I.B.M. Joins Pursuit of $1,000 Personal Genome
- From: as <assidd73@xxxxxxxxx>
- Date: Thu, 29 Oct 2009 03:39:28 -0700 (PDT)
Source: New York Times
http://www.nytimes. com/2009/ 10/06/science/ 06dna.html? _r=2
I.B.M. Joins Pursuit of $1,000 Personal Genome
By JOHN MARKOFF
<http://topics. nytimes.com/ top/reference/ timestopics/ people/m/
john_markoff/ index.html? inline=nyt- per>
One of the oldest names in computing is joining the race to sequence
the
genome for $1,000. On Tuesday, I.B.M.
<http://topics. nytimes.com/ top/news/ business/ companies/
international_ business_ machines/ index.html? inline=nyt- org>
plans to give technical details of its effort to reach and surpass
that
goal, ultimately bringing the cost to as low as $100, making a
personal
genome cheaper than a ticket to a Broadway play.
The project places I.B.M. squarely in the middle of an international
race to drive down the cost of gene sequencing to help move toward an
era of personalized medicine. The hope is that tailored genomic
medicine
would offer significant improvements in diagnosis and treatment.
I.B.M. already has a wide range of scientific and commercial efforts
in
fields like manufacturing supercomputers designed specifically for
modeling biological processes. The company’s researchers and
executives
hope to use its expertise in semiconductor manufacturing, computing
and
material science to design an integrated sequencing machine that will
offer advances both in accuracy and speed, and will lower the cost.
“More and more of biology is becoming an information science, which
is
very much a business for I.B.M.,” said Ajay Royyuru, senior manager
for
I.B.M.’s computational biology center at its Thomas J. Watson
Laboratory
in Yorktown Heights, N.Y.
DNA sequencing began at academic research centers in the 1970s, and
the
original Human Genome Project successfully sequenced the first genome
in
2001 and cost roughly $1 billion.
Since then, the field has accelerated. In the last four to five
years,
the cost of sequencing has been falling at a rate of tenfold
annually,
according to George M. Church, a Harvard geneticist. In a recent
presentation in Los Angeles, Dr. Church said he expected the industry
to
stay on that curve, or some fraction of that improvement rate, for
the
foreseeable future.
At least 17 startup and existing companies are in the sequencing
race,
pursuing a range of third-generation technologies. Sequencing the
human
genome now costs $5,000 to $50,000, although Dr. Church emphasized
that
none of the efforts so far had been completely successful and no
research group had yet sequenced the entire genome of a single
individual.
The I.B.M. approach is based on what the company describes as a “DNA
transistor,” which it hopes will be capable of reading individual
nucleotides in a single strand of DNA as it is pulled through an
atomic-size hole known as a nanopore. A complete system would consist
of
two fluid reservoirs separated by a silicon membrane containing an
array
of up to a million nanopores, making it possible to sequence vast
quantities of DNA at once.
The company said the goal of the research was to build a machine that
would have the capacity to sequence an individual genome of up to
three
billion bases, or nucleotides, “in several hours.” A system with this
power and speed is essential if progress is to be made toward
personalized medicine, I.B.M. researchers said.
At the heart of the I.B.M. system is a novel mechanism, something
like
nanoscale electric tweezers. This mechanism repeatedly pauses a
strand
of DNA, which is naturally negatively charged, as an electric field
pulls the strand through a nanopore, an opening just three nanometers
in
diameter. A nanometer, one one-billionth of a meter, is approximately
one eighty-thousandth the width of a human hair.
The I.B.M. researchers said they had successfully used a transmission
electron microscope to drill a hole through a semiconductor device
that
was intended to “ratchet” the DNA strand through the opening and then
stop for perhaps a millisecond to determine the order of four
nucleotide
bases — adenine, guanine, cytosine or thymine — that make up the DNA
molecule. The I.B.M. team said that the project, which began in 2007,
could now reliably pull DNA strands through nanopore holes but that
sensing technology to control the rate of movement and to read the
specific bases had yet to be demonstrated.
Despite the optimism of the I.B.M. researchers, an independent
scientist
noted that various approaches to nanopore-based sequencing had been
tried for years, with only limited success.
“DNA strands seem to have a mind of their own,” said Elaine R.
Mardis,
co-director of the genome center at Washington University
<http://topics. nytimes.com/ top/reference/ timestopics/
organizations/ w/washington_ university/ index.html? inline=nyt- org>
in St. Louis, noting that DNA often takes a number of formations
other
than a straight rod as it passes through a nanopore.
Dr. Mardis also said previous efforts to create uniform silicon-based
nanopore sensors had been disappointing.
One of the crucial advances needed to improve the quality of DNA
analysis is to be able to read longer sequences. Current technology
is
generally in the range of 30 to 800 nucleotides, while the goal is to
be
able to read sequences of as long as one million bases, according to
Dr.
Church, who spoke in July at a forum sponsored by Edge.org
<http://Edge. org>, a nonprofit online science forum.
Other approaches to faster, cheaper sequencing include a biological
nanopore approach being pursued by Oxford Nanopore Technologies, a
start-up based in England, and an electron microscopy-based system
being
designed by Halcyon Molecular, a low-profile Silicon Valley start-up
that has developed a technique for stretching single strands of DNA
laid
out on a thin carbon film. The company may be able to image strands
as
long as one million base pairs, said Dr. Church, who is an adviser to
the company, and to several others.
“To bring about an era of personalized medicine, it isn’t enough to
know
the DNA of an average person,” said Gustavo Stolovitzky, an I.B.M.
biophysicist, who is one of the researchers who conceived of the
I.B.M.
project. “As a community, it became clear we need to make efforts to
sequence in a way that is fast and cheap.”
.
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