Forwarded message from tsimonds@TheWorld.com

Synthetic DNA on the Brink of Yielding New Life Forms

By Rick Weiss
Washington Post Staff Writer
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 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."

http://www.washingtonpost.com/wp-dyn/content/article/2007/12/16/AR2007121601900_
pf.html

End of forwarded message from tsimonds@TheWorld.com

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