Frances Hamilton Arnold (born July 25, 1956) is an American chemical engineer and Nobel Laureate. She is the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry at the California Institute of Technology (Caltech). In 2018, she was awarded the Nobel Prize in Chemistry for pioneering the use of directed evolution to engineer enzymes.
In 2019, Alphabet Inc. announced that Arnold had joined its board of directors. For the length of his presidency, she also served as an external co-chair of President Joe Biden's Council of Advisors on Science and Technology (PCAST).
Arnold is the daughter of Josephine Inman (née Routheau) and nuclear physicist William Howard Arnold, and the granddaughter of Lieutenant General William Howard Arnold. She has an older brother, Bill, and three younger brothers, Edward, David and Thomas. She grew up in the Pittsburgh suburb of Edgewood, and the Pittsburgh neighborhoods of Shadyside and Squirrel Hill, graduating from the city's Taylor Allderdice High School in 1974. As a high schooler, she hitchhiked to Washington, D.C., to protest the Vietnam War and lived on her own, working as a cocktail waitress at a local jazz club and a cab driver.
The same independence that drove Arnold to move out of her childhood home as a teenager also led to a large volume of absences from school and low grades. In spite of this, she made near perfect scores on standardized tests and was determined to attend Princeton University, the alma mater of her father. She applied as a mechanical engineering major and was accepted. Arnold's motivation behind studying engineering, as stated in her Nobel Prize interview, was that "[mechanical engineering] was the easiest option and the easiest way to get into Princeton University at the time and I never left".
Arnold graduated in 1979 with a Bachelor of Science (BS) degree in mechanical and aerospace engineering from Princeton University, where she focused on solar energy research. In addition to the courses required for her major, she took classes in economics, Russian, and Italian, and envisioned herself as becoming a diplomat or CEO, even considering getting an advanced degree in international affairs. She took a year off from Princeton after her second year to travel to Italy and work in a factory that made nuclear reactor parts, then returned to complete her studies. Back at Princeton, she began studying at its Center for Energy and Environmental Studies – a group of scientists and engineers, at the time led by Robert Socolow, working to develop sustainable energy sources, a topic that would become a focus of her later work.
After graduating from Princeton in 1979, Arnold worked as an engineer in South Korea and Brazil and at Colorado's Solar Energy Research Institute. At the Solar Energy Research Institute (now the National Renewable Energy Laboratory), she worked on designing solar energy facilities for remote locations and helped write United Nations (UN) position papers.
She then enrolled at the University of California, Berkeley, where she earned a PhD degree in chemical engineering in 1985 and became deeply interested in biochemistry. Her thesis work, carried out in the lab of Harvey Warren Blanch, investigated affinity chromatography techniques. Arnold had no chemistry background before pursuing a doctorate in chemical engineering. For the first year of her Ph.D. coursework, the graduate committee at UC Berkeley required that she take undergraduate chemistry courses.
After earning her Ph.D., Arnold completed postdoctoral research in biophysical chemistry at Berkeley. In 1986, she joined the California Institute of Technology as a visiting associate. She was promoted to assistant professor in 1986, associate professor in 1992, and full professor in 1996. She was named the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry in 2000 and the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry in 2017. In 2013, she was appointed director of Caltech's Donna and Benjamin M. Rosen Bioengineering Center.
Arnold served on the Science Board for the Santa Fe Institute from 1995 to 2000. She was a member of the Advisory Board of the Joint BioEnergy Institute. Arnold chairs the Advisory Panel of the Packard Fellowships in Science and Engineering. She served on the President's Advisory Council of the King Abdullah University of Science and Technology (KAUST). She served as a judge for The Queen Elizabeth Prize for Engineering and worked with the National Academy of Science's Science & Entertainment Exchange to help Hollywood screenwriters accurately portray science topics.
In 2000 Arnold was elected a member of the National Academy of Engineering for integration of fundamentals in molecular biology, genetics, and bioengineering to the benefit of life science and industry.
She is co-inventor on over 40 US patents. She co-founded Gevo, Inc., a company to make fuels and chemicals from renewable resources in 2005. In 2013, she and two of her former students, Peter Meinhold and Pedro Coelho, cofounded a company called Provivi to research alternatives to pesticides for crop protection. She has been on the corporate board of the genomics company Illumina Inc. since 2016.
In 2019 she was named to the board of Alphabet Inc., making Arnold the third woman director of the Google parent company.
In January 2021 she was named an external co-chair of President Joe Biden's Council of Advisors on Science and Technology (PCAST). She worked with Biden's transition team to help identify scientists for roles in the administration. She described her main job as helping choose PCAST's additional members and to get to work setting a scientific agenda for the group. She has stated: "We have to reestablish the importance of science in policymaking, in decision making across the government. We need to reestablish the trust of the American people in science ... I think that PCAST can play a beneficial role in that."
Arnold serves on the Board of Advisors for Angeleno Group, a private equity and venture capital firm focused on sustainable energy investments.
Arnold is credited with pioneering the use of directed evolution to create enzymes (biochemical molecules—often proteins—that catalyze, or speed up, chemical reactions) with improved and/or novel functions. The directed evolution strategy involves iterative rounds of mutagenesis and screening for proteins with improved functions and it has been used to create useful biological systems, including enzymes, metabolic pathways, genetic regulatory circuits, and organisms. In nature, evolution by natural selection can lead to proteins (including enzymes) well-suited to carry out biological tasks, but natural selection can only act on existing sequence variations (mutations) and typically occurs over long time periods. Arnold speeds up the process by introducing mutations in the underlying sequences of proteins; she then tests these mutations' effects. If a mutation improves the proteins' function she can keep iterating the process to optimize it further. This strategy has broad implications because it can be used to discover proteins for a wide variety of applications. For example, she has used directed evolution to discover enzymes that can convert sugars directly into iso-butanol, a precursor for many important substances and which can also be used to produce renewable fuels and pharmaceutical compounds.
To effect the directed evolution, Arnold introduces mutations in specific areas of the protein that she has selected based on her knowledge of biochemistry. It is this selected application of mutations that differentiates this method from random mutations and which thus accelerates the development of molecules with desired effects.
Arnold applied directed evolution to the optimization of enzymes (although not the first person to do so, see e.g. Barry Hall). In her seminal work, published in 1993, she used the method to engineer a version of subtilisin E that was active in the organic solvent DMF, a highly unnatural environment. She carried out the work using four sequential rounds of mutagenesis of the enzyme's gene, expressed by bacteria, through error-prone PCR. After each round she screened the enzymes for their ability to hydrolyze the milk protein casein in the presence of DMF by growing the bacteria on agar plates containing casein and DMF. The bacteria secreted the enzyme and, if it were functional, it would hydrolyze the casein and produce a visible halo. She selected the bacteria that had the biggest halos and isolated their DNA for further rounds of mutagenesis. Using this method, she discovered an enzyme that had 256 times more activity in DMF than the original.