New Genome Tech May Pave Way for Personalized Meds

Mason Inman
for National Geographic News
April 16, 2008
James D. Watson, the co-discoverer of DNA's structure, is now the second person in the world to have his whole genome sequenced.

But he's the first to have it done with a next-generation technique that took a mere two months to complete and cost "only" a million U.S. dollars—a figure that might drop to $2,000 within six years, one expert predicts.

The hope for many is that cheaper sequencing will help medicine become personalized, so that people can receive drugs or adjust their lifestyles according to their particular genetic makeups.

The first personal genome sequencing—done for genetics pioneer Craig Venter—was completed in stages as part of a project by Venter's company to create an "average" human genome.

Observers estimate that Venter's genome took years to decode and cost anywhere from $70 million to $100 million.

"Watson is the first of the rest of us," said Jonathan Rothberg, founder of 454 Life Sciences, who invented the new technique that sequenced Watson's genome.

In general the cost of genome sequencing is dropping fast. Some researchers say that in several years the technology may be affordable for most of the public.

"It will become as ubiquitous as [medical] imaging," such as x-rays or MRI scans, Rothberg predicts.

Great Diversity

In research that will appear in tomorrow's issue of the journal Nature, Rothberg and colleagues show that Watson's genome was similar to Venter's in many ways.

This suggests that the new sequencing method is as reliable as older, more costly techniques.

For example, Watson's genome—the full "book" of base pairs that make up a person's genetic code—has about 3.3 million single nucleotide polymorphisms, or SNPs (pronounced "snips").

SNPs are points where a single letter in a person's genome is different from what most people have. (Get an overview of human genetics.) Venter's genome has about 3.5 million SNPs.

Both Watson and Venter have hundreds of thousands of SNPs that are unique to themselves.

In addition to be faster, the new method is more comprehensive, Rothberg said, covering 3 percent of the genome that had either been skipped or couldn't be sequenced by older methods.

Rothberg noted that Watson's genome has about 200,000 larger chunks of DNA that were either added in or missing compared to the "average human genome" produced by the U.S. government's Human Genome Project.

"We now know that the Human Genome Project had made a mistake," Rothberg argued. "It underestimated the great diversity between individual people."

Genomes for the Masses

Although the analysis of Watson's genome was released today, the sequencing was actually done in the spring of 2007. The price has already dropped since then.

"Watson's genome cost a million dollars, and this year [a human genome] costs two hundred thousand," Rothberg said.

"Each year it becomes five times faster and five times cheaper," he said. "In six years, I'll give you a $2,000 genome."

454 Life Sciences was one of the first companies to register for the Archon X Prize for Genomics, a recently established award aimed at bringing personal genomes to the masses.

The first team to sequence a hundred whole human genomes in less than ten days for under $10,000 each will take home the $10-million prize.

Competition aside, the company's work on Watson's genome is "very important to convince people that next-generation sequencing is here to stay," said George Church of Harvard Medical School in Boston, Massachusetts.

But Church warns that the claims by companies of how much it costs them to sequence the human genome may not be reliable.

"The problem is none of these companies are documenting their prices," Church said. Even when the price is published in a journal, "this part isn't peer reviewed."

One way of proving that a price is real is if "you can offer it as a service," Church said. That's the approach of Knome, a company in Cambridge, Massachusetts, that Church co-founded.

If a company can't sequence genomes as cheaply as advertised, then in the long run "it will go broke," Church said.

Knome was the first to offer whole genome sequencing commercially, starting last winter. At their current price tag of $350,000, they've so far had two buyers.

But understanding all this genetic information is another matter.

Figuring out how genes are connected to various traits and diseases is "something we're all going to have to undertake as a society over the next ten years," study author Rothberg said.

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