Theos-Talk Archives (December 2007 Message tt00076)

 Received this article from another site. It may interest some.
  Cass
      
  http://www.washingt onpost.com/ wp-
  dyn/content/ article/2007/ 12/16/AR20071216 01900.html
   
  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."




       
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