Major advance in work on DNA

The Baltimore Sun

Researchers in Rockville have come a step closer to creating artificial life in a test tube by stringing together the longest strand yet of man-made DNA.

Scientists at the J. Craig Venter Institute published an online paper yesterday describing how they lined up synthetic genes that replicated a large chunk of DNA from a simple form of bacteria. They put the DNA into yeast, where its segments joined together as it harnessed some of the yeast's cellular machinery.

Experts say the result - 582,970 units or base pairs of intact DNA of Mycoplasma genitalium - is a milestone in synthetic biology, an emerging discipline focused on manipulating DNA like computer code.

The ultimate goal is the design of mass-produced, plain genetic platforms - like the chassis of a car - for making microbes that could clean up toxic waste and produce new biofuels, pest-resistant crops, wear-resistant fabrics and medicines, experts say.

"I think it's one of the important steps that have to be achieved," Dr. Eddy Rubin, director of the Department of Energy's Joint Genome Institute, said of yesterday's announcement.

The next step, inserting strings of the DNA into microbes to see if they "boot up," might be just months away, according to Venter.

"I will be equally surprised and disappointed if we can't do it in 2008," said Venter, who shares credit for first sequencing the human genome in 2000.

The team's string of man-made DNA, built from blocks of common chemicals, is 20 times longer than the next longest, and if spelled out in single letter coding, it would take up 147 single-spaced pages, Venter said.

"It's indeed a large molecule," he said.

The achievement represents a "technological tour de force," said Pamela A. Silver, a professor of systems biology at the Harvard Medical School. "In principle, the opportunities are great. This is the real and very exciting challenge for synthetic biologists," Silver wrote in an e-mail.

But critics say that Venter is moving too fast - and that his results could put new bioweapons in terrorists' hands and unleash uncontrollable agents that cause epidemics, transform landscapes and threaten food supplies.

"They're creating organisms that have no analogue in nature - and yet there's no biosafety framework for any type of synthetic organisms yet," said Jim Thomas, program manager for ETC, a technology watchdog group.

The rise of antibiotic-resistant strains of bacteria in hospitals should serve as a reminder that they and other life forms can develop unforeseen capabilities, Thomas said.

"They'll mutate, they'll change, they'll adapt to changing conditions," he said.

But Venter said experts at the White House and the National Academy of Sciences have reviewed his research and agree that it's worth pursuing and publishing.

"We even offered to leave things out and self-censor, and were told that would be wrong," Venter said. "The broader implications of this work certainly have not been missed by us."

The report, published online yesterday by the journal Science, was led by Nobel laureate Hamilton Smith and funded by Venter's privately held company, Synthetic Genomics, which was set up in 2005 to develop beneficial microbes.

It builds on work that Venter's team published in June after researchers transplanted DNA from one bacteria-like microbe to another, essentially confirming that DNA can survive transplant.

The bacterium used in the latest study is one of the simplest forms known, Mycoplasma genitalium.

Venter said work on M. genitalium began in 1995 shortly after he sequenced the bacteria's genome.

Scientists chose the microbe for its potential to achieve another key goal: determining exactly which base pairs of DNA are essential for survival of the simplest life forms, he said.

"We want to understand the genome structure - which genes are necessary for life and which are not," he said.

The idea of manipulating microbial genes isn't new. In 2002, Eckard Wimmer, a researcher at Stony Brook University, synthesized viral DNA by creating a new version of the polio virus.

DuPont engineers have used synthetic DNA to produce a chemical woven into high-tech fabrics, while researchers at the University of California at Berkeley have synthesized genes in yeast to produce artemisinin, an antimalarial drug often in short supply.

But making entirely new bacterial DNA from scratch has proved even more challenging.

In a 2006 videotaped presentation, researchers at the Massachusetts Institute of Technology said it might someday be possible to synthetically alter an acorn's DNA so that it sprouts an oak tree shaped like a house.

"It's about taking existing bugs and giving them new capabilities," Rubin said.

The design described by Venter's team yesterday includes overlapping cassettes of DNA, with "watermarks" where new strings of DNA could be inserted to create a custom-designed organism.

"It's done with a specific design in mind," said Paul Rabinow, an anthropology professor at the University of California at Berkeley who studies synthetic biology and has recently published a book of essays on the subject.

The work does not necessarily create life but uses genetics in ways that could change everything about an organism, he said.

"What they're doing is regulating nature, but not doing something that's unnatural," said Rabinow, who was not involved in the artemisinin research. "I don't think the work violates nature, but that being said, keep in mind, nature is dangerous."

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