Randy Scott: Bringing Metcalfe’s Law to Genomic Medicine

By Kevin Davies  

November 30, 2012 | BOSTON—Receiving the 2012 Leadership in Personalized Medicine Award from the Personalized Medicine Coalition (PMC), Randy Scott reflected on his success as the founder and former CEO of Genomic Health, but also looked ahead to new opportunities with his latest venture, InVitae Corporation. 

Scott received the award this week at the 8th annual Personalized Medicine Conference at Harvard Medical School. “Randy has transformed our understanding of how medicine can be practiced by creating one of the most successful personalized medicine companies to date,” stated Brook Byers, a partner with Kleiner Perkins Caufield & Byers and a previous honoree. Past winners of the PMC Award include Janet Woodcock (FDA), Elizabeth Nabel (NIH), Ralph Synderman (Chancellor Emeritus, Duke University), and Leroy Hood (Institute for Systems Biology).   

After a successful stint at Incyte, Scott founded Genomic Health in 2000 and led the firm for nine years, overseeing the development of the Oncotype Dx gene expression test for breast cancer. He modestly shared the credit with numerous colleagues. “My contribution was I probably did a good job of hiring a lot of people at Genomic Health who are way smarter than I was,” he said, naming in particular co-founder Joffre Baker, CMO Steven Shak, and CEO Kim Popovits. 

As a graduate student in the early 1980s, Scott said he had been excited about biotech but worried he was too late. “All the exciting genes had been cloned! TPA, Factor VIII, human growth hormone, insulin,” he recalled thinking. Today, Scott said, “we’re on the precipice of incredible accelerating change in this field… Everything we’ve experienced to date pales in comparison to what we’re going to experience in the next 5-10 years.”   

But he also shed some personal insight into the launch of his latest venture, InVitae Corporation. He said he is “unabashedly excited” about the future of personalized medicine. “Personalized medicine is really when disease happens to you—your friends or your family. Suddenly it’s no longer just an industry we’re working in but something so personal, so intense, and so emotional. We should never forget that.”  

The Network Effect  

Scott said reading Intel founder Andy Grove’s book Only the Paranoid Survive in the mid-90s, during his tenure at Incyte racing to identify human genes, was highly influential. In the book, Grove discussed the impact of Moore’s Law on the revolution in computing; Scott saw parallels with the biotech industry. “The way we were sequencing DNA [at the time] was so embarrassingly simple,” he said. Just as computing costs were plummeting, Scott reasoned it was inevitable that sequencing costs would also fall.  

Perhaps more importantly was the concept of “the network effect.” Just as Metcalfe’s Law—the community value of a network is proportional to the square of the number of its users—drove change in the computing world, so too will it drive the future of biotechnology.   

“Having a really cheap genome sequenced is really not very useful. We still see articles in the New York Times, ten years after the genome project, [saying] ‘so what?’ At some level, they’re horribly wrong, and at some level, they’re horribly right. We’ve not yet seen the network effect or the full implication of Moore’s Law.”  

Scott said the community is still “1-2 years away from the inflection point” where the cost of sequencing reaches the point that will trigger “massive consumer demand.” The value of genome sequencing will be most strongly felt in the network effect. “How we connect that genomic information across millions and millions of individuals… Somebody can be sitting at a computer, link into the network, and find how a mutation and how it correlates with their patient and a patient somewhere else in the world.” 

Scott said he was also a believer in what he called the “Law of Finite Genomes.” The human genome is like a complex finite puzzle with about 150,000 pieces (20,000 genes and 100,000 non-coding RNAs). “All common diseases are really rare diseases,” Scott said, with cancer a prime example. “Medicine goes from an infinite game to a finite game,” he said. By comparing lots of genomic information, we can begin to rule things out.  

Patients, Patients, Patients  

Scott was inspired to launch Genomic Health when a close friend was diagnosed with colon cancer in 1999. For the first time, Scott was personally struck by the chasm between science/technology and medicine. “We’ve got to bridge the gap—bring the science into clinical practice,” he said.  

The focus at Genomic Health, Scott said, was “patients, patients, patients.”  

“I’m not sure we had a model other than this maniacal focus on patients that wouldn’t be denied,” he said. If we could really do the science right, the science would sell.” Genomic Health spent an enormous effort on clinical studies.  

“Clinical data wins over physicians, and it is physicians that win over the payors,” Scott said. “The onus is on us as an industry to build the value proposition [for payors]… so physicians have to adopt those products. If physicians adopt, they will drive payers to cover.”  

Scott left Genomic Health this year to launch InVitae, spurred by the impact of rare genetic diseases affecting members of his family.  

In 2000, Scott’s nephew had a daughter with galactosemia. Fortunately, the disorder was diagnosed within 48 hours of birth, and her diet could be changed, otherwise there could have been “a dramatically different outcome.” In 2005, an adopted nephew collapsed on a tennis court and died from hypertrophic cardiomyopathy. Advanced screening could have saved his life, but nobody knew any family history of cardiac disease, he said.  

Finally, one of his wife’s relatives had a young son who developed serious seizures at age 2 years. The infant is developmentally impaired and severely autistic. Earlier this year, Scott revealed that exome sequencing of the child and his parents revealed a single de novo point mutation as the putative cause of the disorder. This is unlikely to provide any tangible medical benefit, but “it gives a clue into potential causes of these disorders,” he said. 

Ridiculous Goal  

Scott said his goal in launching InVitae was to bring the power of genetics into the real world of clinical practice. “We have a ridiculous goal,” he said. “We want to aggregate all of the world’s genetic tests into a single assay—for less than the cost of a single assay today!”  

In other words, InVitae plans to collapse all Mendelian inherited traits into a single assay that can be performed “reproducibly, at high quality and at reasonable cost for the medical system. So instead of going into these diagnostic odysseys… every parent thinking about conceiving a child can know exactly what their carrier status is and what disease risks lie in their family.” 

The initial assay will essentially be an elaborate gene panel, but Scott’s plan is eventually that this will lead into whole-genome sequencing (WGS). Scott believes that “within 10-20 years, everyone in any developed health care system will be able to be provided with a low-cost [WGS] analysis at birth... We’ll be talking about managing your genome over the course of your lifetime.” 

As for the question of how to deal with the plethora of data, “that’s Metcalfe’s Law, the network effect,” said Scott. “Much of the data won’t be of value to the patient or physician ordering the test. But collectively, they will be massively valuable to the research community.”  

We’re big fans of “Free the Data!” said Scott. The universe of clinical genetic data “won’t be a database held by one company or one academic institution, but you’ll see a massive movement over the course of the next decade to make data broadly available within the research community.” This will create a huge disruption in medicine, Scott predicted, a shift from phenotypically driven medicine to more of a genotype foundation as sequencing costs fall and the network builds.  

“Everything will drive off the genotype and it will move very fast,” he said. “This is a given. To me, this is the investment thesis. This will be the place to be, the chance to help people suffering from rare diseases. At the end of the day, every disease is rare.” 

InVitae is building a strong management team. The company recently merged with Locus Development, a start-up co-founded by Sean George and Michele Cargill, founding scientists at Navigenics. Steve Lincoln and Jill Hagenkord, both formerly with Complete Genomics, also joined the cause this year, as did Reece Hart, former manager of research computing and informatics at Genentech.