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Scientists Build First Man-Made Genome; Synthetic Life Comes Next

Scientists have built the first synthetic genome by stringing together 147 pages of letters representing the building blocks of DNA.

The researchers used yeast to stitch together four long strands of DNA into the genome of a bacterium called Mycoplasma genitalium. They said it's more than an order of magnitude longer than any previous synthetic DNA creation. Leading synthetic biologists said with the new work, published Thursday in the journal Science, the first synthetic life could be just months away -- if it hasn't been created already.

"We consider this the second in our three-step process to create the first synthetic organism," said J. Craig Venter, president of the J. Craig Venter Institute where scientists performed the study, on Thursday during a teleconference. "What remains now that we have this complete synthetic chromosome … is to boot this up in a cell."

With the new ability to sequence a genome, scientists can begin to custom-design organisms, essentially creating biological robots that can produce from scratch chemicals humans can use. Biofuels like ethanol, for example.

"The J. Craig Venter Institute will be able to take a file stored on a computer and using synthetic chemistry, turn that information into life," said Chris Voigt, a University of California at San Francisco synthetic biologist. "I would be shocked if it doesn't come out in six months. I think they've done it."

The technique is basically a reverse of the Human Genome Project, which translated DNA into the letters A, C, T and G, which represent the body's building blocks: the nucleotides adenine, thymine, guanine and cytosine. Synthetic biologists' ambitious goal is to arrange those letters to create never-before-seen organisms that will do their bidding.

The first phase of Venter's three-step process, which he published last year, involved transplanting and "booting up" the genome of one species of bacterium into another. The remaining step is to combine the first two steps, then insert the new synthetic genome into a standard bacterium. Scientists said they expect the announcement of man-made life this year.

The ability to synthesize longer DNA strands for less money parallels the history of genetic sequencing, where the price of sequencing a human genome has dropped from hundreds of millions of dollars to about $10,000. Just a few years ago, synthesizing a piece of DNA with 5,000 rungs in its helix, known as base-pairs, was impossible. Venter's new synthetic genome is 582,000 base-pairs.

"The largest piece that had been published in the scientific literature was 32 kilobases," Venter said. "This is on the order of 20 times the size."

"I would think that you could get to a million base pairs," said Jim Collins, a professor of biomedical engineering at Boston University. "I don't think there's anything that's hindering the use of these approaches to go for much bigger genomes."

The key to the new technique is the yeast's natural ability to staple long strands of DNA together.

"What's really interesting about yeast is that … (it takes) multiple incomplete synthetic parts and assembles them," said Daniel Gibson, a synthetic biologist at the Venter institute and senior author of the paper.

Hamilton Smith, a synthetic biologist who led the Venter Institute research, said that the team's new technique should work for other genomes, although the full potential of the technique is unknown. But scientists were enthusiastic about the possibilities.

"Once this becomes routine, it allows us to build whatever genome we want," Voigt said. "You can design a genome to incorporate a particular chemical process to change what the cells are eating and what the cells are making. You can make robotic cells."

One goal of synthetic biology is to create a so-called minimal genome that would consist of the smallest amount of genes necessary to keep the organism alive. Such a bacterial "chassis" would provide an ideal platform for mounting modules like biofuel production to create tiny biological robots.

Other researchers, like Tom Knight of MIT, Drew Endy of Stanford, and a host of synthetic biology startup companies are all after this prize, which could lead to a replacement for fossil fuels. Voigt sits on the scientific advisory board of a biofuels startup, Amyris.

But synthetic biologists are also planning to scale up from the simplest organisms to the most complex: human beings. The first bacterial genome was sequenced in 1995 and was followed by the landmark sequencing of the human genome in 2001. Based on that trajectory, Voigt estimated that a synthetic human genome -- which could be used in human cloning research -- could be created by 2014.

But before researchers can do that level of synthetic biology, scientists will need to automate their methods. Beyond this work, Voigt said, scientists will need programming tools, in the same way computer scientists use higher level programming languages like Fortran, C++ and Java, to control computer function.

"(Otherwise it's like) writing Vista in binary," he said. "It's just not going to happen."

.. from Wired