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Synthetic DNA on the Brink of Yielding New Life Forms

Jason Lutes sets up fermentation equipment at LS9. The reprogrammed bacteria make the fuel from corn syrup and cane sugar.
Jason Lutes sets up fermentation equipment at LS9. The reprogrammed bacteria make the fuel from corn syrup and cane sugar.

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"I see a cell as a chassis and power supply for the artificial systems we are putting together," said Tom Knight of MIT, who likes to compare the state of cell biology today to that of mechanical engineering in 1864. That is when the United States began to adopt standardized thread sizes for nuts and bolts, an advance that allowed the construction of complex devices from simple, interchangeable parts.

If biology is to morph into an engineering discipline, it is going to need similarly standardized parts, Knight said. So he and colleagues have started a collection of hundreds of interchangeable genetic components they call BioBricks, which students and others are already popping into cells like Lego pieces.

So far, synthetic biology is still semi-synthetic, involving single-cell organisms such as bacteria and yeast that have a blend of natural and synthetic DNA. The cells can reproduce, a defining trait of life. But in many cases that urge has been genetically suppressed, along with other "distracting" biological functions, to maximize productivity.

"Most cells go about life like we do, with the intention to make more of themselves after eating," said John Pierce, a vice president at DuPont in Wilmington, Del., a leader in the field. "But what we want them to do is make stuff we want."

J. Craig Venter, chief executive of Synthetic Genomics in Rockville, knows what he wants his cells to make: ethanol, hydrogen and other exotic fuels for vehicles, to fill a market that has been estimated to be worth $1 trillion.

In a big step toward that goal, Venter has now built the first fully artificial chromosome, a strand of DNA many times longer than anything made by others and laden with all the genetic components a microbe needs to get by.

Details of the process are under wraps until the work is published, probably early next year. But Venter has already shown that he can insert a "natural" chromosome into a cell and bring it to life. If a synthetic chromosome works the same way, as expected, the first living cells with fully artificial genomes could be growing in dishes by the end of 2008.

The plan is to mass-produce a plain genetic platform able to direct the basic functions of life, then attach custom-designed DNA modules that can compel cells to make synthetic fuels or other products.

It will be a challenge to cultivate fuel-spewing microbes, Venter acknowledged. Among other problems, he said, is that unless the fuel is constantly removed, "the bugs will basically pickle themselves."

But the hurdles are not insurmountable. LS9 Inc., a company in San Carlos, Calif., is already using E. coli bacteria that have been reprogrammed with synthetic DNA to produce a fuel alternative from a diet of corn syrup and sugar cane. So efficient are the bugs' synthetic metabolisms that LS9 predicts it will be able to sell the fuel for just $1.25 a gallon.

At a DuPont plant in Tennessee, other semi-synthetic bacteria are living on cornstarch and making the chemical 1,3 propanediol, or PDO. Millions of pounds of the stuff are being spun and woven into high-tech fabrics (DuPont's chief executive wears a pinstripe suit made of it), putting the bug-begotten chemical on track to become the first $1 billion biotech product that is not a pharmaceutical.

Engineers at DuPont studied blueprints of E. coli's metabolism and used synthetic DNA to help the bacteria make PDO far more efficiently than could have been done with ordinary genetic engineering.


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