Tiny DNA Switches Aim To Revolutionize 'Cellular' Computing

Mar 29, 2013
Originally published on March 29, 2013 11:14 am

If you think programming a clock radio is hard, try reprogramming life itself. That's the goal of Drew Endy, a synthetic biologist at Stanford University.

Endy has been working with a laboratory strain of E. coli bacteria. He sees the microbes as more than just single-cell organisms. They're little computers.

"Any system that's receiving information, processing information and then using that activity to control what happens next, you can think of as a computing system," Endy says.

Normally the E. coli follow their own program. Is there food? Is the temperature all right? The bacteria process this information and make simple decisions about what to do next. Mainly, they decide whether to reproduce. Endy sees potential for them to do much more. He wants to take control of a cell's genetic machinery and use it to do human computing.

"For us, what's become exciting is the idea that we could get inside the cells in sort of a bottom-up fashion," he says.

Endy is talking about more than splicing in a few extra genes, as scientists already do with crops. He wants to make cells that can follow different programs, just like a computer. To do that, he needed to create something all computers have to have: the transistor.

Transistors are simple on/off switches. Computers are made of many millions of these switches. And to program a cell, you need a biological version. As Endy reports this week in Science, he managed to make one out of DNA.

His switch, which he calls a "transcriptor," is a piece of DNA that he can flip on and off, using chemicals called enzymes. Endy put several of these DNA switches inside his bacteria. He could use the switches to build logic circuits that program each cell's behavior. For example, he could tell a cell to change color in the presence of both enzyme A and enzyme B. That's a simple program: IF enzyme A AND enzyme B [are present] THEN turn green. For an in-depth look, check out Endy's own explanation on YouTube.

Timothy Lu, a researcher at the Massachusetts Institute of Technology, is also building cellular computers. He can see lots of ways they could be used. For example, you could program cells to automatically scan your bowels for chemical signals of cancer and let you know if they find any.

"These cells could light up, and you could easily see whether the cell has computed [if] you may have early signs of cancer or not," he says. With a little more programming, such cells might be able to produce a drug, or target the cancer directly.

So far, only the simplest logic circuits work. And Endy doubts that these DNA computers will ever outperform a smartphone. But that's not the point.

"We're building computers that will operate in a place where your cellphone isn't going to work," he says.

He's betting that even a little bit of computing in places where cellphones will never roam can be very valuable.

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Transcript

RENEE MONTAGNE, HOST:

We're going to hear, now, about scientists reprogramming life. If you think resetting a clock radio is difficult, try bacteria. NPR's Geoff Brumfiel reports on what researchers are trying to achieve.

GEOFF BRUMFIEL, BYLINE: Walk into Drew Endy's lab at Stanford University and you're not going to see much.

DREW ENDY: It's so crazy, right? It's so invisible. It's like this little invisible stuff. It just looks like we're holding, you know, empty pieces of plastic.

BRUMFIEL: Those plastic Petri dishes aren't empty, though. They're home to tiny colonies of E. coli bacteria. Not the kind of E. coli that makes you sick. These are a laboratory strain, and to Endy, they aren't just single-cell organisms. They're something more.

ENDY: So any system that's receiving information, processing information and then using that activity to control what happens next, you could think of as a computing system.

BRUMFIEL: These little E. coli are out in the world. They're sensing their environment. Is there food? Is the temperature all right? They process this data and make simple decisions about what to do next. Most of the time, it's just whether to reproduce. Endy sees potential for them to do so much more. He wants to take control of a cell's genetic machinery.

ENDY: For us, what's become exciting is the idea that we could get inside the cells and, in sort of a bottom-up fashion, implement computing under our control, under human control, within a biological context within the cells.

BRUMFIEL: Endy is talking about more than splicing in a few extra genes, like scientists already do with crops. He wants to make cells that can follow different programs, like a computer can. To do that, he needed to create, out of DNA something all computers have to have, something that physicists invented way back in the 1940s.

(SOUNDBITE OF PROMOTIONAL VIDEO)

UNIDENTIFIED MAN: The impact of the transistor on the electronic industry and on our society is unquestioned.

BRUMFIEL: This old promotional video from Bell Labs goes on to explain that transistors are simple on/off switches. Computers are made of many millions of these switches. And to program a cell, you need biological switches. As Endy reports this week in Science, he managed to make them.

ENDY: We've made this thing called the transcriptor. The transcriptor is the analog in genetics to the transistor in electronics.

BRUMFIEL: His transcriptor switches are pieces of DNA that he can flip on and off, using chemicals called enzymes. Endy put several of these DNA switches inside his bacteria. That gave him a logic circuit he could use to program the cell's behavior. For example, he could tell a cell to change color in the presence of both enzyme A and enzyme B together.

That's a simple program. If enzyme A and enzyme B, then turn green. This kind of if/then logic is at the heart of computing.

TIMOTHY LU: If my first name is Tim and my last name is Lu, then I am this person Tim Lu.

BRUMFIEL: Tim Lu is at the Massachusetts Institute of Technology. He's also building cellular computers.

LU: This idea of using DNA-based computation is starting to accelerate.

BRUMFIEL: He can see lots of ways that these little biological computers could be used. For example, you could program cells that would automatically scan your bowels for chemical signals of cancer.

LU: These cells could light up, and you could easily see whether the cell has computed whether you may have early signs of cancer or not.

BRUMFIEL: With a little more programming, you might even be able to do something about it.

LU: It could produce drugs that treat the condition, that the circuit is meant to detect or they could express, for example, killer proteins that kill off the cells that are cancerous in nature.

BRUMFIEL: So far, only the simplest logic circuits work. And Drew Endy doubts that these DNA computers will ever outperform a Smartphone. But that's not the point.

ENDY: We're building computers that operate in a place that your cell phone isn't going to work.

BRUMFIEL: And Endy bets that getting even a little bit of computing into places where cell phones will never roam can be very valuable. Geoff Brumfiel, NPR News. Transcript provided by NPR, Copyright NPR.