Joanie January 3rd, 2008
SYNTHETIC DNA ON THE BRINK OF YIELDING NEW LIFE FORMS
By Rick Weiss
Monday, December 17, 2007; A01
It has been 50 years since scientists first created DNA in a test tube,
stitching ordinary chemical ingredients together to make life’s most
extraordinary molecule. Until recently, however, even the most sophisticated
laboratories could make only small snippets of DNA — an extra gene or two
to be inserted into corn plants, for example, to help the plants ward off
insects or tolerate drought.
Now researchers are poised to cross a dramatic barrier: the creation of life
forms driven by completely artificial DNA.
Scientists in Maryland have already built the world’s first entirely
handcrafted chromosome — a large looping strand of DNA made from scratch in
a laboratory, containing all the instructions a microbe needs to live and
In the coming year, they hope to transplant it into a cell, where it is
expected to “boot itself up,” like software downloaded from the Internet,
and cajole the waiting cell to do its bidding. And while the first synthetic
chromosome is a plagiarized version of a natural one, others that code for
life forms that have never existed before are already under construction.
The cobbling together of life from synthetic DNA, scientists and
philosophers agree, will be a watershed event, blurring the line between
biological and artificial — and forcing a rethinking of what it means for a
thing to be alive.
“This raises a range of big questions about what nature is and what it could
be,” said Paul Rabinow, an anthropologist at the University of California at
Berkeley who studies science’s effects on society. “Evolutionary processes
are no longer seen as sacred or inviolable. People in labs are figuring them
out so they can improve upon them for different purposes.”
That unprecedented degree of control over creation raises more than
philosophical questions, however. What kinds of organisms will scientists,
terrorists and other creative individuals make? How will these
self-replicating entities be contained? And who might end up owning the
patent rights to the basic tools for synthesizing life?
Some experts are worried that a few maverick companies are already gaining
monopoly control over the core “operating system” for artificial life and
are poised to become the Microsofts of synthetic biology. That could stifle
competition, they say, and place enormous power in a few people’s hands.
“We’re heading into an era where people will be writing DNA programs like
the early days of computer programming, but who will own these programs?”
asked Drew Endy, a scientist at the Massachusetts Institute of Technology.
At the core of synthetic biology’s new ascendance are high-speed DNA
synthesizers that can produce very long strands of genetic material from
basic chemical building blocks: sugars, nitrogen-based compounds and
Today a scientist can write a long genetic program on a computer just as a
maestro might compose a musical score, then use a synthesizer to convert
that digital code into actual DNA. Experiments with “natural” DNA indicate
that when a faux chromosome gets plopped into a cell, it will be able to
direct the destruction of the cell’s old DNA and become its new “brain” –
telling the cell to start making a valuable chemical, for example, or a
medicine or a toxin, or a bio-based gasoline substitute.
Unlike conventional biotechnology, in which scientists induce modest genetic
changes in cells to make them serve industrial purposes, synthetic biology
involves the large-scale rewriting of genetic codes to create metabolic
machines with singular purposes.
“I see a cell as a chassis and power supply for the artificial systems we
are putting together,” said Tom Knight of MIT, who likes to compare the
state of cell biology today to that of mechanical engineering in 1864. That
is when the United States began to adopt standardized thread sizes for nuts
and bolts, an advance that allowed the construction of complex devices from
simple, interchangeable parts.
If biology is to morph into an engineering discipline, it is going to need
similarly standardized parts, Knight said. So he and colleagues have started
a collection of hundreds of interchangeable genetic components they call
BioBricks, which students and others are already popping into cells like
So far, synthetic biology is still semi-synthetic, involving single-cell
organisms such as bacteria and yeast that have a blend of natural and
synthetic DNA. The cells can reproduce, a defining trait of life. But in
many cases that urge has been genetically suppressed, along with other
“distracting” biological functions, to maximize productivity.
“Most cells go about life like we do, with the intention to make more of
themselves after eating,” said John Pierce, a vice president at DuPont in
Wilmington, Del., a leader in the field. “But what we want them to do is
make stuff we want.”
J. Craig Venter, chief executive of Synthetic Genomics in Rockville, knows
what he wants his cells to make: ethanol, hydrogen and other exotic fuels
for vehicles, to fill a market that has been estimated to be worth $1
In a big step toward that goal, Venter has now built the first fully
artificial chromosome, a strand of DNA many times longer than anything made
by others and laden with all the genetic components a microbe needs to get
Details of the process are under wraps until the work is published, probably
early next year. But Venter has already shown that he can insert a “natural”
chromosome into a cell and bring it to life. If a synthetic chromosome works
the same way, as expected, the first living cells with fully artificial
genomes could be growing in dishes by the end of 2008.
