Can Human Mortality Really Be Hacked?
Backed by the digital fortunes of Silicon Valley, biotech companies are brazenly setting out to “cure” aging
It’s just after 10:30 a.m. on a pleasant weekday morning at SENS, a biotech lab in Mountain View, California. I’ve come to speak to its chief science officer, Aubrey de Grey. I find him sitting in his office, cracking open a bottle of Stone pale ale. “Would you like one?” he offers hospitably. De Grey drinks three or four pints of ale a day, and swears it hasn’t kept him from maintaining the same vigor he felt as a teenager in London.
Now the 54-year-old’s long hair, tied back in a ponytail, is turning gray, a change that would be unremarkable if he weren’t one of the world’s most outspoken proponents of the idea that aging can be completely eradicated. De Grey first gained notoriety in 1999 for his book The Mitochondrial Free Radical Theory of Aging, in which he argued that immortality was theoretically possible. Since then, he’s been promoting his ideas from prominent platforms—the BBC, the pages of Wired, the TED stage. He delivers his message in seemingly unbroken paragraphs, stroking his dark brown wizard’s beard, which reaches below his navel. Unlike most scientists, he isn’t shy about making bold speculations. He believes, for example, that the first person who will live to be 1,000 years old has most likely already been born.
In 2009, de Grey founded the nonprofit SENS, the world’s first organization dedicated to “curing” human aging, not just age-related diseases. The organization, which conducts its own research and funds studies by other scientists, occupies an unassuming space in a small industrial park. Its walls are affixed with large, colorful posters illustrating human anatomy and the inner workings of cells.
The basic vision behind SENS is that aging isn’t an inevitable process by which your body just happens to wear out over time. Rather, it’s the result of specific biological mechanisms that damage molecules or cells. Some elements of this idea date back to 1972, when the biogerontologist Denham Harman noted that free radicals (atoms or molecules with a single unpaired electron) cause chemical reactions, and that these reactions can damage the mitochondria, the powerhouses within cells. Since then, studies have linked free radicals to all sorts of age-related ailments, from heart disease to Alzheimer’s.
De Grey takes this concept further than most scientists are willing to go. His 1999 book argued that there could be a way to obviate mitochondrial damage, slowing the process of aging itself. Now SENS is working to prove this. Its scientists are also studying other potential aging culprits, such as the cross-links that form between proteins and cause problems like arteriosclerosis. They’re looking at damage to chromosomal DNA, and at “junk” materials that accumulate inside and outside cells (such as the plaques found in the brains of Alzheimer’s patients).
The area of research that gives the organization its name has to do with senescent cells. (SENS stands for Strategies for Engineered Negligible Senescence.) These are cells that stop dividing but accumulate inside us, secreting proteins that contribute to inflammation. It’s widely accepted that inflammation is involved in arthritis, heart disease, cancer, dementia and any number of other conditions that define old age. As de Grey’s thinking goes, if we could figure out how to remove senescent cells using approaches like drugs or gene therapy, along with other types of repair, we could potentially keep our bodies vital forever.
This desire to eradicate aging has, in the last decade, inspired a mini-boom of private investment in Silicon Valley, where a handful of labs have sprung up in SENS’ shadow, funded most notably by tech magnates. The secretive Calico was established by Google, in collaboration with Apple chairman Arthur Levinson, to tackle the problem of aging. Facebook’s Mark Zuckerberg and his wife, Priscilla Chan, have invested $3 billion in the attempt to “cure all disease.” Amazon’s Jeff Bezos invested some of his fortune in South San Francisco–based Unity Biotechnology, which has been targeting cell senescence in animal trials and hopes to begin human drug trials next year.
It’s this influx of wealth that has brought novel anti-aging theories out of the scientific fringes and into gleaming Silicon Valley labs. De Grey notes that developing the means to make everyone live forever is not cheap. “This foundation has a budget of somewhere around $4 million a year, not $4 billion, which is what it should be,” de Grey says. He invested $13 million of his own money in SENS, the lion’s share of the $16.5 million he inherited when his mother died. (He says she earned her wealth through property investments.) SENS has also been the beneficiary of PayPal co-founder Peter Thiel, perhaps Silicon Valley’s best-known advocate for curing death. As Thiel told the Washington Post in 2015, “I’ve always had this really strong sense that death was a terrible, terrible thing....I prefer to fight it.”
