Nobel Laureate Frances Arnold Explains the Breakthrough Process of Directed Evolution

Guiding enzymes to compete against one another, which mimics the process of natural evolution, can lead to fascinating results and useful applications.

by Andrew Moseman

Humans have spent thousands of years breeding dogs by selectively controlling their DNA to bring about the familiar breeds we know today. Frances Arnold, the Linus Pauling Professor of Chemical Engineering, Bioengineering and Biochemistry and director of the Donna and Benjamin M. Rosen Bioengineering Center, says she does a similar thing in her lab but on a much smaller scale. Arnold and her team work with enzymes—proteins that are biological catalysts that accelerate chemical reactions.

Arnold won the 2018 Nobel Prize in Chemistry for her work in directed evolution, an approach she developed for creating new enzymes and improving existing ones. By mutating and recombining the gene that encodes the enzyme followed by artificial selection for the desired traits, protein engineers can use her approach to “breed” biomolecules, not unlike how farmers breed crops and animals.

Directed evolution is now widely used to create enzymes for making everything from fuels to medicines, chemicals, and consumer goods. Chemical synthesis using laboratory-evolved enzymes is often more efficient and greener than more traditional methods.

“I decided I wanted to make new enzymes, but I didn’t know how to do it,” she says in the video. “Problem was, no one else knew how to do it either. It’s a terribly complicated problem to design something new, but it was solved by evolution.”

To do this, she explains, her lab copies a gene known to encode an enzyme but in a way that encourages random mistakes to arise. The resulting DNA, containing random mutations, is placed within a bacterium where it can replicate, creating new enzymes. Some of the new creations are nonfunctional; these are discarded. Others are put through multiple rounds of this directed evolution, leading to a single “winner” that can perform the task scientists were hoping it could.

Hal Alper of the University of Texas at Austin, who appears alongside Arnold in the video, compares the process to a demolition derby in which these new enzymes smash each other up until only one remains. Directed evolution could lead to enzymes with helpful abilities such as breaking down the plastic in soda bottles that would otherwise persist in the environment.

Watch the entire clip above.