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news ‘Scientifc wellness’ searches for a business model Proponents of disease prevention and wellness remain bullish, despite Arivale’s demise. rivale was selling ‘scientific wellness’ in the shape of a battery of genetic, Amulti-‘omics’ and molecular tests to flag health concerns to consumers. The idea was to draw insights from personal data clouds made up of whole-genome sequencing, blood analyte testing and daily activity tracking, which, coupled with behavior-modifying coaching, would “manage chronic diseases before they show up,” says Arivale cofounder and DNA sequencing pioneer Leroy Hood, also chief strategy officer, cofounder and professor at the Institute for Systems Biology. It wasn’t to be: Arivale shut down in April. Human Longevity, also offering consumers genetic tests and imaging to elucidate current and future health risks, took an 80% hit to its multi-billion-dollar valuation in late 2018, following a series of management reshuffles. (Human Longevity was cofounded by another high-profile geneticist, Craig Venter.) Optimizing health through -omics and other sophisticated testing has yet to take off as a business These setbacks beg the question, model. Credit: Rawpixel Ltd / Alamy Stock Photo for investors, of whether this emerging sector—packaging up the latest science and technology to detect and prevent disease—is ready for prime time. Arivale’s director and founder of the Scripps Research with support from health professionals, direct-to-consumer formula did not work: Translational Institute, describing the were indeed able to bring their readings to it was unable to convince enough people dangers of overdiagnosis and the anxiety normal ranges. that scientific wellness was worth the $3,500 that can result. Yet were they healthier? Critics point to annual price tag (including tests, coaching Indeed, a more fundamental concern is a lack of evidence that these small changes and regular follow-up). The 6,000 customers that scientists do not yet fully understand in surrogate measures actually influence that Arivale did recruit “loved” the service, the impact on hard health outcomes of mortality and morbidity, and to the risks according to Robert Nelsen, cofounder the myriad patient data that can now be of ‘medicalizing’ what could be normal, and managing director at Arch Venture collected. And even if the links were better or at least non-pathological, readings for Partners, an Arivale investor. But they were understood, steering human behavior to any individual. insufficient to pay back the $50 million or prevent future illness is not straightforward: Determining what normal looks like, more raised by the company since its 2014 many of us are just not wired to change our amid the sea of high-resolution health inception. “We should have focused more on lifestyles today according to what diseases data now available, is the goal of multiple health systems rather than on consumers,” we might contract tomorrow. other private and publicly-funded initiatives, concedes Hood, especially given that Arivale grew out of the Pioneer 100 including Verily’s Project Baseline and “FDA does not allow consumer-genetics Wellness Project (P100) study, designed the US National Institutes of Health’s companies to diagnose disease,” only to to support the notion of ‘precision’ or All of Us Research Program. Project provide patients with data and point them ‘P4’ medicine: predictive, preventative, Baseline is gathering biometric data, health toward a doctor. personalized and participatory (Nat. records and self-reported information from Critics question whether these highly Biotechnol. 35, 747–756, 2017). The nine- 10,000 people over four years, and has taken individualized, whole-body health month P100 study of 108 individuals took a collaborative approach, working with diagnostics can ever be available and multiple genetic, molecular, health and health systems, universities and big pharma. affordable to the masses and thus have activity readings at three-month intervals, Paris-based Sanofi, Basel, Switzerland-based a meaningful impact on public health. generating correlations between and across Novartis and Tokyo-based Otsuka, who Human Longevity’s top-of-the-range the data, aiming to identify biomarkers signed up in May 2019, hope to use the testing suite (including full-body MRI) of disease or disease risk. It identified project’s evidence-generation tools (devices, cost $25,000. “These entities are catering individuals with out-of-range measures patient engagement tools, study enrollment to the hyper-affluent who think having of various common parameters like blood and management platforms) in their own unlimited data will protect them from sugar (48% of the participants were found clinical research. disease. It doesn’t work that way—in fact to be out-of-range) or vitamin D, and one These efforts are not complete. Until it’s quite the opposite,” says Eric Topol, or two with more unusual findings, who, then, Arivale and others “are jumping the