Immortality, it turns out, is not such an easy sell: Most people don’t like the idea of living forever. In legends of old as well as in recent popular culture, eluding death typically comes at a terrible cost; like zombies or vampires, immortal beings must feast on the living. Besides, a large percentage of today’s population also subscribes to religious beliefs in which the afterlife is something to be welcomed. When the Pew Research Center asked Americans in 2013 whether they would use technologies that allowed them to live to 120 or beyond, 56 percent said no. Two-thirds of respondents believed that radically longer life spans would strain natural resources, and that these treatments would only ever be available to the wealthy.
I ask de Grey about how the world would change—socioeconomically especially—if no one ever died. Would people still have children? If they did, how long would the planet be able to sustain billions of immortals? Wouldn’t every norm predicated on our inevitable deaths break down, including all the world’s religions? What would replace them? At what point might you decide that, actually, this is enough life? After decades? Centuries? And once you made that decision, how would you make your exit?
“I find it frustrating that people are so fixated on the longevity side effects,” de Grey says, clearly irritated. “And they’re constantly thinking about how society would change in the context of everyone being 1,000 years old or whatever. The single thing that makes people’s lives most miserable is chronic disease, staying sick and being sick. And I’m about alleviating suffering.”
To explain his vision, de Grey uses the analogy of a car that has its parts continually repaired. People receiving cell regeneration therapies would be able to constantly add more time to their lives whenever their bodies began to break down. “We have a warranty period, it’s true,” he allows. “But cars also have warranty periods, and yet we still have vintage cars—because we know how to do comprehensive, regular, preventative maintenance.”
De Grey spent several years after college working as a computer scientist in the field of artificial intelligence, which might explain why he likes to compare human bodies to machines. He has a PhD in biology from Cambridge, but he received it for theoretical work rather than lab-based research. He often refers to himself as an engineer or a “technologically focused biologist.”
I ask de Grey how a planet full of immortals would support itself. Would people want to work for eternity? He answers that automation will take over most jobs. “We will be able to spend our lives doing things that we find fulfilling and we won’t have to worry about remuneration,” he says. De Grey has been closely associated with transhumanism, a movement that believes technology will help the human race evolve far beyond its current limitations, but he dislikes the term, noting that it “just scares people.”
De Grey has robust faith that humans will come up with “some new way to distribute wealth that doesn’t depend on being paid to do things we wouldn’t otherwise do.” The first step, he believes, is issuing a universal basic income. It’s an idea that’s shared by other Bay Area entrepreneurs, many of whom are in the business of developing automation technologies. Last year, Y Combinator, a highly successful start-up incubator, gave 100 Oakland families between $1,000 and $2,000 a month in unconditional free income to find out how they’d spend it. The city of San Francisco recently announced plans to launch a similar pilot program. But these are small-scale experiments, and if robots do take over more jobs, it isn’t clear whether our economic and political systems would reconfigure to support all unemployed people in time, least of all forever.
And that 1,000-year-old person: He or she has already been born?
“Oh absolutely, yeah,” de Grey assures me. “It’s highly likely.”
In fact, the human body is not at all like a car, in the same way that the human brain is not like a computer. Such comparisons oversimplify the staggeringly complicated organic systems that researchers are only beginning to glimpse. The chaotic interactions between our trillions of cells and their enzymes are still poorly understood. We know almost nothing about why some people hit the genetic jackpot and live much longer and with much more vigor than others who have similar life circumstances. The question is all the more vexing because elderly humans are themselves an extremely recent phenomenon.
Judy Campisi is saying all this to me over coffee near her home in Berkeley. She works 45 minutes north in Novato at the Buck Institute for Research on Aging, a gleaming non-profit research institution. “For 99.9 percent of our human history as a species, there was no aging,” she says. Humans were very likely to die by our 30s from predation, starvation, disease, childbirth or any number of violent events.
Life spans in the developed world have more than doubled over the past century or so, but this hasn’t happened through any interventions against aging itself. Rather, it’s a byproduct of innovations such as clean water, medication, vaccinations, surgery, dentistry, sanitation, shelter, a regular food supply and methods of defending against predators.
