Today, the cost has fallen, but only to around $50 million.
The target price is orders of magnitude away: $1,000 for an
individual's DNA sequence.
That's the price considered essential for giving scientists
the thousands of sequenced samples they need to understand how
genes work, and giving patients access to a personalized DNA snapshot
at the doctor's office that could show the diseases they are at
risk of developing.
Some scientists believe the old methods of sequencing DNA, though
improving, will never produce a $1,000 genome, and they are
exploring radically different ways to map the blueprint of human
life.
Their methods remain far from proven. But there have lately
been signs of headway on several fronts.
"It's not clear which of these things will be the ultimate success,
but I think these are all pieces of the puzzle moving us in the
direction we need to go," said Jeff Schloss, program director
for technology development at the National Institutes of Health
(news
- web
sites)'s National Human Genome (news
- web
sites) Research Institute.
The human genome project (news
- web
sites) yielded the first complete sequence of the 3.2 billion
base pairs that comprise the DNA molecule of a person (actually,
it sequenced a composite of a few people). Each base is one of
four chemicals, their order governing a human being's development.
But that was only a starting point.
While the DNA of one person is 99.9 percent identical to another's,
it is the 0.1 percent of variation that interests many scientists
because the differences may answer questions like why some people
develop certain diseases and others do not.
To answer those questions, scientists must compare the DNA sequences
of thousands of people. To get them, they must find a way to sequence
DNA that, unlike the first sequencing, doesn't require thousands
of lab technicians and dozens of supercomputers.
"To actually deliver everybody's genome, you can't apply that
kind of brute force strategy," said George Church, a researcher
at Harvard Medical School (news
- web
sites).
For years, scientists sequencing DNA have relied on a lumbering
technique called electrophoresis. But it requires expensive chemicals,
and without expensive hardware an average lab would be hard-pressed
to sequence more than 1,000 base pairs a day. At that speed, it
would take almost 10,000 years to get through the 3.2 billion
base pairs in human DNA.
The new techniques start from scratch.
In April, a group led by Caltech researcher Stephen Quake published
the first successful results from "single molecule sequencing,"
or reading DNA one base pair at a time. Quake's group uses a flourescent
label to mark the free molecules that surround DNA, then tracks
which molecules are used when the DNA makes a copy of itself.
The technique works on only five base pairs at a time, but Quake
says many sequences can be read at once.
Meanwhile, in an article published in the August edition of
Science, Church's lab reported progress on bathing DNA in different
frequencies of light to produce a color-coded snapshot revealing
the order of a DNA sequence.
Daniel Branton, a Harvard colleague of Church's, is working
on a method Schloss considers among the most promising: shooting
DNA through a tiny hole called a nanopore and measuring the electric
signals each base pair emits.
And in another recent development, a Branford, Conn., company
called 454 Life Sciences announced it had sequenced the genome
of a virus — about 30,000 base pairs long — by dropping
DNA into tiny wells and is now working on bacteria, with 2 million
to 8 million base pairs. The company hopes to work its way up
to humans.
Other technologies can compare one strand to a reference, like
that provided by the human genome project, and highlight differences.
That could help scientists identify the 99.9 percent of identical
base pairs, and allow them to focus on the remaining 0.1 percent.
Woburn-based U.S. Genomics, for example, tags certain sequences
then shoots them past a laser, which detects the tags as they
go by.
Many of these techniques solve some shortcomings of electrophoresis,
but none solves them all. Knotty obstacles remain, like "blurring"
of the base pairs' fluorescence, or finding computers that can
crunch all the numbers these methods produce.
One skeptic, Elaine Mardis, a genetics expert at Washington
University in St. Louis, worries that too many labs are releasing
"data by press release" rather than subjecting the information
to scientific review. She isn't convinced that scientists are
solving problems such as how to read longer DNA snippets or in
developing precise instruments to perceive fluorescent light.
"Honestly, it's going to take us 10 or 15 years to get there,"
she said of the $1,000 genome. "The non-scientific public
is hearing this and saying that sounds really great, and people
must be at that goal because they're talking about it. That's
totally not the case. This is the plan for the future, and the
future is not now."
___
On the Net:
Human Genome Project background: http://www.ornl.gov/TechResources/Human_Genome/project/info.html
Stephen Quake: http://thebigone.caltech.edu/quake/
George Church's Work: http://arep.med.harvard.edu/Polonator/
Daniel Branton's Work: http://mcb.harvard.edu/branton/index.htm
454 Life Sciences: http://www.454.com/