The evolution of an enzyme engineer who changed chemistry
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What is directed evolution and why did Frances Arnold win the Nobel Prize?
Hey, it's Flora, and you're listening to Science Friday. Today we're bringing back a conversation with an absolute all-star, and it's a conversation I've thought about a lot since we recorded it, so I hope you enjoy it. In nature, enzymes are the catalysts that make much of biology work. They jumpstart chemical reactions that either wouldn't happen or would happen super slowly. They do a lot of basic biological jobs, breaking down food, building other molecules, extracting energy. But what if we could harness evolution to engineer designer enzymes that do other jobs, specific jobs that benefit us? Putting that idea into practice changed the game for chemistry and earned Dr. Frances Arnold the Nobel Prize in 2018.
She called it directed evolution. And this is really big. Today, thousands of labs use these methods to coax enzymes into doing things no one had ever thought of. Dr. Frances Arnold is a professor at Caltech, and we'll hear about where she sees this approach going in the future and her own personal evolutions. the evolution that brought her into science. Welcome to Science Friday, Dr. Arnold.
Oh, thank you so much, Flora. I'm thrilled to be here.
Okay, in our intro, we described enzymes as catalysts that make biology work. I know they're near and dear to you. Do you have a more poetic way of thinking about them?
Poetic? Well, I think about them as the transformation agents of the whole natural world. It's enzymes that take carbon dioxide and sunlight and simple starting materials and build trees and human beings and flowers and birds. They're amazing. They're the best chemists on the planet.
When we talk about directed evolution, should I be thinking about this like enzyme breeding, but like instead of a chihuahua, you're making, you know, a tiny adorable protein?
Well, I think of it that way. It is a way to explain that we have been modifying the biological world at the level of DNA for ages, making strange things like chihuahuas that wouldn't be found naturally and But for some reason, human beings find them charming or useful. So why not use that same very powerful process of directing the evolution, which is what breeding is, of enzymes to make what we want?
I want to get into this a little bit. I mean, let's say you wanted to create an enzyme that's like a stain remover. Can you create conditions that make a stain removing enzyme more likely? Or is it more like trial and error and you find one that gets a little bit better at stain removing and then you breed that one? How does it work?
Well, you're right, Flora. It's a process of incremental change. You don't get a whole new enzyme at once, although that may be coming. But what we do is we start with something that has a little bit of the property that you're interested in. Let's take your example of stain remover. If you start with an enzyme that has a little bit of capability to remove stains, but doesn't work in the presence of bleach and doesn't like your laundry machine, for example, then we can breed in or evolve in those desirable properties one step at a time.
And to do that, you take the gene that makes that enzyme and you put it in a living organism? Is that how that works?
Well, for example, bacteria are wonderful translators of genetic material, of DNA and into enzymes. They can read DNA and spit out the enzymes wonderfully. So we use that capability, like a bag of reagents, basically, of bacteria to make all the mutant enzymes that we'll program in. And then we search through those bacteria to find the ones that harbor the great stain-removing enzymes.
And how do you sort of determine the winner? Are you putting these enzymes in a test tube with a piece of fabric that has a stain on it and seeing which does the best? What does it look like?
Well, I don't do that. In fact, I'll tell you a funny story. Way long ago, back in the early 1990s, I had a grant from Procter & Gamble who wanted me to make an enzyme for all-temperature cheer. their laundry detergent. And it's supposed to work at all.
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