Illumina CEO Jay Flatley on the Future of Genomics, Part 2

4/7/10Follow @xconomy

Yesterday, we ran the first installment of a wide-ranging interview with Illumina CEO Jay Flatley. He talked a bit about some of the major competitors he sees emerging in the fast-paced world of gene sequencing, and how he hopes San Diego-based Illumina (NASDAQ: ILMN) can maintain an innovative edge, even as it grows into a big company with about 1,800 employees.

Today, we offer up the second half of the conversation.

Xconomy: In terms of being in San Diego, you’ve got Illumina, and you’ve got some critical mass with your competitor here in Life Technologies in sequencing. You’ve also got wireless talent here with Qualcomm. How do you see the genomic instrument capabilities converging over time with wireless technology in a way that’s useful for a healthcare system moving more toward wellness?

Jay Flatley: It’s absolutely going to happen. It’s already starting to happen. Our instruments increasingly will be spitting out their data over wireless networks. We already have the ability to monitor and control our HiSeq product from an iPhone application. Our customers can sit in their living room and monitor the quality scores coming off their HiSeqs. From a management of the instrumentation perspective, that’s already happening.

We’ve built a prototype iPhone application that is sort of a delivery vehicle of how someone could carry genomic information and communicate and interact wirelessly. That could be with your physician. It could be over social networks. It could be in a bar. I think wireless is the way it’s going to go. The data will be in the cloud, and it will be moved around wirelessly.

Jay Flatley

Jay Flatley

X: But your bread and butter business is still going to be selling those instruments, which are an expensive piece of equipment. How much bigger do you see this market getting in unit volume, or maybe becoming more democratized as the price of sequencing comes down and more researchers can do it?

JF: Our goal is to make this as ubiquitous as PCR [polymerase chain reaction], and I think that’s where it’s headed. Sequencing will become such a fundamental tool of molecular biology research that every lab that’s serious in the field will have to have access to next-gen sequencing one way or another. Either in their lab or the lab next door. The footprint of the instruments is going to shrink. Usability will get better. Sample prep is going to get simpler. We’re probably less than 10 years from the day when a drop of blood gets put in and the sequence comes out 10 minutes later. That’s the way it’s going to be. We think all babies are going to get sequenced in 10 years, that will be a routine way you do post-birth characterization. The data set will go into an electronic medical record. There will be some filtered masks over that data set that allow different constituents to access it under certain privacy controls for different reasons. You may need to authorize your physician to look at parts of it, you may want them to look at all of it. But I think that’s where the technology will head.

X: It’s interesting that you brought up privacy. I was meaning to ask whether there are any policy changes that you think need to happen before people can become comfortable enough with this idea to really participate in a big, broad way?

JF: The GINA [Genetic Information Nondiscrimination Act of 2008] bill went a long way. It set a framework for preventing discrimination based on genetic information. What’s going to have to happen is there will have to be some test cases. How does that look when it’s applied and executed? No doubt we’ll see some test cases there in the next five years. But the thinking is moving pretty fast there. One of the goals we had in the early launch of our consumer program was to make that thinking go faster. So that when the technology could sequence everybody for $500, that we’re not then beginning to think about privacy and data management problems and regulatory issues. All of that gets pushed out of the way in advance of this becoming an enormous market. It’s moving really quickly. You see full conferences on consumer genomics. You couldn’t imagine something three years ago like a consumer genomics conference, yet here we are.

X: How is this really going mainstream? I noticed you had a release that said [the actress] Glenn Close said she’s gotten her genome sequenced. Are you encouraging people who are recognizable to go out on television, and talk to the public? This is genomics, which is not everyday dinner table talk, right?

JF: One of the challenges that companies like Illumina have is to figure out ways of abstracting the complexity of genomics. That’s what an iPhone app is going to do ultimately. It still doesn’t quite get where we want it to be. Even today, people say “Your doctor doesn’t know what this all means.” Sure, he doesn’t. But the truth today is that when a doctor orders a test today, if you ask them, “Describe how that test works,” he has no clue. Even if it’s an immunoassay. You could say “Tell me what the binding reaction is that gives you that result.” He has no idea. All he knows is that it comes back in some range. Whether it comes back in this range, or that range, he knows what to do differently with those two outcomes. That’s where we need to get with this. We’re a ways away from that. We have to abstract it beyond anybody having to understand what the genomic piece is about. What that’s going to require is another five years of compiling lots of genomes, figuring out what those reading means, and creating actionable data sets from that collection of genomes. That’s where we are headed in the next couple of years.

X: What’s your prediction on when we’ll get to the $1,000 genome?

