Creating first synthetic life
form
By CAROLYN ABRAHAM
Monday, December 19, 2005 Posted at 2:49 AM EST
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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The time has come for man to be a
creator... 
