by Chip Walter
However, as HLI mined its growing reservoir of genomes, it found no such fountain. At least not so far, and probably never. The analysis of the company’s first round of 30,000 to 40,000 genomes showed that people who lived to a hundred didn’t have supergenes that bequeathed long life; they simply had fewer frail ones. Later, researcher Graham Ruby and his team at Calico found pretty much the same thing based on the millions of Ancestry.com records they tabulated and analyzed. It seems centenarians aren’t blessed with any genetic silver bullets. They’re dealt the equivalent of a full house: terrific genetic cards in all the right combinations. If you happen to live a Blue Zones lifestyle, all the better; you might live even longer. But in the end, no matter how well you live, no matter how many colonics you try or heaps of kale you eat, the degradations of your genes will still get you. It wasn’t just Blue Zone living or Pearl’s whisky and cigarettes that kept centenarians going. It was the absence of lousy genes.
After all of HLI’s thousands of genomes were compiled, and after the machine-learning algorithms had done their work, this meant the company was getting a ringside view of what unraveled human youth. The deterioration was so common that based on the way the average genome changed over time, Venter’s team actually could see, within a couple of years one way or another, how old a person was! That’s how precisely the damage was built into the human system. HLI also found that the genes of some people were falling apart faster than usual. Maybe they had been dealt crappy cards; maybe they might personally have damaged their body in other ways (stress, alcohol, obesity). But one way or another, some people were aging faster than others—and that was valuable information.
Generally speaking, scientists had known for a long time that healthy genes meant a healthy body, and vice versa. The difference with HLI’s findings was that now, specific genes (or combinations of them) were being revealed, genome by genome. This was making it increasingly clear where the frailty genes hid themselves, as well as how and why genes fall apart in general. As more and more of these were discovered, the next step would be to create drugs that could slow the damage, or go in and repair the battered genes themselves. That was the long-term goal.
This was, of course, exactly what Venter had hoped for, and precisely what he wanted HLI to deliver: the aggregation and analysis of massive amounts of data. Even at this early stage, the process was proving to be an excellent way to decipher the specific ways the human body shuffled down the road to perdition. And by 2016, Venter was just getting started.
He wasn’t alone though. Others were also now seeing the potential of eliminating aging, and fresh resources were beginning to flow in from—where else?—Silicon Valley. With a little help from Hollywood.
23 | WOBBLING WEEBLES
Hmmmm…mmmmm. The Moroccan phyllo chicken puffs were soooo tasty. Just the right combination of shredded chicken, perfectly spiced and then rolled b’stilla style with that contra-mix of ginger and cumin, cinnamon and coriander. And the way the egg was made: Superb! It made one wonder why no one was eating them.
Perhaps because they were too enthralled? It was quiet. But that wasn’t unusual among the homes in Mandeville Canyon, where, out there beyond L.A.’s fevered highways, the living was good. Certainly no one was dying, at least not in the acute sense. Nevertheless, dying was on the minds of the assembled. This included Goldie Hawn, who sat, stately and erect, on a comfortable couch with her tumble of blond hair. She had a question for Nobel laureate and microbiologist Elizabeth Blackburn about “the mitochondria.”
Hawn had been told about a molecule called glutathione, a brawny antioxidant that boosted mitochondria: the organelles that powered every cell in the human body. Glutathione was sometimes called “the God molecule” (which made scientists cringe because, of course, there was no single molecule that could rewind aging). It also didn’t work very well as an oral supplement. But if anyone did overindulge, by injecting it, for example, they might find they would soon be dissolving their livers and kidneys. Blackburn suggested the best approach might be to simply eat a varied and healthy diet.
The reason for this particular evening’s soiree was the kickoff in early 2016 for the National Academy of Medicine’s Grand Challenge for Healthy Longevity. When raising funds for ventures of these sorts, a cocktail of science, money, and the desire for long life could have a way of creating a nice snowball effect.
