Thinking Tech

World-class innovation: A conversation with a leader in the race to achieve the $1000 genome

World-class innovation: A conversation with a leader in the race to achieve the $1000 genome

Posting in Cancer

SmartPlanet has a conversation with the CEO of Complete Genomics, Cliff Reid, a leader in the pursuit for low-cost human genome sequencing. A technology that promises to have a profound impact on how we practice medicine.

Thanks to remarkable innovation within genetics industry over the last decade we are quickly approaching the era of truly personalized medicine. The ability to read our human genome promises to have an extraordinary impact on our health, from treating cancers to countless other diseases that have so far eluded medical research. Much of this promise relies on the rapidly dropping costs of technologies that will lead to an affordable reading of our personal genome. More than that, however, it relies on the creative minds that have connected those various technologies in exceptional ways.

One such team is behind the groundbreaking work at Complete Genomics. To get an inside look at their top-notch innovation we spoke with chief executive Cliff Reid.

SmartPlanet: So what exactly is the so-called $1,000 genome?

Cliff Reid: Well, whole human genome sequencing is becoming affordable for the first time. But it’s still very early in the research discovery cycle, meaning we don’t know yet what most of the genome does. But it won’t be long before before most or all of us will want to have our genome sequenced to better manage our healthcare.

SP: Can someone get their genome sequenced for $1,000 today?

CR: The recent announcements about the $1,000 genome have been a little confusing, because you can’t buy a genome for a thousand dollars…from anybody. It doesn’t exist. The headlines refer to one of the many cost elements of sequencing genomes, specifically the material cost of sequencing the genome.

SP: What are the other costs?

CR: Well, there are four major costs in fact: Materials, equipment, labor, and overhead. Materials is just one of those four costs. So the thousand-dollar materials cost is really more like a $2,000 to $4,000 total cost genome. But that price will come down, you know, over time. And eventually there’s no question we’ll get to a total $1,000 dollar genome.

SP: What does having our genome sequenced mean for us personally?

CR: Well, today’s examples are not really around healthy people. The examples are more around people with illnesses. A very important example are idiopathic children—children who are born with developmental difficulties, or maybe malformations. And they get run through a whole battery of tests and often the medical community remain confounded; it’s a new ailment that no one’s understood before. Whole human genome sequencing offers the promise of finding an important hint about what to do to help these unfortunate kids with undiagnosed diseases.

SP: I imagine a great deal of what makes breaking open our genome so profound is simply not known yet.

CR: Right. The percent of the human genome that we understand is very, very small. We’re kind of in the golden age of genomic research. And it’s producing, now at a small scale, some very important, powerful medical results. But that’s going to move from a small scale to a large scale of the next few years.

SP: There must be plenty of ethical considerations with all of this.

CR: Yes, we certainly think that there are both ethical considerations between patients and the doctor and also legal considerations. So one of the first things that we need is more legislation that absolutely ensures the privacy and the security of genomic information to the individual patient and, with their consent, to their physician. GINA was a great step in the right direction, but it didn’t go far enough.

SP: What is GINA?

CR: It’s a piece of legislation that passed maybe about four years ago and it stands for the Genetic Information and Nondiscrimination Act. It made sure that insurance companies couldn’t get a hold of your genetic information and then manage your health insurance accordingly. They’re simply not allowed to use that information at all. But it doesn’t apply to life insurance. So there are some holes in the legislation, and we hope those holes get fixed over time.

SP: What is driving the cost down in sequencing a genome? I’m assuming Moore’s Law—the trend of ever-increasing computing power at an ever-decreasing cost—has something to do with it?

CR: What has driven the reduction cost is a massive investment in new technology. Moore’s Law is one of the smaller effects actually. There are really three categories of technology that go into sequencing genomes. They go by the wonderful trio: Bio, nano, info.

SP: Could you explain those three?

CR: All right. So with “bio” we are referring to biochemistry technology—the biochemistry for actually grabbing the A, C, T, G’s that make up DNA. There’s been a revolution over the past decade in the biochemistry of understanding molecular manipulation, and the cost of the chemicals involved in doing that have absolutely collapsed.

SP: And the “nano”?

