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Interview With Jay Keasling, Pioneeer in Synthetic Biology

Aired February 10, 2013 - 14:30   ET


DR. SANJAY GUPTA, CNN ANCHOR: He's creating new life forms.

JAY KEASLING, PROFESSOR, CHEMICAL ENGINEERING AND BIOENGINEERING, UNIVERSITY OF CALIFORNIA: In my mind, the environment is one of the most important reasons to do it, but it's also about energy security.

GUPTA: Engineering cells to produce medicines, fuels and cosmetic compounds from simple ingredients like sugar cane or grass.

UNIDENTIFIED MALE: One day I think he'll be a Nobel Prize winner.

KEASLING: The carpet on the floor, paint on the ceiling, they come from petroleum. We have the potential to produce all of these products from sugar.

GUPTA: Jay Keasling is a pioneer in synthetic biology. A field even he didn't know existed ten years ago. The term synthetic biology, what does that mean?

KEASLING: That means engineering biology to do things it wouldn't naturally do.

GUPTA: Today, Keasling's man-made microbes are having a profound impact, from a new low-cost anti-malarial drug --

KEASLING: The product will be on the market in 2013. That means 100 million people will be impacted by the scientific discovery.

GUPTA: To cleaner, more efficient alternatives to gas and ethanol. They can be programmed to save lives one day, the environment the next. Sound like science fiction? Well, get ready to step inside the Keasling lab and meet a scientist hell-bent on brighter future. I'm Dr. Sanjay Gupta and this is THE NEXT LIST.

KEASLING: Energy is our biggest industry on the planet. But I think governments around the world need to realize that unless we stop putting carbon into the atmosphere, sea levels going to continue to rise and it's going to create huge problems.

GUPTA: So what is JBEI?

KEASLING: JBEI is a research institute. We do basic science on how to turn biomass into biofuels.

GUPTA: It sounds pretty simple when you put it like that.

KEASLING: It's not so simple. It's actually really complicated work. I'm Jay Keasling and I'm a synthetic biologist.

BLAKE SIMMONS, JOINT BIOENERGY INSTITUTE: The Joint Bioenergy Institute or as we call JBEI is funded through the Department of Energy and it's funded at a level of $25 million a year.

KEASLING: So our goal here is to engineer microbes to produce fuels that behave exactly the same as petroleum-based fuels so you can put them into your tank and if you have a gasoline car, they would behave the same.

SIMMONS: We call them drop-in biofuels. Those are fuels or blend stocks, molecules that are identical to those that are in fuels today.

GUPTA: Most people hear microbes and they think something that can cause a problem, cause an infection. You look at microbes and see what?

KEASLING: I see little chemical factories. In fact that's how we treat them.

JACK NEWMAN, FORMER KEASLING STUDENT: A microbe is generally considered to be a single-celled organism. So not a multi-cellular organism like I am, but a single-cell organism would be yeast.

KEASLING: We use it to make bread, beer, wine. It's been used for centuries.

NEWMAN: Yeast has got inside an amazing ability to do different kinds of chemistry. This is map of all of these different chemicals and pathways is basically what yeast can do chemically. One, yeast, we know is really good at taking in sugars, like sucrose, what you put in your coffee. It goes through a series of chemical reactions and I can find my way right down here to ethanol.

KEASLING: Ethanol is okay in gasoline, as a small percentage as an oxygenate. It doesn't have the full value of the petroleum-based fuels that we use and it can't be used as a diesel fuel or a jet fuel.

NEWMAN: What we want to do is reroute this pipeline going down over to this part of the map, which these are the hydro carbons. Hydro carbons are what petroleum is. Our world is built on petroleum, so there are lots of things that you could do.

KEASLING: The way we do this is by engineering the genes. So changing their genetic makeup changes the chemistry that goes on inside them.

GUPTA: Once you figure out how you want to tweak it. What genetic material needs to be in the microbe or the plant? How do you do it? What's the process of actually doing that?