The goal of the challenge was to pool $25 million to sponsor breakthroughs in the field of aging science. The challenge itself hadn’t yet been entirely defined, except insofar as it was similar to Peter Diamandis’s XPRIZE endeavors. Diamandis, in fact, had consulted on other prizes with the man who was behind the evening’s challenge in collaboration with Victor Dzau, the august head of the National Academy of Medicine. That man was Dr. Joon Yun.
In 2014, Yun, an M.D. and hedge fund founder, had launched the Palo Alto Longevity Prize. Yun saw human biology as a complex machine encoded with DNA, and liked to say it was time the human race “hacked the code.” Life was, after all, nothing more than programmable software; therefore, all science had to do was start debugging the suboptimal system. Of course, knowing which code to debug was the crucial issue, and that was the reason for the grand prize and why the scientific teams that signed on had bought in.
Yun’s family had been farmers in Korea for generations, but he grew up in the United States where he graduated from Harvard, earned his medical degree at Duke, and then undertook his clinical training at Stanford. Finding himself in Silicon Valley, Yun switched from medicine to hedge funds, where he was the president and managing partner of Palo Alto Investors, LLC, a company that specialized in health care investments. In 2017, the fund’s assets topped one billion dollars.
Being an M.D., Yun was bothered enough by death and dying that he gave away one million dollars of his own money to get the Palo Alto Longevity Prize rolling. In 2014, two goals were set: First, take any wild animal and, by some acceptable intervention, increase that animal’s life span by 50 percent. Second, using the heart as a baseline, improve an aging mammal’s “homeostatic capacity” so effectively that it acted young again. In other words, turn back the clock. Prize Number One had to come before Prize Number Two, and the award for both was to be split down the middle: $500,000 each.
Yun had a marvelously simple way of explaining what he meant by “homeostatic capacity.” Imagine a Weeble, the little toys with the round bottoms that refuse to fall over. That was what good homeostasis did in any living thing: enabled it to bounce back, just like a Weeble, or a healthy 20-year-old. Neither fatigue nor soreness keeps a young healthy human down for long, because the genetics of the creature is optimized to ensure all the biological mechanisms operate at top homeostatic capacity. Youth and health were synonymous.
But, alas, humans do, in time, wobble as aging sets in, and they eventually fall down. Life’s abuses—radiation, loathsome chemicals, inflammatory and damaging foods, stress, and all the other ongoing deoxyribonucleic pilferings of the cells and stem cells of living things—batter genes unremittingly. The goal of the prize was to find a hack that boosted homeostatic capacity.
Despite Yun’s Weeble analogy, the Palo Alto Longevity Prize had so far struggled to meet its challenge. Initially, Prize Number One was scheduled to be completed by the summer of 2016, two years following its inception. But by early 2019, despite several comers, no prizes had yet been awarded. Prize Number Two was “yet to be determined.”
The $25 million National Academy of Medicine’s Grand Challenge for Healthy Longevity also remained a work in progress. But Yun never felt that any of these efforts was about the prize itself. In his mind, they were beacons: ways to draw attention to the complications of aging so that more of the right kind of people would develop the resources needed to change the world. It was time to rethink the conduct of the medical system. The National Academy of Medicine seemed a good place to start.
Prizes like the Grand Challenge were only a small part of an ever accelerat
ing drive for death-defying endeavors. In 2017, suddenly and everywhere, the media were again alight with discussions of radical life extension, just as they had been three and four years earlier. Except now there was a twist: It was all about Silicon Valley. Longevity venture funds and start-ups had begun popping up like little brown mushrooms. Companies with high-tech names like Verily (founded by Bill Maris’s friend Andy Conrad), Unity Biotechnology, Navitor, United Therapeutics (Ray Kurzweil was on the board), Alkahest, ZeroCater, Stemcentrx, Nootrobox, and Bulletproof, all now existed on California’s corporate rolls. These also included Venter’s Human Longevity, Inc., and Aubrey de Grey’s SENS Research Foundation.
