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Rapid DNA Test Could Reveal Patient Genome in Minutes Some Day

By John Lauerman and Rob Waters

Nov. 20 (Bloomberg) -- A new technique could map DNA sequences 30,000 times faster than current methods, accelerating researchers' work to unravel the complex mutations that cause human disease.

The approach, called single-molecule real-time sequencing, has the potential to decipher a person's entire genome in about 15 minutes, said Stephen Turner, founder and chief technology officer of Pacific Biosciences Inc. in Menlo Park, California. Turner helped write a description of the new technique, called SMRT, appearing online today in the journal Science.

Faster, more accurate methods of analyzing the DNA of humans and other organisms will lead to a better understanding of how normal organs and tissues develop, and how they go awry in conditions such as diabetes and Alzheimer's disease. The SMRT approach may allow scientists to speed-read the genome within five years, Turner said.

``If you can sequence a human genome for less than $1,000 in a matter of minutes, that will revolutionize health care'' said Hugh Martin, chief executive officer of Pacific Biosciences. Fast, cheap results would make it possible to look for the complex series of genetic mutations that are involved in many diseases, he said.

Using older gene-sequencing machines, like those used to fully map the human genome for the first time, takes six months with 1,500 machines running 24 hours a day to decipher one person's genome, said Martin. The process requires $1 million to $5 million worth of chemicals and solvents, he said.

Cheaper Screening

``You could take 100 men with prostate cancer and take a sample of the malignant cells and sequence each of them,'' Martin said Nov. 18 in a telephone interview. ``Then you can put it into a computer and look for common irregularities and patterns. If it costs a million dollars to sequence each person's cells, you're not going to do it. But if it's a lot cheaper you can.''

Outgoing Health and Human Services Secretary Michael Leavitt said Nov. 14 that U.S. president-elect Barack Obama should make use of genetic and computer tools to individualize care for patients and bring down the cost of health care.

If Pacific Biosciences' SMRT technique can deliver a patient's genome in 15 minutes, ``at that point, this becomes a market dominating technique,'' Turner said in a telephone interview Nov. 19 from company headquarters in Menlo Park, California. ``There would be no reason to use any other.''

The annual market for genome sequencing equipment made by Swiss-based Roche Holding AG, San Diego-based Illumina Inc. and other companies is about $1 billion and will to rise to $1.5 billion by 2013, said Ross Muken, a Deutsche Bank analyst in New York. Invitrogen Corp., based in Carlsbad, California, is scheduled to complete its $6.7 billion purchase of the sequencer maker Applied Biosystems Inc. of Norwalk, Connecticut, Nov. 21.

Chemical Code

DNA is four-chemical code for making all the proteins in an organism. Various reshufflings of the chemicals, called bases, instruct cells' DNA as to which proteins to make, when to make them and in what amounts. Virtually every human cell has two strands of DNA, each 3 billion bases long.

Each time cells replicate, a complete copy of its DNA must be made for each of the two new cells made by its division. Turner was part of a team developing a sequencing method that mimics the cells' DNA-copying technique as a graduate student at Cornell University in Ithaca, New York.

The SMRT technique allows scientists to observe another set of bases bind to those on a single strand of DNA, one by one, just as they do when DNA copies itself. Each chemical is individually colored to show which of the four bases -- adenosine, cytosine, guanine or thymine -- it has attached to, allowing scientists to read three to five bases per second with about 99.3 percent accuracy, Turner and his colleagues said in the paper published today.

2013 Finish

While it will take until 2013 to finish developing machines that can sequence genomes in less than an hour, Martin said that within one year the company will begin delivering to customers an early version able to do the job in three days. The price will be between $300,000 and $500,000, he said.

The SMRT technique ``is really what it will take to bring the cost of sequencing the human genome down to $1,000 and perhaps below,'' said Stephan Schuster, a Pennsylvania State University geneticist, in a telephone interview on Nov. 18. ``It's the most anxiously awaited jump in the technology.''

The company will initially sell its machines to government- funded research laboratories studying the genetics of disease and to drugmakers wanting to select patients with genetic profiles that make them likely to benefit from new drugs, Martin said.

$120 Million Investment

In the bleakest financing environment in decades, Pacific Biosciences has raised $120 million from venture capital firms this year. Since Turner and his Cornell colleagues founded the company four years ago, it has brought in $200 million from investors.

``We invested in them when they were just three post-docs out of Cornell,'' said Rowan Chapman, a partner at Mohr Davidow Ventures, the Menlo Park, California venture fund that was the first to finance the company. Other heavyweight venture firms, including Kleiner Perkins Caufield & Byers and the Blackstone Group later joined in.

``We viewed them as having the ability to become the gold standard for genetic analysis,'' Chapman said in a Nov. 18 telephone interview. ``We truly believe it will develop into a multi-billion dollar market-cap company.''

To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net; Rob Waters in San Francisco at rwaters5@bloomberg.net.

Last Updated: November 20, 2008 14:00 EST

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