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`Synthetic biology' offers reasons for hope, fear

WASHINGTON—When scientists announced the reconstruction of the lethal 1918 Spanish flu virus this month, they opened a window on a booming new research field with enormous promise for good—or for harm.

Known as "synthetic biology," it's the artificial creation of DNA, genes and cells that mimic, or surpass, natural systems. Dozens of laboratories around the world—some public, some commercial—have begun to churn out materials to make synthetic drugs, vaccines, pollution sensors, even biological computers.

Some experts warn that such artificial systems could be accidentally or deliberately released into the environment, possibly with harmful, even deadly, effects. A clever bioterrorist, for example, might be able to re-engineer the smallpox virus and cause an epidemic. People would have no immunity against such an artificial organism.

An article in the Nov. 9 issue of the magazine New Scientist pointed out that a terrorist could order the genes to make smallpox or bird flu to be sent to him through the mail. The gene sequences are publicly available, and there's no system to prevent their misuse.

"If we want to make a new organism, we need oversight, maybe regulation," said Lisa Geller, a lawyer who specializes in high-tech products at the Wilmer, Cutler & Pickering law firm in Washington. "Hopefully, nothing bad will happen."

Alarms about possible negative consequences of biological tinkering aren't new. Genetic modification of plants and the cloning of animals, for example, are highly controversial, even though these operations use natural, not synthetic, raw materials. Author Michael Crichton wrote a best-selling science-fiction novel, "Prey," about artificial particles taking over.

To perform synthetic biology, scientists use the tools of modern biochemistry to add, subtract or alter the tiny units, called nucleotides, that make up the DNA in a gene. They can, say, change a "C" to an "A," or vice versa, in the four-letter genetic alphabet.

They then can insert a tiny ring of modified DNA, called a plasmid, into a bacterium to make it do something it didn't do before, such as produce insulin for diabetics.

"We can design DNA to encode anything you can think of," said Pamela Silver, a microbiologist at the Harvard Medical School's Department of Systems Biology in Boston. "The genie is out of the bottle."

For example, Blue Heron Biotechnology, a private company in Bothell, Wash., boasts on its Web site that it "can synthesize any gene, regardless of sequence, complexity or size, with 100 percent accuracy."

Genemed Synthesis Inc., in South San Francisco, says it can create synthetic genes containing up to 15,000 nucleotides in two or three weeks.

"I hope people wake up and realize this is a whole new biology," said Peter Ward, author of a new book called "Life as We Do Not Know It."

"In the last five years, we've come to realize that we can make microbial life in a lot more ways than Mother Earth did," said Ward, an expert on alien life at the University of Washington in Seattle.

The first complete artificial creature, the virus that causes polio, was assembled at the State University of New York in Stony Brook, in Long Island, N.Y., in 2002. The next year, a virus that preys on bacteria was manufactured from scratch at the J. Craig Venter Institute in Rockville, Md.

Venter now has a government contract to construct an artificial bacterium, an organism much larger and more complicated than a virus.

To build an artificial biological system, Silver said, scientists can draw on a set of synthetic "modules" or parts, much like an electronics engineer designing a new computer chip.

The Massachusetts Institute of Technology in Cambridge maintains a Registry of Standard Biological Parts (http://parts.mit.edu), which contains thousands of bits and pieces of genes, proteins and other components of living systems. There's a part to make nerve fibers in the brain glow so doctors can detect them in an MRI scan. Another part is used in "bacterial factories" to produce insulin.

Silver's lab is designing cells that can do rudimentary computing.

"We're working on a cell that can count to two," she said. Such a "bio-counter" could keep track of the number of times a cell divides, thus determining its age. That can be important in understanding cancer or Alzheimer's disease.

Some other examples of synthetic biology at work:

_ The Gates Foundation, founded by Microsoft Chairman Bill Gates, has donated $40 million to the University of California, Berkeley, to design a low-cost synthetic drug to treat malaria, one of the world's top killers.

_ Israeli scientists have used DNA molecules to build transistors, the building blocks of computer circuits.

_ Researchers at the University of Colorado in Boulder have synthesized a molecular "water wheel" made out of a few hundred atoms for use in miniature medical pumps.

_ Students at Silver's lab in Boston have engineered bacteria to write letters or draw patterns on a screen. "It's kind of a biological Etch A Sketch," Silver said.

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For more information online, go to http://syntheticbiology.org

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(c) 2005, Knight Ridder/Tribune Information Services.

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