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For the last few decades, scientists have been intently decoding the genes of dozens of organisms, from bacteria to humans. The effort, which culminated in 2000 with the deciphering of the human genome’s roughly thirty thousand genes, reflects researchers’ increasing adeptness at “reading” the language of DNA. It’s a biological literacy that has meant dramatic advances in understanding the genetic basis of health and disease, bringing with them the promise of safer and more effective drugs.

But now a small group of researchers are looking to a far more ambitious goal than simply reading the sequence of genetic material: they are attempting to write entirely new genomes from scratch. In essence, they hope to create new synthetic forms of life, the likes of which have never before existed, by painstakingly spelling out exact sequences of DNA that hold all the instructions for the new organisms.

It is biotech’s most brazen attempt, so far, to play God. So the fact that Craig Venter, the legendary self-aggrandizing visionary of genomics, is leading the charge should come as no surprise. After all, it was Venter, then the president of Celera Genomics, who headed the controversial private effort to sequence the human genome-and to do so ahead of the public Human Genome Project. Now through the Rockville, MD-based Institute for Biological Energy Alternatives, a nonprofit organization Venter launched last April, he is gearing up to build a synthetic bacterium, by first writing out its genome. It’s a project that would not only help meet the center’s goal of creating high-utility microorganisms specifically designed to mop up carbon dioxide, say, or produce hydrogen fuel with the utmost efficiency; it’s a project that could also upend genetic engineering itself.

Venter’s objective is not merely to tweak existing life forms by inserting genes that confer specific traits-the main tactic in conventional genetic engineering. Instead he wants to assemble an entire genome, DNA letter by DNA letter, putting together only the genes he wants: those necessary for an organism’s survival and those that will allow it to carry out a desired task. “The long-term advantage of creating an organism from a chemically synthesized genome is that it allows complete flexibility of design,” says University of North Carolina biologist Clyde Hutchison. No longer limited to nature’s repertoire, researchers could create a wide variety of synthetic organisms, each made to perform a specific chore, such as sopping up oil slicks or producing a plastic. And because such a bacterium would devote most of its energy to its assigned job, it could, in theory, be much more efficient than a counterpart made via conventional genetic engineering.

Building such an organism “would be a momentous achievement,” says Eugene Koonin, an evolutionary biologist at the National Center for Biotechnology Information, a part of the National Institutes of Health. But, Koonin points out, creating life from scratch presents a few daunting challenges. Even a simple single-celled organism such as a bacterium can have hundreds of thousands or millions of DNA letters. And even if scientists do figure out the exact sequence of DNA that would create the organism they want, they would still have to figure out how to “write” those letters in long stretches of DNA. Though researchers routinely synthesize short DNA strands, today’s DNA-making machines can’t handle anything longer than a hundred letters or so. And piecing together an entire genome from such tiny fragments is a monumentally time-consuming, error-prone task.

Still, despite the audacity of the endeavor, Venter is not alone in his ambition to rewrite the language of life. A small cadre of researchers in academia and industry are working out the details of technologies that could make genome writing routine; one such tool is a machine capable of synthesizing, automatically and with high accuracy, genome length stretches of DNA. And while those scientists are honing their DNA-writing skills, others are looking to transform the genetic language itself by adding entirely new letters to the DNA alphabet-thus creating the potential to give organisms abilities not seen in nature. “The program got written four billion years ago,” says MIT computer scientist Tom Knight, who studies the interface between biology and computing. “It’s time to rewrite the program.”


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