Researchers at the Institute for Systems Biology in Seattle developed a way to test for microbiome diversity from a blood sample. (Artist rendering courtesy of ISB) If you want to know what’s going on in your gut microbiome, the community of bacteria in our intestines that are tied to overall health, there are plenty of companies willing to help. You just have to pay them — and send in a poop sample. But it turns out that bottling feces isn’t the only way to gain insights into the gut. Researchers at the (ISB) in Seattle have devised a new way to look into the state of your microbiome with a blood test. Microbiome startups have proliferated in recent years. Some are going after drug discovery for specific diseases, such as Finch Therapeutics and Maat Pharma. Others, including Seattle-based , are selling microbiome insights directly to consumers for overall health. Given the relatively early stage of microbiome research, how useful insights from the gut can be. That’s why ISB researchers decided to focus on the diversity of microbes. “There’s not a good correlation between diversity in and of itself and clinical health. But there are specific cases in which it does seem to be a huge risk factor,” said, who worked with on the study, which was published today in Nature Biotechnology. Low microbiome diversity is a strong risk factor for patients with recurring Clostridium difficile (C. diff), Gibbons said. C. diff is a potentially life-threatening bacterium that comes back in nearly a third of patients following antibiotic treatment. ISB researchers Dr. Nathan Price and Dr. Sean Gibbons. (ISB Photos) “Getting these recurrent infections is super hard on patients,” Gibbons said. “If you could avoid that cycle, you could not only decrease the cost of healthcare, you would actually be saving lives and producing a lot less suffering.” Patients with C. diff can be treated with a fecal transplant, but those are only administered after antibiotics have failed. Gibbons thinks that a blood test could pre-screen patients at risk of recurring C. diff and avoid the painful cycle. Related: To create the test, researchers leaned heavily on data compiled by Arivale, a Seattle startup that aimed to help people become healthier and avoid disease through wellness. in April after it failed to find a market for its pricey service. But Dr. Lee Hood, who co-founded both Arivale and ISB, rescued much of the data and technology from the startup and brought it to ISB. That resource gave Price and Gibbons extensive data on hundreds of former Arivale customers who had their microbiomes sequenced and their blood tested, among other tests. The researchers were able to train a model to predict which individuals are likely to have very low microbiome diversity by looking at 11 blood metabolites. Arivale customers gave permission for their data to be used for research, and the information was anonymized. The ISB study is a “beautiful example” of how personal data clouds can give new insights into biology and disease, Hood told GeekWire in an email. They also found what they believe to be a “Goldilocks zone” of gut diversity. People with low diversity tended to have diarrhea and inflammation, whereas those with very high diversity tended to be constipated or have toxins in the blood. With the help of Arivale’s data, ISB researchers think more microbiome-related insights can be found. “We’re trying to build a real map that can lead to actionable insights of how to manipulate the microbiome,” Gibbons said. One disadvantage of the dataset is that it skewed toward white, health-conscious people, who were more likely to be Arivale’s customers. “It is a bit of a biased sampling,” said Gibbons. In the future, ISB intends to partner with Providence St. Joseph Health, which would give researchers access to a more representative population.
Arivale’s offices were empty this week after the company’s abrupt closure. (GeekWire Photo) Founded in 2015, Seattle startup Arivale aspired to pioneer a new sector called scientific wellness, combining genetic testing with personal coaching to improve the health of its members. Arivale raised more than $50 million in funding, employed 120 people, and served about 5,000 members over the life of its program. PREVIOUSLY: So optimistic was the company about this field that it trademarked the term “scientific wellness.” Seattle’s tech community voted Arivale the 2016 GeekWire Startup of the Year. Its co-founder, genomics legend Leroy “Lee” Hood, said when Arivale launched that the company “really stands a chance of being the Google or Microsoft of this whole arena.” It wasn’t to be. Four years later, Arivale , surprising its customers and employees, many of whom were left wondering what happened. Clayton Lewis, Arivale’s CEO, said in an interview that the