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Superheroes often have one defining trait, a strength or characteristic that doesn’t just make them who they are, but also guides them in their approach to the challenges they face. Frances Arnold is a classic example of this trope; she was a rebellious figure from a very early age, but rarely a headstrong one, and her approach to challenges has always been to adapt rather than fight. In applying these methods to her work, she has successfully developed some of the most important innovations in modern biochemistry, with applications ranging from greatly accelerated pharmaceutical development to green aviation fuel. In the process, she has inspired countless scientists to follow in her highly adaptable True Superhero footsteps.

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The adaptable rebel

The rebellious traits that would serve Frances in such good stead were developed at an early age. As a child she was a voracious reader of books, ripping through her parents’ bookshelves and showing a particular interest in scientific and medical texts, but her teachers did not see a future for her in those fields. As Frances tells it: “No one knew what to do with a smart little girl in the 1960s… My brilliant success in elementary school got me into typing class.” 

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Young Frances enjoyed typing but it did not fulfill her intellectually and she grew increasingly disinterested in her education. There was enormous social upheaval happening outside the school gates and she wanted to be a part of it. By the age of 13, she was skipping school to hitchhike to Washington to participate in Vietnam War protests. The private girls’ school she had been sporadically attending let it be known that she was no longer invited to attend, and the public school she was moved to barely saw her. By the time she was 15, her parents gave Frances an ultimatum: shape up or move out. She moved out.

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The next few years were tough but Frances displayed tremendous adaptability in adjusting to her new life. She largely educated herself, only occasionally showing up at the high school in order to ace the tests she needed to graduate. Meanwhile, she said she supported herself for several years by working various low-paid jobs in Pittsburgh; these included: “Pizza parlor helper (15), department store clerk (16), receptionist (16), cocktail waitress (17, ‘I told them I was 22 and no one ever checked, as fewer young people had driver’s licenses then’), waitress in Pittsburgh’s famous jazz club Walt Harper’s Attic, and finally taxi driver (age 18).” Her stint as Pittsburgh’s youngest taxi driver came to an abrupt end when - somewhat improbably - she was accepted by Princeton to study mechanical and aerospace engineering.

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The optimistic engineer

Frances continued to drive taxis to support herself as she worked through college but she still needed to adapt to turbulent circumstances. The shockwaves from the 1973 oil crisis reverberated throughout the decade and had a substantial impact on Frances, whose interests increasingly turned away from aerospace engineering and toward renewable energy solutions. As she later told the Academy of Achievement: “I took it on myself to help implement President Carter’s plan of 20 percent renewable energy by the year 2000.” After graduating from Princeton, she took up an internship in Brazil on solar energy projects with Professor José Goldemberg, a preeminent expert on environmental science who would later become Brazil’s Minister for the Environment, and when she returned to the US in 1979 she took a position at a new national laboratory, the Solar Energy Research Institute (now the National Renewable Energy Laboratory). The next two years were spent developing passive solar heating and cooling technologies, and Frances also helped write position papers for the United Nations on solar energy in the developing world. 

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The frustrated scientist

In 1981, political events once again forced Frances to adapt. The election of Ronald Reagan spelled the end of America’s interest in renewable energy, with research grants curtailed and subsidies withdrawn. With opportunities in solar research drying up, Frances decided to pivot toward biochemical engineering, earning a  Ph.D. at Berkeley before moving to Caltech to begin research in the field that would become her life’s work: engineering new proteins. 

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As Dr. Arnold later explained: “The problem was that no one really knew how to engineer useful proteins… The prevailing view at that time was that proteins could not exhibit highly non-natural properties, such as the ability to function in organic solvents. The argument seemed to be that because nature never did it, it could not be done. But, in fact, that was precisely why it could be done, and why it might even be easy to do so.” Arnold set about trying to create targeted mutations of enzymes that would perform specific functions but the task proved to be close to impossible: “My feeble attempts at ‘rational design’ of enzymes for organic solvents were failures, as were most experiments aimed at improving proteins at that time…  the process was difficult - it required having the enzyme’s crystal structure, of which there were very few, and then understanding the protein’s structure and function sufficiently well to identify not just the sites of useful mutations, but which amino acids ought to be placed there”. 

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The director of evolution

Up to this point, Frances’ life had been characterized by a willingness to quickly adapt when the dice did not fall her way and she took a similar approach with her research. Instead of trying to use ‘rational design’ to impose her will on genetic mutations, she adopted a method more in tune with natural processes and also her own nature: she allowed genes to mutate randomly and then screened the results for mutations that were beneficial. The most promising mutations were used to generate new proteins and those new proteins would provide the seed for more DNA mutations. By repeating and refining the process, Frances had developed an entirely new method of enzyme engineering: directed evolution. 

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The early results were encouraging, but Arnold described how her work was viewed with skepticism and even derision by many biochemical engineers: “People would tell me that, ‘Oh, gentlemen don’t do random mutagenesis, and we make mutations at random because you’re supposed to sit with your big brain and figure things out.’ Or, ‘That’s not science.’” To which she would respond, “Hmm. Well, I’m not a gentleman, and I’m an engineer, so maybe that’s okay.”

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The inspirational Laureate

The skepticism did not last for long. Directed evolution has led to innovations in countless areas; everything from pharmaceutical development to pesticide production has seen radical change as a result of new enzymes that have been developed using these processes, and it came as no great surprise when Dr. Arnold’s work led to her being awarded the Nobel Prize for Chemistry in 2018. What’s more, the new enzymes made possible by directed evolution often provide a cleaner, more environmentally sound alternative to existing toxic chemical processes. Frances has launched several companies to promote these new products, including sustainable yeast-based aviation fuel and crop protection solutions. She’s also been appointed to the board of Google’s parent company, Alphabet, and is co-chair of President Joseph Biden’s Science and Technology Advisory Council. 

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Frances’ work has led to hugely beneficial innovations in an enormous number of fields, but one area that should not be overlooked is the inspiration that she provides to those hoping to follow in her footsteps. When asked by the Nobel committee what advice she would give to budding scientists, she gave a simple but typically pragmatic response: “When you come to the fork in the road, take it. Do something… even if you don’t know what it is and where it will lead you. Do it. Do something and do it as well as you can. If you don’t like it, take another path. Life is not doors closing, it should be doors opening.”

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