The plan is to mass-produce a plain genetic platform able to direct the
basic functions of life, then attach custom-designed DNA modules that can
compel cells to make synthetic fuels or other products.
It will be a challenge to cultivate fuel-spewing microbes, Venter
acknowledged. Among other problems, he said, is that unless the fuel is
constantly removed, “the bugs will basically pickle themselves.”
But the hurdles are not insurmountable. LS9 Inc., a company in San Carlos,
Calif., is already using E. coli bacteria that have been reprogrammed with
synthetic DNA to produce a fuel alternative from a diet of corn syrup and
sugar cane. So efficient are the bugs’ synthetic metabolisms that LS9
predicts it will be able to sell the fuel for just $1.25 a gallon.
At a DuPont plant in Tennessee, other semi-synthetic bacteria are living on
cornstarch and making the chemical 1,3 propanediol, or PDO. Millions of
pounds of the stuff are being spun and woven into high-tech fabrics
(DuPont’s chief executive wears a pinstripe suit made of it), putting the
bug-begotten chemical on track to become the first $1 billion biotech
product that is not a pharmaceutical.
Engineers at DuPont studied blueprints of E. coli’s metabolism and used
synthetic DNA to help the bacteria make PDO far more efficiently than could
have been done with ordinary genetic engineering.
“If you want to sell it at a dollar a gallon . . . you need every bit of
efficiency you can muster,” said DuPont’s Pierce. “So we’re running these
bugs to their limits.”
Yet another application is in medicine, where synthetic DNA is allowing
bacteria and yeast to produce the malaria drug artemisinin far more
efficiently than it is made in plants, its natural source.
Bugs such as these will seem quaint, scientists say, once fully synthetic
organisms are brought on line to work 24/7 on a range of tasks, from
industrial production to chemical cleanups. But the prospect of a
flourishing synbio economy has many wondering who will own the valuable
rights to that life.
In the past year, the U.S. Patent and Trademark Office has been flooded with
aggressive synthetic-biology claims. Some of Venter’s applications, in
particular, “are breathtaking in their scope,” said Knight. And with
Venter’s company openly hoping to develop “an operating system for
biologically-based software,” some fear it is seeking synthetic hegemony.
“We’ve asked our patent lawyers to be reasonable and not to be
overreaching,” Venter said. But competitors such as DuPont, he said, “have
just blanketed the field with patent applications.”
Safety concerns also loom large. Already a few scientists have made viruses
from scratch. The pending ability to make bacteria — which, unlike viruses,
can live and reproduce in the environment outside of a living body — raises
new concerns about contamination, contagion and the potential for mischief.
“Ultimately synthetic biology means cheaper and widely accessible tools to
build bioweapons, virulent pathogens and artificial organisms that could
pose grave threats to people and the planet,” concluded a recent report by
the Ottawa-based ETC Group, one of dozens of advocacy groups that want a ban
on releasing synthetic organisms pending wider societal debate and
“The danger is not just bio-terror but bio-error,” the report says.
Many scientists say the threat has been overblown. Venter notes that his
synthetic genomes are spiked with special genes that make the microbes
dependent on a rare nutrient not available in nature. And Pierce, of DuPont,
says the company’s bugs are too spoiled to survive outdoors.
“They are designed to grow in a cosseted environment with very high food
levels,” Pierce said. “You throw this guy out on the ground, he just can’t
compete. He’s toast.”
“We’ve heard that before,” said Jim Thomas, ETC Group’s program manager,
noting that genes engineered into crops have often found their way into
other plants despite assurances to the contrary. “The fact is, you can build
viruses, and soon bacteria, from downloaded instructions on the Internet,”
Thomas said. “Where’s the governance and oversight?”
In fact, government controls on trade in dangerous microbes do not apply to
the bits of DNA that can be used to create them. And while some industry
groups have talked about policing the field themselves, the technology is
quickly becoming so simple, experts say, that it will not be long before
“bio hackers” working in garages will be downloading genetic programs and
making them into novel life forms.
“The cat is out of the bag,” said Jay Keasling, chief of synthetic biology
at the University of California at Berkeley.
Andrew Light, an environmental ethicist at the University of Washington in
Seattle, said synthetic biology poses a conundrum because of its
double-edged ability to both wreak biological havoc and perhaps wean
civilization from dirty 20th-century technologies and petroleum-based fuels.
“For the environmental community, I think this is going to be a really hard
choice,” Light said.
Depending on how people adjust to the idea of man-made life — and on how
useful the first products prove to be — the field could go either way,
“It could be that synthetic biology is going to be like cellphones: so
overwhelming and ubiquitous that no one notices it anymore. Or it could be
like abortion — the kind of deep disagreement that will not go away.”
The question, if the abortion model holds, is which side of the synthetic
biology debate will get to call itself “pro-life.”
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Published by David Sunfellow
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