company faced significant business headwinds, including the high costs of customer acquisition and genetic testing. But bigger picture, he said, the company also grappled with societal challenges, including the reluctance of Americans to invest in their health despite success stories among Arivale’s members. “I do not believe at this point that there is a meaningful market in the United States for a program that’s going to help people do something in the future,” he said. “I think that Americans, related to their health, are so living in the moment that the idea of optimizing your health so you can live this vibrant, joyful life as you age” isn’t appealing to enough people. But some former employees said Arivale also made things more difficult for itself. One former employee, who requested anonymity, told GeekWire that Arivale didn’t spend its marketing dollars effectively, focusing too much on events and parties rather than more effective digital campaigns; hired too many coaches and had many of them sitting idle for significant portions of the day; and had a culture where top executives seemed unwilling to take feedback from rank-and-file employees on ways that they and the company could improve. Arivale launched at a cost of $3,500 per year for its flagship program but had shifted to a model where many of its members were paying a $99/month subscription for ongoing genetic testing and coaching. Lewis said, in hindsight, he would have changed the way the company rolled out and priced its service. The company believed that it would see more adoption when it lowered its pricing and rolled out its service nationally after starting with a small number of states. “The mistake I would tell you I made as a CEO is that I drank my own Kool-Aid,” Lewis said. “For the first few years, we were not trying to rapidly scale the business because we wanted to prove the efficacy of the program. … Instead of launching with lower-cost, simpler programs, we stayed laser-focused on our flagship offering and we clearly did that to our peril.” Genomics pioneer Lee Hood, left, and Clayton Lewis, the CEO of Arivale. (GeekWire File Photo) Earlier this month, Hood about the future of Arivale. “In the future, we’ll be able to manage chronic diseases before they show up,” he said at an event hosted by Town Hall Seattle and the Institute for Systems Biology, which Hood co-founded. “We’re already doing this with Alzheimer’s, and early results look spectacular.” But Hood also admitted that Arivale’s wellness approach was “pretty expensive” at more than a thousand dollars per year. “In principle, most people spend a lot more money than that utter trivia. And if you could get healthy, I’d argue it’s a real bargain,” he said. Of Hood, Lewis said that “I’ve never met a man who’s a more determined optimist.” In the wake of the company’s closure, Lewis was blunter than Hood about the cost issues, calling the company’s research-based approach to wellness “wickedly expensive.” The startup’s resources were strained both by customer acquisition costs and the high price of novel testing services. Lewis said, “We tried an extraordinary number of ways to get people to join Arivale and we could not find a path to actually make that work as a viable business. Getting people into the program, the customer acquisition cost, we couldn’t master that.” Arivale CEO Clayton Lewis and co-founder Lee Hood accept the award for Startup of the Year at the 2016 GeekWire Awards. The company also had problems bringing down the costs of its services, such as tests for a person’s genetic makeup, microbiome and more than 40 blood markers. Arivale had expected the cost of those tests to fall more rapidly than they did. Paula Ladd, an entrepreneur who founded a genetic testing startup called SNPgenomics around the same time Arivale was getting started, said that the science can’t yet provide broad-based wellness advice. “What role does genetics plays in wellness? As a researcher, I don’t understand it well enough. How could the general public understand it?” Ladd said. Lewis agreed that Arivale arrived on the scene before its time. “We were very audacious,” he said. “What I believe is we were probably a decade too early.” Dr. Darren White, CEO of employee health and wellness startup Aduro, said a version of Arivale’s approach to personalized health coaching will inevitably reach consumers. “Health systems are already putting genetic testing inside primary care. It will be part of your annual visit with your doctor,” he said. Aduro does not yet incorporate genetic testing but plans to once costs decline sufficiently. Arivale competed in the wellness space with genetic testing companies like 23andMe, Orig3n and the Mayo Clinic’s GeneGuide. Startups that offered health advice based on microbiome tests include