The vehicle for all of life’s variety and complexity has found a new driver in La Cañada’s Frances Arnold.
In her laboratories at Caltech, Arnold is harnessing the evolutionary process to create new proteins and enzymes that have the potential to wean the world off of fossil fuels, advance doctors’ understanding of disease and addiction and solve other pressing social problems.
Like an animal breeder working at the molecular level, Arnold manages the growth and reproduction of microscopic life-forms to reshape them for practical scientific purposes — a yeast that could effectively convert plants into jet fuel or plastics, for instance, or a microbe with the power to help map the human brain.
For her pioneering work in the emerging field of “directed evolution,” Arnold was earlier this year awarded the prestigious Draper Prize, an honor established by the National Academy of Engineering that carries the scientific clout of a Nobel Prize. Arnold shared that award — and split its $500,000 in prize money — with Willem Stemmer, who has used directed evolution to develop advanced biopharmaceuticals. In previous years, Draper Prizes have gone to inventers of the global positioning system (GPS), architects of the Internet and developers of the turbojet engine.
A uniquely diverse scientific career path helped Arnold, also a mother of two teen boys who attend La Cañada High School and a son serving in the armed forces, make the link between evolutionary biology and renewable energy research.
After studying mechanical engineering at Princeton, Arnold went to work on the development of solar energy collectors at the National Renewable Energy Lab in Colorado. When federal research funding priorities changed after President Reagan succeeded President Carter, Arnold became interested in biofuels research and obtained a doctorate in chemical engineering at UC Berkeley, where she was also exposed to emerging breakthroughs in DNA research. She arrived at Caltech in 1986, and has lived in La Cañada for 10 years.
Outside of her research at Caltech, Arnold has founded a now publicly traded company that taps directed evolution techniques to produce an ingredient for renewable fuels.
Arnold, 54, also has the distinction of being one of only eight scientists — and the only woman — elected to serve concurrently on the National Academy of Science, National Academy of Engineering and the Institute of Medicine.
The Valley Sun: How does a person direct evolution?
Arnold: DNA encodes a protein, and evolution has created a whole bunch of proteins you can literally scrape from the bottom of your shoe, but they aren’t made to solve human problems. They’re made to solve problems for the organism that makes them. So if you want to take proteins and solve a human problem — if you want to have a better laundry detergent, if you want to have a solution to the energy crisis, if you want to cure cancer — these are not necessarily proteins that nature made for you. So I have to make them. And since I don’t know what sequence encodes that new function, I was at a loss.
But then it seemed obvious to me that since there’s this simple algorithm [evolution] that made them in nature, the appropriate way to make new proteins was not to sit down and design them from first principles but to use the same algorithm. Evolution is a recipe: Make lots of mutations, see who’s better. It’s like breeding, basically. You have a litter of cats, you choose the ones you like, give away the rest and breed these new properties into them. We do that now with DNA. We can take millions of copies of DNA that have mutations in them. We can stick them into yeast or bacteria and they will start synthesizing the new proteins. Then I have to look at them and see which ones start acquiring the properties I’m interested in. I choose the better ones, and then I take the DNA that encodes those and I repeat the process. So I do it over multiple generations, breeding the properties in, little by little, until I have something that’s useful.
What applications are you focused on?
The things that I’m most interested in are retooling the chemical industry so that we can use renewable resources to make chemicals. Right now, we pump chemicals out of the ground, in the form of oil, and that gets converted to plastics. Oil is a finite resource, and so I would like to see us move to a renewable and sustainable chemicals industry where we use energy in the form of sunlight that gets stored in plants. To do this, we have to build new organisms that can convert sugars in plants into fuels and chemicals.
So you aren’t changing the plant, but inventing a new way to extract energy from it.
You make ethanol with yeasts. We’d use the same sort of organisms, but they would now be genetically engineered so they would eat the [plant] sugars and produce something else. Or you could engineer algae to take sunlight and convert that directly to oils.
What kind of progress have you been making?
Five years ago I started a company called Gevo, and it went public three weeks ago on the NASDAQ. It makes isobutanal, a gasoline substitute. You can make a whole bunch of things from isobutanal, from jet fuel to diesel to gasoline, and you can make plastics from it.
We have a really interesting project right now to develop protein-based imaging agents for the brain, so we can understand the molecular basis for things like addiction. When activities go on in the brain, it all involves these signaling molecules called neurotransmitters, and we’d like to be able to see their levels going up and down in real time in different parts of the brain.
You’ve seen maps of the brain — that all comes from looking at oxygen so that you can image blood flow in the brain. We’re trying to make new sensor molecules that can allow us to image these actual neurotransmitters going up and down. We’re working on dopamine, which is a very important neurotransmitter involved in everything from Parkinson’s disease to cocaine addiction. We’re making proteins that bind to these neurotransmitters and then emit a signal you can actually see in an MRI.
What would you say to someone who worries that directed evolution crosses an ethical line of playing God?
Humans have been manipulating the environment as long as we’ve been on the planet. We have bred all sorts of organisms that would not survive in the natural world. All of the organisms that I breed in the laboratory are less fit for survival in the natural world. When they’d escape, they’d get eaten. So we’re not creating any kind of superbug. Also, what we’re creating are really molecules. They’re not really living organisms until you implant them in living organisms. We create DNA sequences that encode new proteins. That said, there’s always an opportunity when new technology is developed for it to be used for nefarious purposes. What you hope is that the good outweighs the bad, and I’m trying to make sure that the applications really benefit humans.
Fear of a superbug seems to have deep roots in the popular imagination.
Nature is much, much better at designing such things. If I make something that kills people, it’s not going to survive [in the natural world]. Nature’s made much more dangerous things than I ever will.
Still, we haven’t done a great of a job controlling the spread of genetically modified seeds and non-native species.
I think the scars left on the planet by humans are much greater from parking lots and roads. Just about every activity we engage in leaves scars on the planet, and if we were smarter we’d try to mimic nature a whole lot more. That’s what I’m trying to do. Rather than having oil pumped out of the ground to provide fuels and chemicals, we should mimic nature to [create it], and to do that efficiently will have a lot of benefits. Biology is by far the best engineer.
As one of only a handful of scientists in three different national science academies, do you think science is embraced in this country or threatened by social and political ideologies?
Science is more threatened by poor education. What we need is a strong education system that allows creativity to grow and encourages students to be interested in science and technology. Science and technology are going to be the basis for many of the solutions to social problems. Only by ignorance is science threatened.