Entrepreneurs and scientists are pursuing the ability to sequence an entire human genome for around a $100 price tag. Sequencing is a way of “reading” DNA molecules — two strands twisted together to form that famous double helix. The entire human genome contains roughly 3 billion molecular base pairs, which researchers study to find variations that might play a role in the development of diseases. Right now it typically costs $1,000 to $4,000 to map out an individual’s genome. (Specialized sequencing — for, say, a cancer patient — often costs more.)
Since 2007, the cost of genome sequencing has been in free-fall, dropping by as much as 90% several years in a row.
Dozens of startups are trying to carve off their chunk of a genetic testing market that UnitedHealthcare estimates could reach $25 billion annually by 2021.
Innovations like “ion torrent” sequencing, created by a startup acquired in 2010 by Life Technologies, aim to slash costs. Sequencing has traditionally been done optically, by flooding DNA snippets with chemicals called reagents that contain one of DNA’s four bases. Every base has only one match; when a base finds a match, a light flashes. The sequencer sees it and records the base.
With the Ion Proton System — a $100,000 machine that can sit on top of a table — it’s not light that’s being recorded, but changes in pH balance. The DNA snippets being sequenced are attached to tiny beads sitting in as many as a billion tiny wells on a custom-designed semiconductor chip. The chip is flooded with DNA nucleotides, and when a base snaps into place, a hydrogen ion is released and recorded.
Right now the company can sequence the exome — the 1 percent of the genome we know how to interpret — for $500. “In three months, we’ll be able to do one entire human genome for $1,000,” predicts Rothberg, whose first company, 454 Life Sciences, was the one that sequenced James Watson’s genome.
Eric Topol, a professor of genomics and director of the Scripps Translational Science Institute in San Diego, says chip sequencing — without expensive reagents — has the potential to be “remarkably cheaper” than traditional optical sequencing.
The industry standard today for sequencing and “genotyping,” which looks only at a select number of DNA variations, are arrays and sequencers from a company called Illumina (ILMN). Most labs using the San Diego firm’s equipment can sequence an entire genome for $3,000 to $4,000. “Everyone likes lopping zeros off the price of the genome, but it’s really not at $1,000 yet — although it’s starting to inch up on that,” says company president and CEO Jay Flatley.
Illumina’s arrays are quickly becoming cheaper and denser. Other advances are also driving down prices.
Topol cites innovations like nanopore sequencing, which passes DNA through a protein nanopore: “That’s a very efficient way of getting millions and millions of bases read.” That approach still has “significant problems with accuracy,” he noted.
Another startup trying to slash costs is InVitae, a sequencing company in San Francisco that targets rare, inherited diseases. Individually, these diseases — like cystic fibrosis, Tay-Sachs, Canavan disease and Lynch syndrome — are rare, but in the aggregate millions of people have them or carry the gene for them. InVitae tests for 264 genetic conditions and charges $1,500. By 2014, it expects to test 1,000 inherited conditions for $1,000.