Los Angeles Times

The birth of ‘directed evolution’

$1-million Millennium Technology Prize goes to Frances Arnold, a Caltech bioenginee­r who started new field.

- AMINA KHAN amina.khan@latimes.com

A $1-million prize goes to Frances Arnold, a Caltech bioenginee­r who started new field.

Inspired by the biological processes that drive natural selection, Caltech biochemica­l engineer Frances Arnold launched a field called “directed evolution” and revolution­ized the way researcher­s design more effective drugs and create cleaner industrial processes.

This week, Arnold’s pioneering work was recognized with a Millennium Technology Prize, making her the first woman to win the prestigiou­s award. The prize is awarded every two years by the Technology Academy Finland and comes with $1.1 million in cash. Previous winners include Linux creator Linus Torvalds and blue LED inventor Shuji Nakamura, who went on to win the 2014 Nobel Prize in physics.

Arnold began her career in renewable energy, and she 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, she aims to create cleaner, more environmen­tally friendly methods to make the products we use every day.

Arnold 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 — the first woman to achieve this rare feat.

The Times caught up with Arnold, 59, on the night before she received the prize in Helsinki, Finland, to discuss her groundbrea­king work.

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 had a goal of renewable energy developmen­t. But then Reagan was elected, and then the political climate changed a lot.

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.

What drew you in?

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.

You manipulate DNA to modify the types of proteins known as enzymes. What do these proteins do?

Enzymes 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.

I wanted to make enzymes that would solve human problems, not just problems for a cell that makes them.

What kinds of problems did you have in mind?

I was interested in the industrial side: How do you use biology to make the chemicals and products we use in our daily lives? That has developed now to where it’s a really vibrant industry.

Can you give me some examples?

You can make biofuels with enzymes. You can cure diseases with enzymes. You can clean your clothes better with enzymes.

The diabetes drug Januvia is manufactur­ed now using an enzyme. In the past, it was manufactur­ed using a chemical process that involved toxic metals and tons of organic solvent waste.

How did you get the idea for directed evolution?

It came in almost a fit of desperatio­n.

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.

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. Aren’t you ner vous about manipulati­ng DNA?

We’ve been modifying the biological world at the level of DNA for thousands of years. We’ve made corn that can feed people, and we’ve made chickens that have big breasts and we’ve made cats with 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.

You have four brothers and three sons. It sounds like you’re surrounded by men at work and at home!

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 not always the smartest people on paper that come up with the best ideas.

This conversati­on has been edited for length and clarity.

 ?? Caltech ?? FRANCES ARNOLD, who launched the field of “directed evolution,” says she “fell in love with engineerin­g proteins” and uses them to solve everyday problems.
Caltech FRANCES ARNOLD, who launched the field of “directed evolution,” says she “fell in love with engineerin­g proteins” and uses them to solve everyday problems.

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