When the X Prize Foundation announced on October 4 the Archon X Prize for Genomics - $10 million to the first team to build a device that can sequence 100 human genomes in 10 days with at least 98% coverage and less than one error per 100,000 bases, for under $10,000 per genome - it met both excitement and skepticism.
"This is far beyond what anyone has done at any price," says Chad Nusbaum, codirector of the genome sequencing and analysis program at the Broad Institute of MIT and Harvard. "We've sequenced one genome, but not nearly as well as is being asked by this competition." The Human Genome Project has resulted in just 93% completion, with about one error per 10,000 base pairs, says George Church, professor of genetics at Harvard Medical School. And it doesn't even represent a single individual, adds Nusbaum, "It's a crazy quilt of haplotypes from several individuals."
So I wanted to find out who was going for the potentially quixotic X Prize. There are several obvious contenders: 454 Life Sciences, Solexa, Helicos BioSciences, VisiGen Biotechnologies, Applied Biosystems, and Church. 454 Life Sciences and VisiGen Biotechnologies have already registered, as has a consortium based out of Gainesville, Florida, comprising the Westheimer Institute for Science and Technology, the Foundation for Applied Molecular Evolution, and Firebird Biomolecular Sciences.
Others won't: Applied Biosystems, which entered the next-gen game when it acquired Agencourt Personal Genomics (which has a relationship with Church) earlier this year, will abstain, instead concentrating on commercializing its DNA sequencing technology, says Gina Costa, the company's director of R&D projects, high-throughput analysis. Church won't, either; he's focused on using his technology for the Personal Genome Project, his attempt to sequence one percent of the genome sequence from each of "10 individuals this year and a million individuals as soon as possible." Of course, Church also says, "If we wake up one morning and say we can snatch up $10 million easily, I don't think anyone's going to turn that down."
Tony Smith, vice president and chief scientific officer at Solexa, wouldn't say whether his company would enter. Steve Lombardi, senior vice president of marketing at Helicos, says his company hasn't yet decided.
All five companies ultimately plan to be able to sequence human genomes quickly and inexpensively; the common thread for those entering seems to be that their corporate goals and milestones parallel the Prize. "The X Prize fits VisiGen's company mission statement," says president Susan Hardin. Likewise, 454 president and CEO Chris McLeod says, "We were founded with the vision that there should be a way to make sequencing whole genomes economical and quick. It is logical for us to be a contestant."
There are a few hundred genetic alterations whose functions are known and which can be tested for, but just a fraction of those would change clinical practice - things like syndromic loci, known oncogenes, and so on. We don't need whole-genome sequences to monitor those loci. We don't even need next-generation sequencing technology really, except to make the analyses timely. Even if we could tie every one of our 25,000 or so protein-coding and regulatory RNA genes to a health problem or predisposition that still would represent less than two percent of the human genome.
So when I asked company reps why, given how little we understand the genome now, they were pursuing whole-genome sequencing, I got a range of answers, from understanding human variation to improving cancer diagnosis and therapy. Most were variations on the idea that, even if we can't use the data today, the more sequence information we accumulate the more we'll learn from subsequent work. "The value of whole-genome sequencing gets better and better the more genomes we have to compare," says Hardin.
I'll buy that. Still, why set the bar so high? "The key here is radical breakthrough," says Ian Murphy, director of public relations for the X Prize Foundation. "At the end of the day, unless we have the capability to map hundred of genomes, unless we can map genomes in hours as opposed to days or months or years, we're never going to be able to use this science to its full application."
"We don't want incremental gains," he adds, "we want to change the way we live our lives."