If we’re still in the Wild West of genomics, Steve Burrill could be called one of the major ranchers. In a landscape new and still quite unknown, Burrill has tamed a large plot and established Burrill and Co. as a place newcomers to the area as well as the local population can come for advice, knowledge of the surroundings, and perhaps a deal. Burrill is comfortable in his frontier lifestyle. He pioneered the biotech industry 40 years ago, sits on the board of a list of life science companies, and puts on six conferences a year around the world.
Last week Burrill and Co held their 7th annual Personalized Medicine Ho-Down. This year’s show packed a power line-up into a day and a half, including the major CEO’s of the sequencing industry--Greg Lucier of Life Technologies, Jay Flatley of Illumina, Hugh Martin of Pac Bio, and Cliff Reid from Complete Genomics--as well as George Poste, speaker extraordinaire, and NIH Director, Francis Collins. Burrill kept the conference tightly focused on three main issues facing the industry: complexity, complexity, and complexity. The science is not as simple as one gene, one disease. Regulation and reimbursement continue to allude. And that issue everyone is talking about--what to do with all the data.
Burrill shepherds his conferences from beginning to end. Beginning with a cold reality check, he didn’t want folks going home without some meat. Burrill has all the numbers and vision to inspire, but there’d be no pie in the sky at this meeting. Citing articles from the New York Times and other publications, and a statement even from Craig Venter asserting that the genome was essentially useless information, Burrill was ready to put it all on the table. “The science is more complex than we thought,” he admitted. “And business has moved faster than the science. . . I don’t mean to be negative, I’m just listening to the real world.” He talked about all the different players in the field. “Pharma gets it, the patients get it, but the doctors are way behind.” No doubt Burrill keeps his finger on the pulse by producing these conferences. And he aimed to put this group of pioneers to work. “Are we there yet?” he provoked.
The science ain’t as easy as we thought
“In 2001, we thought diagnostics meant we’d be a SNPs company. It’s more complicated than that.” Steven Little, Qiagen
To address the issue of the complexity of the science and the interpretation of the data, Burrill called on George Poste of Arizona State University. Poste has a way of layering one level of complexity on another. There are multiple pathways, multiple targets when looking at a disease. There’s a vast amount of data yet to be understood. Of that data, an increasing portion is bad science. And what to do with the data--where will it all be stored? Once it is stored, there is no common ontology to make sense of it. And once there is analysis, the doctors aren’t up to speed. Poste’s method is to throw fast ball after fast ball and simply overwhelm. I had a teacher who used this method. It works. When one feels sufficiently screwed, the new ideas begin to emerge. Poste’s solutions included a quote from General McCrystal, the former commander in Afghanistan, “it takes a network to stop a network.” Speaking of how single cells have multiple routes for the same function, Poste urged a more comprehensive approach. “Target the pathways, the modules, the network. . . Let’s take on disease earlier with advanced network deregulation.” Urging new paradigms he asserted, “ahead, there will be a fusion of life science with engineering and communications.”
Getting reimbursed ain’t as easy as we thought
“FDA Clearance did nothing for us in the clinic.” Pierre Cassignuel, XDx
There are two themes to the reimbursement topic: regulation and payment capture. One panel called, “The Business,” was populated by four companies successful at both: XDx, CardioDx, PrimeraDx, and Tethys Bioscience. Pierre Cassignuel, president of XDx has done everything right (including leaving the unfriendly attitude toward Personalized Medicine in France behind and sitting on the current board of the Personalized Medicine Coalition). XDx offers a blood test for heart transplant management. The test replaces the current method of taking biopsies. Not only is there risk associated with the biopsies, Pierre’s test offers a reduction in cost, selling for $3,000 compared to the $5,000-$15,000 for the biopsies which can be taken up to 35 times a year. Test is FDA cleared. Test is better than previous standard of care. Test is cheaper. Win/win/win, right? Pierre says his biggest challenge is that hospitals are still preferring the biopsies because management and doctors look at total revenue. They make more money the old way.
Dietrich Stephan has served time in the trenches. Founder of the personal genetic testing company, Navigenics, Stephan is also founding the Ignite Institute with the goal of changing the paradigm in health care from reactive and generalized to proactive and personalized. Stephan asserts that the FDA’s guidelines for diagnostics are based on those developed for devices in the 1970’s. He says he’s seen both sides, that of business and of FDA regulators. “I’d love to see a grey-haired panel helping the FDA out with the science. We need a new process which is revisable.” Stephan finds it ridiculous “that everyone these days has two tracks--one through the FDA and one around. Whenever investors look at the business plan of a new device company, the investors insist that the company go abroad with the product first, then to the FDA!”