JF: We’ve been a little cautious to not go too far out on a limb there, and it will matter a lot what you count. If you count bioinformatics, if you count sample prep, if you count data storage in the number. If you count it all, then it’s somewhere in the three to five-year timeframe. There are lots of people who say, “We’ll get there faster than that.” And they are talking about the sequencing only. The sequencing will get there faster than that.

X: What’s one of the more exciting experiments you’ve seen come out lately with people who are using the better/faster/cheaper form of sequencing? The kind of questions that were never possible or practical to ask even a couple of years ago?

JF: That’s one of the most exciting things about where we are today. We founded Illumina 11 years ago now. We knew someday it would be directly applied medically, but we were still a long way from that. But now we are at the cusp where sequencing is being directly used for patients. The work of professor Marco Marra in Canada, about a year ago, looked at an individual who had exhausted all the existing treatments. The individual started out with cancer of the tongue, and it had metastasized to the lungs. They had used all traditional treatments and nothing was working. They sequenced, and they discovered a novel pathway in the cancer that wasn’t known before, and they went and surveyed the drugs that were already on the market. And they found a drug that had never been applied to this cancer previously that hit this pathway. They got permission to administer the drug, and the tumors dramatically receded. It’s a great example of how understanding cancer at the molecular level will modify treatment.

That’s just the first example; there are now a whole series of these now over the past year. There’s a couple of cases at Yale, one was in an infant with a severe bowel condition that they couldn’t diagnose through any other means. Sequencing gave them exactly the right diagnosis and they cured the patient. There have been a handful of examples like that. I think sequencing is really at the cusp of being applied medically.

X: Were these experiments done by people who are physician/scientists, or were they done with scientists and physicians working in tight collaboration? Because that seems to be where things often break down, in the silo-ization of specialties which creates issues that make it hard for people to talk each other.

JF: It’s the latter model. Typically what happens is you have a treating physician, or treating oncologist, who somehow gets connected with a scientist who has access to the technology and an understanding of what it can do. They work together to make this happen. The scientist doesn’t understand the background of the cancer itself. They might understand the genetics but not the cancer details, so they have to work together with the physician.

I think you’re going to see in the very near future, very significant efforts to begin to apply sequencing directly to cancer. Our view here is that in five years or so, every biopsy will be sequenced. We’ll know it, and we’ll have characterized these cancers well enough that that’s the way you’ll figure out on the molecular level what it really is, and how to treat it.

X: Five years out, will we be doing this sequencing in a completely different way with none of the fluorescent tags that are used now, more like what Oxford Nanopore does [direct detection of ion charges associated with chemical units of DNA]?

JF: We hope so. If Oxford works, it will be, for sure. There’s probably a home for fluorescence based instruments at least out to a five-year time frame. But the newest ways will not use laser-based fluorescence instruments five years out, it will be more about direct detection. That’s how you get the size down, and the capital costs down, and you begin to scale the market in a serious way.

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  • http://www.xconomy.com/author/ltimmerman/ Luke Timmerman

    Here’s a good follow-up question I got from a reader, Dan Meyer. I relayed this to Jay Flatley, and you can read his response below:

    Dan Meyer: “The industry has been focused on cost and throughput, but hasn’t really focused on accuracy, certainly not in a way that will make sequencing a clinical reality. For example, in the clinical oncology market, we can’t apply the existing offerings if we are concerned about large scale variation (which we have known for a couple years now is more of an issue that we thought—see http://bit.ly/cioRRr).

    So I’d be interesting in knowing how he thinks the industry needs to improve in accuracy performance and measurement. And also if accuracy will be the next key differentiating factor as cost and throughput/speed reach levels that are closer to commodity levels (e.g., sub-$1000 per genome in an afternoon).”

    Jay Flatley: The goal of improved accuracy is being aggressively addressed in multiple ways:

    —Better chemistry that reduces read errors

    —Improved informatics to more accurately extract bases

    —Increased output and more affordable sequencing

    Illumina’s recently released HiSeq 2000 is a significant milestone in this regard, reducing the cost of human genome wide sequencing to less than $10,000 and providing intuitive single operator workflow systems that dramatically increase output (200G). This machine has the potential to improve accuracy by sequencing more genomes to a greater depths as a result of the huge increase in read output, in a short time period (about one week per human genome, though two human genomes can be sequenced simultaneously on this machine).

    Note that the HiSeq 2000 achieves an output of 200 Gb of data per run with 80% of the reads error-free at a sequencing depth of 1X. This is a significant improvement over what could be achieved just a couple of years ago.

    More evidence of increased accuracy by the Illumina system is seen with the dramatic increase in routine read lengths of 100-150 bases reported by Illumina customers.

    Better chemistry and informatics are also contributing to accuracy. On this front, Illumina is offering customers reagents with improved chemistry and enzymes with higher proofreading properties.