View attachment 51965 I recently received in the mail a small cardboard box, solidly constructed and colored a subtle metallic gray, from the future. ELYSIUM HEALTH was printed on it in white sans-serif capital letters. Inside, a smaller crisp white box, banded in blue and imprinted with a letterpress E, described its contents as “a daily health product designed to optimize and support your most critical metabolic systems,” including “DNA repair,” “Cellular detoxification,” “Energy production,” and “Protein function.” Within was an elegant pillbox containing 60 capsules. The technical language obscured an arresting truth: Basis, which I had ordered online without a prescription, paying $60 for a month’s supply, was either the most sophisticated fountain-of-youth scam ever to come to market or the first fountain-of-youth pill ever to work.
By the time I bought it, the brand had been pummeling my awareness for weeks, the ads barreling into my Facebook feed with claims of being the “world’s first cellular health product informed by genomics.” Under usual circumstances, a self-promoting nutraceutical with a dystopian name and the implied gift of life extension would be easily dismissible, akin to reiki or juicing. Basis, which first became available last year, bypassed the FDA’s screening process, and Elysium is effectively using its customers as human test subjects, sometimes reviewing their Fitbit and other health-tracking data to determine if the pill delivers on its promise — or causes unexpected problems.
But what promise! Basis and the other pills that will likely follow it in the next five to ten years are the fruits of a scientific backwater that has been working toward this moment for a quarter-century. These drugs and supplements are aimed to be a hack of the heretofore most intractable condition of human existence, the invisible countdown clock with which evolution has equipped our bodies. They just might postpone the onset of the most common afflictions of our dotage, from cancer to heart disease to diabetes to Alzheimer’s. We won’t necessarily enjoy longer maximum life spans (though that’s a possibility), but we very well might enjoy longer health spans, meaning the vital, productive chunk of our lives before degeneration kicks in.
Others who’d taken Basis before me had described effects including fingernail growth, hair growth, skin smoothness, crazy dreams, increased stamina, better sleep, and more energy. Once I began taking it, I did feel an almost jittery uptick in mojo for a few days, and I slept more soundly as well. Then those effects seemed to recede, and there were also mornings where I felt a little out of it. If these were placebo effects, they were weird ones, because they didn’t make me feel better, only different.
Still, the pill’s seduction was powerful. The potential benefit was profound. The cost seemed manageable. And any qualms I might have had about whether this was simply next-generation snake oil faded in the halo of the six Nobel Prize winners who sit on Elysium’s scientific advisory board. Most impressively, the company’s co-founder is Leonard Guarente, who heads MIT’s aging center and is one of the pioneers of aging science, a contender for the Nobel Prize should geroscience ever get a nod from the Swedish academy.
If I were going to trust anyone in a lab coat promising a magic pill to stay healthy longer, Guarente appeared a good bet. As the month’s end drew near, I was reluctant to stop taking Basis. It seemed foolish not to continue.
Until very recently, aging was just a thing that happens, a decay or breakdown, chaotic and impossibly complex, that seems to accelerate only after we’ve reached the age of reproduction. At that point, as Guarente told me over lunch in Cambridge recently, “natural selection says: ‘I don’t care anymore.’ ” But in the past few decades there have been significant advances in maximum life spans. The number of people reaching 100 has risen and continues to rise. The record officially belongs to Jeanne Calment, who as a child sold colored pencils to Vincent van Gogh and died in 1997 at the age of 122.
Could a little tinkering turn us all into Jeanne Calments? A large number of men who have made fortunes in Silicon Valley believe so — or at least are trying to recast aging as merely another legacy system in need of recoding. Oracle co-founder Larry Ellison’s Ellison Medical Foundation has spent more than $400 million on aging research. In 2013, Alphabet’s Larry Page announced a moonshot life-extension project called Calico, and XPrize founder Peter Diamandis partnered with genome sequencer J. Craig Venter to found a competing company called Human Longevity Inc. Paul F. Glenn, an 85-year-old venture capitalist who watched his grandfather die of cancer, launched an aging-science foundation more than 50 years ago that has since funded a dozen aging-research centers around the country. Peter Thiel is 37 years Glenn’s junior but equally desperate to find a death cure: He has given at least $3 million to the Methuselah Foundation, the research vehicle for the extravagantly bearded, Barnumesque immortality promoter Aubrey de Grey. Thiel has also said he takes a daily dose of human growth hormone, and he was reported to have seriously explored the transfusion of blood from the young to the old.
