[tt] WSJ: DNA Decoding Maps Mainstream Future

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DNA Decoding Maps Mainstream Future
http://online.wsj.com/article/SB119144984347648190.html?mod=googlenews_wsj
[Thanks to Sarah for this.]
7.10.4

Dropping Costs May Make
Gene Sequencing of Patients More Common
By KEITH J. WINSTEIN

This past summer, biologist J. Craig Venter published his own
complete genetic blueprint on the Internet, a multiyear effort than
cost more that $60 million.

Now, Dr. Venter is decoding himself again, this time using new,
less costly technology. He hopes by December to redo the gene job
for just $300,000.

The price of reading a person's genome is plummeting, raising hope
for new medical discoveries and cures. It cost the Human Genome
Project $3 billion to extract the first complete genetic blueprint,
which was completed in 2003. Now four companies are racing to bring
the cost to below $10,000.

At that price, it may become more common for patients to have their
genes sequenced for medical tests. Cancer researchers hope to use
sequencing to learn what went wrong in the DNA of cells that became
tumors. Drug companies hope to usher in an era of personalized
medicine with custom-made medicines that change cell behavior.

Whichever company reaches the $10,000 mark first has a shot at
winning a $10 million prize offered by the X Prize Foundation,
based in Santa Monica, Calif., which is trying to encourage faster
and cheaper gene sequencing.

"Once people see the value of this information, nobody will want to
go backwards," says Dr. Venter, who has put up $500,000 of the
prize money.

The contenders -- Illumina Inc., of San Diego; Applera Corp.'s
Applied Biosystems unit in Foster City, Calif.; Roche Holding AG's
454 Life Sciences in Branford, Conn.; and Helicos BioSciences
Corp., of Cambridge, Mass. -- haven't achieved the $10,000 level
yet. It currently costs between $300,000 and $3 million to sequence
a genome. But with better chemicals and faster computers, the
companies say, the cost will fall to $10,000 within a few years.

One reason for the advances is that sequencing machines no longer
have to start from scratch. Human DNA is made up of 23 pieces, or
chromosomes, and each chromosome has roughly 100 million chemical
letters arranged like beads on a string -- A's, T's, C's and G's.
It isn't possible today to read 100 million letters at a time, so
to sequence a person's DNA, researchers traditionally chopped up
the chromosomes into overlapping pieces, each about 700 letters
long.

In both the government-funded Human Genome Project, and Dr.
Venter's first effort, scientists used a technique invented in the
1970s, called Sanger sequencing, to input each piece into a
computer. Then the overlapping pieces were put back together, with
software, to form an entire chromosome, a painstaking process
somewhat like putting together a jigsaw puzzle without a picture on
the front of the box.

The new machines take advantage of those existing genetic
blueprints -- in effect, supplying the missing picture. Instead of
dividing chromosomes up into 700-letter strings, the new sequencers
make the jigsaw pieces much smaller -- sometimes 25 or 30 chemical
letters long -- and read many pieces at once. For example,
Helicos's machine, which isn't yet on the market, will be able to
scan in at least 300 million such pieces simultaneously, compared
with just 96 for the older machines.

The newer machines run faster than the old methods and require
fewer chemicals, which account for the bulk of gene sequencing
costs. The new machines match the tiny pieces to where they fit
best on the existing genetic blueprints, a process known as
"resequencing."

To date, only one new machine has successfully resequenced a human
genetic blueprint -- Roche's 454 Genome Sequencer FLX, which costs
about $500,000. This summer, the company assembled the genes of
James Watson, the DNA pioneer, by putting together pieces of his
DNA about 250 letters each on top of the blueprint published by the
Human Genome Project. The company estimates it costs about $2
million to $3 million, and takes about a month, to sequence a human
genome with its machine.

Dr. Venter says he plans to resequence his own DNA for $300,000
using a new machine from Applera called the Solid System. The aim
is to test the accuracy of the new, faster systems, and compare
them against the copy of Dr. Venter's DNA published this summer
using the old method. After that, his research institute plans to
sequence between 10 and 30 human genomes in 2008, with the goal of
finishing 10,000 such sequences in the next 10 years.
[DNA]

Illumina says it has sold more than 100 of its sequencers, known as
the Genome Analyzer. The company also is one of the biggest sellers
of DNA arrays, or "gene chips," a hot product that allows doctors
and researchers to test if patients have certain genes. Sequencing,
which can test for every single gene at once, threatens to make
such chips obsolete, if it can be made more affordable. "What we'll
see is sort of a gradual transition in the marketplace as
sequencing becomes easier and cheaper," said Adam Lowe, a spokesman
for Illumina.

Another candidate in the race is Helicos's Heliscope, which the
company calls the first "DNA microscope." Unlike the other
machines, Helicos's skips a step where pieces of DNA are duplicated
before being read into a computer. Helicos says that will make its
machine cheaper and easier to operate. The company estimates its
equipment, set for release later this year, will cost $2 million.
With it, the price of sequencing a person's genome will drop to
$100,000, the company says.

Write to Keith J. Winstein at keith.winstein at wsj.com