Kevin McKernan was a scientist at the pre-Broad Whitehead genome center at a time when the Amersham MegaBace was the sequencing standard. In 1998, he recalls, Applied Biosystems swooped onto the market with its brand new 3700 sequencing instrument. It had shorter reads and lacked first-mover advantage — but in the long run, it was hardly even a contest for ABI. McKernan, now CSO of Agencourt Biosciences, remembers “watching them blitzkrieg the market with an instrument that was basically developed in 18 months. They’ve got product development nailed.”
That memory came back to McKernan when ABI and Agencourt started discussing the possibility of teaming up in the next-generation sequencing market. While McKernan’s company, Agencourt Biosciences, was bought by Beckman Coulter last year for $140 million, his startup Agencourt Personal Genomics — a player in the next-generation sequencing field — was kept separate, with Beckman acquiring a 49 percent interest in it.
That left the door open for other instrument developers to partner with APG as it continued to develop a commercializable sequencer. As it turns out, it also left the door open for Applied Biosystems to buy APG outright in a deal worth $120 million — $50 million of which went to Beckman for its minority stake.
APG’s technology relies on a bead-based stepwise ligation process, emulsion-based PCR, and the polony technology from George Church’s lab. The technology, known internally as SOLID, or supported oligo ligation and detection sequencing, currently reads about 25 bases — but thanks to paired end reads, that’s the equivalent of a 50-base sequence. “There’s optimism here that those read lengths will get longer in time,” McKernan says, though he believes that the scientific community will become increasingly receptive to shorter reads from sequencers faster than many industry observers expect.
McKernan says it was the accuracy of the APG technology that convinced ABI to buy in. “Applied Biosystems did their homework on every technology out there and we won hands down on accuracy,” he says.
According to Kevin Corcoran, VP and general manager of ABI’s genetic analysis business, his company did indeed evaluate a number of candidates in the next-gen sequencing field. Technologies were ranked for scalability, data quality, read length, cost per finished base, and other parameters; “APG scored the highest in most” of those areas, Corcoran says. APG particularly impressed its suitor by sequencing a BAC, of which 35 percent of the sequence was repeat units, to at least 99.9 percent accuracy. Thanks in part to an internal error-checking procedure built into the APG platform, McKernan says, “I think this is going to be the highest-accuracy system out there.”
Corcoran anticipates getting an instrument on the market in 2007, with an early access sequencing service starting by the end of this calendar year. “Right now we’re doing close to 100 million bases per run,” he says. “We think this technology could reach raw data outputs on the order of 1.2 gigabases per run.” At present, each run is taking about three days, he adds.
Corcoran expects the APG sequencer to deliver on the $100,000 genome and says that as far as pricing goes, “the instrument will be competitive on a cost basis with the 3730 xl series.” The sequencer looks like it will be especially promising for digital gene expression as well, Corcoran says. In the long run, ABI will continue to look at other next-gen sequencing technologies. For its next investment, be it internal or another acquisition, ABI will target a real-time, single-molecule sequencing technology generating at least 500-base reads. “We think those are probably seven to eight years out,” Corcoran says.
As for APG, the entire staff of about 20 people will join ABI but will remain based in Beverly, Mass. Until early this year, the team’s work went mostly unnoticed by the larger community. Despite the occasional scientific conference presentation, APG never got involved in the publicity game that has largely characterized this sequencing field. McKernan says that wasn’t necessarily a part of the strategy, though. “I don’t really know how intentional that was,” he says. “It’s just our way. We’re not into chest-pounding.”
— Meredith Salisbury