[tt] NYT: Pursuing Synthetic Life, Dazzled by Reality

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Pursuing Synthetic Life, Dazzled by Reality
http://www.nytimes.com/2008/02/05/science/05angi.html
New York Times, 8.2.5

Basics
By NATALIE ANGIER

When scientists announced on Jan. 24 that they had reconstituted the
complete set of genes for a microbe using just a few bottles of
chemicals, the feat was hailed as a kind of shining Nike moment in
the field of synthetic biology, the attempt to piece together living
organisms from inert scratch.

Reporting in the journal Science, Dr. J. Craig Venter and his
colleagues at the J. Craig Venter Institute said they had fabricated
the entire DNA chain of a microbial parasite called Mycoplasma
genitalium, exceeding previous records of sustained DNA synthesis by
some 18-fold. Any day now, the researchers say, they will pop that
manufactured mortal coil into a cellular shell, where the genomic
code will "boot up," as Dr. Venter puts it, and the entire construct
will begin acting like a natural-born M. genitalium -- minus the
capacity, the researchers promise, to infect the delicate tissues
that explain the parasite's surname.

Yet even as researchers rhapsodize about gaining the power to
custom-design organisms that will supply us with rivers of cheap
gasoline, better chemotherapeutic agents or -- here's my latest
fantasy -- a year-round supply of fresh eggnog, the most profound
insights to emerge from the pursuit of synthetic life just may be
about real life.

Scientists who seek to imitate living cells say they can't help but
be perpetually dazzled by the genuine articles, their flexibility,
their versatility, their childlike grandiosity. No matter what
outrageous or fattening things we may ask our synthetic cells to do,
scientists say, it's nothing compared with what cells already have
done of their own accord, usually in the format of bacteria.
Microbes have been found to survive and even thrive in places where
if they had any sense they would freeze, melt, explode,
disintegrate, starve, suffocate, or at the very least file a very
poor customer review.

"We have micro-organisms that live in such strong acid or base
solutions that if you put your finger in, the skin would dissolve
almost instantly," Dr. Venter said in an interview. "There's another
organism that can take three million rads of radiation and not be
killed." How can a microbe withstand a blast of radioactivity that
is a good 1,500 times greater than what would kill any of us
virtually on the spot? "Its chromosome gets blown apart," Dr. Venter
said, "but it stitches everything back together and just starts
replicating again."

Given the wealth of biological and metabolic templates that nature
has invented over nearly four billion years of evolutionary
tinkering, scientists say, any sane program to synthesize new life
forms must go hand in hand with a sustained sampling of the old. "My
view is that we know less than 1 percent of what's out there in the
biological universe," Dr. Venter said.

Last year, he and his colleagues went prospecting for new organisms
in the deep midocean, long thought to be one of earth's least
animate regions. Sure, life evolved in the seas, but shallow seas,
where sunlight can penetrate, were considered the preferred site for
biodiversity. Even with the startling discovery in the 1980s of life
on the ocean floor, around the hydrothermal vents, the midocean
waters couldn't shake their reputation as an impoverished piece of
real estate: too far down for solar energy, too high up for its
geothermal equivalent.

Yet when the Venter team began sampling the waters for the most
basic evidence of life, the presence of genetic material, they found
themselves practically awash in novel DNA. "From our random
sequencing in the ocean, we uncovered six million new genes," he
said, genes, that is, unlike any yet seen in any of the mammals,
reptiles, worms, fish, insects, fungi, microbes or narcissists that
have been genetically analyzed so far. With just that first-pass act
of nautical sequencing, Dr. Venter said, "we doubled the number of
all genes characterized to date."

Researchers assume that most of the novel DNA is microbial in
origin, but they have yet to identify the organisms or see what they
can do, because most microbes are notoriously difficult to cultivate
in the lab. Bacteria may happily swim through toxic waste, but when
it comes to confinement on an agar plate, thank you, they'd rather
be dead.

Technical challenges notwithstanding, scientists have made some
progress in investigating preposterous life forms and tallying the
biochemical tools that such extremophiles use. Thermophilic
microbes, for example, which can withstand temperatures of 238
degrees Fahrenheit, well above the boiling point of water, have
stiffening agents in their membranes, to keep them from melting
away, and they build their cell proteins with a different assortment
of amino acids than our cells do, allowing the construction of
strongly bonded protein chains that won't collapse in the heat.

By contrast, said Steven K. Schmidt, a microbiologist at the
University of Colorado in Boulder, when you look at organisms that
thrive in subzero conditions, "their membranes are really
loosey-goosey, very fluid," and so resist stiffening and freezing.
It turns out there are a lot of these loosey-gooses around. Dr.
Schmidt and his colleagues study the fridgophile life forms that
make their home in glacial debris high in the Andes Mountains,
20,000 feet above sea level, where the scene may look bleak, beyond
posthumous, but where, he said, "we've been pretty amazed at the
extreme diversity of things we've found." The complexity of the
Andean microbial ecosystem, he said, "is greater than what you'd
find in your garden."

Yes, microbes were here first, and they've done everything first,
and synthetic lifers are happy to scavenge for parts and ideas. Drew
Endy, an assistant professor in the biological engineering
department at the Massachusetts Institute of Technology, and his
colleagues are putting together a registry of standardized
biological parts, which they call BioBrick parts. The registry
consists of the DNA code for different biological modules,
interchangeable protein parts that they hope may someday be pieced
together into a wide variety of biological devices to perform any
task a bioengineer may have in mind, rather like the way nuts,
bolts, gears, pulleys, circuits and the like are assembled into the
machines of our civilization. Numbering some 2,000 parts and
growing, the registry contains many recipes for clever protein
modules invented by bacteria. One sequence engineered by researchers
in Melbourne, Australia, encodes the instructions for a little
protein balloon, for example. "It's based on a natural part found in
a marine micro-organism that controls the buoyancy of the cell," Dr.
Endy said.

Invisible though it may be, the microbial community ever keeps us
afloat.