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 Nobel Prize in Chemistry for pioneering the use of directed evolution
to engineer enzymes.
== Early life and education == 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 grew up in Pittsburgh suburb Edgewood, and 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.Arnold
graduated in 1979 with a B.S. 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 advance 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 finish out her studies.
Back at Princeton, she began studying with Princeton's 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 key focus of Arnold's
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 Ph.D. degree in chemical engineering in 1985 and became deeply interested
in biochemistry in the process.
Her thesis work, carried out in the lab of Harvey Warren Blanch, investigated affinity
chromatography techniques.
== Career == 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, her current position, 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 is a member of the Advisory Board of the Joint BioEnergy Institute and
the Packard Fellowships in Science and Engineering, and she serves on the President's Advisory
Council of the King Abdullah University of Science and Technology (KAUST).
She is currently serving as a judge for The Queen Elizabeth Prize for Engineering.
She worked with the National Academy of Science's Science & Entertainment Exchange to help Hollywood
screenwriters accurately portray science topics.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.
=== Research === 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 randomly mutating proteins' genes
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 design proteins for a wide
variety of applications.
For example, she has used directed evolution to design enzymes that can be used to produce
renewable fuels and pharmaceutical compounds with less harm to the environment.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, Arnold 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).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 a highly unnatural environment, namely in the organic solvent DMF.
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 designed an enzyme that had 256 times more activity in DMF than
the original.Following her seminal work, Arnold 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.
In addition to improving the existing functions of natural enzymes, Arnold has designed enzymes
that perform functions for which no previous specific enzyme existed, such as when she
evolved cytochrome P450 to carry out cyclopropanation and carbene and nitrene transfer reactions.In
addition to evolving individual molecules, Arnold has used directed evolution to co-evolve
enzymes in biosynthetic pathways, such as those involved in the production of carotenoids
and L-methionine in Escherichia coli (which has the potential to be used as a whole-cell
biocatalyst).Arnold has applied these methods to biofuel production.
For example, she evolved bacteria to produce the biofuel isobutanol; it can be produced
in E. coli bacteria, but the production pathway requires the cofactor NADPH, whereas E. coli
makes the cofactor NADH.
To circumvent this problem, Arnold evolved the enzymes in the pathway to use NADH instead
of NADPH, allowing for the production of isobutanol.Arnold has also used directed evolution to design
highly specific and efficient enzymes that can be used as environmentally-friendly alternatives
to some industrial chemical synthesis procedures.
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 hazardous
heavy metals.
The method has been adopted by some groups in pharmacology.
For example, one of Arnold's former students, Jeffrey Moore, and colleagues used directed
evolution to evolve an enzyme to produce the diabetes drug sitagliptin (Januvia).Arnold
also uses structure-guided protein recombination to combine parts of different proteins to
form protein chimeras with unique functions.
She developed computational methods, such as SCHEMA, 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.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.
== Personal life == Arnold lives in La Cañada Flintridge, California.
She was married to James E. Bailey and they had one son, James.
Bailey died of cancer in 2001.
She later married Caltech astrophysicist Andrew E. Lange and they had two sons, William and
Joseph.
Lange took his own life in 2010 and one of their sons, William Lange-Arnold, died in
an accident in 2016.
Arnold was diagnosed with breast cancer in 2005 and underwent treatment for 18 months.
Her hobbies include traveling, scuba diving, skiing, dirt-bike riding and hiking.
== Honors and awards == Arnold's work has been recognized by many
awards, including the 2018 Nobel Prize in Chemistry, the 2011 National Academy of Engineering
(NAE) Draper Prize (the first woman to receive it), and a 2011 National Medal of Technology
and Innovation.
She was elected to the American Academy of Arts and Sciences in 2011 and inducted into
the National Inventors Hall of Fame in 2014.
She was the first woman to be elected to all three National Academies in the United States
– the National Academy of Engineering (2000), the National Academy of Medicine, formerly
called the Institute of Medicine (2004), and the National Academy of Sciences (2008).Arnold
is a Fellow of the American Association for the Advancement of Science, the American Academy
of Arts and Sciences, the American Academy of Microbiology, the American Institute for
Medical and Biological Engineering and an International Fellow of the UK's Royal Academy
of Engineering in 2018.In 2016 she became the first woman to win the Millennium Technology
Prize, which she won for pioneering directed evolution.
In 2017, Arnold was awarded the Raymond and Beverly Sackler Prize in Convergence Research
by the National Academy of Sciences, which recognizes extraordinary contributions to
convergence research.In 2018 she was awarded the Nobel 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.
She received a one-half share of the award, with the other half jointly awarded to George
Smith and Gregory Winter "for the phage display of peptides and antibodies."
She is the first female graduate of Princeton to be awarded a Nobel Prize and the first
person who got their undergraduate degree from Princeton (male or female) to receive
a Nobel Prize in one of the natural sciences categories (chemistry, physics, and physiology
of medicine).
Nobel Prize in Chemistry (2018) Elected an International Fellow of the Royal
Academy of Engineering (2018) Raymond and Beverly Sackler Prize in Convergence
Research (2017) Spiegelman Lecture, University of Illinois
(2017) Society of Women Engineers' 2017 Achievement
Award Honorary Degree of Doctor of Science from
Dartmouth College (2017) Honorary Doctorate, University of Chicago
(2016) Millennium Technology Prize (2016)
Honorary Degree of Doctor of Science from the ETH Zurich (2015)
Elmer Gaden Award, Biotechnology and Bioengineering (2015)
Inducted into the National Inventors Hall of Fame (2014)
Golden Plate Award, Academy of Achievement (2014)
Emanuel Merck Lecture of the Technische Universität Darmstadt, Germany (2013)
ENI Prize in Renewable and Nonconventional Energy (2013)
Honorary Degree of Doctor of Science from the Stockholm University (2013)
Charles Stark Draper Prize (2011) National Medal of Technology and Innovation
(2011) American Academy of Arts and Sciences (2011)
Honorary Degree of Doctor of Science from Stockholm University (2013)
Elected fellow of the American Association for the Advancement of Science (2010)
Elected fellow of the American Academy of Microbiology (2009)
Elected to the National Academy of Sciences (2008)
FASEB Excellence in Science Award (2007) Enzyme Engineering Award from Engineering
Conferences International and Genencor (2007) Francis P. Garvan–John M. Olin Medal, American
Chemical Society (2005) Elected fellow of American Institute for Medical
and Biological Engineering (2001) National Academy of Engineering (2000)
== See also == Timeline of women in science
List of International Fellows of the Royal Academy of Engineering
== References ==
== External links == Chemical Eng, Caltech Faculty Page
Arnold Research Group Video of Arnold talking about her work, from
the National Science & Technology Medals Foundation Frances Arnold publications indexed by Google
Scholar