NATURE BIOTECHNOLOGY | VOL 37 | JULY 2019 | 699–706 | www.nature.com/naturebiotechnology 705 news gun,” says Topol. “They don’t have the data, of [measuring] everything will approach the Serono to pilot Nebula’s and they have no right to charge people.” cost of [measuring] one thing.” blockchain for genomes But the data supporting scientific Hood, a self-proclaimed optimist, also wellness come not, Hood argues, from the predicts that the falling cost of testing Nebula Genomics announced in June its traditional, double-blinded randomized means that in five years “we’ll persuade first partnership with pharma to use its controlled trial that his critics call for. payers to fund” the battery of tests Arivale blockchain-based platform. EMD Serono Randomized controlled trials wipe out, was offering. Meantime, he’s going to bring will use Nebula’s network of anonymized rather than enhance, the individual variation the “best of Arivale” to family practitioners genomic data in a lung cancer project. that is the key to predicting disease and within Providence St Joseph Health, the Founded in 2016 by George Church maintaining health. What’s needed are “n-of- not-for-profit health system of which he is and two Harvard students, Kamal one” studies, in which each individual acts CSO. Other payers have also begun to use Obbad and Dennis Grishin, Nebula as his or her own control. “Evidence-based genomic tools more systematically in disease is one of a small cadre of companies medicine as we know it is a disaster,” says prevention: Geisinger Health in 2018 added that have set up blockchain-based Hood, who predicts that it will eventually be DNA (exome) sequencing to its routine platforms to enable people to maintain replaced by n-of-one studies that he terms screening program. control of their genome and manage “dense phenotyping.” Scientific wellness is coming, but not as access to it in a secure, yet transparent, Notwithstanding the massive challenge of fast as Arivale’s investors hoped. The company environment. For Serono, a subsidiary focusing on wellness and prevention, rather was perhaps too bold in offering so much of Merck KGaA of Darmstadt, Germany, than disease, investors have not lost faith. novelty in one go: new science, a new kind of the collaboration has the potential to “There’s a huge future in consumer wellness,” evidence generation, a new delivery channel, provide scientific insights that will help tweeted Arch’s Nelsen; it’s just about getting and a new way to think about health and researchers understand the causes of the right combination of price, product and disease. Its challenge was not only diagnosis, disease and accelerate discovery and drug distribution channel. For Hood, Arivale but also behavior change. Indeed, working development. In exchange for access was not a failure. It was an “unmitigated out how to motivate a broad population to to their data, lung cancer patients will success,” as it demonstrated the power of engage in a healthy lifestyle over the long be offered a free, high-coverage whole- dense phenotyping to generate actionable term is the really hard question, says Geoffrey genome sequencing, which could help possibilities to improve health and prevent Smith, founder and managing partner at them make better treatment choices. disease and, finally, in underscoring the health technology firm Digitalis. Do people According to Nebula’s founders, two importance of psychology in supporting have to be motivated at the individual level, or issues primarily keep people from getting individuals to change their behavior. The could they be grouped? What pricing model their genome sequenced: cost and privacy coaching was what distinguished Arivale would lead to the greatest engagement? In concerns. As a result, relatively few from rivals like 23andMe, a genetic testing short, “despite being a technology and data- human genomes have been sequenced company; Orig3n; Mayo Clinic’s GeneGuide; driven investor, I suspect that getting to better so far, slowing the development of and Helix. [scientific wellness] solutions will have more genome-based therapies. This new A similarly comprehensive offering to do with behavioral economics than merely effort aims to solve these problems, to Arivale’s is from Q Bio, cofounded better sensor technologies,” he predicts. leading to greater numbers of genomes in 2015 by Michael Snyder, Garry Choy Given those remaining challenges, it is becoming available to drug developers. and entrepreneur Jeffrey Kaditz. Q Bio perhaps not surprising that this early variation By far the largest collections of genomic promises consumers a full health snapshot did not work out. Arivale 1.0 did not get the information are in the hands of direct- in 75 minutes, but at $3,500 a go, it’s still right combination of price point, product and to-consumer genomics companies, like expensive. Perhaps learning from Arivale’s distribution model. “But we’re not giving up,” 23andMe and Ancestry.com, which mistakes, the company is focused on “being comments Arch Ventures’ Nelsen.