On this glorious spring day in Cambridge, England, the heraldic flags are flying from the stone towers, and I feel like I could be in the 17th century–or, as I pop into the Eagle Pub to meet University of Cambridge longevity theorist Aubrey de Grey, the 1950s. It was in this pub, after all, that James Watson and Francis Crick met regularly for lunch while they were divining the structure of DNA and where, in February 1953, Crick made his breathless announcement that they had succeeded.
Aubrey de Grey has no victory pronouncements to make as of yet, but he is vigorously pursuing an even more challenging project. Using the legacy that Watson and Crick bequeathed us, he proposes to tinker with the essential biochemical pathways that drive the aging process. De Grey contends that we know enough to intelligently map out a program of anti-aging intervention research such that sometime in the next 100 years, and quite possibly much sooner, the average human life span may be 5,000 years, a figure brought short of outright immortality by the small number of people who will die from non-age-related diseases and everybody else who, given the boggling amount of time available to them on the planet, will eventually do something unlucky or stupid like walk in front of a moving rocket car. In de Grey time, the 400-year span between Shakespeare’s England and today would be but the blink of an eye.
I slide in behind a venerable wooden table at the Eagle and take my first measure of the man. De Grey, 41, is lanky
and favors the classic combination of T-shirt, old jeans and sneakers. He has a Rasputin-length beard that he strokes incessantly. He’s a confirmed drinker of fine English ales, and when he makes a strong point, which is often, he raps his pint glass on the table like a judge bringing his court to order. The pronouncements are delivered in a moderately posh English drawl, with a touch of a lisp. “Cambridge is so full of eccentrics,” he says, “nothing surprises anybody over here. And there are plenty of people with beards my size. But some in the university do find it hard to get used to the idea that someone would actually be doing seriously significant academic work in his spare time.” De Grey, you see, is not, as he is sometimes mistaken to be, a professor of genetics at Cambridge but a half-time research associate with a day job managing a genetics database.
The history of radical solutions to the problem of human aging is colorful yet rather lacking in distinction. Until the dawn of modern medicine, the standard prescription was that old men should inhale the sweet breath of virgin girls to restore “innate moisture.” At the end of the 19th century, the physician Charles E. Brown-Squard recommended an injection of the macerated sex glands of monkeys or dogs to keep the sands of time at bay. In the go-go 1990s, a Virginia medical school professor, William Regelson, sold a ton of books touting the “melatonin miracle” as an aging cure-all and hormonal good-for-what-ails-you.
To distinguish themselves from the charlatans and hype purveyors, mainstream academics tend to be circumspect about the work they do in the biology of aging. But in the past 15 years, the field has been revved by startling breakthroughs. The human genome, our entire complement of DNA, has been decoded, opening the possibility of tinkering with our genetic makeup. And scientists are learning to manipulate embryonic stem cells to make them grow into any kind of tissue. The long-term implications of these discoveries have barely been teased out by biologists, who tend to be cautious by nature and training. So the speculative arena has been left largely to a theoretician, de Grey, who wouldn’t know a DNA analyzer from a protein sequencer but who is promoting the unthinkable: that the human race is on the verge of figuring out how to live darn near forever.
The key to this rosy scenario is a sort of biological Ponzi scheme that de Grey has dubbed “escape velocity.” The idea is simple. If scientists can find ways to intervene in the cellular processes that cause our bodies to age–managing to keep middle-aged people alive an additional 40 years, say–that extra 40 years will buy enough time for biogerontological engineers to solve other damage problems before they emerge. Think of the body as a leaky boat. You don’t have to keep it bone-dry to stay afloat; you just have to bail out the water at the same rate it’s coming in. Or, as de Grey says, “You don’t have to fix everything you’re ever going to get. You only have to fix things in time.”
De Grey’s scientific career, like everything else about him, smacks of oddness and self-invention. A Cambridge-educated computer scientist, he hasn’t taken a biology class since he was a 15-year-old schoolboy at Harrow. He is essentially self-taught, originally tutored by his wife, a former biology professor. He acquired his doctorate in biology by way of a hoary, little-used Cambridge shortcut: Without ever registering for graduate study, he submitted to the university a book he’d written on the mitochondria, the power plants of cells. His paying work involves managing a database on fruit flies, that staple of genetics research. But in recent years he has progressed from fruit flies to gadfly, becoming a jet-setting provocateur at a seemingly nonstop parade of gerontology conferences, as well as editing a somewhat fringy quarterly journal, Rejuvenation Research. Everything but the editing gig he does on his own time, pro bono, subsidized by expenses-paid invitations and a few patrons and true believers. Whatever else you can say about de Grey, he gives a good PowerPoint presentation. My favorite image from his bag of lectures is a chart that compares aging with fox hunting. Both are traditional, both are effective ways to keep a population down, and both are “fundamentally barbaric.”