KEASLING: Well, that process has been around for 40 years. In the early '70s we learned how to clone DNA. We learned how to cut pieces of DNA that contain genes and splice them into other pieces of DNA. That technology has come a long way in the last 40 years to the point now where it's not just one gene that we can cut and splice. It's many genes.

NEWMAN: So this is, this is an example of some of the coding that people have been doing putting together these pieces of DNA. What that actually ends up giving you is colonies of yeast in a grid fashion like this. That are all the output of coding you've done in the DNA so from the computer into a living yeast cell.

GUPTA: Is there any danger to this? Like if these microbes got out, or were not adequately sterilized, could they be a problem?

KEASLING: There are two answers to that the first is we're working to make sure that those microbes don't survive. So we can actually build kill switches in them so that they will self-destruct once they get out of the tank. We can build in mechanisms that give them a nutrient source in the tank they would never find out in nature and the third answer is that these microbes have been so heavily engineered, they won't compete.

GUPTA: So they're not going to go out there and suddenly turn a bunch of sugar that's in wastewater into oil?

KEASLING: That's right. They're not even going to survive. Our first success using synthetic biology was using yeast to produce a precursor to malaria cure.

NEWMAN: It's a 95 percent effective cure against uncomplicated malaria meaning 95 percent of the time you'll take the drug and three days later you'll be cured of malaria.




KEASLING: Our first big success using synthetic biology was to engineer a yeast to produce pre-cursor to anti-malarial drug organism. We were engineering microbes to produce chemicals and one of my graduate students happened on paper that described this drug that treats malaria.

NEWMAN: It's a 95 percent effective cure against uncomplicated malaria. Meaning 95 percent of the time you'll take the drug, three days later, you'll be cured of malaria. The problem is it comes from a plant, which is seasonally in short supply.

KEASLING: So we read about this and we looked at the chemical structure and we said boy, I think we can make that.

NEWMAN: That's where the Bill and Linda Gates Foundation came in. So they put in the first trench of money that allowed us to work on the anti-malarial and give it away for free. KEASLING: The product will be on the market in 2013. They plan to produce 100 million treatments annually. That means 100 million people will be impacted by the scientific discovery. Their lives will be made better or their children's lives could be saved. That project allowed us to start Amyris. We brought together some fantastic scientists, a small team to nucleate the company and it's blossomed into a 500-person company.

UNIDENTIFIED MALE: I think that's what Jay gave to his students to the founders, a chance to move from the lab to the real world.

NEWMAN: At its foundation, Amyris is a renewable products company. So we bring renewable products to the market place. Currently most of our effort is in the recoding to make something called "Farnesine." "Farnesine" is a hydro carbon that can be used to make all different kinds of products.

KEASLING: It can produce flavors and fragrances that we find in our perfumes. That we find in some of our processed foods, even things like detergents to make them smell better.

NEWMAN: One most people know about what's running the bus in the Brazil is the diesel.

JOEL VELASCO, AMYRIS: At the base of all of this is sugar and that's why we're here in Brazil, and this sort of ground zero of sugar production. Why, because sugar is ultimately the most basic source of energy.

JOSE LUIS POLI: (Inaudible)

VELASCO: Brazil will produce about 500 million to 600 million tons of cane this year. Generally most of these mills about half of this would go to make raw sugar, sugar that we'll consume in our food and the other half goes for ethanol. In the case of this company, what they're doing is reducing the amount of ethanol they're going to produce.

And taking some of the sugar cane and in essence selling it to Amyris. We need the sugar to basically feed the microorganisms that are going to eat the sugar, and take the energy and produce hydro carbons, oils.

A truck comes in and they'll use hydraulics to dump the cane into what are in essence large shredding machines. Think of very large garbage disposers. It will crush it and squeeze every little bit of juice, which is water and sucrose and separate that from the straw. The company takes that juice and it comes up by a pipe system. We will purify it and sterilize it so we can produce our products.

