Twenty years after creating the first single-molecule sequencing company, Kevin Ulmer has unveiled a bold new vision for next-generation sequencing and consumer genomics. Ironically, his solution is to reinvent and optimize the most traditional method of all: Sanger sequencing.
Ulmer founded SEQ to develop a method of exonuclease single-molecule sequencing back in 1987. The method was never commercialized, and SEQ’s assets were eventually acquired by Amersham Biosciences. But Ulmer, who has remained an in-demand consultant and advisor to biotech start-ups, most notably Helicos, is returning to the personal genomics field with a new venture called Genome Corp.
Ulmer believes that massively parallel Sanger sequencing can greatly accelerate the speed and lower the cost of whole genomic sequencing.
“Despite having spent the last 20 years for my professional career professing the notion that you’re going to need some fundamentally different way of sequencing other than Sanger, I’ve sort of been born again,” Ulmer told Bio-IT World. “I’ve come to realize there’s nothing fundamentally wrong with Sanger [sequencing]. It needs some polishing and updating, but we believe it can outperform all of these next-gen methods by a substantial margin, without having to abandon what has generated 99.999 percent of everything that’s in GenBank.”
Genome Corp. has received $250,000 in seed funding from the Slater Technology Fund, which invests in new companies based in Rhode Island. Based in Providence, Ulmer is co-founder, president and chief science officer. Richard Horan, a former colleague of Ulmer’s at SEQ and now senior managing director of the Slater Fund, is Genome Corp.’s chairman. Another member of the board of directors is another former SEQ executive, Jay Trautman, currently VP of discovery research and technologies at Cytokinetics.
Ulmer’s vision is to develop the most efficient production line for DNA sequencing. Rather than be confined by producing commercial instruments, Ulmer’s focus is on developing an ultra high-throughput DNA sequencing factory.
“We will never sell hardware,” he says. “We will be selling sequence information. It will be produced in a factory that will be designed and built with technical solutions and economies of scale that allow you to produce sequence far faster and cheaper than you could on a stand-alone basis.”
Ulmer will harness the known quantity of Sanger electrophoresis sequencing – the traditional form of DNA sequencing prior to the advent of “next-generation” technologies such as those from 454 Life Sciences and Illumina – with advances in single-molecule biochemistry. He says there are two main ingredients to making the technique reach the scale of affordability to compete with the latest technologies.
“You essentially have to move to what three out of four of the next-gen platforms have done,” says Ulmer, “which is to do some form of in vitro amplification as the first step, prior to whatever form of sequencing they’re applying. So you have to move to essentially a one-pot amplification to give you tens of millions of reads.”
Back to the Future
The other aspect is a major rethink of the downstream separation process. “It comes back to another fundamental philosophy I’ve had from the beginning, which is that sequencing is an information services business, it’s not an instrument reagent business. It will go the same way that oligonucleotide synthesis has gone.” Not so long ago, labs used their own oligonucleotide synthesizer to make short custom strands of DNA. “That’s all gone away,” says Ulmer. Now, “you just hop on the Internet, you tap away, and it comes in a tube. It’s cheap, it’s fast, it works. It’s become a commodity, an institutionalized service business. I can see sequencing going the same way.”
Besides SEQ, Ulmer previously collaborated with Stanley Lapidus, CEO of Helicos BioSciences, to form a genetic diagnostics company, Exact Sciences. He also founded Pavonis, a genomics company applying DNA analysis to human appearance traits. Ulmer consulted for Lapidus and Helicos through 2004.
As for the company’s moniker, Ulmer has reclaimed a familiar name from genome history: the name of a commercial DNA sequencing operation founded by Harvard Nobel laureate Walter Gilbert. “Wally and I used to get together in ’87 and debate the merits of how to do the genome in the private sector,” says Ulmer.
“When the market crashed in October ’87, Wally gave up on Genome Corp., and found his outlet in Myriad [Genetics]. I kept pushing the boulder up the hill. When it came time to do this one, we were looking around for names. My main concern was whether Wally would have problems with it, and he said, ‘No, I can’t object.’ It’s somewhat gratifying to come full circle.”
Apparently in more ways than one.
----------------------
Editor's note: Kevin Ulmer will be giving a keynote address on Wednesday, October 17, at CHI's Next-Generation Sequencing conference in Providence, RI.
Subscribe to Bio-IT World magazine.