I photographed Frances Arnold on a partially disassembled motorcycle in her backyard, beside the garage. At 18, she drove a Yellow Cab through Pittsburgh’s steep hills and narrow streets. She continued driving taxis while studying engineering at Princeton. During a year away from college, she rode a 1956 Moto Guzzi from Milan to Istanbul and back.
I first photographed Frances in November 2021. We began with coffee at her home, then continued through Caltech’s Athenaeum, her office, and her laboratory. Over the years, those visits became a friendship.
Her scientific work addressed a practical difficulty. Enzymes accelerate chemical reactions, often with a precision chemists would like to reproduce in manufacturing. But an enzyme that works inside a living organism may fail in an industrial process. Heat or an unfamiliar solvent can render it useless. Changing its amino acid sequence might help, if you could determine which changes to make.
Frances approached the problem through repeated experiment and selection. She did not need to predict every molecular consequence before testing a change. Her laboratory introduced mutations into the DNA encoding an enzyme, produced variants, and tested them for a desired property. The best performers became the starting material for another round. Useful changes accumulated through successive generations.
The method is called directed evolution. Researchers choose the task and devise the test; variation supplies possibilities they might never have thought to design.
In work published with Keqin Chen in 1993, Frances applied this approach to subtilisin, an enzyme that breaks down proteins. Repeated rounds of mutation and selection produced a version that worked far better in a concentration of organic solvent that severely reduced the original enzyme’s activity.
The approach became a way to adapt enzymes for manufacturing, including the production of medicines. It could also extend their chemistry. In 2016, her laboratory reported evolving a protein to join carbon and silicon atoms, a reaction no enzyme was then known to perform in nature. In 2018, she received half of the Nobel Prize in Chemistry for directed evolution of enzymes.
Her life during these years included devastating losses. Andrew Lange, the astrophysicist with whom she had two sons, died in 2010. Their son William died in 2016, at 20.
Frances once told me that the family tragedies had also had an unexpected consequence at Caltech. The institute had not pressed her to take on administrative roles, such as becoming a dean. She had been able to remain focused on her research.
We have ridden electric bikes through Pasadena and around JPL, and gathered at her home with her son and colleagues. On my most recent visit, she hosted a dinner for me with Caltech’s new president, Ray Jayawardhana, and Judge Lance Ito. There are always interesting people in her orbit. Frances brings them together with a generosity I have come to know well.
A few weeks ago, we were texting updates about our lives and travels. She told me that we were similar in many ways. It was one of the nicest things anyone has ever said to me.