Last year, MIT named Guarente’s lab the Paul F. Glenn Center for the Science of Aging Research. Guarente has done his best to ignore the whiff of panic emanating from aging billionaires and instead be grateful for the funding. Scientists have recognized since the 1930s that calorie-restricted diets extend life in mammals (we evolved, the thinking goes, to withstand periods of famine, downshifting our metabolism in order to defer reproduction until we were again in a time of plenty). Guarente was one of the first to discover a single gene with a linchpin role in the process: in his case, a class of molecules called sirtuins. Now, aging science is in a growth spurt, with an accelerating race to develop compounds that target such master genes. The idea, and the premise of Basis, is that certain compounds might trick our bodies into thinking they’re starving (thereby extending our lives) without our having to feel hungry.
But from its birth in the early 1990s, the field of geroscience has faced significant impediments. Coming on the heels of centuries of humbug (e.g., Ponce de Leon, crushed dog testicles, Ted Williams’s frozen head), it has had to overcome a near-universal presumption of quackery. It is also an awkward match with contemporary drug research, which is organized around addressing specific maladies. Since aging is a risk factor rather than a disease — in the language of the FDA, it’s never been considered an “indication” — pharmaceutical companies are disincentivized from developing broadly aging-targeted drugs, and foundations tend to reserve their grant money for cancer, Alzheimer’s, and the like. Also, the FDA requires expensive human trials to move a drug through its approval process. Since a drug designed to treat people who are already healthy would have to be remarkably free of side effects to justify approval, and since there isn’t consensus on precisely which biomarkers would prove an anti-aging drug’s effectiveness, no FDA-approved anti-aging drug has come to market. It took until last year for the agency to greenlight the first aging-targeted human trial, one that tests whether the drug metformin, which has already been approved to treat diabetes, might also target calorie-restriction genes. But even if that test is successful, it would still take years for the FDA to approve the drug’s use for non-diabetic consumers.
Guarente has a higher risk tolerance than most of his peers (as a kid, he sprinted past security to get into a Beatles concert), and when he was convinced he had developed a pill that could extend his own health span, he chose to pursue a novel path to market. Because the two active compounds in Basis, pterostilbene and NR, are natural (occurring in blueberries and milk, respectively) and have long been available separately as supplements, Elysium has been able to skip the FDA gauntlet and sell its capsules immediately.
The agility that comes with bypassing federal regulation has an obvious cost: Guarente and his advisory board are the only scientific credibility Elysium can claim. The company stresses that it is using only compounds supported by hundreds of peer-reviewed papers, that it enforces high manufacturing standards, and that it is conducting a human trial (currently 120 people between the ages of 60 and 80 are participating). But the primary way in which Elysium distinguishes itself from the retail supplements business is Guarente himself, who is in a very real sense monetizing his reputation. “I’m there to really keep a lot of pressure on the company to do human trials and testing,” he told me. “Never, ever, make a claim that’s not substantiated by evidence.”
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These steps haven’t spared the company from critics leery of eminent academics slumming it in the nutraceuticals sewer. Even colleagues sympathetic to Guarente’s enthusiasm point out that Elysium’s rigor is provisional, its evidence incomplete — while animal studies have been encouraging, the company is selling a product whose effects on humans have yet to be proved. “I am someone who is disappointed when I see efforts from major scientists to try to profit from something like this before the clinical trials are in that are designed to test for safety and efficacy,” says S. Jay Olshansky, of the University of Illinois at Chicago, who studies the public-health implications of longevity and is involved in the FDA metformin trial. Both pterostilbene and NR are generally recognized as safe under FDA guidelines (though an FDA spokesperson stressed that only NR had been evaluated by the FDA, and not in capsules.).Still, even Guarente wrestled with the decision to launch the company. “I had second thoughts,” he says. “I thought it was going to work, but I thought along the way there would be raised eyebrows and skepticism.”
Guarente has been taking Basis for two years, but it’s a good bet that he is not among those who have observed hair growth as one of the pill’s effects. At 64, he looks neither particularly young nor particularly old. His genes favor a long life, but he has seen how health span can be as important as life span. His father lived to be 83 and was in good health until being diagnosed with pulmonary fibrosis, whereupon he quickly lost lung function, requiring oxygen tanks; Guarente’s mother lived till age 89 but was “very frail and demented” by the time she died this June. After a rocky start — in his memoir, Ageless Quest, Guarente cops to quitting smoking when he was in third grade — he has lived a generally healthy life. Besides Basis, he takes a low-dose statin, aspirin, and vitamin D; weighs himself every day; eats a mostly Mediterranean diet (red wine included); and does a mix of cardio (on the elliptical machine, ever since his knees wore out and he had to stop running) and strength training three days a week at a gym near his home in the Boston suburb of Newton.