EDUARDO LOOSLI, AMYRIS: So this is a control room to monitor the fermentation process, where we convert sugar into the farnesine. Mainly monitoring or controlling ph, air flow rates, temperatures and things like that.

NEWMAN: This is a mixture of yeast, water and farnesine, the oil that's in there. The hydro carbon is less dense than water. So if you let this sit, it will just float to the top, but we have a way to do that a little bit faster by just using something like a dairy creamer. What that will do is separate basically the cream, the oil farnesine which comes out in here, from all the other stuff, yeast, basically water and salt is what's left.

This is about 93 percent, 95 percent pure. We do a quick clean- up step and it's water weight. It's more than 98 percent pure. We hydrogenate it and it becomes diesel that you would use in a bus in Rio or Sao Paolo.

Currently, everything comes from petroleum. As renewables come online, what I would like to do is have Amyris that showed people you could get materials from something other than petroleum.

KEASLING: My father said to me, are you trying to put me out of business? And I said no, it's exactly the opposite. We want to help American agriculture. We want to give farmers other crops to produce.




KEASLING: I grew up on a farm in Nebraska. It was farm that's been in my family for five generations. The first 18 years of my life I had this smell of pig manure on my hands. We go back to Nebraska twice a year, to see my father, my sister and her family and the boys just love it. So it's still very close to my heart.

I'd like to return something to Nebraska, to the farm economy, because I think they deserve it. Energy is our biggest industry, 225 billion gallons of transportation fuels alone in the U.S. So it's going to take a lot of biomass. The typical plant is about two-thirds sugar whether it's a tree in the forest or the grass in your lawn.

Those sugars can be used to produce fuels. In order to produce the fuels we have to get the sugars out of the plant. Now, the genetic modification of the plant could make this process much easier.

For instance, you might be able to extract the sugars much faster using the genetically-modified plant than the normal plant.

GUPTA: So you're doing two things. You're genetically modifying the plants to have more sugar available and you're genetically modifying microbes to use the sugar?

KEASLING: Exactly. What we really want is a plant that grows well and at the same time is able to release its sugars when we want them released.

GUPTA: Is there an ideal plant from what you've learned so far?

KEASLING: There's no one plant that's going to be the silver bullet. It will all depend on the climate and the location. So in the U.S. Midwest, the plains states might have switch grass. The Pacific Northwest might have trees. The very Deep South could have sugar cane. It all depends on the climate, the amount of rain, sunshine, et cetera.

GUPTA: Let me guess where you're originally from, Nebraska, Cornstover.

KEASLING: The interesting thing about Cornstover we could have our food, the corn and use the rest of the crop for producing energy.

GUPTA: Right. It sounds like you're changing agriculture.

KEASLING: We hope to change agriculture. When we got the grants, we said we're going to do fuels that could go in all modes of transportation, not ethanol and that we were going to use cellulose crops, rather than corn, which is a food crop.

My father said to me, are you trying to put me out of business and I said no, exactly the opposite. We want to help American agriculture. We want to give farmers other crops to produce. Farmers could be producing energy as well as food.

GUPTA: What does it mean in terms of the average person's life? Will products be cheaper? What does it mean for them?

KEASLING: Let me answer this in a couple of ways. First we use about 225 billion gallons of transportation fuels in the U.S. on an annual basis, diesel, jet fuel, gasoline. To replace about a third of that, we'll take about 100 million acres.

U.S. has about 450 million farmed acres. That's about a quarter of the farmed land in the U.S. and that's going to take many generations to do. And it's not going to be cheaper for the American citizens, right? It's going to be cleaner. It will also be home grown.

GUPTA: What's the down side?

KEASLING: The down side is it's going to take us a while to get there. It's going to take money to get there.

GUPTA: Do you feel a sense of urgency? I mean is there, is there the drum beat for you to move as fast as you can here?

KEASLING: Well, I mean, the sea is rising, right? And now we've got half of the world population in China and India that want to have the same lifestyle as ours, so there's huge urgency here.