With each speaker and panel, Burrill gave time to the audience for questions and comments. This opened up the real questions, such as one asked by a diagnostics company CEO, “what is the value proposition for my investors when there’s such resistance on the part of the FDA and the payers to a very effective product?” Burrill let the panel do their best to deal with this daunting question, then took the reins. “There’s no doubt about it. Investors are cynical today. Early investors drank the cool-aid, now they’re saying show us the revenue. At first we thought that the regulatory burden was the problem, but no. There are ‘perverse incentives’ built in which are more real than previously thought.” Burrill urged companies to get their technology into the clinical workflow. To get it adopted in protocols and guidelines. “Clinicians are creatures of habit” he reminded.
Translation ain’t as easy as we thought
“For now, digital pathology is the entry into the clinic.” Cliff Reid, Complete Genomics
To lighten things up, Burrill called on Kevin Davies, author of The $1,000 Genome. (It’s a time-honored practice in America--call in the English for a bit of history, drama, and humor.) Davies gave a nice overview of the history of genomics aided by some terrific slide pictures, from a snapshot of Cambridge where things began to a picture of the Faroe Islands whose current population of 50,000 will all have their genome sequenced. It was at the end of his presentation that Davies, who may need to write another book about the $100 Genome, gave examples of recent clinical use of the genome. They are few, so the examples are a bit over-used. For instance Davies told the positive story of Nicholas Volker. The young boy's illness alluded his doctors until his genome was sequenced, and an unexpected mutation convinced them to do a bone marrow transplant. This turned things around for little Nick, who is doing well today.
Mentioning the “thousand-dollar genome with the million dollar interpretation,” Davies was the first of the audience to question the panel of sequencing company CEOs (and CMO in the case of Paul Billings of Life Technologies) about what would move us further toward clinical use of the data. While Hugh Martin of PacBio talked about his company being able to offer the fastest sequencing and Jay Flatley revealed that half Illumina’s revenue comes from sequencing, Cliff Reid of Complete Genomics had the most to say about the clinical use of the data. Perhaps this is because his company is exclusively focused on sequencing human genomes and, in fact, is now beginning to do diploid sequencing (current genome sequencing is really for only half the genome.) “We rely on two services,” Reid said, “sequencing and FedEx.” Complete Genomics recently announced they would be sequencing genomes for 1,000 people who have lived long lives in collaborations with Scripps Health in a project to discover the genomic secrets of healthy elderly people. Reid acknowledged the difficulty of reading the data and spoke of the format the company uses to present the results. Pushing all of the CEOs to share their thoughts on the future, Burrill asked about the need for standards so that the data might be more easily digested. To this Reid pushed back asserting that “standards too early are harmful.” For clinical applications, Reid suggested, pathologists are the most willing and prepared to accept and use sequencing data. “Genomics has to come to the same point in medical schools that radiology has come to. And this will take decades,” Reid concluded.
The future is bright
“We live in the century of biology. Bio is the best investment today.” Francis Collins
Burrill introduced NIH Director Francis Collins, saying that Collins had called and asked him if he could speak at the conference. If Burrill is an established rancher in this new untamed land, Collins is the man sent by government to oversee and make awards for various mining and surveying projects. The NIH as a $30 billion annual budget and Collins assured the crowd that he was focused on “reengineering the therapeutic development pipeline.” He pointed to fields such as drug repositioning and better prediction of drug safety as great opportunities for business. “So far finding new uses for drugs or retired compounds has been serendipitous.” Now, Collins urged, we can predict new connections and purposes. (See our upcoming interview with NuMedii, a spinoff from Stanford focused on drug repositioning.) Collins wants to see the NIH “serve as an honest broker” between those who have the compounds and those who could create new opportunities. Collins affirmed that despite tightening budgets in Washington, he was “determined not to slip into a conservative approach.” He urged the crowd to tell the story of personalized medicine to others. “Contact your local congressmen and invite them over to your businesses. We have a great story to tell.”
Grabbing a coffee between sessions I met David Ewing Duncan, life science journalist and author of The Experimental Man. Duncan had been comparing notes with a very talkative and animated Martin Reese, founder of Omicia, a company established to make clinical interpretations of the Genome. (Stay tuned for our interview with Omicia who launches officially next week.) Duncan was cutting out early to head to another engagement and told me he’d heard some of the talks before. “We’re just in the beginning,” he said. “It’s happening, but it takes time.” This is not lost on Burrill who has spent his career taming new territory. “The industry has not perceived the complexity of capturing payment” he repeated wrapping up the show-down. In a final challenge to the audience to find new models he used Twitter as an example. “Increasingly the value capture lies outside of the product.”
Just another day at the ranch for Burrill and Co.