Word: venter
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Dates: during 2000-2009
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...shuttled between his ship and his lab, Venter was overseeing another, equally grand and potentially revolutionary science project: creating life in the lab. Among the organisms he and his team sequenced in the years leading up to the human-genome work was Mycoplasma genitalium, an unlovely bacterium whose preferred target on the animals it infects is evident by its name. That organism, which the team sequenced in 1995, has one of the smallest known chromosomes of any self-replicating life-form - just 485 genes. What, Venter wondered back then, was the minimum genome an organism needed to survive and reproduce...
...whether the microbe needed a gene was to knock each of the 485 out, one by one and then in combinations, and see if the bug survived. By 2002, however, advances in both genetic understanding and gene-handling technology had leaped forward. Instead of having to deconstruct Mycoplasma genitalium, Venter's team could build it from scratch. This meant that whereas once they had to reverse-engineer the organism and see when it quit working, they could take the more elegant approach of assembling it from off-the-shelf nucleotides and seeing when it switched on - essentially building life...
...elegant does not mean easy. DNA's nucleotides are strung together like beads on a string, but because it adopts a crystalline structure, that string behaves more like glass. "Even doing normal things like pipetting the pieces would shatter it," says Venter. And although tiny in the microbe world, the mycoplasma's genome still required more than 580,000 nucleotides to assemble...
...Venter decided to start small, with one or two genes, and work his way up by splicing together longer and longer pieces of DNA. That very act of sticking them together proved to be a challenge, since the strands often fall apart. The answer was to design a section of Velcro-like DNA at the ends of each fragment. Since adenine sticks only to thymine and cytosine only to guanine, all the team had to do was end each strand with a nucleotide that would adhere to the one that began the next...
...Such painstaking cut, study and paste eventually did the job. Not only did Venter's team members succeed in building their own mycoplasma at their own lab benches, they also took the opportunity to rewrite its genetic score. First, they introduced a mutation that would prevent it from causing disease. Then they branded it with a series of watermarks that would distinguish it as a product of their lab. Using a code built around selected genes, they spelled out five words that Venter coyly refuses to reveal, saying only that any molecular-biology study can suss them out and promising...