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Exclusive: Navigenics Co-Founder on Consumer Genomics (Part I)

In 2005, a modest, soft-spoken researcher from TGen (Translational Genome Research Institute, Phoenix) flew to Washington, DC, to accept a Bio-IT World Best Practices Award for Discovery & Basic Research. Dietrich Stephan was the lead investigator behind a series of successful high-throughput gene mapping projects, including one for sudden infant death syndrome, in work

 Dietrich Stephan
conducted with Affymetrix and Silicon Genetics (now Agilent). He still proudly keeps his trophy on his desk.

We lost touch with Stephan after that, but a recent announcement revealed what he’s been doing in his spare time over the past couple of years: conceiving and launching a new consumer genomics company, Navigenics, funded by a pair of prestigious venture capital firms, and boasting a rich pedigree of advisors and partners. Stephan also serves as the chief science officer for Navigenics.

Stephan oversees all Discovery Research and also heads the Neurogenomics Division at TGen, searching for genes for conditions including autism and amyotrophic lateral sclerosis. He previously held positions at the National Human Genome Research Institute, Johns Hopkins, George Washington University, Arizona State University and the University of Arizona.

Bio-IT World’s editor-in-chief, Kevin Davies, recently caught up with Stephan. In Part I of this exclusive two-part interview, Stephan discusses the genesis of Navigenics, the promise of consumer genomics, and his ultimate goal of offering full genome sequencing, or what he calls “newborn screening for adults.”



KD: Dietrich, what is the concept behind Navigenics?

Stephan: The problem is we’ve never been enabled with the technology to resequence the genome in a cost-effective and accurate way. We still don’t have that ability. But today we can look into predispositions to common human diseases caused by common genetic variants floating around the population at large. You’re starting to see the discovery work with the whole-genome association papers coming out.

KD: When did you get the idea to start Navigenics?

Stephan: What Navigenics was born out of was frustration regarding the implementation of common genetic risk factors for common human diseases. The idea crystallized in my mind in the late ’90s, but was always untenable at that point. It seemed way out in the future. It was really only two years ago that it started becoming possible -- to really get enough coverage of the genome to capture at-risk alleles in a genome-wide way. So that’s when I started exploring the idea of this company.

I met my co-founder [David Agus -- director, Spielberg Family Center for Applied Proteomics, Los Angeles], who’d had the same idea independently. We were introduced by a mutual friend, [Jeffrey Trent, director of TGen, previously the scientific director of the National Human Genome Research Institute], and the topic came up. And in a five-minute conversation on the phone, we had the same vision, we banded together, and started reaching out for VC money. It was a defining moment, less than a five-minute call: we should run high-density SNP (single-nucleotide polymorphism) chips and predict what [people] are at risk for. We passed a slide deck back and forth, and started presenting to the venture [capital] community.

What we decided right off the bat was this idea would get a lot of rocks thrown at it. We’re at a grey zone of genetics, but it will eventually happen and someone has to do it. We’d assemble the gold standard team in every sector. On the business side, we had the best venture capital houses in the world: Kleiner Perkins Caufield & Byers and Sequoia, consistently ranked #1 and 2. They immediately got the idea, and intuitively understood it.

We next started walking down the line assembling world-class teams in ethics, legal affairs, legislative/policy… genetic counseling, a world-class scientific team, epidemiology, risk communication, and so on. We have an editorial team – how do you communicate this very sophisticated information to a lay audience? This is totally new information… How do you assemble and wrap in physicians and educate them?

We’re partnering with medical centers across the country [to do that].

KD: I remember you saying you run an “Affy shop” at TGen. Was it inevitable that you’d partner with Affymetrix at Navigenics?

Stephan: The company is technology-agnostic – we’re going to go into sequencing at some point. Certainly in the short term, Affymetrix was the partner of choice. It has a CLIA-certified diagnostics lab in place, the platform has been through FDA approval, the P450 chip was approved by FDA, and Affymetrix has a wonderful new product in the 6.0 array …

The [Affymetrix] 500K chip array did poorly when first launched, but we’ve been monitoring the situation and knew that 6.0 would do much better. And it’s half the price of competitors. It was a no-brainer, but much vetting had to be done.

KD: When do you plan to launch the service, and will the genotyping be done by Affymetrix itself?

Stephan: The service will probably be made available early next year. Yes, we’ll be working with Affymetrix and using their CLIA-certified diagnostic laboratory.

KD: How will you decide which sequencing technology firm you’ll eventually partner with?

Stephan: We haven’t picked a technology partner -- no one knows which technology will win… We’re going to try and anticipate which technology will satisfy our needs. We won’t jump quickly into a technology… We’ll wait for the technology to stabilize so we don’t have any issues when we go to implement that.

KD: Craig Venter just published his entire genome sequence. What are the advantages of completely sequencing an individual genome?

Stephan: You’re hearing a lot about the personal genome project, all of those are geared just to sequencing the known coding regions of the genome. But we already know that there’s probably twice as much information in the genome as currently articulated and annotated…. Genes and regulatory elements in the “junk” DNA, for example, are critically important to doing risk-assessment on a genome-wide scale. For example, there was a wonderful trio of papers [Haiman et al., Gudmundsson et al., and Yeager et al., 2007] in Nature Genetics on the [chromosome] 8q24 prostate cancer locus – irrefutable evidence that that’s a risk locus but there are no genes there! Or take a pair of papers papers on coronary artery diseases and myocardial infarction in Science [Helgadottir et al., McPherson et al., 2007] – no genes sitting under the risk locus. So at face value, if you just sequence annotated regions, you’re not going to get all the [medical] information.

You can look for rare and private mutations -- at some point we’ll drop in that engine and be able to identify all Mendelian mutations, all de novo and private mutations, and all common variants in a bundled package. We really see this as, at some point in your lifespan, everyone will get their genome sequenced and get risk mitigation for “actionable” conditions. [Think of it as] newborn screening for adults.

Read Part II of this interview.

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