making insect sex pheromones. When you spray a small amount of authentic insect “perfume” into the field, it confuses the males. They fly around looking for a mate, but cannot follow her perfume trace, because it is everywhere. No mating means no caterpillars, and that means less crop damage and less reliance on pesticides.

My former PhD students, Pedro Coelho from Brazil and Peter Meinhold from Germany, did all the work to start and grow the company, which is now carrying out demonstrations all around the world. I provided the encouragement and a few introductions.

Ziabari: You were awarded the Nobel Prize for the pioneering use of directed evolution to engineer enzymes. Do you know of other scientists in the world who have come up with innovations in this field or do you take the full credit for this breakthrough? Can you tell us more about your work on enzymes?

Arnold: Science, like all human endeavors, is evolutionary. We build by adding to and recombining what is already there. Important things were happening in the late 1980s and early 1990s: phage display of peptides, the other half of this year’s chemistry Nobel, was being developed, and Gerry Joyce was directing the evolution of RNA using error-prone PCR.  After my paper on enzyme evolution was published in 1993, I met and started collaborating with Willem “Pim” Stemmer; I became part of his 1997 start-up, Maxygen. He and I were jointly awarded the Charles Stark Draper Prize of the National Academy of Engineering in 2011. Sadly, he passed away in 2013.

Enzymes were fascinating to me — they are the best chemists on the planet and responsible for essentially all the remarkable chemical transformations that make life possible. I wanted to make new enzymes, to help us use clean, green biological systems produce the fuels, chemicals, materials we need in our daily lives. But no one knew how to engineer new enzymes reliably. Inspired by the work of others on peptides and RNA, I developed the strategies that would be useful for evolving the much bigger and more complex proteins that are enzymes.

Ziabari: Is it accurate to say that your innovative work in the use of directed evolution to create enzymes accelerates the process of evolution by natural selection? I understand that your method can help with the designing of enzymes that can be used to produce renewable fuels or pharmaceutical compounds that are more environment-friendly. Can you please expand on this?

Arnold: I am not sure it accelerates evolution by natural selection, but our work, and others, certainly accelerates evolution by artificial selection. We don’t breed whole new organisms, as humans have done for 10,000 years with corn or dogs. Instead, we make new molecules, and those molecules can be useful on their own or they can confer new traits to living organisms.

In my career, I have focused primarily on making catalysts that improve how we make desirable products like pharmaceuticals, fuels, chemicals and materials. I am happy when a chemical process that produces a lot of toxic waste or relies on a precious metal whose mining causes significant environmental damage is replaced by a clean, “green” enzymatic or microbial process. This reduces our huge environmental footprint. Many researchers now use directed evolution to make such enzyme catalysts, which are becoming much more widely used throughout industry. Codexis in Redwood City, a spin-out of the original Maxygen does this well, for example.

Ziabari: Why is it important to be able to engineer biological systems? Beyond the conventional realms of agriculture, food production and manufacturing medicine, are there other areas where engineered biological systems are used?

Arnold: Fuels: Many companies make ethanol, isobutanol and jet fuel such as Gevo, another company I co-founded. However, it is hard to compete with the current low cost of oil. Unless we change our priorities and start worrying a lot more about climate change, fuels from renewable resources is a difficult business. Consumer products: Laundry aids, powered by enzymes, use many engineered enzymes, as do a number of other consumer products. DNA sequencing: Engineered enzymes form the basis of the top sequencing technologies. Diagnostic devices: Many diagnostic assays and devices incorporate engineered enzymes. Materials: Engineered biological systems make a wide variety of materials, from strong threads to fungal mats. Chemicals: Engineered biological systems are used to make flavors, fragrances, and other high value chemicals. They are used to make bulk chemicals as well, for example butene diol (BDO) for plastics.

This is just a small fraction of a very long list.

Ziabari: The first biological engineering program is said to have been created in 1966 at the University of California, San Diego. Is this discipline sufficiently known to the general public and young people? Please tell us about some of the most important applications of biological engineering and how it employs knowledge and expertise from a variety of sciences to contribute to the design of medical devices, diagnostic equipment and renewable bioenergy.

Arnold: Bioengineering attracts a lot of young people who are interested in biology and the intersections with medicine and engineering. It attracts people who want to assist humans through biomedical engineering, and it attracts people, like me, who are inspired by biology and want to use biological principles and even the biological systems themselves for engineering applications.

Bioengineering is a very broad discipline that covers all the things you mention and more. It is a new discipline and just getting started, with whole new areas of inquiry popping up every year: neuroengineering, biocatalysis, genomics and personalized medicine, machine learning and all the interfaces with the more traditional science and engineering disciplines. It’s an exciting place to be, to create the future.

Ziabari: You told The Guardian that you were given some hints. But had you ever envisioned winning a Nobel Prize? Did the prize come as a surprise?

Arnold: Lots of people get “hints,” many hope for it and some even think they deserve the Prize. But, in reality, few get it. To expect a Nobel Prize is silly. I was sound asleep in a Dallas hotel room when the phone rang.

Ziabari: Many of the Nobel Prize laureates whom I’ve interviewed told me that they never worked to win a prize and even the Nobel Prize. Where do you get your inspiration and motivation from? Do you keep up trying and working hard even if you are not recognized?

Arnold: I know no one who works as hard as we do just for the chance to win prizes. We work, often at low pay, because we love what we do. We love every day, especially if one is as lucky as I am to work in a top-notch institution such as Caltech. I look forward to going to work, I look forward to being with the young scientists. I look forward to and enjoy talking about my science with other like-minded and curious people.

Recognition might come more slowly than one would like, but the slow pace is part of the culture. Recognition has to be earned, and often that can take long years of hard work. Scientists need discipline and a strong stomach for criticism, since there is plenty to go around.

Ziabari: And what advice would you have for young researchers who want to achieve high honors in their work and become distinguished and venerable scientists?

Arnold: Achieving high honors and becoming distinguished and venerable should not be the goal. Doing creative work every day, and encouraging others to do their best work, is a much more achievable goal. It’s a goal that makes life pleasurable and might someday lead to these others things. Remember, it’s not all about you.

The views expressed in this article are the author’s own and do not necessarily reflect Fair Observer’s editorial policy.

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