[NYTr] Synthetic DNA on the Brink of Yielding New Life Forms - Scary

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The Washington Post - Dec 17, 2007
http://www.washingtonpost.com/wp-dyn/content/article/2007/12/16/AR2007121601900_pf.html

Synthetic DNA on the Brink of Yielding New Life Forms

By Rick Weiss
Washington Post Staff Writer

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 reproduce.

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
phosphates.

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 Lego pieces.

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 trillion.

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 by.

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 regulation.

"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, Light said.

"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."