Voime, uBiome and Thryve. But Lewis said he considered Arivale unique in providing a comprehensive approach, with testing and coaching. Assessing rival firms, Lewis said that he thought genetic testing companies like 23andMe have been successful due to their lower, one-time price point and simpler offering, but he said that approach offers “surprise and delight” and “genetic entertainment” rather than improving health. As for those that give health advice based on microbiome tests, he said that some startups have made “false” claims. Last week, the wellness industry suffered a major blow after a looking at nearly 33,000 employees in workplace wellness programs found “no significant effects on clinical measures of health, health care spending and utilization, or employment outcomes after 18 months.” Human Longevity, a genomics startup backed by Celgene and DNA-sequencing company Illumina, late last year as investors lost faith in its ability to sell its services to wealthy individuals and pharmaceutical companies. Yet some data-driven wellness startups continue to draw funding. Viome, a startup that makes nutritional recommendations based on microbiome testing, recently in a round that included backing from Salesforce CEO Marc Benioff. Arivale attempted to win customers directly through a healthcare system to no avail. Working with Michigan-based Spectrum Health, Arivale launched a test program directly in a health clinic. “Despite the fact that, if you walked in, it basically was an Arivale commercial, we saw about a 10% conversion into the program,” Lewis said. Ladd said she thought the general public does not yet crave this sort of service. “I don’t come home from work wishing I had tested my microbiome, but I do wonder whether I have influenza or not,” she said. Despite the startup’s challenges, Lewis said it was able to bring around 20 percent of customers with prediabetic or heart disease indicators to within a normal range in six months. Lewis, who competes in Ironman triathlons, was able to overcome a prediabetic diagnosis by following Arivale’s program. In a statement this week, Hood acknowledged the company’s business challenges but said he’s still a believer in the larger vision. “We started Arivale with the goal of helping people improve wellness and avoid disease through personalized data and actionable health coaching. This approach has positively changed many lives and has shown great scientific merit. While Arivale’s direct-to-consumer model isn’t yet sustainable because of the high cost of the assays, I am proud of and thankful to everyone at Arivale for their dedication and devotion to this mission. They gave real meaning to the term scientific (or quantitative) wellness, which will be a major component of 21st century medicine.”
Genomics pioneer Lee Hood, left, and Clayton Lewis, the CEO of Arivale. (GeekWire File Photo) Arivale, the genetic testing and personal health coaching startup co-founded by genomics pioneer Leroy “Lee” Hood, shut down unexpectedly Wednesday — bringing an abrupt end to its ambitions to transform the lives of Americans through a new field that Hood dubbed “scientific wellness.” All of the Seattle-based company’s approximately 120 employees were let go as of noon today, confirmed Arivale CEO Clayton Lewis in an interview. Arivale raised more than $50 million over its lifetime. The company offered ongoing wellness and nutritional coaching tailored to the results of each person’s genetic, blood and microbiome tests. The decision was a surprise to many Arivale employees and customers. In a message to Arivale customers this afternoon, the Seattle-based company attributed the decision to “the simple fact that the cost of providing the service exceeds what our customers can pay for it.” The message added, “We believe the costs of collecting the genetic, blood and microbiome assays that form the foundation of the program will eventually decline to a point where the program can be delivered to consumers cost-effectively. However, we are unable to continue to operate at a loss until that time arrives.” Lewis told GeekWire that the high cost of acquiring customers also played a role in the decision. “What is tragic on so many levels is that we were not successful in going out and convincing consumers that you could optimize your wellness and avoid disease with a little bit data and some changes in your lifestyle — that there’s not a market for that product that I believe in passionately,” Lewis said. “And that’s what we were trying to do.” About 5,000 people took part in the Arivale program over the lifetime of the company, and Lewis said he is “incredibly proud” of the results. The program launched at a cost of $3,500 per year, but the price had dropped to the point where most customers were paying $99 per