A biochemist and professor of biogerontology, Campisi has spent her career studying aging and cancer, and the role senescent cells play in both. She has researched these cells in her lab and published widely on the possible evolutionary reasons they remain in our bodies. She posits that for most of human history, natural selection didn’t favor living to old age. Evolution protected younger people so they could pass along their genes, and senescent cells play a very important role.
“One thing evolution had to select for was protection from cancer,” she says. “Because we are complex organisms, we have lots of cells in our body that divide, and cell division is a very risky time for a cell because it’s easy to pick up a mutation when you are replicating three billion base pairs of DNA.” If a cell doesn’t divide, there are fewer chances for such a mutation to creep in. “So evolution put into place these very powerful tumor suppressant mechanisms—senescent cells—but they only had to last for 40 years at the most.”
What serves as a preventive mechanism in early life later can become a cancer-causing agent of its own, Campisi says. Senescent cells contribute to inflammation, and “inflammation is the number one risk factor for all diseases of aging, including cancer.” Eliminating these cells might cut down on various ailments, but no one is yet sure what the side effects would be.
The idea that senescent cells contribute to aging was first postulated in the 1960s. Yet 50 years later, scientists still don’t entirely understand the role they play. All Campisi can say definitively is that, for most of human history, there was “no evolutionary pressure to make that system better because everybody died young.”
When I ask Campisi why some scientists talk about “curing” aging, she says it comes down to getting interventions approved. “There are people who want to consider aging a disease for the purposes of going to regulatory agencies and having a specific drug able to treat a specific symptom, which you can only do if it’s recognized as a disease.” But Campisi stresses that living forever is not the goal of most research on aging. Instead, she says it’s primarily aimed not at life span but “health span”—increasing the number of years that people can remain physically and mentally agile.
Campisi has known de Grey for years, collaborates with SENS and even serves on the organization’s advisory board. I ask what she makes of his assertion that someone alive today will reach the age of 1,000.
“I have to tell you Aubrey has two hats,” she says, smiling. “One he wears for the public when he’s raising funds. The other hat is when he talks to a scientist like me, where he doesn’t really believe that anyone will live to 1,000 years old. No.”
One thing we do know is that there are more elderly people alive now than there have ever been in the history of the planet. Even if today’s life-extension researchers made meaningful breakthroughs, the therapies wouldn’t be available for many years to come. That means we’re about to face a lot of death, says Rachel Maguire, a research director focusing on health care at the Institute for the Future, in Palo Alto. “By 2025 or 2030, there will be more of a culture of dying and lots of different ways of experiencing it. There are early signs of new types of funerals and spiritual formations around this.” Maguire foresees new end-of-life plans, including assisted dying. When it comes to aging, she points out that biological research is only one piece of a puzzle that must also include economics, politics and cultural change. “I don’t think we have answers yet for how we’d do the other pieces. And the financial piece alone is huge.”
There’s already a huge disparity between the life spans of rich and poor Americans, and critics of the new longevity research worry the gap may only grow wider. A 2016 report from the Brookings Institution found that, for men born in 1920, there was a six-year difference in life expectancy between men at the top 10 percent and bottom 10 percent of the earnings ladder. For men born in 1950, the difference was 14 years. For women, the gap grew from 4.7 to 13 years. In other words, advances in medicine haven’t helped low-income Americans nearly as much as their wealthier counterparts.
I had a glimpse of that discrepancy as I used ride-hail apps to get around the Bay Area. On my way to Mountain View, where the median household income is $103,488, my driver, a woman in her 50s, told me she had trouble paying for gas and was sleeping in the car between nights on relatives’ couches. Sometimes, she said, she was stricken by bouts of rheumatoid arthritis. If her joints seized up while she was driving, she had to pull over and wait until the episode passed, usually not working anymore that day. I did not want to ask how she would feel if she ended up living so long that her future included another two decades of driving.
Jake Dunagan, the director of design futures at the consulting firm Very Nice, studies the cognitive biases that make it difficult for people to plan ahead. “That’s one of the conundrums of futurist work: The future doesn’t exist,” Dunagan tells me. “It’s always a projection.” Our minds, he says, have not evolved to be very good at seeing our future as connected to our present, as we spent so much of our early existence concerned with outwitting immediate threats.
