Discount DNA

Complete Genomics says it can sequence a human genome for a fraction of the current cost; a savings that could make DNA scanning affordable to millions.

I'm standing in a balmy room kept warm because the chemicals swishing through dishwasher-size machines on either side of me like it that way. The light is low as small robotic arms inside the devices-they have clear, Plexiglas housings-are moving around samples of DNA, injecting them into flat, microfluidic chips that are a key component of separating out each of the six billion G's, T's, A's, and C's embedded in a human cell.

Right now, gene-testing companies will sell you a near-complete perusal of your own DNA for somewhere between $100,000 and $350,000. A year ago it cost $1 million. Five years ago, the cost of the first complete human genome was $2.7 billion.

Now, this company I'm visiting-Complete Genomics, based in Mountain View, California-says that, come next spring, it will be able to tease out virtually every nucleotide-the A's, C's, T's and G's that make up DNA-inside you or me for a mere $5,000.

If true, this breakthrough in cost reduction will allow thousands (possibly millions) of people to be given the sort of top-to-bottom genetic scan that has been so costly that only about 20 or so people have done it-including famed geneticists James Watson and Craig Venter.

Having one's complete genome sequenced is far more thorough than the scans done by companies such as 23andMe (also in Mountain View) and DeCodeMe of Iceland. These companies offer direct-to-consumer testing of a person's DNA for between $399 and $995. But they test only about million genetic markers out of the six billion nucleotides that reside inside human cells.

The one million markers have been chosen because they are useful for finding genetic traits that can cause one person to have a higher risk factor for a disease than another.

But these assessments are only outlines of a person's entire genome and thus cannot provide a total assessment of a person's genetic proclivities. They are like having the CliffsNotes to Leo Tolstoy's War and Peace rather than the actual novel.

The significance of knowing so much about people's genetics will be important in understanding disease and eventually designing drugs tailored to individual people.

"Many chronic and life-threatening human diseases have a genetic basis," said Harvard geneticist George Church, a member of Complete Genomics' scientific advisory board, in a Complete press release. "The ability to compare a significant number of genomes of people with a disease against those without the disease is central to enabling drug discovery and the development of new diagnostics."

Founded in 2006, the company recently emerged from stealth mode using technology developed primarily by chief scientific officer Radoje Drmanac, a key scientist for the Department of Energy during the Human Genome Project and a co-founder of Hyseq, a gene-discovery and drug company.

The technology employs arrays (the chips I see in the warm room) that are extremely dense and use chemicals to separate out the DNA, special enzymes to join them together, and imaging methods to identify them-patented processes that Complete's C.E.O. Clifford Reid says have dramatically reduced costs.

So far, Complete has raised $46 million in venture capital, including a small investment from Genentech. It plans to sell its services to pharmaceutical companies, researchers, and businesses offering genetic testing, not directly to consumers.

One direct-to-consumer company, Massachusetts-based Knome, currently offers a full genomic sequencing for $350,000. Knome C.E.O. Jorge Conde has said that he is in discussions with Complete to buy its service, a move that would substantially reduce Knome's fee-which includes the cost of both the sequencing and a personalized analysis of the data produced.

Complete Genomics' business plan has another twist that sets it apart from most other sequencing companies, explains Reid in the company's conference room. He says the company plans to sell just the data, and not the expensive sequencing machines that have been the mainstay of companies such as Applied Biosystems and Illumina. "We handle the machines and the data management," he says.

Reid's company is now building the world's largest commercial human-genome-sequencing center. It expects to sequence 200 genomes per day by the end of 2010, he says. Over the next five years, the company plans to build 10 more centers with a goal of sequencing 1 million complete human genomes. "The cost will go down as we scale up," says Reid.

The downside to this whipsaw reduction in the cost of sequencing is that the technology to produce the data is ahead of anyone's ability to analyze and understand. Even the few dozen genetic markers now being sold by direct-to-consumer companies such as 23andMe for disease risk factors and other traits have yet, in most cases, to be fully tested and validated (see column series: You 2.0).

Recently, the science journal Nature Biotechnology described a "data glut" that is going to slow down the usefulness of this information and possibly create a barrier in the potential market.

Reid says his company is attempting to deal with this by providing a massive computer system to manage the data and to "reduce it to a form suitable for doing science with it." He also expects the applications of the data to catch up with the data generation.

"The thought leaders in pharmacogenomics and disease research are dying to get their hands on these high-quality complete sequence data sets," he says. "It will first roll out to the early adopters, who blaze the trail for everyone else. The early adopters are ready to go."

I just wonder what a genome will cost, say, in a couple of months. At the rate the cost is dropping, it may soon cost the same as, say, a tank of gasoline-or the cost of War and Peace. But I hope the price will include not only the CliffsNotes for a quick summary, but also extensive annotation for those of us not up on our 19th century Russian history-or the intricacy of our own six billion nucleotides.

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