Bio-IT World: You’ve just ordered 100 sequencing instruments from Life Technologies for your new Ignite Institute. Why so many, and why did you select SOLiD 4 sequencing system?
STEPHAN: We’re really excited about this partnership. I feel very good about the SOLiD technology, namely its accuracy, price points and throughput. Having reviewed recent data, it looks like the SOLiD platform is extremely accurate. I really like that, because we don’t have to sequence with as much redundancy. The other aspect of it is that we’re really creating a strategic partnership with Life Technologies to do co-development around the technology and understanding the interpretation in a clinical setting of the information. So it’s more a strategic partnership that swayed the decision.
Why did we go big is maybe more relevant. The technology is robust across multiple vendors. I think we’re finally approaching a price point for full-genome sequencing where we can realistically start to redo all the whole genome sequencing studies (GWAS) that have been backed up for the last five years waiting for this technology. You need some horsepower to do that, and we needed some infrastructure. That’s on the research side.
We also are extending on my Navigenics days, putting the technology into a CLIA environment and using it in a clinical setting. So for example, is there a role for sequencing the entire cancer genome out of a diagnostic biopsy from someone newly diagnosed with cancer – so pull single sells out, sequence them, and try to understand if we can prioritize the standards of care, and develop salvage therapies for the 50% of people who will eventually progress before they do so. We want to start learning how to apply the technology in a clinical setting and how to interpret it immediately.
So you feel it is worth revisiting all the GWAS data over the past few years but at the full sequence level?
I’m of the bent that all these heritable risk factors will be relevant in the aggregate. Common variants were extremely valuable in many cases, not only in risk assessment but as guideposts to uncover rare variants in those portions of the genome. But there’s epigenetic modification and copy number variation that we can now capture with the current technologies. We’re finally at a point where we can, in a systematic way, go back and rip through all those case-control studies and get close to capturing the totality of heritable risk for complex genetic disease -- step 1 -- and then maybe even start to sub-classify those common, complex diseases, and re-name those molecularly homogenous sub-types which will likely be differentially triggered by environmental exposures and be responsive to different therapies. I believe this systematic discovery strategy will form the foundation for individualized medicine which should improve clinical outcomes.
What will be the focus of your sequencing efforts in the clinical realm?
It’s an extension of Dan Van Hoff’s work at Scottsdale Health Care, where he ran a beautiful clinical trial using expression profiles of patients. When someone presented with end-stage cancer and was asked to be assigned to a Phase I trial, Dan would randomly assign a Phase 1 trial, the other he would profile and then intelligently assign to a trial. He’s presented beautiful data that he can improve response rates. So trying to use that same strategy but with the next evolution of technologies to see if we can’t improve outcomes with experimental or off-label therapies for those individuals who progress through current standards of care. Our work will begin in a clinical research setting than as a clinical service and hopefully soon make a similar strategy the standard of care to optimize outcomes.
Was there any hesitation in making such a big investment now when there are so many new technologies waiting in the wings?
There’s always a danger, yes, but it’s a stable technology that’s available today, that we can get started on with great accuracy and great price points. In some ways, that’s the purpose of a genome institute is to be able to have the horsepower that very few places have to take on very large projects. So why buy something now when in a year you could buy something else? Unfortunately, that’s the life we have to lead in terms of always having to make large investments in technology in short cycles to allow us to push the envelope of discovery in hopes of making a clinical impact.
You used the term ‘genome institute.’ How have your plans and ideas for Ignite evolved in the past year? It is, after all, called an institute for individualized health…
There’s a couple of aspects in the Ignite model that we think are unique – that may not be true of course – it is more likely that all of these aspects combined together are what make the project unique. One is the horsepower to drive out pure molecular subclasses of disease as a starting point for personalized medicine. So renaming complex genetic diseases according to new nomenclature around molecular homogeneity. That’s one strategic principle. A second is aligning the disease foci to the market needs out there in the world. Basically that means the most prevalent, intractable diseases will be the ones we research.
The third aspect will be that we’ll have commercialization infrastructure surrounding the institute so we can make early go/no-go decisions. We can model the economics of new tools and strategies. For example, who is going to pay for this when we turn it on? Additionally, we have strategically located the institute in the National Capital region so that we can build trusted relationships with policy and regulatory bodies as well as access the best thinking around health policy to allow us to streamline the process of moving from “research grade” tools to “clinical grade” tools and strategies.
Another aspect is that we’ve aligned it with a tier-one partner in terms of the Inova Health System which is an excellent high-volume community healthcare system. The notion here being that if we can drive new validated tools and strategy into the community health system where most individuals receive their care through a trusted relationship than we obviate the need for years of physician education and adoption.
So if you take a big genome institute, surround it with a commercialization infrastructure, and then place that in close partnership with a healthcare system, hopefully you can build those trusted relationships to quickly move from a robust discovery around a pathogenic pathway to a little biotech or drug company and then into a clinical setting quickly. We used to call the “valley of death” the disconnect between a scientist like me in the basement writing and publishing papers that no-one would read and the commercial sector. There exists a second “valley of death.” Once you have a little company it often takes years and tens of millions of dollars to educate doctors, get regulatory approval, and change the standards of care and get any of them to use it. So can we compress both of those valleys of death? For chronic disease the stakes are high because they are increasing in prevalence so quickly that we felt a need to compress the cost and timelines.
Finally, we view our project as a national and international resource and look forward to partnering and collaborating extensively. The permanent facility will be located on a campus so that we can expand operations as these collaborations and spin-out companies take root. Through establishing a center of excellence in a robust geo-political region we hope to act as a magnet to recruit established businesses in this section. We feel this is realistic given that Virginia has been named the “#1 state to do business in” and is currently putting in place tax and opportunity fund incentives to make this a reality. Similarly, the County of Fairfax has been a delight to work with as a partner to recruit this industry sector.
What’s the status of settling on a permanent location for Ignite?
We’re currently building out our temporary space, which will be ready shortly. We’re in the Center for Innovative Technology building near Dulles Airport, it’s a state-owned building (the black upside-down pyramid building visible from Dulles). The state will put in some money to refurbish it, and we’ll leave it behind as a biotech incubator for the Commonwealth of Virginia. On the permanent site, we’re still evaluating a couple of options through a process led by, in my opinion, the best full-service healthcare facilities owner representative in the country - Nancy Kelley of Murphy-McManus from Boston. It looks like we’ll purchase a pre-existing shell so we can go in and very rapidly refurbish floors to grow in real time.
What about the support you’ve received from state and local government?
It’s been a true public-private partnership. The Commonwealth of Virginia has been spectacular, committing $25 million to the project. Fairfax County is committed to building us a building and letting us occupy that for a certain period of time for free. And we’ve got private sector partners like Life Technologies and the Inova Healthcare System. We have a number of excellent academic partners like George Washington University, which wants to continue to make a name for itself in health care policy. We’ve aligned with George Mason University around neurological diseases and Virginia Tech around bioinformatics and supercomputing. Virginia Tech just recruited a spectacular head of the Virginia Bioinformatics Institute, Skip Garner (who worked on the 1000 Genomes Project). We’re going to generate data and then collaboratively with them, we’ll make sense of it. As always, we are committed to open access data dissemination to facilitate research by all and look forward to delivering large “data packets” to groups like Sage Biosciences for sophisticated analysis. We want to measure success in improving clinical outcomes and within that framework try to make health care a sustainable enterprise.
Ed Note: An expanded version of this interview will appear in the March-April issue of Bio-IT World.