Personal genetics is having a bit of a 1983 moment. Back then, the majority of Americans had never used a computer or heard the word “internet.” A year later, Apple launched the Mac and the rest, as they say, is history. Purveyors of personal genetics platforms---products that tell you exactly what’s in your DNA---say they are at a similar tipping point. The only question is: Who will be the Apple of individualized genomics?
The latest contender is Genos, a genetic sequencing startup that is unveiling its whole exome-sequencing service today. The hot, shiny object of the industry, this type of next-generation sequencing offers a complete profile of all the expressed genes (the ones that code for proteins) in your genome. While a growing number of targeted genetic testing kits are currently on the market (Color, Myriad, and 23andMe, to name a few), whole exome sequencing produces 50 to 100 times more data.
Those extra nucleotides cost more, but at $499, Genos is still a steal over sequencing ordered up by physicians, which can run up to $2,000, and may or may not be covered by insurance. A Genos competitor, Helix, offers an ancestry discovery kit that sequences the whole exome for just $149 but doesn't yet delve into health-related variants. Veritas will do your whole genome for the higher fee of $999. The idea is that all this extra information will land consumers deeper personal insights. Bigger net, more fish.
That all sounds great, in theory. But some doctors and geneticists caution that biologists' ability to sequence DNA has far outpaced their ability to understand how those genes interact with each other and the environment to cause diseases like cancer, Alzheimer’s, and autism. Most of the 180,000 protein-coding bits of DNA in your body? Scientists don’t know enough about them to be useful.
“Most people ordering this testing are going to be underwhelmed by the results they get back,” says Geoffrey Beek, a genetic counselor at Children’s Hospital of Minnesota. “It’s so unlikely to find something that changes the way we treat somebody. Doctors already say eat well, sleep well, and get regular exercise. Do you really need a genetic test to push you over the edge to do those things?”
Probably not. But Genos is telling its customers to ask not what your data can do for you, but what your data can do for science. In a first for the personal genomics movement, the company is creating a research pipeline with academic and commercial partners, and paying customers to donate their data. The incentives range between $50 and $200 per project; the first four include a vaccine for breast cancer, a clinical trial for treating lymphoma, and research into prion diseases and common neurological disorders.
“At some point people are going to develop a disease in some way, shape or form," says Genos co-founder and CEO Mark Blumling. “This is a way to feel directly empowered to contribute to research and make a change.”
Erik Vallabh Minikel is in a race against time. Five years ago, his wife Sonia Vallabh discovered that she carries a rare genetic mutation for a fatal prion disease, a gene she inherited from her mother who passed away from the affliction in 2010. Together, they dropped out of their careers and became full-time prion research scientists at the Broad Institute of MIT and Harvard, where they are working to find a cure before her prion proteins start folding up the wrong way, killing off the neurons in her brain in the process.
Large sets of genetic data have provided one promising approach. Last year, Minikel and Vallabh analyzed an exome database maintained by the Broad; out of 60,000 people, they found three with an interesting mutation. Compared to the one that Vallabh has, which will cause her prion protein to misfold, their mutation essentially deletes one copy of the gene. That makes them, at least theoretically, much less likely to develop a prion disease than the average person you’d pluck off the street. Minikel and Vallabh want to find more people like this, and see if they’re healthy or not. If they confirm that the mutation has a protective effect, it could lead to drug and gene therapy strategies. There’s just one problem: The Broad’s database isn’t designed to get health information on individuals.
But Genos’ is.
“The genotype we’re interested in occurs in one in 20,000 people, so it’s already really hard to find,” says Minikel. “We need to also be able to go back and look at people’s health and ask questions. Genos is building a platform to allow people like us to do that.” Genos customers who consent to sharing their data with Minikel and Vallabh will fill out health surveys that the pair can access whenever they need. Then, as the data rolls in, they’ll be able to go back and line up phenotypes with genotypes to figure out which mutations have protective effects, and maybe, the key to a cure. While this treasure trove of data is only currently available to researchers in the four pilot projects, Genos plans to expand the platform in the next few years to create a robust research pipeline that customers can contribute to directly.
For Vallabh, the potential impact of the Genos platform is clear. But for the average user, the immediate benefits of whole exome sequencing are a bit murkier. While consumers will be able to see the full results of their exome sequencing---all the As, Ts, Gs and Cs---the interpretation of those results has a ways to go. Robert Green, who has been studying direct-to-consumer genetic testing for close to 15 years at Brigham and Women’s Hospital, is an expert in how access to genetic data changes consumers’ behaviors and interactions with the healthcare system. And his studies show that genetic information isn’t as provocative as some have hoped (or feared).
The fear is that patients will misunderstand or misuse genetic information in these early days, with so much uncertainty about how to interpret results. Remember that time the FDA ordered 23andMe to stop offering health reports with its genetic analysis kits?1 The company was marketing its tests as a way to test your risk for conditions like breast cancer and heart disease but couldn't prove the tests worked. The feds deemed it an unapproved medical device and stepped in on behalf of patients. But Green's data suggests that people aren't as quick to freak out as you might think. “The notion that people would have either catastrophic emotional reactions or misunderstand to the degree they would do dramatic things to harm their health, most of those have not been borne out by the research,” says Green. “But there’s a real lag time between making discoveries and using those discoveries for a clear-cut clinical benefit.”
One recent study showed that only 20 to 30 percent of direct-to-consumer genetic test takers thought enough of their results to share them with a physician. But he says it’s also important to remember that early adopters aren’t necessarily representative of the larger population. They’re the information seekers, people curious about their health and technology. The reactions of the rest of society are hard to predict. “When everyone has access to genetic information, will it send people off on wild goose chases, or will it really benefit people’s health?” he asks. “We don’t know that yet.”
Genos hopes to avoid any wild goose chases by providing customers with access to genetic counseling (for an additional fee of $150 per hour). Blumling says they’re not getting any compensation from the service, which is provided by an independent third party, and are doing it out of a responsibility to provide the necessary context for users. He stressed that they are not a diagnostic company, and more of a “personal exploration tool.” This is an important distinction from a regulatory standpoint; the FDA recently expanded its oversight of laboratory testing, specifically in regards to direct-to-consumer diagnostic tools.
And the company isn’t bothered that the results may indeed be underwhelming now. Those results are set to change drastically, as more and better information connecting variants to genetic conditions comes online. Genos is betting that a one-time investment will yield more valuable insights down the road for its customers, beginning a lifetime of engagement and increasing returns.
But the biggest dividend, says George Church, decorated Harvard geneticist and Genos advisory board member, will come when it comes time to start a family. “There are thousands of diseases for which we’re all at risk of being a carrier---that’s a high stakes thing we’re not handling right now,” he says. More limited panels catch the big ones, like Tay-Sachs, but leave out more rare but equally devastating disorders. “If you do the whole exome you can eliminate almost all those diseases overnight.”
But if you can afford to wait, you should. While the results of exome sequencing are static, the price tag isn’t. And it’s only going down.
1UPDATE 6:45 pm Eastern 12/15/16: This story has been updated to correct the fact that in 2013 the FDA ordered 23andMe to stop marketing its genetic analysis kits. A previous version of the story stated that the FDA shut down 23andMe.
