Frances H. Arnold is the Dickinson Professor of Chemical Engineering, Bioengineering, and Biochemistry at the California Institute of Technology. She is a pioneer of “directed evolution,” which mimics Darwinian evolution in the laboratory to create new biological molecules. Her research is particularly focused on how enzymes evolve new catalytic functions.
She delivered the Eugene Wigner Distinguished Lecture Nov. 2, 2015, on the topic “Innovation by Evolution: The Expanding Enzyme Universe.” We asked her about the accelerated evolution of proteins and the application of these methods to clean energy technology and health care.
1. You pioneered methods to accelerate the evolution of proteins for a variety of uses. How do you go about directing protein evolutions?
It’s actually simpler than you can imagine. The tools of molecular biology developed in the last 30 years have given us an unprecedented ability to manipulate DNA sequences any way we want. The problem is we don’t know what to write out in the DNA to solve a problem. So we use evolutionary algorithms of mutations, recombination—molecular sex, so to speak—to create new DNA sequences. And then bacteria read those and start making proteins. And the human being, the breeder of molecules, has to come in and decide which ones have the properties of interest. Those become the parents for the next generation. So, in a sense, it’s like breeding cats. You don’t really understand what’s happening at the level of DNA, but you choose the parents, you choose the progeny that you’re interested in, and you can breed over multiple generations to solve a particular problem.
2. Your work earned you a National Medal of Technology and Innovation in 2011 for pioneering research on biofuels and chemicals. How can these techniques promote clean energy?
It turns out that bacteria or other microbes are these incredible chemical factories. They can take renewable resources like carbon dioxide, biomass, even garbage and convert it into more microbes. Now imagine if you could rewrite the DNA so that instead of turning those renewable resources into microbes, they turned it into fuels or chemicals. They have all the catalysts that could do that, and you can string them together in new ways, or even add whole new catalysts in the form of new DNA sequences. So we were interested in how you would rewrite the DNA of a microbe to become an advanced clean chemical factory.
3. How can they also lead to advances in health care?
There are many health care applications. They can be used to discover new drugs, and they can be used to make better drugs. Many of the drugs we use to treat diseases, from cancer to arthritis, are proteins themselves. Imagine that you would be able to improve the lifetime of a protein in the bloodstream, or its ability to withstand the immune system. We can envision properties that we would like to confer on biological systems, and then use directed evolution to obtain those properties.
4. Why was it important to visit ORNL, meet with researchers here, and participate in the Wigner Lecture Series?
As a former national laboratory employee myself, I understand the critical role that the national laboratories play in bringing science to society and in solving difficult problems that reach across multiple disciplines. Academia is great for solving individual problems, maybe even inventing some new technologies. But somebody has to integrate this all and tackle the really challenging problems for the future. I really enjoy coming to Oak Ridge and learning about some of the impossible problems that you’re tackling.