Arnold is the daughter of Josephine Inman (née Routheau) and nuclear physicistWilliam Howard Arnold, and the granddaughter of Lieutenant GeneralWilliam Howard Arnold.[5] She has an older brother, Bill, and three younger brothers, Edward, David and Thomas. She grew up in thePittsburgh suburb ofEdgewood, and the Pittsburgh neighborhoods ofShadyside andSquirrel Hill, graduating from the city'sTaylor Allderdice High School in 1974.[6] As a high schooler, she hitchhiked to Washington, D.C., to protest theVietnam War[7] and lived on her own, working as a cocktail waitress at a local jazz club and a cab driver.[8]
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.[9] 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".[10]
Arnold graduated in 1979 with a Bachelor of Science (BS) degree inmechanical andaerospace engineering fromPrinceton University, where she focused on solar energy research.[11] 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.[12] She took a year off from Princeton after her second year to travel to Italy and work in a factory that madenuclear reactor parts, then returned to complete her studies.[13] Back at Princeton, she began studying at its Center for Energy and Environmental Studies – a group of scientists and engineers, at the time led byRobert Socolow, working to develop sustainable energy sources, a topic that would become a focus of her later work.[13]
After graduating from Princeton in 1979, Arnold worked as an engineer in South Korea and Brazil and at Colorado'sSolar Energy Research Institute.[13] 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.[12]
She then enrolled at theUniversity of California, Berkeley, where she earned a PhD degree inchemical engineering in 1985[14] and became deeply interested in biochemistry.[15][13] Her thesis work, carried out in the lab of Harvey Warren Blanch, investigatedaffinity chromatography techniques.[14][16] 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.[9]
After earning her Ph.D., Arnold completed postdoctoral research inbiophysical chemistry at Berkeley.[17] In 1986, she joined theCalifornia 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, her current position, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry in 2017.[18] In 2013, she was appointed director of Caltech's Donna and Benjamin M. Rosen Bioengineering Center.[19]
In 2000 Arnold was elected a member of theNational 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.[15] She co-foundedGevo, Inc., a company to make fuels and chemicals from renewable resources in 2005.[15] In 2013, she and two of her former students, Peter Meinhold and Pedro Coelho, cofounded a company called Provivi to research alternatives topesticides for crop protection.[15][22][23] She has been on the corporate board of thegenomics companyIllumina Inc. since 2016.[24][25]
In 2019 she was named to the board ofAlphabet Inc., making Arnold the third woman director of the Google parent company.[26]
In January 2021 she was named an external co-chair of President Joe Biden'sCouncil of Advisors on Science and Technology (PCAST). She is working with Biden's transition team to help identify scientists for roles in the administration. She says her main job now is to help 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."[27]
She currently serves on the Board of Advisors for Angeleno Group, a private equity and venture capital firm focused on sustainable energy investments.[28]
Arnold is credited with pioneering the use ofdirected evolution to createenzymes (biochemical molecules—often proteins—thatcatalyze, or speed up, chemical reactions) with improved and/or novel functions.[29] Thedirected evolution strategy involves iterative rounds of mutagenesis and screening for proteins with improved functions and it has been used to create usefulbiological systems, includingenzymes,metabolic pathways,genetic regulatory circuits, and organisms. In nature, evolution bynatural 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.[30] 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.[31] For example, she has used directed evolution to discover enzymes that can be used to producerenewable fuels and pharmaceutical compounds with less harm to the environment.[29]
One advantage of directed evolution is that the mutations do not have to be completely random; instead, they can be random enough to discover unexplored potential, but not so random as to be inefficient. The number of possible mutation combinations is astronomical, but instead of just randomly trying to test as many as possible, she integrates her knowledge of biochemistry to narrow down the options, focusing on introducing mutations in areas of the protein that are likely to have the most positive effect on activity and avoiding areas in which mutations would likely be, at best, neutral and at worst, detrimental (such as disrupting proper protein folding).[29]
Arnold applied directed evolution to the optimization of enzymes (although not the first person to do so, see e.g. Barry Hall[32]). In[29] her seminal work, published in 1993, she used the method to engineer a version ofsubtilisin E that was active in the organic solventDMF, a highly unnatural environment.[33] She carried out the work using four sequential rounds of mutagenesis of the enzyme'sgene, expressed by bacteria, through error-pronePCR. After each round she screened the enzymes for their ability tohydrolyze the milk proteincasein 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.[29] Using this method, she discovered an enzyme that had 256 times more activity in DMF than the original.[34]