KEASLING: I have two sons, they're adopted. We adopted them when they were very young, one four months and one two weeks old. They're great. I don't know that they'll end up being scientists although my older son is getting very enthusiastic about chemistry and math.

So there's hope. They do see that I spend a fair amount of time working. So they think I work too hard and that all scientists work this hard. I tried to explain to them that not everybody works as hard as I do.

You never know if something is going to be a success. Things can fail and in fact, I would argue that a fair fraction of things you do should fail. Otherwise you're not -- you're not being entrepreneurial enough or you're not being, taking enough risk.

You have to be patient to watch something grow and oftentimes, things will go through bubbles. We saw this with biofuels business, for instance, where it was over-hyped. But if we have patience, I'm sure that we can get there and there's a great case study and that's Brazil.

In the late '70s, Brazil and the U.S. were on track to do research and produce fuels. In the early '80s, we stopped the research in the U.S. and in Brazil, they just kept going and just a few years ago, they became petroleum-independent. In the U.S., we restarted all of the research about five years and we're trying to play catch-up.

But we'll get there as long as the government has steady policies and policies that at least balance favorably biofuels with petroleum- based fuels. Oil companies have invested heavily in renewables and to be frank if we're going to get renewable fuels in people's tanks, it's going to be through the petroleum companies.

Because they're the ones who have the pipelines, they have the trucks that will get it to the gas stations and they have some of the gas stations. So they're an important part of it. And from their perspective, I think they would want a piece of it. I don't think we'll ever see a day when biofuels cost less than petroleum-based fuels.

Biofuels have the advantage that they don't put additional carbon into the atmosphere. When we take petroleum from the ground and we refine it into fuels and then we burn those fuels in our engine that puts excess carbon into the atmosphere. That wasn't there before.

When you make fuels from sugars, those sugars in the plant are made, taking carbon dioxide out of the atmosphere, makes the plant material, we turn the plant material into the fuel, you burn it in your car and the carbon goes back. So you have a complete cycle, a carbon cycle.

And if you're really good in this process, it can be carbon- neutral. This means that we won't put additional carbon in the atmosphere. We won't have global warming to the degree we have it now and we might save the planet from increases in temperature.

GUPTA: Is there a point now when you look at the work that you're doing, and say -- I will one day be done?

KEASLING: I don't think I'll ever be done because there are always more things to do. And as the capabilities increase, we're able to build more inside of a microbe or inside a plant that opens up huge possibilities. There are so many big problems that we could solve and a lot of them we could solve with biology.

We spend a huge amount of energy and money putting fertilizer on crops like corn. In fact we spend about 1 percent of the world's energy just making fertilizer for corn in the U.S. if that corn could take the nitrogen out of the air and fix it like beans do, then we wouldn't have to fertilize corn.

Another important problem, we don't have enough drugs for diseases. We see these multidrug-resistant microbes popping up in hospitals and it's kind of scary. We need better drugs. I think this is an area where synthetic biology can really help.

If you look around this room, nearly everything that we're in contact with is derived from petroleum. The carpet on the floor, the paint on the walls, the ceiling tiles, they all come from petroleum we have the potential to produce all of these products from sugar.

So it could open up an entirely new avenue for agriculture, it could open up an environmentally-friendly way to produce all of these products that we use on a day-to-day basis.

GUPTA: Is that part of what drives you? Do you look at the world just differently as a result of knowing how sugar could be substituted for these petroleum-based products?

KEASLING: I don't know if I look at the world that differently. I have a very good hammer and so I see a lot of nails. And I see that we could use this tool that we have, this capability, to make lives better and so I think it's, it's one of my goals is to try to make the world a better place.


GUPTA: By reprogramming cells to produce cleaner, more efficient versions of fuels and other chemicals we've all grown so dependent on, Jay Keasling has opened the door to a brighter, more sustainable future and that's what puts him on THE NEXT LIST.

I'm Dr. Sanjay Gupta. Hope to see you back here next Sunday.