De Grey’s delight in his own powers of persuasion is so guileless, it’s barely off-putting. “At one workshop/conference I organized last year,” he recalls, “I got an interminable standing ovation at the end.” But even if no one thinks as highly of de Grey as de Grey himself, it would be a mistake to write him off as just another charismatic kook. Two years ago, he helped create the Methuselah Foundation, which is now privately funded to the tune of half a million dollars. The foundation will award a succession of prizes to scientists as their lab mice break either of two records: for overall longevity, or for longevity after interventions beginning at middle age–lab-manipulated rodents being the essential stepping-stone to human life extension. One of the advisers to the Methuselah Foundation is no less a scientific entrepreneur than Peter Diamandis, whose X Prize helped wrap people’s minds around another initially implausible idea, commercial spaceflight. And sitting opposite de Grey and me at the Eagle is John Archer, a bona fide Cambridge professor and a leading authority on bioremediation, the use of microbes to clean up toxins in the environment. De Grey has sold Archer on the feasibility of identifying tenacious strains of bacteria in soil (“You can find bacteria that digest rubber,” de Grey says), genetically modifying them for compatibility with humans, then delivering the bacterial genes to human cells to aid with the never-ending job of breaking down the metabolic waste that leads to macular degeneration (the leading cause of blindness in the elderly), heart disease and Alzheimer’s. “It’s sort of human engineering,” Archer says. “It crosses boundaries, and that’s exciting.”
But funding experimental science that treads too far off the beaten path is, Archer says, “bloody hard.” And so de Grey’s bacterial project is moving along at a deliberate pace, not helped by Archer’s inability to find enough time away from the responsibilities of his primary, funded research and his young family to do the preliminary work necessary to jump-start a proper grant application. De Grey, who has no children and a monomaniacal amount of energy to pour into his projects, is not entirely sympathetic. “My emphasis is to get more people like John involved, preferably ones who aren’t so lazy,” he says, indifferent to the fact that Archer is sitting across from him, hearing every word. “It bounces off me,” the very British Archer tells me later. “Aubrey is a cross between Svengali and a Methodist firebrand preacher, and yes, he can drive you up the wall. But in science, people like him are far too rare.”
The minence grise of U.S. aging research, Leonard Hayflick of the University of California at San Francisco, says people are like cars, which reliably age “even though there’s nothing in the blueprints that shows a process for doing it.” In other words, there is no “death gene,” no mechanism that offs us after a certain time limit; aging is just a by-product of evolutionary neglect. Humans are mortal delivery systems for immortal genes. After we’ve made the delivery of those precious genes to the next generation through reproduction, evolution doesn’t care if we drive off a cliff. Which we all do, at various rates of speed. The mechanism here is natural selection. Because people who live a long time don’t generally have more progeny than people who have a middling life span, those long-lived genes don’t get selected for. Consequently, we have little protection against the bad things that happen to us later in life–the accumulation of metabolic waste products in our cells and harmful mutations in our genes that over time overwhelm the repair systems that, in most of us, work so splendidly when we are young.
The difference between a 20-year-old and a fit 30-year-old may seem relatively minor, de Grey points out, but something is going on in the cells of the latter, some ineluctable early-stage rot that explains why, statistically speaking, that 30-year-old is 10 years closer to his or her eventual demise. As gerontologists are fond of pointing out, you could solve all the major age-related diseases, and you’d still add only about 15 or 20 years to our current average life span of nearly 80. Even if we cured cancer and heart disease, we’d wind up dying of pneumonia or passing away in our sleep as frail geezers in our 90s. The problem with our bodies is that, absent a radical intervention of the sort that de Grey proposes, we simply wear out over time.
As de Grey explains, there are currently two ways of dealing with aging. The first, geriatric medicine, is a finger-in-the-dike approach that buys older people more time by battling, often at the symptomatic level, the diseases that typically characterize the last chapter of our lives: coronary-bypass surgery to improve circulation, pharmaceuticals to combat osteoporosis, radiation and chemo to blast away malignant tumors, and so on. This is a losing battle–yet from a certain point of view, so is life. Inarguably, there has been an enormous rise in the average American life span over the past century, thanks to vaccines, antibiotics, improved diet and a host of new treatments and surgeries, but we seem to have reached a point of diminishing returns, where further improvements are likely to bring only marginal life-span gains.