She has further developed her methods and applied them under different selection criteria in order to optimize enzymes for different functions. She showed that, whereas naturally evolved enzymes tend to function well at a narrow temperature range, enzymes could be produced using directed evolution that could function at both high and low temperatures.[29] In addition to improving the existing functions of natural enzymes, Arnold has discovered enzymes that perform functions for which no previous specific enzyme existed, such as when she evolvedcytochrome P450 to carry outcyclopropanation[35] andcarbene andnitrene transfer reactions.[29][36]
In addition to evolving individual molecules, she has used directed evolution to co-evolve enzymes in biosynthetic pathways, such as those involved in the production ofcarotenoids[37] andL-methionine[38] inEscherichia coli (which has the potential to be used as a whole-cell biocatalyst).[29] She has applied these methods tobiofuel production. For example, she evolved bacteria to produce the biofuelisobutanol; it can be produced inE. coli bacteria, but the production pathway requires thecofactorNADPH, whereas E. coli makes the cofactorNADH. To circumvent this problem, she evolved the enzymes in the pathway to use NADH instead of NADPH, allowing for the production of isobutanol.[29][39]
Arnold has also used directed evolution to discover highly specific and efficient enzymes that can be used as environmentally-friendly alternatives to some industrial chemical synthesis procedures.[29] She, and others using her methods, have engineered enzymes that can carry out synthesis reactions more quickly, with fewer by-products, and in some cases eliminating the need for hazardousheavy metals.[34]
She uses structure-guided protein recombination to combine parts of different proteins to form protein chimeras with unique functions. She developed computational methods, such asSCHEMA, to predict how the parts can be combined without disrupting their parental structure, so that the chimeras will fold properly, and then applies directed evolution to further mutate the chimeras to optimize their functions.[40][41]
At Caltech, Arnold runs a laboratory that continues to study directed evolution and its applications in environmentally-friendly chemical synthesis and green/alternative energy, including the development of highly active enzymes (cellulolytic and biosynthetic enzymes) and microorganisms to convert renewable biomass to fuels and chemicals. A paper published in Science in 2019, with Inha Cho and Zhi-Jun Jia, has been retracted on January 2, 2020, as the results were found to be not reproducible.[42]
Arnold was in a common-law marriage with Caltech astrophysicistAndrew E. Lange,[46] beginning in 1994, and they had two sons, William Andrew Lange (1995) and Joseph Inman Lange (1997).[47][45] Lange committed suicide in 2010 and one of their sons, William Lange-Arnold, died in an accident in 2016.[24] Her father,William Howard Arnold died in 2015.[48]
Her hobbies include traveling, scuba diving, skiing, dirt-bike riding, and hiking.[8]
In 2018 she was awarded theNobel Prize in Chemistry for her work in directed evolution, making her the fifth woman to receive the award in its 117 years of existence, and the first American woman.[53][54] She received a one-half share of the award, with the other half jointly awarded toGeorge Smith andGregory Winter "for thephage display ofpeptides andantibodies."[29] She is the first woman graduate ofPrinceton to be awarded a Nobel Prize and the first person who got their undergraduate degree from Princeton (man or woman) to receive a Nobel Prize in one of the natural sciences categories (chemistry, physics, and physiology or medicine).[11] In November 2018, she was listed as one ofBBC's 100 Women.[55] On October 24, 2019,Pope Francis named her a member of thePontifical Academy of Sciences.[56] In 2022 she was the guest in an episode ofThe Life Scientific onBBC Radio 4.[57]
She portrayed herself in the 18th episode "The Laureate Accumulation" of the 12th season of the TV seriesThe Big Bang Theory.[79] In September 2021 in the 10th anniversary of PME UChicago she jokingly claimed that this appearance was the greatest accolade of her life. She also appeared in a brief interview in theNOVA episodeBeyond the Elements: Life. She was interviewed byJim Al-Khalili on the BBC'sThe Life Scientific on September 6, 2022.[57]
^abFernholm, Ann (October 3, 2018)."A (r)evolution in chemistry"(PDF).The Nobel Prize in Chemistry 2018: Popular Science Background. Archived fromthe original(PDF) on October 3, 2018. RetrievedOctober 3, 2018.
^May, O.; Nguyen, P. T.; Arnold, F. H. (March 1, 2000). "Inverting enantioselectivity by directed evolution of hydantoinase for improved production of L-methionine".Nature Biotechnology.18 (3):317–320.doi:10.1038/73773.ISSN1087-0156.PMID10700149.S2CID20991257.
^Spiegelman, Sol."Enduring Legacy of Sol Spiegelman".Spiegelman Lecture. University of Illinois Dept of Microbiology. Archived fromthe original on November 12, 2018. RetrievedNovember 12, 2018.
.jpg)
