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The DNA Day interview: Jay Flatley, Executive Chairman of Illumina

Helix couldn’t exist without the work of many people over the years—individuals who’ve pushed science forward to understand what DNA is, how it works, and how it can be accurately and reliably sequenced.
It also couldn’t exist without the work of Jay Flatley.
Flatley already had an accomplished career leading life sciences and technology companies before he joined Illumina in 1999, but his work at Illumina has become a defining period in modern genomics. As CEO, he helped turn Illumina into the most important name in DNA sequencing technology at an especially critical moment, just as the Human Genome Project was wrapping up and the field of personal genomics was getting its start.
Illumina’s technology, investment, and guidance was instrumental in making Helix a reality. Along with Helix co-founders Justin Kao, James Lu, and Scott Burke, Jay Flatley defined the concept of a marketplace for DNA products, underpinned by a state-of-the-art sequencing lab.
Today, Flatley chairs the boards of both Illumina and Helix. On National DNA Day, we couldn’t think of a better person to speak to about the development of personal genomics, the opportunity it holds, and the future of the field.


Helix: You can’t mention Illumina without mentioning your name, or vice versa—your stories are deeply intertwined. But you had a career before Illumina, too. Can you talk about what led you to biotech, and specifically to genetics?
Jay Flatley: My career got started in analytical instrumentation, and then I was in the computer business for about seven years. I got a call from a friend of mine who was starting a life sciences company; he had another co-founder, and they wanted a third person to come in to essentially run the company. One founder was a rocket scientist type, the other was a marketing guy. So, I checked out the technology, and I didn’t know anything about life sciences—I barely knew what DNA was, this was 1987!
I decided to join those two as co-founders of Molecular Dynamics. So that’s when it really started, in ’87. Essentially, in the early days, we were imaging electrophoretic separations, and developed a whole series of different imaging products. That ultimately led to building the world’s first capillary DNA sequencer called MegaBACE, which we launched in ’96.

“Early in my career, I was fortunate to have assignments in many different parts of organizations.”

And that led you to Illumina shortly thereafter. How would you say that your professional and personal backgrounds have informed the way you built Illumina?
I had a great opportunity to do both a deep engineering and math curriculum as well as a business program—a joint program between Claremont and Stanford. Three years at one, two years at the other. That gave me the right combination of technical and business background to ultimately become a CEO of a company, and to do that well.
Early in my career, I was fortunate to have assignments in many different parts of organizations, giving me the broad background to understand how companies work across functions. Building Illumina required very different skills when we were 50 people than it did when we had thousands of employees. In the CEO role, it’s about the breadth of your knowledge as opposed to the depth, and so I haven’t done a lot of engineering in many years. But I can understand technology at almost any level, while also understanding how to read balance sheets!
You joined Illumina at a very interesting moment in the Human Genome Project. But in the years since, there have been many twists and turns in the development of the genomics industry. What has surprised you the most in the years since the HGP wrapped up?
The unbelievable complexity of human biology. There were many who thought that once we sequenced the first human genome, it would only take a few years to then uncover what the variation in the human genome meant, and thought that we would rapidly go on to solve common diseases.
A key part of what Illumina did is provide the technology in the 2002 to 2007 timeframe that invalidated the common variant/common disease hypothesis. It was a surprise to many that we weren’t able to unravel biology by doing deep genotyping that was all the rage during the GWAS era. And that truly led us into next generation sequencing—the realization that we needed to go much, much broader and deeper to understand the fundamentals of human biology.
Speaking of NGS, was there a specific moment or event where you realized that the cost of genome sequencing was going to fall off of a cliff?
I think there were two steps to that. The first was when we acquired Solexa in 2007; it was a rare moment in time when we found a technology that was a hundred times faster and a hundred times cheaper. That is a very rare occurrence! Even when industries take big leaps, they’re usually by factors of 2, not factors of 100. So that was really the impetus for us doing the acquisition of what was then called the 1G Analyzer—we could sequence a billion bases in a single run.
The second magic moment was when we realized how extensible this underlying chemistry was that we call SBS. And we always knew we could take the 1G Analyzer up to 10 or 20G, but all of a sudden we realized that we might be able to take it up to 500G or even a T of output. And this was probably in 2010, when we got onto the HiSeq roadmap and realized that we really had orders of magnitude left in extensibility.

“In general, people are becoming more educated about genomics.”

