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DARPA to Offer $30 Million to Jump-Start Cellular Factories

The Defense Advanced Research Projects Agency (DARPA), the U.S. Defense Department's high-risk granting body, is about to jump into synthetic biology in a big way. One of the latest research buzzwords, synthetic biology means different things to many. But for a new DARPA program, it represents modifying the metabolic and genetic machinery of cells to produce useful products. "We want to create a new manufacturing capability for the United States," says DARPA Program Manager Alicia Jackson. Approved barely a month ago, the $30 million Living Foundries program should be sending out a request for proposals in the next few weeks and making awards several months from now.

With its investment, over the next 3 years DARPA will support academic and corporate researchers for developing and applying an engineering framework to biology for biomanufacturing. The goal is to "break open the field to new players so [they] will not have to be experienced in genetics to design new biological systems," Jackson said yesterday at a DARPA "Industry Day" meeting in Arlington, Virginia.

She drew parallels between synthetic biology and the semiconductor industry, pointing out that applications for integrated circuits really took off once transistors and other components were standardized, enabling many more people to come up with new circuits. She would like to see that happen with synthetic biology, as newcomers to the field are likely to come up with products and applications not considered by the typical synthetic biologist. "A classically trained biologist grows accustomed to limitations," explains Zach Serber, a technologist at Amyris Inc., a synthetic biology company in Emeryville, California. "Having some ignorance about biology can be an asset."

The vision of using cells as factories, with DNA as the instruction set, has been difficult to realize. A single product takes years and millions of dollars to develop. It took DuPont from 1992 to 2007, and an amount of research time equal to the efforts of 575 scientists over the course of a year, to begin making a polymer building block from corn syrup using genetically engineered bacteria, for example. Biosynthesis of artemisinin, an antimalarial medication initially derived from plants, cost $25 million to develop. "And we are not getting any better; we're not getting any faster," Jackson notes. It now takes hundreds of thousands of experiments and many iterations of the DNA instructions to work out the kinks for each cell factory.

DARPA's new program will further encourage the application of an engineering approach so as to lower costs and shorten timelines by a hundred-fold, she asserts. To accomplish that, Jackson says, there's need for the standardization of parts—genes, regulatory DNA, and so forth—the development of interoperable design tools for piecing DNA into the right instructions, quicker and cheaper methods for synthesizing and assembling DNA, and more streamlined methods for assessing these cellular factories. Unlike most programs, DARPA will fund all the meritorious proposals, and has a variety of funding mechanisms, grants, contracts, etc., to meet the needs of the grantee, Jackson pledged. The new DARPA program will also support informatics and the development of new ways to characterize cells, areas not always lumped into synthetic biology.

"There's a lot of foundation work that needs to be done," says Julius Lucks, a synthetic biologist at Cornell University. The fundamental tools that need to be developed to make synthetic biology more affordable and commercially viable are lacking and not really in the purview of typical academic research, Lucks explains. He sees the new DARPA program as "a funding source to bridge the gap between what can be done in the lab and what industry will do."

The Living Foundries program breaks new ground for DARPA's Microsystems Technology Office (MTO), which typically supports electronics, photonics, materials science, and computer modeling research designed to improve communication and sensing systems in war fighters. It's not the agency's first foray into synthetic biology, however. In March, a different part of DARPA issued another call for proposals related to synthetic biology, this time for research related to biosecurity, and there is a vaccine program that uses tobacco that could quality as engineering biology, says Jackson.

The first phase of the Living Foundries effort will support work that advances the tools needed to make synthetic biology more efficient and cheaper. Jackson would like to see vast improvements in how quickly and cheaply researchers can order DNA. Right now, DNA designed for a particular experiment costs at least 45 cents a base and can take up to 2 months to procure. "DNA should cost next to nothing," she says. A second phase will follow that will push to integrate these advances so as to greatly decrease the cost and time for developing and making new products.

DARPA "has a very bold vision," says Daniel Drell, a program manager at the U.S. Department of Energy. "But I don't think this is going to be easy." He predicts it will be challenging to make living systems conform to engineering principles. And Steven Benner, a synthetic biologist from the Foundation for Applied Molecular Evolution in Gainesville, Florida, says that Jackson doesn't appreciate that commercially produced synthetic DNA is really quite reasonably priced given the cost of the chemicals used for making it. Dieter Söll of Yale University notes that while synthetic biology can be sped up, it is still limited by how fast the organisms used reproduce. "Biology is going to fight them," adds Drell.

DARPA isn't the only government agency pushing synthetic biology. This year, NASA set up a synthetic biology group at the Ames Research Center in Moffett Field, California. NASA sees the potential of shipping microorganisms through space to the moon or Mars, where they can be harnessed to convert local soils into bricks and mortar or to produce pharmaceuticals, food, or fuel. As part of that vision, the group is developing ways to encapsulate these living factories for transport, perhaps even for implanting into the human body.

The Department of Energy is "not quite yet" invested in synthetic biology, says Drell. But in the president's request for the 2012 budget, DOE's Biological and Environmental Research Program announced that it would start a program. The fate, size, and scope of its effort is unclear at this point.

The National Science Foundation (NSF), on the other hand, has helped sponsor several leaders in the field. And although synthetic biology is hard to define, NSF already spends at least $40 million a year on the field, according to one of its program officer, Theresa Good. One of NSF's flagship programs, the Synthetic Biology Engineering Research Center is halfway through its $40 million, 10-year award. It includes about 10 senior investigators who "are really going from basic science to [the] translation to industry," says Good. The center has spun off several companies, most focused on producing high-value feedstocks for the chemical industry, sponsors an international student contest for synthetic biology, develops graduate and undergraduate curriculum, and studies the ethical, legal, and social implications of this new field. "They understand how to put circuits together and how to [make] pathways in bacteria much faster than could be done 5 years ago," Good adds.