Md. Scientists Build Bacterial Chromosome

By Rick Weiss
Washington Post Staff Writer
Friday, January 25, 2008

Scientists in Maryland yesterday said they had built from scratch an entire microbial chromosome, a loop of synthetic DNA carrying all the instructions that a simple cell needs to live and reproduce.

The feat marks the first time that anyone has made such a large strand of hereditary material from off-the-shelf chemical ingredients. Previous efforts had yielded DNA strands less than one-twentieth the size, and those pieces lacked many of the key biological programs that tell a cell how to stay alive.

On the basis of earlier experiments, the researchers believe the new, full-length loop would spontaneously "boot up" inside a cell, just as a downloaded operating system can awaken a computer -- a potentially historic event that would amount to the creation of the first truly artificial life form.

Team members emphasized that they have not done that yet but expressed confidence that they would do so before the end of the year.

"There are barriers . . . but we are confident that they can be overcome," said J. Craig Venter, who led the effort with Daniel G. Gibson and Hamilton O. Smith at the J. Craig Venter Institute in Rockville. The work appears in yesterday's online edition of the journal Science.

Venter said the goal is to design novel microbes whose handcrafted genomes endow them with the ability produce useful chemicals, including renewable synthetic fuels that could substitute for oil.

Critics, however, countered that without better oversight of the fledgling field, synthetic biology is more likely to lead to the creation of potent biological weapons and runaway microbes that could wreak environmental havoc.

"Venter is claiming bragging rights to the world's longest length of synthetic DNA, but size isn't everything. The important question is not 'How long?' but 'How wise?' " said Jim Thomas of the ETC Group, a Montreal-based group that has called for a moratorium on the release and commercialization of synthetic organisms pending further public debate.

Venter's team started by determining the precise order of all 580,076 base pairs, or "letters" of DNA code, inside one of the simplest microbes known to science: Mycoplasma genitalium, a bacterium that can infect the human genital tract. The scientists bought small pieces of DNA, then perfected painstaking methods to stitch them together inside bacteria and yeast cells in exactly the right order.

The final product -- 582,970 base pairs in all -- is a near-exact replica of M. genitalium's genome, with a few intentional differences. The team omitted a DNA snippet that allows the microbe to infect other cells, for example, and added extra DNA as "watermarks" to differentiate their construct from the naturally occurring variety.

"It's the first synthetic bacterial chromosome," Venter said. "Every one of those base pairs started as a chemical in a bottle."

George Church, a Harvard geneticist leading competing efforts to develop novel life forms -- not from scratch but by modifying existing bacteria -- said the work marks something less than the dawn of a new era.

"This is not a 'creating life' paper. It is not a test of vitalism. It's an assembly paper," Church said. "The question is: Is it faster or cheaper than other methods? But they don't lay out their economics. They missed an opportunity there."

Venter said he could not provide an estimate of the project's cost.

Venter and others have already made synthetic genomes for viruses, which are about one-hundredth the size of bacterial genomes. Some activists contend that synthetic bacteria pose more dangers because, unlike viruses, they can replicate on their own and can survive a long time in the environment.

Venter said the work was green-lighted by government offices, the National Academies and an independent ethics review board.

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