May 24--Caltech biochemical engineer Frances Arnold has become the first woman to win the Millennium Technology Prize for her pioneering work on so-called directed evolution. Inspired by the biological processes that drive natural selection, Arnold launched a field that revolutionized protein engineering -- allowing researchers to design more effective drugs and to create cleaner industrial processes.
Arnold, who began her career in renewable energy, has spent a lot of time thinking about the damage humans are doing to the environment. By mixing up DNA in test tubes and putting it into microbes that pump out specialized proteins, Arnold aims in part to create cleaner, more environmentally friendly methods to make the everyday products we use.
The scientist draws from many fields to do her research, and consequently has been elected to all three branches of the National Academies of Sciences, Engineering and Medicine -- making her the first woman to achieve this rare feat.
The prize, which is awarded every two years by the Technology Academy Finland, comes with a cash prize of $1.1 million. Previous winners include Shuji Nakamura, inventor of the blue LED who went on to win the 2014 Nobel Prize in physics, and Linus Torvalds, creator of the Linux kernel.
The Times caught up with Arnold on the night before she received the prize to discuss her groundbreaking work.
So you started off as a mechanical engineer. How did you make your way into biology?
I was employed at the Solar Energy Research Institute in the late '70s when Carter was president, and as a country we actually had a goal of renewable energy development. This was in the first set of oil crises back in the '70s and President Carter was quite visionary and said, you know, we should develop renewable resources for replacing oil. Novel idea, huh? But then Reagan was elected and then the political climate changed a lot, and I decided to go back to college and get a PhD -- only this time I wanted to do it in the emerging field of biotechnology. I made a small switch from mechanical to chemical engineering and started learning some biology, and fell in love with engineering proteins.
Engineering the biological world was even more interesting than engineering the mechanical world. Because to me, nature is the best engineer -- having created, over 4 billion years of evolution, some pretty amazing molecular machines that humans can't even begin to compare.
So you manipulate DNA to modify the types of proteins known as enzymes; what do these proteins do?
Enzymes, which I work on, catalyze all the reactions of life. They're what allow you to extract materials and energy from your environment, and turn that into muscle and tissue and fat; that's all done by enzymes. They're pretty remarkable chemists. They're even better than Caltech chemists. I wanted to make enzymes that would solve human problems, not just problems for a cell that makes them.
What potential did you and your colleagues see when the field was just starting?
We thought that we would be able to build new biological things that would solve human problems, starting with curing diseases .... I was interested in the industrial side. How do you use biology to make the chemicals and products we use in our daily lives? And that has developed now to where it's a really vibrant industry.
I talk a lot about replacing toxic chemical manufacturing processes with clean biologically based enzyme processes. If you used enzymes to replace the chemicals industry, so you don't have to pump oil out of the ground to make the materials we need for our daily life, maybe you could use carbon dioxide and sunlight, just like the biological world does.
The blockbuster diabetes drug Januvia made by Merck is manufactured now using an enzyme, whereas in the past, it was manufactured using a chemical process that involved toxic metals and tons of organic solvent waste. They've replaced that completely with a clean enzyme-based process. You can make biofuels with enzymes, you can cure diseases with enzymes, you can clean your clothes better with enzymes. You can use enzymes made by directed evolution in clinical diagnostics, in brain imaging; there's a list, probably a hundred things long.
How did you get the idea for directed evolution?
It came in almost a fit of desperation. Because here I was, an assistant professor at Caltech, which has lofty aspirations for doing really important work, and I was pretty clueless. I didn't know how to make proteins. So I started doing lots of experiments simultaneously, and I realized that's exactly what nature does. So within a few years of setting out to become a protein engineer, I realized that the best way to do that was to realize that I didn't know what I was doing and let evolution tell me what the rules are.
What we realized quickly on is that nobody knows how to compose the code of life. We can manipulate it, we can copy it, we can cut and paste it, we can mix it like a deejay does with music, but nobody knew how to compose it from the beginning. The only algorithm that worked for composing DNA was evolution, the process by which all those wonderful biological things that inspired me came about.
We've been modifying the biological world at the level of DNA for thousands of years ... we've made corn that can feed [a lot of] people and we've made chickens that have big breasts and we've made cats with stripes and non-stripes.
Now with these new techniques of being able to actually go in to cut and paste DNA, we could do that in a very directed fashion.
How long does it take for you to "evolve" a protein with the particular qualities you want?
Sometimes it's one generation, sometimes it's 31 generations; it really depends on where you start, how good is your starting point and how far you have to go -- and that's entirely determined by the application.
You have four brothers and three sons; it kind of sounds like you're surrounded by men at work and at home!
Yeah, it's true. [In my lab] I've always made a conscious effort to have as diverse a group as possible. I love the fact that new ideas can come from anywhere. It's impossible to predict -- and it's not always the smartest people on paper that come up with the best ideas.
This conversation has been edited for clarity.
amina.khan@latimes.com
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