Volume 3, Issue 22 August/September 2006
Life 2.0
Jay Keasling (center) with graduate students Doug Pitera (right) and Sydnor Withers (left). "My dream is to see my laboratory's technology producing inexpensive drugs for the Third World," says Keasling. (Bart Nagel photo)
For 3.6 billion years, evolution has governed the biology of this planet. Molecular biologists can now shift bits of DNA from one organism to another, but the parts they play with are limited to what Mother Nature provides. Recently, Mother Nature teamed up with a handful of researchers whose aim is nothing short of reengineering life. UC Berkeley chemical engineer Jay Keasling is leading a new center funded by the National Science Foundation to create the future of synthetic biology, where genes, proteins, and cells are snapped together to build living systems.
"The idea of synthetic biology is to do for biology what electrical engineers have done for circuit design and chemists have done for the synthesis of chemicals," says Jay Keasling, professor in the Departments of Chemical Engineering and Bioengineering. "We're turning biology into an engineering field."
Already, Keasling--who also heads the Lawrence Berkeley National Laboratory's Synthetic Biology Department and QB3's Berkeley Center for Synthetic Biology--has made strides in converting bacteria into chemical factories that produce the anti-malaria treatment artemisinin for pennies instead of dollars. Similar microbial factories could crank out the costly anti-cancer drug Taxol, synthesized naturally by the Pacific yew tree, or produce a promising anti-AIDS drug derived from the Samoan mamala tree.
Under the umbrella of the new Synthetic Biology Engineering Research Center (SynBERC), funded with a $16 million, five-year NSF grant, Keasling and his colleagues are beginning to engineer organisms that produce hydrogen, octane, or molecules for alternative energy applications. The Synthetic Biology researchers are also prototyping a bacterium that eats toxic waste, such as heavy metals. Keasling is leading the charge to engineer a single-cell soil microorganism, Pseudomonas putida, that would swim into a pool of pesticides or nerve agents and degrade the chemicals. Another project's goal is to develop the next-generation of tumor-fighting drug delivery systems in the form of a novel microbe.
Sweet wormwood, or Artemisia annua, used by Chinese herbalists since A.D. 150 to treat fevers, today holds promise of a cure for malaria, a disease that kills one African child every 30 seconds. (Bart Nagel photo)
SynBERC is a collaborative effort among UC Berkeley, Harvard, the University of California, San Francisco, and the Massachusetts Institute of Technology. Together, the researchers will create a "parts store" of interchangeable components that can be combined together to make devices, for instance a microorganism that "eats" heavy metals or nerve agents for bioremediation of hazardous waste sites.
"We'd want to build devices that can be put inside a chassis, a cell," says Keasling. "Energy will be one of the greatest applications of this."
Recently, the group began designing an organism that can ferment cellulose as a raw source of renewable energy. While ethanol is often touted as an ideal alternative fuel whose production could be boosted with synthetic biology, Keasling points out that it can't be piped easily and has relatively low energy content. Instead, he'd like to engineer a benign organism to degrade waste paper or biomass and convert it into octane. However, inserting cellulose-converting proteins into a bacterium and scaling the process up to be practical is no easy task.
"You've got a relatively complicated and dirty system," Keasling says. So you've got to engineer a microbe to actually go in, find the cellulose, turn it into sugar, and then through its metabolism turn that into fuel."
UC Berkeley's Jay Keasling (left) and ethnobotanist Paul Alan Cox (right) sign agreement with village elders in Samoa, agreeing to share with them any royalties from sales of an anti-AIDS drug derived from the native mamala tree. (Photo courtesy Steven King)
Along with energy, Keasling envisions a revolution in medicine driven in part by advances in synthetic biology. Someday, he hopes to engineer stem cells that can be programmed to build replacement organs for transplant into patients without rejection. Closer to reality, though, are microbes that hone in on tumors in the body and release drugs to attack the cancer cells.
"It's the ultimate in detection, deployment, and tumor killing in a single apparatus," Keasling says.
While progress is rapidly accelerating, synthetic biology is still in its infancy. In many ways, it's where genetic engineering was before the launch of the Human Genome Project. And the public fear surrounding genetic engineering is not lost on Keasling. Ideally, synthetic biology will be self-regulated, he says, without the need for government intervention. But before scientists can convince the public that the field is safe, they themselves have to be sure that it is safe. To that end, the SynBERC researchers will also be exploring the societal implications of their work, from how intellectual property laws may need to be reconsidered to the ethics of reinventing biology from the bottom up.
"It's getting easier to engineer life, and synthetic biology will make it simpler still," Keasling says. If the public doesn't realize you can use it to make new drugs or renewable energy, it will look like we're tinkering with life. As scientists, it's our responsibility to prove that synthetic biology has tremendous potential to save lives."