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FEATURE STORY 77
George Church, a sequencing pioneer at Har vard Medical
School, says cost is the key. As their prices fall in the next
few years, he says, these machines will become a democ-
ratizing force that will make traditional sequencers all but
obsolete, much the way personal computers displaced main-
frames. And this will lead to applications that no one can
yet fathom. "If we were still working with mainframes, a
lot of cool stu wouldn t be happening," he says.
Church, who was among the dozen researchers to pro-
pose the Human Genome Project in the mid-1980s, is one
of the few biologists whose lab equipment includes a table-
mounted vise grip and a drill press. He uses equipment like
this to build his own next-generation sequencers, of which
his lab currently has eight (see TR35, September/October
2006 ). Convinced that companies are overcharging for their
machines, he makes a point of freely sharing his know-how
with any interested colleagues. He compares his philosophy
to the "wiki and Linux mentality," saying, "If a bunch of ants
get together, they can move a r ubber-tree plant."
Church s grand vision is to channel the cheap ood of As,
Cs, Ts, and Gs into what he calls the Personal Genome Proj-
ect. In the Human Genome Project, researchers obtained
DNA from several people, each of whom, for privacy rea-
sons, remains anonymous. So the nal sequence represents
a composite person with a conglomerate of di erent genetic
backgrounds and medical histories. Church wants his Per-
sonal Genome Project to decode the DNA of individuals,
who will also volunteer their medical records. He will post
all the resulting data on the Inter net. Ultimately, he imag-
ines, millions of people will join the project, posting their
sequences, medical records, and, if they choose, even facial
photographs online. The entire world will then have access
to all the data it needs to freely test hypotheses.
Although Church has received substantial funding from
the National Institutes of Health to develop sequencing
technology, the ethical, legal, and social questions raised
by the personal Genome Project have kept NIH from sup-
porting it, despite a positive review of a grant application
in August 2005. "As soon as I got approval, NIH got all
excited, and not necessarily in a good way," he says. He s
attempted to address the privacy and con dentiality issues,
noting that no one s identity needs to be made public and
that NIH already funds human genetics projects that have
fewer safeguards in place.
Church recognizes that intimate knowledge of their own
DNA might be too much for many people. "You don t let
your kids browse to Internet pornography sites," he says,
"and to some extent you don t allow yourself to browse the
scariest, grossest sites." He expects that rather than access-
ing their raw genomes, people will have professionals help
them interpret the information.
Despite the lack of federal funding and the ethical objec-
tions, Church is proceeding, con dent that advances in
sequencing technology will drive the idea of a Personal
Genome Project forward---just as advances in information
technology have led strangers to share data in ways that
no one dreamed of when the dual- oppy-drive Apple II
debuted 30 years ago. As sequencers become more e cient,
he believes, and costs continue to drop, personal genomics
will take o on a scale that few people have yet imagined.
Winning the Lottery
Last October, the X Prize Foundation announced a $10 mil-
lion award for producing highly accurate sequences of 100
human genomes in 10 days or less without spending more
than $10,000 per genome. One of the rst entrants was 454,
which plans to develop even smaller beads that it hopes
will allow its machines to read even more DNA per run at
roughly the same cost. "We don t need any new physics or
math to get to the $1,000 genome," says Rothberg.
Leaving aside the question of when---or if---anyone will
claim the X Prize, DNA sequencing will surely continue to
plummet in price and increase in accuracy. "Until last year,
sequencing was really str uggling to have the impact on the
next era of genomics that it needed to have," says David
Bentley, Illumina s chief scientist. Basically, the price of tra-
ditional sequencing was just not dropping quickly enough.
"Now the eld is far more optimistic than it was," he says.
Next-generation sequencing "has a huge role to play."
Hearing scientists tick o the possibilities is like listening
to lottery winners. And personalized medicine like the type
of cancer testing and treatment that Dana-Farber s Meyerson
hopes to help usher in is just a starting point. Bentley says
the new sequencers will open windows on the vast "non-
coding" regions of the genome that tur n genes on and o .
Egholm of 454 notes that the Human Genome Project did
not actually sequence every last bit of human DNA; there
may still be undiscovered genes that additional sequencing
can nd. Broad s Lander imagines a torrent of new infor-
mation about what leads a cell to di erentiate into one type
or another (a central mystery in developmental biology) and
what controls di erent cellular states. "I realize that s harder
to explain than curing cancer," he says, "but it s ultimately
more important, because it will a ect all diseases."
Within the next year, Lander predicts, scientists will be
able to begin studies that generate "terabases" of informa-
tion---one trillion As, Cs, Ts, and Gs. "I never even spoke
the word terabase before last year," he says. "And if all those
data are on the Web and freely available, it s going to drive
a completely di erent kind of biology."
Jon Cohen, a San Diego--based freelance writer and correspondent
for Science, is working on a book that looks at the genetic differences
separating chimpanzees from humans.
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