The second standard approach is the gerontologist’s, which consists of investigating the mechanisms of aging itself. Compared with the billions spent on disease research, this is penny-ante stuff. Still, in the past decade or so, a handful of prominent scientists–Cynthia Kenyon of the University of California at San Francisco, Leonard Guarente of the Massachusetts Institute of Technology, George Roth of the National Institute on Aging–have whetted the media’s and the public’s appetite for a genetic fountain of youth. Some researchers have put their lab animals on severe diets, a method known as caloric restriction, which results in longevity gains of about 30 percent. Others are closing in on genes that may be responsible for long-livedness in yeast, worms and rodents.
De Grey has carved a middle way between geriatric medicine and gerontology; he aims to reach what he calls “engineered negligible senescence.” His is a pragmatic approach, he tells me emphatically over another pint, because by the time the gerontologists have cracked the mysteries of cellular metabolism, we’ll all be worm’s food. We’re at an unprecedented time in the history of science, he says, having learned enough about the genetic and biochemical processes that lead to metabolic damage that we can begin to sketch out a plan to repair it. After all, it’s easier to play engineer and fix a problem than to play God and truly understand it. Unlike those researchers who theorize about some prime mover in the aging process–the usual suspect these days being “free radicals,” the unstable and thus troublemaking molecular by-products of metabolism–de Grey looks at aging as a group of interdependent processes that resist tidy prioritization. “We shouldn’t spend a lot of time navel-gazing, trying to figure out which things are more important than others,” he asserts. “We should just fix them all. And if we fix a couple things we didn’t need to, then no harm done, is what I say.”
Which brings us to de Grey’s Seven Deadly Sins of Aging, his formulation of the cellular and molecular culprits that he believes account for human decline. They are: the atrophying of tissues as a result of cell loss; the havoc caused by old cells that linger rather than self-destruct; waste buildup inside lysosomes, the garbage compactors of our cells; the waste products that build up between cells; the improper bonding of sugar and protein molecules that reduces the elasticity of our tissues; genetic mutations in the mitochondria; and genetic mutations in the cell nucleus that lead to cancer. Biologists are not convinced that these processes all contribute to aging, but de Grey is, and he has proposed solutions to each [see “Seven Deadly Sins,” below]. How practical or realistic those solutions are is another matter. “Aubrey will say something that’s the biological equivalent of ‘Let’s build a 1,000-story building on the head of a pin, and then we can–,’ and I’m like, ‘Wait, wait, let’s go back to that first part again,'” says Judith Campisi, a top cell biologist at Lawrence Berkeley National Laboratory. (On the other hand, though Campisi has yet to feel compelled to do an experiment because of a conversation with de Grey, she
doesn’t rule it out. “I wouldn’t waste my time talking to him if I thought it would never happen,” she says.)
If de Grey has an idol, it’s the biologist Mike West, founder of Advanced Cell Technology, who for the past decade has led the anti-aging phalanx of the biotech revolution by pursuing, among other avenues, the promise of embryonic stem cells. These, the first cells that result after an egg starts to divide, ultimately give rise to the many varieties of specialized cells in the body. “I do see myself as following in Mike’s footsteps,” de Grey says, hitting an unusually humble-sounding note. Never mind that comparing himself to an experimentalist like West is a bit of a stretch, de Grey being in the enviable position of never needing to make anything work in the lab or to answer to academic supervisors or stockholders. “All I have to do is make a cogent case, and people say, â€That would be a cool experiment,'” he says. “And I don’t have to worry about offending someone who is going to be reviewing my next grant proposal, because I don’t write grant proposals. So I piss people off whenever
I like, and there is, more or less, no reason why I shouldn’t.”
De Grey dreamed up the Methuselah Mouse prizes to light a fire under the skeptics. A decade or two from now, he says, we will be able to take a middle-aged mouse, one that’s two years old, and by tinkering with its damage-control systems, triple its remaining life span, enabling it to live for five years instead of three. (One lab mouse, 11C of Southern Illinois University, was nearly five when it died in 2003; it is the yardstick for de Grey’s overall-longevity prize. But 11C came from a genetically modified strain of mice; when you tinker with a normal mouse starting at middle age, each extra day is harder won.) Perhaps another decade or so after this mouse-rejuvenation goal is met–though de Grey acknowledges that this next step could take as long as 100 years–we will be able to do the same for humans: to wit, engineer a 60-year-old to live to be 120 instead of the usual 80, every person a Jeanne-Louise Calment, the most reliably documented world’s oldest human, who died in France in 1997 at the age of 122. At that point, de Grey declares, “we’re done,” because from there, incremental gains in biological life extension should arrive quickly enough to stave off death indefinitely. A key tool in this endeavor will be huge research farms of apes, which, since they age at roughly twice the rate of humans, will serve as primate “canaries in the coal mine,” hitting super-old age and its attendant problems increasingly far ahead of humans, giving us time, de Grey argues, to defuse the toughest problems before they hit us.