CR: The second is the revolution in "nano." Nanotechnology. This is the semiconductor technology for holding biological samples, and then also the optical technology for measuring those samples, the DNA samples. The semiconductor industry has continued to drive the revolution. We in the sequencing industry take full advantage of that.

SP: How?

CR: Consider the camera industry. Optical detectors have gone through an amazing revolution in the last ten years. Consider your pocket digital camera or the camera in your phone. It’s an extraordinary optical device. Ten years ago the optical sensors would have cost thousands and thousands of dollars, and now they cost twenty bucks.

SP:  And the third revolution you mentioned?

CR: The third revolution is the “info” revolution, and that is driven by Moore’s Law. When the human genome sequencing project was done—over a decade ago now—the primary costs were not the “info.” The two biggest costs in that project were the “bio” and the “nano.” And those costs have come down so dramatically that you’ve gone from billions of dollars ten years ago to thousands of dollars today.

SP: Interesting that the entire computer and cell phone world has been made possible by the ability for transistors to be shrunk down yet still function. And with sequencing the genome you are saying there are three such industries going through a remarkable revolution in cost.

CR: It really is. It’s odd that the whole semiconductor world, the computer world and the cell phone world has kind of been driven by this one dynamic, Moore’s Law, whereas in the sequencing world we’ve been driven by three parallel dynamics that’s going on, one in the bio area, one in the nano area, and one in the info area.

SP: In a recent New York Times article Bill Banyai, your optical physics expert, said, “There is this remarkable thing that happens in start-ups. You make up this plan and then you step off a cliff and magically a little bridge appears.” What did he mean by that?

CR: Yes, we’re going out and investigating and selecting these advancements in other industries. And then in very clever and innovative ways—and Bill Banyai among the most clever and innovative on the planet—we would pull together these new technologies that are really being developed for other purposes and organize them into a solution to the problem of sequencing genomes.

When Bill and I started working together on this back in 2006, he would lay out a high-level plan say, “Here’s what we need to do, let me go out an investigate and find the pieces of the puzzle that can be plugged in to this high-level plan to make it work.”

And I’d say, “Gee, Bill, you mean you don’t know all the details of what’s going to plug in to this high-level plan to make it work?” And he says, “No I don’t. But I’ve got a lot of confidence that there are a lot of other industries that are doing terrific technology development work. We’re going to go learn about them and then we’re going to port their advancements in technology into our application space.”

SP: So you need to understand the big problem to be solved, then find the tools, then integrate them in new ways to build the solution.

CR: We often don’t know the details when we set out, but it always seems to work out really, really well. Regarding the magical little bridge: You don’t have to invent anything you just have to go out and track them down and find the pieces of the amazing stuff they’ve invented and then integrate it all together into a particular solution to your particular problem, which in our case is sequencing the genome.

SP: That is considered the essence of innovation, isn't it?

CR: It is. My favorite definition of innovation came from a Harvard Business School book on entrepreneurship, New Business Ventures and the Entrepreneur. They define an entrepreneur as someone who pursues opportunity without regard to resources currently controlled. I just love that dearly because that applies to an entrepreneur in a financial sense. But it also applies to an entrepreneur in a technology sense. That is what Bill is. He pursues an opportunity without regard to the technological resources he currently controls, because he figures that he’s going to solve that problem over time.

SP: You mentioned the cost of sequencing the genome will drop to the same cost of getting a thorough blood test.

CR: Well in the short term not at all, but in the long term I absolutely believe that in the distant future we are going to have genome sequence at the same price as a blood test.

SP: How?

CR: I think the only way to do that is volume. If we’re doing a whole lot of them we will use classic manufacturing techniques to cut the cost way, way down. Similar to the situation where if you want to make eight chips in the semiconductor lab it’s very expensive. If you want to make ten million of them the unit cost goes way, way down.

And that’s going to apply to genome sequencing too. So I think the ten millionth genome that we as a society sequence probably will cost about a hundred dollars. But we’re a long way away from sequencing ten million genes.

SP: We know that Moore’s Law is reaching its limit, the transistor can’t get much smaller because it simply won’t work anymore. Are there similar limits in the other two industries you rely on, the bio and nano areas as you referred to them?