month for the flagship Arivale program, Lewis said. CEO Clayton Lewis and members of the Arivale team accept the GeekWire Award for Startup of the Year in 2016. (GeekWire File Photo) The larger personal wellness industry includes heavyweights such as 23andMe, a genetic testing startup valued at more than $1 billion, and smaller players including EverlyWell, which , and Viome, the microbiome company led by Naveen Jain that . Global Wellness Institute that the preventative and personalized medicine and public health industry is worth $575 billion. Some of Arivale’s underlying work will continue at the Institute for Systems Biology (ISB), the not-for-profit biomedical research organization co-founded by Hood, where the ideas that led to Arivale were originally developed. ISB is now part of Providence St. Joseph Health, where Hood is chief science officer. Clayton said ISB is expected to hire some of the employees let go by Arivale as part of its closure. He declined to disclose details of the severance offered to employees, but said the same package was provided to all executives and employees. Investors in Arivale included Arch Venture Partners, Polaris, and Maveron, where Lewis worked full-time before joining Arivale as co-founder and CEO. Its scientific advisory board included George Church, a professor at Harvard and MIT; James Heath, president of Institute of Systems Biology; and Ed Lazowska, computer science professor at the University of Washington. “Lee Hood sees the future with unmatched clarity,” said Lazowska, an early participant in the Arivale program. “A clear view, however, does not always imply a short path. Scientific wellness, as pioneered by Arivale, will be a foundation of 21st century medicine. But not right now. Right now, the cost of providing the service (the tests, the coaching) exceeds what people are willing to pay. Those costs will fall in time, and Arivale’s model and Arivale’s discoveries will see another day.” Lewis said he has come to the believe that Arivale was about a decade too early. Arivale’s executive team included Sean Bell, chief operating officer; Jennifer Lovejoy, chief translational science officer; Mia Nease, head of healthcare and life sciences partnerships; Andrew Magis, director of research; Ashley Wells, chief product officer; and others. Hood, who led the Caltech team that pioneered the automated DNA sequencer, that Arivale was “the opening shot in a whole new industry called scientific wellness, and it really stands a chance of being the Google or Microsoft of this whole arena.” GeekWire chief business officer Daniel Rossi was a longtime customer of the program, and we chronicled his early experience with Arivale Here’s the text of the message sent to Arivale customers earlier today, a version of which was . To Our Customers, We are very sorry to inform you that, effective immediately, Arivale can no longer provide our program to you and our other customers. This letter explains why we are ending the consumer program and answers the questions you are likely to have about the process. Our decision to terminate the program today comes despite the fact that customer engagement and satisfaction with the program is high and the clinical health markers of many customers have improved significantly. Our decision to cease operations is attributable to the simple fact that the cost of providing the program exceeds what our customers can pay for it. We believe the costs of collecting the genetic, blood and microbiome assays that form the foundation of the program will eventually decline to a point where the program can be delivered to consumers cost-effectively. Regrettably, we are unable to continue to operate at a loss until that time arrives; in other words, we have concluded that it is simply too early for a direct-to-consumer scientific wellness offering to be viable. We founded Arivale with the vision of making personalized, data-driven, preventive coaching a new wellness paradigm in the United States. Since its launch in 2015, the results of the Arivale program have been remarkable. To cite but one example, our scientific paper describing the improvements seen in multiple health markers in ~2500 participants was recently accepted for publication in the journal Scientific Reports. While our direct-to-consumer model isn’t yet sustainable, we know that the Arivale program improved the lives of our customers and showed great scientific merit. We are proud of everyone at Arivale for their dedication and devotion to our mission and grateful to you and all of our other customers for joining us on this journey. Together, our efforts have launched a new paradigm—scientific or quantitative wellness—which, we are confident will become a major component of 21st century medicine. Developing story, more to come.