Chemical engineers like to work on a large scale, putting the right
pieces together to make manufacturing plants purr. Not Jay Keasling.
Sure, this University of California,
Berkeley professor thinks a lot about the mechanics of production
and how to improve the output of such vital products as anti-malarial
drugs and alternative fuels. But the factories he works on are very,
very small. So adjust your eyes. You’ll need to see things
on a microscopic level to understand just how big his research is.
Start with Keasling’s Berkeley lab on any given day. Here, you’ll find a flock of graduate students and post-docs working the bench, designing tiny cells to be the clean chemical factories of the future. By cloning genes from various plants and microbes, they retool the metabolism in cells to make substances—like drugs—that are difficult to extract from individual plants or aren’t found naturally. It’s called synthetic biology, and Keasling’s lab is at the forefront of the field.
“The problem and challenge with a lot of chemistry is that some of the most important drugs or molecules are difficult to make with synthetic chemistry,” says Keasling, a professor of chemical and bioengineering, and the director of the Berkeley Center for Synthetic Biology and the Physical Biosciences Division of Lawrence Berkeley National Laboratory. “Nature has these enzymes that catalyze reactions. You can take natural enzymes from different sources and put them together in a microbial cell and build chemicals. Our goal is to rebuild biology, rapidly and reproducibly.”
Rapidly and reproducibly are the key words, and if Keasling sounds like a man on a deadline, he is. After all, minutes matter for a laboratory determining the most efficient way to produce a ready and inexpensive synthetic supply of the anti-malarial drug artemisinin. In the developing world, malaria kills a child every 30 seconds and up to 3 million people each year. Add to that the fact that the Gates Foundation, which funds his research, is watching the clock, and it’s easy to see why there might be pressure.
Artemisinin is a compound found in wormwood plants that grow in Southeast Asia. Its healing benefits have been known for decades, but the drug is time-consuming and expensive to produce. Environmentally, the process is not sound. Gasoline is used as the solvent to extract the active chemicals. And the drug sells for about $2.50 a dose, a price that is way beyond the means of most people with malaria. With this in mind, Keasling and his team decided that making synthetic artemisinin was a worthy, albeit lofty goal. By 2005, after many trials, Keasling’s team had cloned the genes responsible for making artemisinin. Now, they’re trying to retool those very metabolic pathways inside a microbe to produce larger quantities of the drug that can be sold for pennies.
Farnaz Nowroozi, a graduate student in bioengineering who works in Keasling’s lab, says Keasling not only cares about the scientific process but also about creating products that make a difference. “He really gives you the feeling that you’re doing something good, that you’re doing something that will affect other people in parts of the world that a lot of people don’t care about,” she says.
Social responsibility certainly plays a role in Keasling’s research. In 2002, he and a number of his post-docs founded a company called Amyris over many long nights of takeout food and bottles of wine. They knew their research was promising, and they wanted to be able to commercialize their products, especially drugs like artemisinin that could cure millions of people. But for a professor and his post-docs—not exactly the usual targets of venture capitalists—funding was a problem. With the urging of his peers, Keasling made a pitch to the Gates Foundation. The reply turned out to be as innovative and multi-faceted as Keasling’s work. In 2004, the Gates Foundation awarded a $42.6 million, five-year grant to Keasling’s university lab, Amyris and the Institute for OneWorld Health, a not-for-profit pharmaceutical company. While Amyris would work to commercialize the technology developed at Berkeley, OneWorld Health would figure out the most efficient way to manufacture the drug.
“People at Amyris—present company included—are almost fanatical about doing work they find impactful and significant,” says Neil Renninger, vice president of development for Amyris Biotechnologies. “You combine this with some of the brightest scientists in the world, and the atmosphere is electric. Passionate scientists doing work that they love! If someone wants to label us as socially responsible, we’ll take it.”
The race against time to produce synthetic artemisinin in large quantities is motivated by another factor. “Rogue pharmaceutical companies are making artemisinin-based drugs, and some manufacturers are developing monotherapies, which have only one drug in them,” Keasling says. The World Health Organization recommends that anti-malarial drugs be given as combination therapies. This reduces the risk of people developing a resistance to artemisinin. “If we could produce this drug in quantity, we could decide who gets it,” Keasling says, and put the rogue manufacturers out of business. But that will take some time. Keasling estimates that the earliest the drug will be marketed is late 2009.
More Than Malaria
Meanwhile, Amyris is tapping the potential of synthetic biology to help solve other global problems. The technology to make synthetic drugs can be directly applied to other products, such as biofuel, if the metabolic process is modified. It’s a matter of designing microbes to produce the right product—in this case, efficiently converting cellulose to sugar and sugar to fuel. It somehow sounds simple (“It’s my job to make it sound simple,” Keasling says), but it will take years to perfect. Fortunately, it looks like Keasling will have some strong backers. In January, the petroleum giant BP announced that it’s setting up a new $500 million Energy Biosciences Institute with Berkeley and the University of Illinois to create renewable energy. Berkeley was chosen in part because of Keasling’s synthetic biology lab.
“He’s very optimistic and open-minded to different ideas that students in the lab have,” says Howard Chou, a graduate student in bioengineering who is working on the biofuel project. “He’s very energetic. If you approach him with a project and it sounds reasonable, he’ll say go for it. If you’re having trouble with something, he’ll say it’s all right, just keep at it. He understands that it takes a good amount of time to do the experiments right in molecular biology.”
That kind of rapport and an inspiring work ethic are Keasling’s keys to motivating his graduate students, says Renninger. “He expects a lot but doesn’t do so with a stick, or a carrot for that matter, but by providing an example of an unbelievable work ethic. His work ethic is certainly a product of his days growing up on the farm in Nebraska, cleaning up after the pigs and such.”
Yes, Keasling was raised on a farm and he spent a lot of time with pigs. “I’m not terribly fond of them,” he says, which is one reason he got off the farm and turned his focus toward engineering. He got his Ph.D. in chemical engineering from the University of Michigan, did a postdoc at Stanford and started teaching at Berkeley in 1992. He liked the fact that engineers manipulated systems to behave in predictable ways: He just wanted to do it with cells instead of, say, computer chips.
Now, Keasling’s work on biofuels may take him back to the farm. After all, cellulose needs to come from somewhere. “The Midwest could become the new Mideast,” Keasling says. Farms in Nebraska and Iowa could grow the grasses needed to produce cellulose. “We might be able to produce all the fuel we’re going to need for transportation from farmland,” he says. One calculation shows that transportation fuel for the entire country could be produced on about a quarter of the current farmland in the United States. “We’ve got a lot of work to do. This is 15 to 20 years off, but it’s really essential that we do this … Just think of the implications if we had been working on this for the last 20 years,” Keasling says.
The implications are huge, just as they will be if synthetic artemisinin effectively cures malaria. Keasling says he hasn’t been to Africa yet, one of the continents plagued by the disease, but he hopes to go when the drug is launched. “There’s just so little time to do everything. We’ve been working so hard, so fast and so furious on getting it done,” he says. Still, despite his frenetic, never-boring work life, he has the motivation to go to the gym every day. “I often wonder if he sleeps,” Renninger says, “or if somewhere along the way he learned to clone himself and just isn’t sharing his secret methods with the rest of us!”
Alice Daniel is a freelance writer based in Fresno, Calif.