As we walked around the MIT campus one day this spring, Guarente pointed out a memorial to Sean Collier, the police officer shot and killed by one of the Boston Marathon bombers. A film about the bombing happened to be shooting in the area, and Guarente had recently received a call from the office of director Peter Berg, who was interested in having dinner. “I think it’s gotta be because of the pill,” Guarente said. Besides presenting him with interesting opportunities like meeting Berg, his work is also a magnet for kooks. There was the inventor who sent him an “anti-aging toothpaste” (hitch: The active ingredient was an enzyme known to degrade DNA), and also the woman who sent him unhinged letters and then showed up at MIT. “I’m a little worried, once Elysium starts to get a lot of attention, that it’s going to be a negative for my family,” Guarente said.
We passed the day-care center where his 5-year-old son is enrolled. The boy’s mother, to whom Guarente is married and with whom he also has an 11-year-old daughter, is a Bulgarian woman 20 years his junior who has an administrative job at MIT. Guarente has a third child, a son from his first marriage, but is unable even to find him, because he is a computer programmer specializing in encryption who has managed to scrub the internet of clues to his whereabouts. “I have a few addresses that I think are candidates,” Guarente said.
Guarente got into the whole defy-death racket as an outgrowth of a midlife crisis. He’d always been drawn to areas of research where there were still large blank spots on the map. He’d studied molecular biology because at the time it was a hot new field, but by 1990, he was divorced and single and looking for a new direction for his lab. Around then, two new graduate students proposed that they study aging in yeast. Two years later, they had identified specific yeast strains that aged less well than others. It was an opening.
“I was thinking if we were lucky, there’d be one cause of aging,” Guarente recalls of those early days. That was wishful, but they did find a cause of aging. It was an exciting finding (as yeast findings go). Though not generalizable to higher life-forms, much less humans, it was still a breakthrough, and the discovery resulted in Guarente sitting across from Willow Bay on Good Morning America. A later study would link NAD, a coenzyme critical to metabolism and which is known to diminish with age, with sirtuins. (NR, one of the two compounds in Basis, is a precursor that converts to NAD in the body.)
At the time, Guarente lived alone, often blasting Green Day at home and sinking all his time into research. His lab, populated with a growing number of ambitious students, thrummed with a boisterous spirit that was part camaraderie, part rivalry. Guarente and many of those students tell similar stories of peers and friends thinking they were crazy. There were no lucrative arrangements being proposed by biotechnology firms.
But that would soon change. In 1999, Guarente became co-founder of Elixir Pharmaceuticals, which aimed to develop drugs targeting sirtuins. And Guarente’s lab graduates would become some of his most prominent competitors. Matt Kaeberlein was on the front page of the New York Times recently for his experiment aimed at extending the lives of dogs with rapamycin, a compound first found in a soil sample on Easter Island in 1964, which for decades had been used as an immunosuppressant in organ transplants and which turns out apparently to operate on the body using the same mechanism as calorie restriction. Brian Kennedy, one of the two original Guarente grad students doing yeast-aging research, now heads the Buck Institute for Research on Aging (another Glenn center) and chairs the board of Mount Tam Biotech, a company developing a rapamycin-based anti-aging drug. And then there’s David Sinclair, an Australian who joined Guarente’s lab as a post-doc in 1995 and who made resveratrol, of red-wine-is-good-for-you fame, a household molecule. It was Sinclair who parlayed this discovery into the field’s biggest biotech firm, Sirtris, which was acquired by GlaxoSmithKline in 2008 for $720 million.
Sinclair’s discovery also provided a lesson about the danger of hype for a cluster of scientists exploring such a wish-fulfilling field. Suddenly, Sinclair was bouncing around TV calling resveratrol “as close to a miraculous molecule as you can find.” “David was a little over the top,” Guarente says. “I mean, he was saying, ‘If we’re right about this, it’s the most important discovery of all time.’ And that ticks people off.” When GSK shut down the biotech’s Cambridge offices a few years after buying it, laying off a number of employees and folding what remained into the larger corporation, many scientists in the field pounced. They included Guarente-lab alumni like Kennedy and Kaeberlein, who believe a molecule called Target of Rapamycin is a better bet than sirtuins for anti-aging efforts. While resveratrol had been shown to activate sirtuins in yeast, they pointed out, it had mixed results in animal studies, proving effective in fat mice but not regular-size ones. Both Sinclair and Guarente, who are paid consultants to GSK, insist that the company hasn’t given up on sirtuins, or resveratrol-related activators, but Sinclair has clearly been chastened. “At the time, I thought it important to bring attention to the field and show that it was legitimate,” he told me, “but I regret that I was a lightning rod for criticism.”
