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DNA decoding maps mainstream future; lower costs may make gene sequencing more common

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This past summer, biologist J. Craig Venter published his own complete genetic blueprint on the Internet, a multiyear effort that 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 Venter, who has put up $500,000 of the prize money.

The contenders — Illumina Inc. (Nasdaq: ILMN), of San Diego; Applera Corp.'s (NYSE: ABI) Applied Biosystems unit in Foster City, Calif.; Roche Holding AG's (NYSE: AG) 454 Life Sciences in Branford, Conn.; and Helicos BioSciences Corp. (Nasdaq: HLCS), 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 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' 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.

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 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.

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' 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.

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