Dunagan has little patience for Silicon Valley’s longevity research; he says proponents are not sufficiently interested in the details. “The rich people are defining the terms of the longevity conversation and have enhanced access to these technologies,” he says. “Everyone wants to live longer, to some degree, but it’s also the sense of privilege, of selfishness to it that’s ‘I want mine. I always want mine.’ Well, what if everyone had this? What would be the long-term implications of that?”
In 2006, the magazine MIT Technology Review published a paper called “Life Extension Pseudoscience and the SENS Plan.” The nine co-authors, all senior gerontologists, took stern issue with de Grey’s position. “He’s brilliant, but he had no experience in aging research,” says Heidi Tissenbaum, one of the paper’s signatories and a professor of molecular, cell and cancer biology at the University of Massachusetts Medical School. “We were alarmed, since he claimed to know how to prevent aging based on ideas, not on rigorous scientific experimental results.”
More than a decade later, Tissenbaum now sees SENS in a more positive light. “Kudos to Aubrey,” she says diplomatically. “The more people talking about aging research, the better. I give him a lot of credit for bringing attention and money to the field. When we wrote that paper, it was just him and his ideas, no research, nothing. But now they are doing a lot of basic, fundamental research, like any other lab.”
In marked contrast with de Grey, however, Tissenbaum doesn’t see aging itself as the problem. “I don’t think it’s a disease,” she says. “I think it’s a natural process. Life and death are a part of the same coin.”
Instead of seeking out a universal cure for aging, Tissenbaum finds it more useful to look at the genes involved in specific factors, such as good metabolic function and resistance to stress. For her own research, she has artificially extended the lives of C. elegans roundworms and mice, but she’s found that the creatures are sluggish and frail during that extra period of life. In other words, extending life through lab-based means doesn’t necessarily lead to good health. “If applied to humans, this would likely lead to unsustainable healthcare costs,” she and her co-authors concluded in a 2015 study published in the Proceedings of the National Academy of Sciences.
There are all kinds of theories about how to close the gap between life span and health span, and not all of them focus on senescent cells. Some scientists think taking aspirin and vitamin D could reduce inflammation throughout the body and lower the incidences of all kinds of diseases. Others believe the key is to repair telomeres, the sequences at the ends of each chromosome that unravel with stress and age. Research is still very much in progress on all of these ideas.
Meanwhile, scientists are trying to understand why the brain deteriorates over time, losing mass and neural circuitry. Tissenbaum and others are trying to understand these mechanisms, hoping to find new treatments for neurodegenerative diseases. But she doesn’t expect any intervention to keep humans healthy forever. “It may be that the brain has a finite life span,” she says.
For now, Tissenbaum recommends the usual methods of fending off frailty. Studies have shown that regular physical exercise can stimulate neural networks and keep connections alive. So can challenging mental activities. “If you always do crossword puzzles, try Sudoku,” she says. “Where we have really progressed is in our understanding of how keeping your mind and body active is fundamental to healthy aging.”
Many of the world’s oldest stories are quests for eternal life, from Herodotus’ fountain of youth to the medieval Holy Grail. There’s a great deal of money and brainpower invested in the hope that science will finally deliver on this promise. The research in these labs might yield more incremental breakthroughs, revealing the mechanisms behind Alzheimer’s or certain types of cancer. But for some true believers, that won’t be enough. De Grey, for one, dislikes the idea of seeking cures for individual age-related diseases. “I believe that the term ‘disease’ has become one that does far more harm than good, as has ‘cure,’” he says, “such that some aspects of aging are inappropriately described as curable diseases and others as ‘aging itself.’”
I asked Judy Campisi if she thought there was an upper limit to the human life span. “I suspect there is,” she said. “Like you’d say there’s a limit to running a marathon. You aren’t going to ever run one in 30 seconds.” When it comes to extending life, she says, “we think the upper limit we could get to is around 115 to 120 years old—if we don’t blow ourselves up before then, or the planet doesn’t melt down.”
If Campisi and others are right, we may come to accept that we’re profoundly mortal creatures after all. Still, we seem to be driven, as a species, to overcome every adversity we encounter. We may not live forever, or even to 1,000, but a more vibrant old age could yet be on the horizon for all of us.
Editor’s Note, May 25, 2017: An earlier version of this article erroneously called the Buck Institute a “gleaming profit institution”, as opposed to a non-profit, and described its distance from Berkeley as two hours instead of 45 minutes.