For Guarente, watching the boom and bust of resveratrol was as motivating as it was unnerving. He redoubled his own efforts to be the first to bring an anti-aging pill to market, even as he and Sinclair squabbled with Kennedy and Kaeberlein in the press. At times, the interpersonal strife can seem like nothing so much as the professional equivalent of a red Maserati convertible, a time-slowing denial of the ultimate stakes that bind the men: their shared obsession with combating aging, as every one of them gets older. “I’m increasingly eager to get something, a product that will slow down the train,” Guarente acknowledges.
For a company seeking to profit from life’s endgame, the Elysium Health offices in Soho hum with youthful energy. On a recent morning, Guarente, who was visiting from Boston, joined one of his two young co-founders, COO Dan Alminana, in a meeting with a prospective investor for a $20 million funding round. They sat in a glass conference room while dozens of young employees worked in the main space, speaking quietly or typing at computers. A row of service representatives sat fielding customer inquiries.
Not accidentally, the room had the feel of a Silicon Valley start-up. A Warby Parker “platform innovation” specialist sits on Elysium’s advisory board, as do a Nike designer and a “communications” professional from the DNA-testing company 23andMe. Eric Marcotulli, Elysium’s CEO, told me that the company aspires to be seen not as another supplement retailer, like GNC, or Big Pharma player, like Merck, but alongside tech companies like SpaceX, Tesla, ancestry.com, and Uber. Companies that are, he says, “retrospectively obvious.”
Marcotulli is an alumnus of prominent Menlo Park–based venture firm Sequoia Capital. A compact former wrestler who has long experimented on himself with protein powders and the like, he was self-quantifying before it was a thing, and he wears his Apple Watch at night to track his sleep. He also practices intermittent fasting, which means he consumes no calories during the 18 hours between 6 p.m. and noon. He was getting his M.B.A. at Harvard when a teacher assigned a case study on Sirtris. Later, during his VC days, he began reaching out to geroscientists, and he and Guarente found common cause. “We think we’re the world’s first consumer life-sciences company,” Marcotulli says. “What was the last new product in the consumer health market?”
The theory behind Basis is in part an evolution of the theory behind drinking red wine: One of its main ingredients, pterostilbene, is considered a more powerful version of resveratrol, with a more convincing track record in the lab. As for NR, by increasing NAD levels in our cells, it in turn appears to reverse mitochondrial decay. In a 2013 scientific paper, Sinclair announced that a single week of injections of an NAD precursor into elderly mice had made their muscles look young again, though without restoring their strength. Both compounds aim to activate sirtuins, and the hope is that together they might amplify what each does individually. View attachment 51967
Like others I’d spoken to, Marcotulli studiously avoided saying anti-aging, a forbidden term among anti-aging scientists loath to be associated with the field’s dubious past. At the same time, Elysium can’t help but trade on the hope and ambition implicit in that hype — hence a certain amount of consternation about the eminent scientists on the company’s payroll. “There are lots of desperate boomers looking for something,” says Bill Gifford, the author of the best-selling book Spring Chicken, which chronicles developments in anti-aging science. “But frankly, I’m kind of shocked all those big-name scientists signed on to this thing that’s two very common, easily obtained supplement ingredients.”
That day at the Elysium offices, advisory board member Jack Szostak, who won the Nobel Prize for Physiology or Medicine in 2009, was visiting, and we spoke in an empty space down the hall where the company would soon be expanding. Szostak has known Guarente for 30 years (“the yeast-genetics community, everybody knows everybody”), and his official role at Elysium is to keep an eye out for compounds that, like Basis, could target health maintenance rather than specific diseases. I asked him if he had any discomfort selling an unproven product. “To follow a large number of people for a long period of time is an expensive undertaking,” he observed.
This argument, that the cart had to be put before the horse in order to get the horse to move, is one I heard from several defenders of Elysium’s approach. But even advisory board member James Kirkland, who leads the Mayo Clinic’s Robert and Arlene Kogod Center on Aging, said, when asked about this concern, “I think that’s a good point.” Kaeberlein, Guarente’s former protégé, is sharper: “They have the legal right to market this compound to people without any real knowledge of what it’s going to do — good, bad, or indifferent — in the long run. Is it something they should be doing? I’m not qualified to make that moral argument. We each have our own view as a scientist what level of evidence do we need to feel comfortable staking our scientific reputation on that and making general recommendations to the general public. You can probably guess where my opinion is.”