Personal genomics has really started to move from microarray to full-on sequencing, and obviously Helix is at the forefront of that trend. Why is that happening now?
In general, people are becoming more educated about genomics. There is much more personal empowerment to manage your own health because of widespread disappointment in how the health system does that for us. If you combine the genome with what’s happening in data technology—wearables, the ability to have an iPhone in your hand that has health information on it—we’re really beginning to empower personal management of your own health. Genomics is a critical portion of that, and more and more people are realizing the contribution that genomics makes.
What organizations and people have inspired you over the years?
Apple is a stand-out for me. Interestingly, I used to be very much a Microsoft fan during the PC operating system wars. I’ve been around a long time, and back in my career, there was a long period where Apple computers were underpowered and not very good. But then there was a clear change when Steve Jobs came back to Apple, and they developed the iMac, and since that point in time I’ve tracked Apple very closely and have been quite an advocate of the innovation model that they use—the ability to create step-function changes in technology and to disrupt industries. And so I’ve used that model and those concepts a lot in how we’ve managed Illumina, ensuring that we take large leaps as opposed to just small steps.
I think Steve Jobs was clearly behind much of that thinking. And it doesn’t always mean that you’re first to market with every technology, but that when you do come, you come with the best technology that’s dramatically better.
And interestingly, his return to Apple was right around the time that you became CEO at Illumina.
It’s doubly interesting, because my wife worked for him at the time! She was at Pixar. He was CEO, and she was VP of Finance.
What advice would you have for young people who want to work in this field right now or might be considering it?
If last century was the informatics technology century, I think this is the century of biology. It’s an absolutely explosive field. There’s incredible opportunity to explore a new space, and to create startup companies that innovate around human and plant biology.
I also think that technology and biology are intersecting in very interesting ways, with Illumina being a clear example. We’re really a technology company, but every application of our technology is directed at understanding biology. I think that point of interface takes people who have the ability to have a foot in both worlds, and so I think that’s an incredibly interesting place to be.
In terms of overall advice for young people, one thing I always tell the young and ambitious is to get as many different types of experiences early in your career as you possibly can. I find that young people are often always looking for the next promotion vertically. They get to a certain level in a company and they’ve only done marketing, or they’ve only done informatics, and they expect to ultimately become a vice president or a CEO—but they don’t have any idea what supply chain is or how operations works or anything about finance. And so for those who aspire to be executives, getting that broad exposure both educationally and within a corporate environment early in your career is critically important.

The Helix launch event in New York City. From left: Justin Kao, Robin Thurston, Jay Flatley, and James Lu.

In 2017, more people had been genotyped or sequenced through a consumer genomics product than in every prior year combined. It was an inflection point. A lot of what you’ve worked on at Illumina helped build to that moment. What has you excited next, and what are the game changers you see on the horizon?
Technologically, we’re going to continue to drive the cost of sequencing down. One of the models that I’ve always adhered to is that as you drive prices down in this market in particular, you open up gigantic new applications, so it’s a market that clearly demonstrates economic elasticity. And as we get toward the $100 genome, sequencing will have the opportunity to become pervasive.
It’s truly our vision that everyone gets sequenced at birth, that it becomes part of their normal medical record, that it gets used routinely in managing their health throughout their lifetime, and that we can actually make the technology disappear into the background. People won’t actually have to know what sequencing is—it will be so simple and easy to use, that interpretation will be like reading the results of a blood test. That’s where we need to take genomics in order to make it individually useful to everyone in the world.
Do you see this as eventually being an at-home test?
As I said, our vision is that everyone gets sequenced at birth. Some subsequent readouts may be useful to do at home from saliva samples, but I suspect blood based tests will require a medical professional for some time.
Clearly, the technology is going to get this closer and closer to patient care. We’ll ultimately wind up with handheld sequencers. It’s probably not necessary for those to be in every household, but we’ve always imagined things like “the sequencing toilet,” where your microbiome is constantly measured and an alert gets triggered whenever there’s anything awry in the microbiome.
2018 is a big year for health products at Helix. Are there any that have you the most excited?
I think what we need to really push Helix forward is a broad set of health applications, because different people want to answer different questions. One of the powers of the Helix model is the breadth of different applications that all have a somewhat different focus. So, depending upon what one cares about, they can pick an application that’s more suited to what they want to know.
This whole area of consumer genomics is something I’ve been working on in one form or another since about 2005. It’s been a personal passion of mine. It’s one of the reasons we created Helix and spent years working on the business model for it, and I’m convinced we now have it right and Helix is the platform that really has the opportunity to springboard consumer genomics to a whole new level.

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