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Synthetic Genome Brings New Life To Bacterium
Synthetic Genome Brings New Life To Bacterium
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GENOMICS bogged down, in part because M. genitalium
grows so slowly that one experiment can
Synthetic Genome Brings New take weeks to complete. The team decided
to change microbes in midstream, sequenc-
CREDITS (TOP TO BOTTOM): J. CRAIG VENTER INSTITUTE; T. DEERINCK AND M. ELLISMAN/NCMIR, UNIVERSITY OF CALIFORNIA, SAN DIEGO
losopher at Reed College in Port- lapped with its neighbors. So that
land, Oregon, and editor of the sci- the assembled genome would be
entific journal Artificial Life. “It recognizable as synthetic, four
represents an important technical of the ordered DNA sequences
Life re-created. Blue
milestone in the new field of syn- colonies (top) indicate
contained strings of bases that, in code, spell
thetic genomics,” says yeast biolo- a successfully trans- out an e-mail address, the names of many of
gist Jef Boeke of Johns Hopkins planted genome, with the people involved in the project, and a few
University School of Medicine in self-replicating bacteria famous quotations.
Baltimore, Maryland. revealed in an electron Using yeast to assemble the synthetic
The synthetic genome created micrograph. DNA in stages, the researchers first stitched
by Venter’s team is almost identi- together 10,000-base sequences, then
cal to that of a natural bacterium. 100,000-base sequences, and finally the com-
It was achieved at great expense, an estimated suggested by those experiments required plete genome. However, when they initially
$40 million, and effort, 20 people working for synthesizing a full bacterial chromosome put the synthetic genome into M. capricolum,
more than a decade. Despite this success, cre- and getting it to work in a recipient cell, nothing happened. Like computer program-
ating heavily customized genomes, such as two steps that have taken years because the mers debugging faulty software, they system-
ones that make fuels or pharmaceuticals, and technology to make and manipulate whole atically transplanted combinations of syn-
getting them to “boot” up the same way in a chromosomes did not exist. In 2007, Venter, thetic and natural DNA, finally homing in on a
cell is not yet a reality. “There are great chal- Smith, Hutchison, and colleagues finally single-base mistake in the synthetic genome.
lenges ahead before genetic engineers can demonstrated that they could transplant The error delayed the project 3 months.
mix, match, and fully design an organism’s natural chromosomes from one microbial After months of unsuccessfully trans-
genome from scratch,” notes Paul Keim, a species to another (Science, 3 August 2007, planting these various genome combinations,
molecular geneticist at Northern Arizona p. 632). By 2008, they showed that they the team’s fortune changed about a month ago
University in Flagstaff. could make an artificial chromosome that when the biologists found a blue colony of
The “synthetic” bacteria unveiled this matched M. genitalium’s but also contained bacteria had rapidly grown on a lab plate over
week have their origins in a project headed by “watermark” DNA sequences that would the weekend. (Blue showed the cells were
Venter and JCVI colleagues Clyde Hutchison enable them to tell the synthetic genome using the new genome). Project leader
III and Hamilton Smith to determine the mini- from the natural one (Science, 29 February Daniel Gibson sent Venter a text message
mal instructions needed for microbial life and 2008, p. 1215). declaring success. “I took my video camera
from there add genes that could turn a bac- But combining those steps became in and filmed [the plate],” says Venter.
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They sequenced the DNA in this colony, Nonetheless, “this experiment will certainly a team that in 2002 created the first synthetic
confirming that the bacteria had the synthetic reconfigure the ethical imagination,” says virus (Science, 9 August 2002, p. 1016).
genome, and checked that the microbes were Paul Rabinow, an anthropologist at the Uni- Venter says that JCVI has applied for
indeed making proteins characteristic of versity of California, Berkeley, who studies several patents covering the work, assign-
M. mycoides rather than M capricolum. The synthetic biology. “Over the long term, the ing them to his company, Synthetic Genom-
colony grew like a typical M. mycoides as approach will be used to synthesize increas- ics, which provided much of the funding for
well. “We clearly transformed one cell into ingly novel designed genomes,” says Kenneth the project. A technology watchdog group,
another,” says Venter. Oye, a social scientist at the Massachusetts ETC Group in Ottawa, has argued that these
“That’s a pretty amazing accomplish- Institute of Technology in Cambridge. “Right actions could result in a monopoly on synthe-
ment,” says Anthony Forster, a molecular now, we are shooting in the dark as to what sized life (Science, 15 June 2007, p. 1557),
UNITED KINGDOM
Although his background is in the humani- will attend cabinet meetings, although he is U.K. researchers point out that in
ties, Willetts was a Conservative spokes- not a member. response to the recession, some countries
person for education and science during The most pressing concern for research- increased science spending as a way of
the last Parliament. In a briefing earlier ers is how their funding will fare, as the new boosting their economies. “Success breeds
this week, Willetts said: “I understand the coalition has made reducing the govern- success,” says Rees. “The U.K. is strong
crucial importance of blue-skies research. ment deficit its top priority. The coalition in science, and it would be sad if any-
Scientific research can’t all be reduced to has committed to cutting £6 billion from thing happens to jeopardize that.” Willetts
utilitarian calculations”—a very different government spending this year, the broad acknowledges that there are difficult times
message from that of earlier Conservative details of which are due to be announced ahead. “It’s going to be tough. … The boom
administrations. Robert Kirby-Harris, chief next week. But the specif ic impact on has now come to an end.”
executive of the Institute of Physics, says he research spending is more likely to emerge –DANIEL CLERY