CR: There’s no end in sight. Of course in some physics sense yes, there has to be a limit, but in a practical sense there’s no end in sight right now. Over the next decade they’ll go into the single-digit hundreds of dollars. They may make it into the single-digit tens of dollars, depending on how fast volumes grow. There’s no number you can point out today and say it hits the wall right here. There is no such number.

SP: How many companies are competing in this space?

CR: Maybe half a dozen. It’s pretty competitive stakes. Illumina and Life Technologies are well-known. The stakes are very high in this industry so it’s attracting new competitors, but the challenge is that it’s a very complex technological area, and so the cost of developing new technology in this area is very high because you have to develop the bio, nano, and info and make it all work together. To enter this space takes somewhere between a hundred and five hundred million dollars.

SP: So it’s not like the super low barrier to entry that exists within the Internet industry?

CR: Right. The in Internet space you can create a new company for a million dollars. We’re not seeing the same rate of the of new start-up companies in this space just because the costs to participate are so unbelievably high.

SP: How does Complete Genome get its competitive edge?

CR: Our edge comes in the category of focus. The only way small companies compete and win against big companies is by focusing in on one particular thing and doing it particularly well. And we are focused on whole human genomes. All of the other technology companies in the DNA sequencing space sequence everything. Plants, and animals, and bacteria, and viruses, and RNA and DNA. They do everything. And to do that they build these very general purpose instruments. They build the Swiss Army knife folks of sequencing. We took a different approach. We said the only thing we want to sequence is humans. So every technology decision that we make around bio, nano, and info is going to be designed to sequence the whole human genome and nothing but the whole human genome. And that focus enabled us to build a better solution.

SP: And that is?

CR: By better we mean more accurate. We get the A, C, T, G’s right more often than anyone else. And that’s not the only thing because cost matters, and turnaround time matters, and scale matters. But getting the right answer we think is the first and most important thing. We pretty much won that war with the most accurate DNA sequencing company in the world. And I think we’ll be able to maintain that lead in future.

SP: I know there are big differences between a product company and a service company. You’ve chosen to be a service company, yet your competitors are producing a product.

CR: Yeah, absolutely, that’s our second differentiator in the market. Again, all of the other DNA sequencing companies are instrument companies. They’re product companies that sell hardware and chemicals. And we are the only information service. We don’t sell hardware and chemicals we’re an information service. People send us samples, we sequence them and we send them back the data.

SP: But service-based companies are notoriously harder to run and scale than product-based companies.

CR:  Yes it is harder to run a service-based company. But it’s not less scalable than a product company. Services companies are typically hard to scale because of their labor content, because most services companies are things like professional services companies. And what they’re actually selling is the services of people. We’re not doing that; we’re selling the services of robots. So our business scales beautifully because it doesn’t take a lot of people to build the business it takes a lot of robots, and that makes it highly scalable.

SP: Can you tell us how you personally got involved in this business?

CR: Yes. Well I came across this industry in 2000 through MIT. I’m an alum there and I met some their top people in the systems biology area. And they laid out before me the challenge of the twenty-first century in biology. I became convinced and quite enthusiastic about the marriage of the computing technologies that I’d been doing for twenty-five years professionally as a software guy, with the biochemistry technologies there were in a nascent stage.

My history personally is working on big, fascinating problems on the leading edge of technology. The first big problem I worked on was astrophysics and the origin and nature of the universe. The second big problem was artificial intelligence, which is sort of the origin and nature of cognition. And this is my third big problem, which is the origin and nature of life. It’s fun to work on big problems and I’m happy to use my tool kit, that is big data. And so the combination of the importance of the problems to humanity and the tractability of the problems to the tools in my toolkit that made genomics a perfect match for me.

SP: This is an amazing revolution to be part of over next decade. You are going to have a great time working on this.

CR: We already have!

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Christie Nicholson

Contributing Writer

Christie Nicholson produces and hosts Scientific American's podcasts 60-Second Mind and 60-Second Science and is an on-air contributor for Slate, Babelgum, Scientific American, Discovery Channel and Science Channel. She has spoken at MIT/Stanford VLAB, SXSW Interactive, the National Science Foundation, the National Research Council, the Space Studies Board and Brookhaven National Laboratory. She holds degrees from the Columbia University Graduate School of Journalism and Dalhousie University in Canada. She is based in New York. Follow her on Twitter. Disclosure