Technology: The $1,000 genome

In Silicon Valley, Moore's law seems to stand on equal footing with the natural laws codified by Isaac Newton. Intel co-founder Gordon Moore's iconic observation that computing power tends to double and that its price therefore halves every 2 years has held true for nearly 50 years with only minor revision. But as an exemplar of rapid change, it is the target of playful abuse from genome researchers.

In dozens of presentations over the past few years, scientists have compared the slope of Moore's law with the swiftly dropping costs of DNA sequencing. For a while they kept pace, but since about 2007, it has not even been close. The price of sequencing an average human genome has plummeted from about US$10 million to a few thousand dollars in just six years (see Falling fast). That does not just outpace Moore's law it makes the once-powerful predictor of unbridled progress look downright sedate. And just as the easy availability of personal computers changed the world, the breakneck pace of genome-technology development has revolutionized bioscience research. It is also set to cause seismic shifts in medicine.

In the eyes of many, a fair share of the credit for this success goes to a grant scheme run by the US National Human Genome Research Institute (NHGRI). Officially called the Advanced Sequencing Technology awards, it is known more widely as the $1,000 and $100,000 genome programmes. Started in 2004, the scheme has awarded grants to 97 groups of academic and industrial scientists, including some at every major sequencing company.

It has encouraged mobility and cooperation among technologists, and helped to launch dozens of competing companies, staving off the stagnation that many feared would take hold after the Human Genome Project wrapped up in 2003. The major companies in the space have really changed the way people do sequencing, and it all started with the NHGRI funding, says Gina Costa, who has worked for five influential companies and is now a vice-president at Cypher Genomics, a genome-interpretation firm in San Diego, California.

The $1,000 genome programme, now close to achieving its goal, will award its final grants this year. As technology enthusiasts look to future challenges, the coming milestone raises questions about how the roughly $230-million government programme managed to achieve such success, and whether its winning formula can be applied elsewhere. It benefited from fortuitous timing and the lack of an entrenched industry. But Jeffery Schloss, director of the division of genome sciences at the NHGRI in Bethesda, Maryland, who has run the programme from its inception, says that its achievements also suggest that there are ways to navigate publicprivate partnerships successfully. One of our challenges is to figure out what is the right role for the government; to not get in the way, but feed the pipeline of private-sector technology development, he says.

The quest to sequence the first human genome was a massive undertaking. Between 1990 and the publication of a working draft in 2001, more than 200 scientists joined forces in a $3-billion effort to read the roughly 3 billion bases of DNA that comprise our genetic material (International Human Genome Sequencing Consortium Nature 409, 860921; 2001). It was a grand but sobering success. The project's advocates had said that it would reveal 'life's instruction book', but in fact it did not make it possible to interpret how the instructions encoded in DNA were transformed into biology. Understanding how DNA actually influences health and disease would require studying examples of the links between genes and biology in thousands, perhaps millions, more people.

The dominant technology at the time was Sanger sequencing, an inherently slow, labour-intensive process that works by making copies of the DNA to be sequenced that include chemically modified and fluorescently tagged versions of the molecule's building blocks. One company, Applied Biosystems in Foster City, California, provided the vast majority of the sequencers to a limited number of customers generally, large government-funded laboratories and there was little incentive for it to reinvent its core technology.

Still, researchers had seen some advances, including robots that replaced some human work and improvements in devices capable of handling small amounts of liquid. At a 2002 meeting convened by the NHGRI, scientists predicted that such developments would drive costs down at least 100-fold over the next five years. But that was not enough.

They debated what price target would make human genome sequencing routine, the kind of thing a physician might order to help diagnose a patient on a par with a magnetic resonance imaging scan. Somebody threw out, to great rolling of eyes, 'a thousand dollars', recalls Schloss.

That seemed too ambitious, given the state of the technology. The risk associated with that is not one that your normal investor is willing to spend any money on, says Eric Eisenstadt, a retired official from the US government's Defense Advanced Research Project Agency who is now a consultant in Reston, Virginia.

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Technology: The $1,000 genome