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The All New Synthetic

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Randy Rettberg is building an industry -- or at least he's trying. While interest in synthetic biology continues to grow by leaps and bounds, its use in real-world science has remained fairly minimal. Synthetic biology, or the goal of developing an engineering discipline that can build biological systems in the way that other engineers can build chemical or computational systems, is still young. "I think that the field is very, very early," says Rettberg at MIT. While it's 2007 for the rest of us, "in many ways it's much more like 1850 in this corner of the world. The standards for measurement aren't there. There aren't that many parts. There aren't huge conventions in Las Vegas," he adds.
But there is a jamboree, and that's something.

Rettberg cofounded iGEM, or the International Genetically Engineered Machine competition, with his fellow synthetic biology proponents and MIT scientists Drew Endy and Tom Knight. It stemmed from a course they taught first in 2003, and again in 2004. The competition, now an annual event featuring teams of undergraduate students working to design innovative biological parts or synthetic biological systems, has grown from five teams in 2004 to 38 last year. "It's almost tripled each year," says Rettberg, who's beginning to make plans for this year's jamboree, where he's expecting as many as 100 teams and up to 1,400 people. (Calling all synthetic-biologists-to-be: Rettberg says the winter months are when teams sign up to be part of the competition, which is held on the first weekend of November.)

The participants in iGEM may be young, but they represent the beginnings of a new generation of synthetic biologists. Teams hail from schools around the world -- in the most recent competition, half the teams were based in the US and the other half were from Canada, Latin America, Europe, Africa, and Asia -- and range from just four students to close to 20, with a few professors to act as guides. "In general, I recommend the teams be half biology, half not," Rettberg says. Students do most of their work over the summer months between semesters; while they're not given guidelines on what to build, they are sent DNA to fashion some rudimentary parts.

All work is presented at the November jamboree, where prizes are awarded for best device, system, and more. In the jamboree held late last year, the grand prize went to the team from the University of Ljubljana in Slovenia, which engineered a feedback in the TLR signaling pathway to control cellular response to infection with the goal of preventing sepsis.

"It's kind of astonishing that you can have a team of undergraduates work for one summer" and come up with functional designs that could one day have an impact on human health, Rettberg says.

Among other projects: the team from MIT engineered scented E. coli by adding the genes necessary to produce a banana smell. Then, they connected a promoter sensitive to a certain growth stage, resulting in E. coli cells that start to smell like bananas when they reach stationary phase. It's not exactly curing cancer, but it's an advance that makes some strides in synthetic biology, and one that could improve the quality of life of postdocs squinting at their E. coli colonies.

Another team, this one from Edinburgh, designed E. coli to contain an arsenic detector that could be used in parts of the world where wells are contaminated with the toxin. The detector includes a simple color change that responds to pH. The team was "able to measure arsenic concentration down to the five parts per billion level," Rettberg says. The arsenic detector isn't ready to be shipped just yet: Rettberg notes that E. coli, of course, couldn't be used as the host to test water. But the concept is there, and it's a pretty good start.

It's not the only good start. One of the major benefits of iGEM has been to help expand the Registry of Standard Biological Parts — a resource of the biological nuts and bolts that scientists can dip into to help build their own synthetic biological system of choice. That registry is up to 1,000 parts, Rettberg says. "One of the keys to an engineering discipline is to have an idea of interchangeable parts," he adds.

"We think of synthetic biology as an engineering discipline where you are trying to build things," Rettberg says. "You have to know enough to make it work and make it work reliably, but you don't have to understand everything completely."

Rettberg and other synthetic biology supporters hear a lot about the potential harm of synthetic biology, such as scientists deliberately engineering a dangerous biological device and unleashing it on the public as a weapon. "That's kind of the negative moral imperative," Rettberg says. He looks at the arsenic detector example from the Edinburgh team as "a positive moral imperative. Aren't you almost obliged to go forward with it [if there's good that can be done]?"

The people who have fears about synthetic biology hope that it can be quashed. But if Rettberg is any judge, it's simply a matter of time before the field really gets moving. "At some point in time it will be kind of reaching a critical mass," he says. "What you're heading toward in the long run with this is an industry. One of the things that's happening with iGEM is that we're planting the seeds for that all over the world."

 

In Retrospect: Synthetic Biology Roundup

Amyris Biotechnologies, a company cofounded by synthetic biology leader Jay Keasling, announced late last year that it had raised $20 million in its first round of venture capital funding. At the same time, the company hired John Melo, former president of US fuels operations for BP, as its CEO. Amyris was first started to help take Keasling's Berkeley research on a synthetic treatment for malaria into the commercial realm. The company has since formed a partnership with Berkeley and the Institute for One World Health to help develop a cheap treatment for malaria using synthetic chemistries to produce a compound similar to artemisinin, the anti-malarial drug.

In community news, synthetic biologists are rallying to ward off the kind of negative publicity that's threatening the field as outsiders grow increasingly worried about engineered viruses and other threats. Repeatedly during the past year, scientists have met with government representatives, lawyers, ethicists, and a host of other people to iron out a community declaration that could help spell out the promise of synthetic biology while taking steps to prevent ne'er-do-wells from using the nascent engineering discipline for malevolent aims.

The community's declaration — which, at press time, was still a work in progress — supports having an open working group to help coordinate software and other measures to keep an eye out for people looking to synthesize sequences of "hazardous biological systems," according to the declaration. It also encourages vendors of DNA synthesis tools and reagents to have validation practices for their customers — again, to prevent people from ordering potentially hazardous DNA sequences.

Also in the past year, NSF committed $20 million to the establishment of SynBERC, or the Synthetic Biology Engineering Research Center. The center is an alliance of MIT, Berkeley, Harvard, UCSF, and Prairie View A&M University. Keasling serves as director, and SynBERC resides at the QB3 institute in California.

"SynBERC is the first time we've had long-term support to improve the technical foundations that underlie the engineering of biology," said MIT's Drew Endy in a statement at the time of the funding award.

 

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