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In 2000, Venter delivered on his promise, finishing just ahead of Collins, but a government official who knew both men, hoping to quiet the feuding, brokered a truce between the groups, which included the sweetener of a joint announcement at the White House in 2000. President Bill Clinton lauded the completed genome as "the most important, most wondrous map ever produced."
The high times did not last long. Back at Celera, the competing interests of a free public database and a corporation's stockholders proved hard to reconcile, and just two years after the White House ceremony, Venter was fired by the board. For solace, he decided to get away. Still a sailing enthusiast, he hit on a grand plan to mimic the journey of the H.M.S. Challenger, the vessel that in the 1870s conducted the first global mission to sample life from the oceans of the world. Venter would circumnavigate the globe with a crew of scientists and sailors and every 200 miles (320 km) would dip canisters into the ocean at various depths, filter whatever life-forms floated in mostly microscopic and send them back to his newly created lab, the J. Craig Venter Institute in Rockville. Over 2½ years, the journey yielded 6 million new genes and 400 new microbial species. "Most people thought the ocean was a homogenous soup," Venter says. "But 85% of the species we found were unique."
As he 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? If you could figure that out, you could determine the basic DNA chassis of all living things and then use it to design your own souped-up or dressed-down versions of life.
A decade ago, the only way to establish 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.
But 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.
So 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.