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Minimalism

The roots of Venter’s ambitions lie in an earlier effort called the Minimal Genome Project. In the mid-1990s, researchers at Venter’s Institute for Genomic Research sequenced the first two complete genomes-both bacterial. Armed with new information on the genes that make each species unique, the researchers were curious to see which of those genes were necessary to sustain life. It wasn’t just curiosity that drove the project though. If researchers could identify those genes, they reasoned, they would be able  to model the most basic of cell activities. “That would be helpful in understanding more complex cells and in designing new ones,” says Hutchison.

The team started with a lowly bacterium called Mycoplasma genitalium, whose tiny genome consists of just 517 genes made up of about 580,000 DNA letters. “I raised the question: Does the bacterium need all those genes?” says Hutchison, who had taken a sabbatical from the University of North Carolina to work on the project. By selectively disabling different genes, the researchers discovered that only 265 to 350 were essential: few enough to make it conceivable that researchers could assemble the entire genome from scratch, though the endeavor might take a decade or more.

But the group put the Minimal Genome Project on hold in 1999, while Venter focused on sequencing the human genome. Now he has revived the project-this time with a specific application in mind: creating artificial bacteria that could help provide cleaner sources of energy. Under the guidance of Nobel Laureate Hamilton Smith, who left Celera last fall to become the scientific director of the Institute for Biological Energy Alternatives, researchers will try first to build a minimal genome and place it inside a bacterial cell whose own genome has been destroyed. The researchers’ hope is that the synthetic genome will take over, and a new life form will be born. If they succeed with this preliminary experiment, the researchers will then begin to create organisms whose minimal genomes will be supplemented with additional genes that provide instructions for metabolizing carbon dioxide, say, or producing hydrogen fuel.

Not only does designing genomes from scratch allow researchers to engineer new organisms with extreme precision, Venter says, it also allows them to strip the cells of a host of natural functions needed to survive and reproduce in the wild. As a result, synthetic organisms would function only under tightly controlled or rarified conditions such as those inside a biological pollution filter on the smokestack of a fossil-fuel-burning power plant.

“By our back-of-the-envelope calculations,” Venter says, “it wouldn’t be that complicated to have a carbon dioxide scrubber, directly associated with those power plants, that captures all the carbon dioxide and converts it into something economically useful”-like a plastic. Or researchers could engineer bacteria that use methane from waste sites, for instance, to produce hydrogen fuel. “As far as I know, there is no existing organism that can either capture carbon dioxide or produce hydrogen efficiently enough with its existing metabolism to make it economically feasible,” says Venter.

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