For me, as that first month taking Basis ticked by, this question had become more than academic. This was true for many of these scientific advisers, and at least some of them are guinea-pigging themselves. Sir Richard Roberts, a 72-year-old Nobelist who also sits on Elysium’s board, says that both he and his wife take Basis. “The only thing I’ve noticed, and this was only because someone mentioned they’d noticed it too,” Sir Richard said, “the skin on my elbows, which I always noticed was pretty rough, was now much smoother.” Robert Nelsen, a leading biotech venture capitalist who has invested in Elysium and takes Basis, told me, “I feel younger than I am,” and said he can do more push-ups now. (Nelsen, who is 53, also takes metformin, despite not having diabetes. “My partners think I’m nuts,” he says.)
Then again, all these people are financially and reputationally incentivized to believe in Basis. Even Nelsen acknowledged he could be experiencing a placebo effect. I asked other scientists, outside Elysium’s orbit, whether they take the pill. Olshansky told me he takes nothing: He tries to exercise daily and watch what he eats. Kennedy, likewise, takes nothing: “I said I’m going to wait till I’m 50 before I start taking anything. I run, I try to keep my caloric level down, I manage stress.” Kaeberlein takes nothing but says he’s “getting more and more tempted to take rapamycin in a low dose.” Sinclair, who now co-directs a Glenn-funded center at Harvard, still takes resveratrol every day and also takes an NAD booster (he has his own biotech company, currently in stealth mode, focused on that booster).
Sinclair did say that Basis is “based on solid science” and, if he didn’t have his own NAD booster, he’d “strongly consider” taking it. Was I, then, on safe ground taking it? There was a long pause on Sinclair’s end of the line. “You’re never safe assuming anything,” he said. “The results from studies indicate it should be safe.” And effective? Another pause. “I’d rather not say anything that definitive.”
My confidence waned. None of these scientists deemed Basis something they urgently need to be taking. Maybe it would help. Maybe it wouldn’t. Like Dylar, the black-market drug in Don DeLillo’s White Noise that cures the fear of death, the true payload of Basis and its coming wave of peers, whatever their physical benefits, may be a balm for existential terror. Side effects may include an obsession with death, reinforced every morning when you swallow your pill.
“I’ve had many interesting conversations with aging baby-boomers with money wanting to know what to do with it,” says Father Nicanor Austriaco, a bioethicist at Providence College. “People say, ‘I want to live longer, ’cause the last 40 years I’ve messed up.’ My question is: If you’ve not gotten 40 years right, what makes you think you will if you have another 40?”
Austriaco has unique credentials to opine on the matter. His religious conversion, and decision to become a Catholic priest, occurred just as his time in Guarente’s lab was coming to an end; he had been the second of the two graduate students who first undertook aging research in yeast back in 1991. “For a long time, he thought I was incredibly crazy and nuts,” Austriaco says.
Austriaco recently took part in a conversation at the Vatican about “enhancement” — everything from transhumanism to crispr technology (a new technique that allows us to edit DNA very efficiently) to sirtuin regulators of the sort that Guarente has focused on — and laments how capitalist concerns have invaded molecular biology. “I’ve seen how it can distort the human person,” he says. “I’m hoping it will not distort the science at least in this field.” I asked him for his own longevity practices. “I pray,” he said.
Guarente, a scientist and by necessity a salesman, has chosen a more worldly path. The morning after his meeting with the investor in Soho, he arrived at the U.N. to give a talk at something called the World Summit on Innovation & Entrepreneurship. Another panelist approached him, said he was taking Basis, and asked Guarente’s advice on the optimal time of day to take it. Guarente said morning was best, then returned his attention to his forthcoming presentation, which he was nervous about. His business partners had edited his slides and introduced mistakes he found embarrassing, including the made-up word neurogeneration.
Guarente has never been entirely at ease with the adjacency of science and money. He left Elixir, his previous biotech effort, after seven years, having lost power to the company’s venture capitalists. They ended up “not wanting to work on anything science-based but wanting to just import stuff that was already being sold elsewhere in the world, marginally related to aging, and call that an anti-aging company,” he told me. But he has also seen public funding of aging research, never particularly robust, become even scarcer. His disappointment with Elixir seems not to have tempered his enthusiasm for Elysium. As we talked, he sketched a vision of the new company’s future rich with possibility, bringing cutting-edge science to customers and contributing not just to the company’s bottom line but also to the greater social good. Elysium could, for instance, produce “the gold standard vitamin-D pill, and sell it basically at cost to get it out there.” I asked him why his business partners would want to forfeit a profit.
“They won’t,” he acknowledged. “It won’t turn out that way. ”
By Benjamin Wallace - New York Magazine/Aug. 2016 Issue
Photo: Benedict Evans