MOTHER NATURE'S DNA

By Michael D. Lemonick (TIME MAGAZINE)
It may seem as if J. Craig Venter is on an extended vacation as he sails his 95-ft. luxury yacht on a 25,000-mile voyage around the world. But the iconoclastic scientist who took on a consortium of national governments in a race to map the human genome--and fought them to a photo finish five years ago--is actually hard at work. He's prospecting--not for gold but for DNA, applying the same techniques developed to decode human genes to the genes of microbes scooped from the ocean and out of the air. On a pilot voyage, through the Sargasso Sea in the North Atlantic, he found more than 1,800 new species of bacteria and viruses--a surprise, since he had always thought of the Sargasso as a biological desert, relatively devoid of life.
Indeed, half a decade after Venter and his archrival, Francis Collins, director of the National Human Genome Research Institute, stood together at the White House to announce that the human genome had been sequenced, biologists have come to re-evaluate just what that milestone really meant. Back then, it was widely assumed that the emerging science of human genomics would quickly lead to spectacular cures for cancer and other diseases and even allow couples to have "designer" babies with desirable traits plucked from a catalog.
Although researchers around the world have made solid progress in understanding the genetic basis of disease--and the pharmaceutical industry now relies on gene sequencing in its search for new drugs--revolutionary new treatments have yet to emerge. "It's actually extremely exciting," says Collins. "But we're still probably a decade or maybe 15 years away from the real revolution in medicine that genomics promises."
At the same time, however, scientists have come to appreciate what can be gained from decoding other genomes, from modern chimps and ancient cave bears to microscopic bacteria and viruses. As the cost of sequencing each base pair has dropped, from $10 in 1990 to less than 9¢ in 2002 to 1/10 of 1¢ today, researchers are doing more all the time. Although 99% of the planet's genomes have yet to be decoded, researchers have identified hundreds of thousands if not millions of genes, dwarfing the paltry 24,000 or so we carry in our DNA.
Additionally, scientists are getting a much better understanding of what individual genes do, no matter where they're from. The challenge, explains Venter, is to identify the genes that allow some microbes to change sunlight into sugars, others to absorb carbon dioxide from the air and still others to transform dead plant matter into clean-burning hydrogen.
So researchers have set out to look for those genes--and not just in the ocean. Venter is also sampling the air over New York City, and other scientists are looking into hot springs, digging into the ground and even testing toxic-waste sites. "You can pick up a gram of soil," says Aristides Patrinos, who oversees the Department of Energy's genome program, "and there's DNA in it. By sequencing that DNA, you can infer what's there in terms of diversity." As a rule, the more diverse a given ecosystem--the more genes present, even at the microbial level--the more resistant it is to damage.
It's not easy to culture wild microbes in the lab, but much can be learned by sequencing the genes contained in a sample of earth, air or water. Just this past April, scientists from the Joint Genome Institute (JGI), a Department of Energy lab in Walnut Creek, Calif., announced in the journal Science that they had for the first time identified the unique mixes of microbes that thrive in different sorts of ecosystems. In farm soil, for example, there are any number of genes that produce substances that break down plant material--rotting genes, you might call them. In seawater, by contrast, there are very few rotting genes but lots of genes that process salts. By understanding the microbial gene profile of a healthy environment, scientists will be able to gauge the health of other ecosystems.
In the Sargasso Sea, meanwhile, Venter was shocked to find nearly 800 genes for making light-sensitive proteins like those found in the human retina--quadrupling the number of photoreceptors known to science. "This suggests," Venter wrote in New Scientist last May, "that some new type of light-driven biology may explain the Sargasso Sea's unexpectedly high diversity of species."
But environmental indicators and surprising biology are only part of what makes wholesale gene prospecting so promising. Hydrogen has been touted as a clean-burning replacement for fossil fuels, for example, and, says Patrinos, "there are already bugs out there that produce hydrogen." If gene prospectors could isolate the responsible gene, he explains, and splice it into a common bacterium, just as genetic engineers have done for years with the gene that produces human insulin, "we can duplicate it on industrial scales."
Or take ethanol, the gasoline substitute manufactured today mostly from corn. It currently takes a lot of harsh chemicals to process ethanol, but microbes could do the same thing. "I think it's doable within this decade," says Patrinos, "that we will develop a superbug that can make that conversion in a very clean way." Indeed, JGI, in collaboration with the San Diego-based biotech company Diversa, is sequencing communities of bacteria from the guts of termites in an effort to find genes that make hydrogen and ethanol. It's also looking for genes that enable microbes to metabolize radioactive waste.
Hundreds more equally promising samples are being fed into the sequencers at JGI, at the J. Craig Venter Institute Joint Technology Center in Rockville, Md., and at other labs around the world. Venter's take from the Sargasso Sea was impressive enough on its own, but he is taking a new ocean sample every 200 miles or so as he circumnavigates the globe. Some 85% of the gene sequences he hauls up are unique to that site, suggesting that each 200-mile stretch of ocean represents a vastly different ecosystem. And that's just from scratching the surface, says JGI director Eddy Rubin: "There are whole domains of life that haven't been touched yet."
With reporting by Melissa August/Washington, Laura A. Locke/Walnut Creek