Many of these were included in a New Yorker article published in April 2017 entitled, “Silicon Valley’s Quest to Live Forever.” Similar pieces quickly followed. Articles in Time, Smithsonian, even Town and Country of all places, began popping up with titles like “How Silicon Valley Is Trying to Hack Its Way Into a Longer Life,” and “Can Human Mortality Really Be Hacked?” The subjects of Silicon Valley and immortality seemed to be suddenly joined at the hip.
All the emerging ventures were happy to meet with the media to explain the progress they were making. The articles revealed how advancements in genomics, genetics, stem cells, proteomics, something called a Bod Pod, DNA repair, advanced supplements, pig placentas—all of them—would soon have death on the run. There were explorations of senescent cells, “young blood” transfusions, also known as parabiosis, and a raft of others. But the science mostly felt shallow, and there were still no big breakthroughs.
None of these ventures had the financing of Calico or HLI, although interest in them was growing. Some efforts had the support of Aubrey de Grey’s SENS Research Foundation, the Buck Institute, or the occasional angel investor like Amazon CEO Jeff Bezos or PayPal’s Peter Thiel. But these fell into the categories of mere millions, not hundreds of millions. Nevertheless, the new enterprises happily set out to spread the word to the media. All except one: Calico.
Since its inception in 2013, Calico seemed to have vanished. Sure, there was the obligatory press release now and then, and clearly the company existed. But was it getting anywhere? It had been more than three years, and yet Art Levinson, the seer of biotech, the chair of Apple, the man who was running the show, had offered nothing—not the day Calico announced its existence, and not any days, months, or years afterward. None of the talk that had taken place at the Google board meeting in early 2013 had been revealed—none of the mysterious funding details, none of the dinner conversations in Palo Alto or anywhere else. Every Silicon Valley reporter from the New York Times, Washington Post, Fortune, Forbes, Wall Street Journal, and more yearned for some morsel of information that explained why Google was funding this remarkable undertaking. And yet Levinson was as silent as a Buddhist monk. Which, of course, only made its secrets all the more tantalizing.
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TO BE BLUNT, Art Levinson didn’t feel that what he, or Calico, was up to was anyone’s business. This was vexing—not only to journalists, but also to Levinson’s peers. Ray Kurzweil was listed as an adviser to Levinson, through his connections with Larry Page and Alphabet, but Kurzweil knew only that Art seemed to be playing things “very close to the vest.”
Venter also wondered what all the secrecy was about. In separate conversations, he and Kurzweil and de Grey each mentioned to me that if all parties in the scientific world shared their insights, everyone in the field would benefit—and that included Calico.
Naturally, theories about how the company came to be and where it was headed abounded. Nir Barzilai, the director of the Institute for Aging Research at the Albert Einstein College of Medicine, and the scientist who was working to raise $50 million for an FDA trial using metformin, said he didn’t know what the company was doing, but whatever it was, it didn’t seem to be attacking the problem.
Another scientist who claimed to be familiar with Calico said the company began as a vanity project, “as self-serving as the Medici [family] building a Renaissance chapel in Italy, but with a little extra Silicon Valley narcissism thrown in.” And then just a few weeks after the New Yorker piece came out, the news and opinion website Vox published a piece entitled “Google Is Super Secretive About Its Anti-Aging Research. No One Knows Why.” Julia Belluz, the reporter, decided to poke around the Valley and get to the bottom of it. The piece ranged far and wide, from scientists who continually offered comments on how perplexed or frustrated they were, to theories that Levinson had learned to be secretive from none other than Steve Jobs himself. Remarks like these really chapped Levinson’s hide; nevertheless, he kept his tongue and never responded publicly.
There was one other theory about Levinson’s silence: Being a product of the highly competitive world of biotechnology, maybe he preferred to keep his mouth shut to maintain a competitive edge. There was something to that. But Levinson told me the main reason he was being so quiet was because he abhorred overpromising. Overpromise and all you do is create unfulfilled expectations. He hated that; it undermined the credibility of the whole enterprise. Science was hard and humbling, and it was pitiful how little we understood the human organism. So best to simply stand silently before the immensity of thing and gird your loins—because you were in for a battle, and handing out headlines was just a waste of valuable time.
