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Posted: 12/21/2005 9:05:04 AM EDT
By CAROLYN ABRAHAM

Monday, December 19, 2005 Posted at 2:49 AM EST

Globe and Mail Update

Work on the world's first human-made species is well under way at a research complex in Rockville, Md., and scientists in Canada have been quietly conducting experiments to help bring such a creature to life.

Robert Holt, head of sequencing for the Genome Science Centre at the University of British Columbia, is leading efforts at his Vancouver lab to play a key role in the production of the first synthetic life form -- a microbe made from scratch.

The project is being spearheaded by U.S. scientist Craig Venter, who gained fame in his former job as head of Celera Genomics, which completed a privately-owned map of the human genome in 2000.

Dr. Venter, 59, has since shifted his focus from determining the chemical sequences that encode life to trying to design and build it: "We're going from reading to writing the genetic code," he said in an interview.

The work is an extreme example of a burgeoning new field in science known as synthetic biology. It relies on advances in computer technology that permit the easy assembly of the chemical bits, known as nucleotides, that make up DNA.

Several scientific groups are trying to make genes that do not exist in nature, in hopes of constructing microbes that perform useful tasks, such as producing industrial chemicals, clean energy or drugs. Dr. Venter and his colleagues are pushing the technology to its limits by trying to put together an entirely synthetic genome.

"We have these genetic codes that we have been determining, so part of the proof [that they encode an organism] is reproducing the chromosome and seeing if it produces the same result," he said.

Government and scientific bodies in the U.S. have investigated safeguards for the new technology, given its potential to yield new pathogens as weapons of bioterror. Ethicists have raised concerns about humans altering the "nature of nature."

But proponents feel the many benefits of redesigning micro-organisms to do human bidding far outweigh the risks.

The Venter team is starting small, working to construct a simpler version of the bacteria known as Mycoplasma genitalium, a common resident of the human reproductive tract. They hope to determine the minimum number of genes required to breathe life into an organism.

M. genitalium is a single-cell bacterium with just one chromosome and 517 genes. But the Venter team is paring the recipe down and believes their version will be able to survive with as few as 250 to 400 genes -- each of which they are making themselves, one chemical piece at a time.

"I grew up doing that with cars and clocks and radios and things like that," Dr. Venter said. "You take them apart to understand them and then you try and see if you can reassemble them."

But even if the team can assemble all of the bug's 500,000 DNA chemicals (roughly 35,000 has been the record so far), no one knows if the organism will be viable. Will simply synthesizing a chemical sequence spark life?

"Nobody has ever done it before so absolutely it is a key hurdle," Dr. Venter said.

Dr. Holt, a Vancouver native who worked in the United States with Dr. Venter until 2002, described it as a "chicken and egg" problem.

"You need an egg to make the chicken, but you also need the chicken to make the egg," Dr. Holt said.

"So the profound problem is what do you do with this DNA once you get it? How do you turn it into an actual organism? You need the genome to encode and make the organism.

"But the way biology works, you need the organism to make the genome."

Dr. Holt and his UBC group are tackling that very problem.

One option for sparking life in a lab-made genome, he explained, is to transplant the synthetic DNA into the shell of an existing microbe. But unlike a human cell, the genetic material of bacteria is not neatly contained in one nucleus that can be removed and simply replaced with another.

"Their chromosomal DNA is floating throughout the entire organism," Dr. Holt said.

So the Vancouver group is researching the use of high-voltage electricity to essentially zap open a host bacteria and slowly infuse it with small pieces of new DNA.

No method exists to insert large DNA fragments. The UBC experiment involves breaking down the DNA of Haemophilus bacteria, a bug common to the upper respiratory tract, into 19 separate pieces and inserting it into the shell of an E. coli, commonly found in the human gut.

"That's the strategy, though we don't know if it will work," Dr. Holt said.

"I thought this was one of the most important problems and one that we should get working on here."

The problem, Dr. Venter said, is worth solving first with bacteria.

Having launched a company called Synthetic Genomics, Dr. Venter believes "the whole world is open" in terms of the commercial applications of being able to build or redesign micro-organisms for specific tasks.

He insists the main goal of his project to build the first synthetic life form, however, is to understand the essence of life, how it evolved and the essential elements that sustain it.

"Here we are trying to understand the human genome with 24,000 some odd genes and 100 trillion cells and we don't know how 300 or 400 genes work together to yield a simple living cell," he said.

"So if we ever have any hope of understanding our own genome, we need to start with something we can actually tear apart, break down and rebuild. So we're starting with a four-cylinder engine instead of a space shuttle."

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