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THIS APPROACH REVEALED some of the basic differences between Craig Venter and Art Levinson. Both believed deeply in the power of knowledge, but how they went about gathering knowledge and executing on it was another story. One was the tortoise, and the other the hare. Levinson was patient; Venter, aggressive and swift. Levinson valued focus and effectiveness. He tended to stand back, survey the landscape, search out chinks in the armor of whatever problem he was trying to solve, and then attack where he saw promise: Drill deep.
In Venter’s case, it was no accident that his big breakthrough for speeding up the sequencing of the human genome had been called “shotgunning.” Do the experiment! Onward! This did not mean that he was foolhardy, although he had been accused of that more than once in his life. He may have shot himself in the foot here and there, but nowadays he made a distinction between risky behavior and flat-out stupidity. Yes, a venture might look risky to those unwilling to try something new. But if you did your homework, weighed the risks against the rewards, there were reasons to take the plunge. In fact, in his mind the whole problem with the scientific community was that it was way too soft on risk. Risks made the world go round. Mistakes created knowledge! And that was why he planned to ensure that HLI fundamentally change the way medicine was practiced.
None of this made Levinson the total opposite of Venter, timid and risk-averse. Far from it. But he liked to chew on problems, and he liked the idea of spreading his bets with moves like the two-hemisphere approach. And he was still going after the Ultimate Problem: aging itself. Don’t just disrupt the old-fashioned practice of medicine; disrupt the killer at its root, period.
Luckily, Levinson had been handed the opportunity for a moonshot. Venter did not have that luxury. But did that really matter? What was the alternative? Stop doing the experiment? That wasn’t going to happen. No, Venter’s goal was to develop a new approach to medicine, one that got ahead of death and dying, rather than waiting until it was too late and already shoving you out the door.
24 | REVOLUTIONIZING MEDICINE
Even before the Human Genome Project marked its completion way back in 2000, Craig Venter used to carry a holographic information-bearing silicon chip around in his wallet—the kind that you sometimes saw on credit cards—with the photo of a regular-looking guy. This card, Venter would proudly tell people, contained every bit of the man’s genetic code. It could tell you that if he smoked, or that his chances of developing cancer before age 60 were almost 4 out of 10. It revealed whether he might have a genetic tendency toward some mental or emotional illnesses, and explained that he was among the
30 percent of the population that benefited from taking aspirin to fight heart disease (which was good news, because he was carrying the APOE gene—DNA that made him more likely to suffer from strokes and heart disease). Armed with this information, the man could decide what sort of diet might be best for him, explore the time of day he was most productive, maybe even improve his chances of finding a compatible mate.
Where did this font of biological data come from? How could anybody, even Craig Venter, have information like this in his back pocket in 1999? Well, he couldn’t. It was just a mock-up Venter used during lectures, a fake illustration. But back then, he assured people, once genomes were cheap enough to be sequenced, once all the nitty-gritty details of selfness were properly nailed down, the day would come when people would have that card in their hands and could take control of their lives—because the vast genomic database at their disposal would allow each and every person to know all there was to know about their medical future.
It took 15 years, but in October 2015, Venter finally envisioned a service at Human Longevity, Inc., that could begin to deliver the very insights that faux chip had only pretended to provide. At last, the technology was catching up with the concept. Venter even had a name for it. He called it the Health Nucleus. For an eye-watering $25,000, it guaranteed that whoever cared to come to HLI’s San Diego offices could be as biologically scrutinized as any human on the planet.
In the corporate world, companies often examined the health of potential CEOs or other corner-office executives. But Health Nucleus made those checkups look like the diagnostic equivalent of a grade school nurse asking little boys to turn their heads and cough. Several of the tests were so advanced that under FDA rules, HLI had to characterize the service as part of a study. This essentially made the patient a complicit lab rat in a large experiment designed to accumulate the highest quality genotypic and phenotypic information HLI could gather, while generating some income along the way. Whoever signed on to Health Nucleus would not only have their genomes inspected, but also their bodies, brains, gaits, and bone density—even their metabolites and microbiomes—all the better to delay the inevitable date of their particular demise.