It’s a big job, but we’ve got to start somewhere. What de Grey is pushing Archer and others to pursue is an anti-aging solution he’s dubbed “lysosomal enhancement” [see graphic, opposite page]. Lysosomes, the garbage compactors in cells, fail over time, allowing potentially dangerous waste to accumulate. De Grey wants to lend them a hand by identifying waste-chewing enzymes in soil bacteria, isolating the bacterial genes responsible for producing those enzymes, and then tinkering with those genes so that they’ll perform a similarly hygienic function inside the human lysosome. Delivery of the new genes into our bodies might be accomplished by piggybacking them onto viruses, a technique known as gene therapy that scientists have been trying to make work for more than a decade.
Long shot though it may be, the lysosome helper is, de Grey says, “the crazy idea that I’ve had the least difficulty in persuading people might actually work.” Last summer, the National Institute on Aging subsidized a de Greyâ€organized workshop in Bethesda, Maryland, to brainstorm the approach. “Aubrey is not an alien to us,” says David Finkelstein, administrator of the NIA’s Biology of Aging program. “With his ideas, there are an awful lot of what-ifs, but that’s what science is about.”
For de Grey’s overall plan to succeed, however, all his projected fixes would have to work; woe be to us if he has overlooked some essential aging process and there are eight deadly sins, not seven. He allows that this is a possibility, but he considers the fact that scientists haven’t discovered any relevant biochemical processes in the past 20 years excellent circumstantial evidence that his list is complete. As for his attempt to extrapolate accurate life-extension timescales from the current state of lab research, well, that’s another matter. “It’s like asking me what the stock market will look like in 25 years,” Campisi says. “Who knows?” One recalls highly rational predictions that failed to anticipate the underlying variables changing–for instance, the prediction made in the 1890s that within half a century the streets of London would be buried under nine feet of horse manure owing to the steady rise in horse-carriage traffic.
Not long after my visit with de Grey, I attend a conference at the New York Academy of Sciences in Manhattan, where a handful of the nation’s most eminent gerontologists had been corralled by the American Federation for Aging Research to make pretty before the media. After the presentation, I conduct my own symposium-within-a-symposium in the Upper East Side courtyard of the NYAS on the always loaded subject of Aubrey de Grey. I show the list of Seven Deadly Sins to Len Hayflick, who throws up his hands at what he regards as de Grey’s faux precision. “I’ve seen lists like these going back for decades,” he says. “It’s just unrealistic.” I compare projected-life-span figures with Jay Olshansky, a demographer and aging expert at the University of Illinois. “To get that figure of 5,000 years,” he says, “you would have to have some people living to 10,000 to 15,000 years to make up for anyone dying in the first few years of life.” Aubrey accepts that in his work, I say. “And that’s the only place it’s going to happen: in Aubrey’s work” is the quick rejoinder. Mind you, these people like de Grey. “He’s a super guy,” Hayflick says. “We get along famously,” echoes Olshansky.
Back in Cambridge, within the cozy confines of
de Grey’s circle, not even friendly skepticism emerges to mar the mood. My second day in town, again at the Eagle, I meet Adelaide Carpenter, de Grey’s wife of 13 years, who is 19 years his senior. She is a friendly Yank, of all things, her pleasant features somewhat roughened by a lifetime of chain-smoking unfiltered cigarettes and a paucity of teeth, a cosmetic defect that seems not to trouble her or de Grey in the least. They are devoted to each other. The union goes back to her days as a tenured fruit-fly geneticist on sabbatical from the University of California at San Diego, looking for midcareer rejuvenation at Cambridge. She didn’t find that, but, arriving at a party thrown by a grad student, she did find de Grey. “I was immediately accosted by this handsome young gentleman who demanded that I â€justify my existence,'” she recalls. (“I was even more of an arrogant bastard back then,” de Grey chimes in.) A few pints later that evening, they danced, retired to a bedroom, and have been inseparable ever since.
De Grey became the most passionately sponge-like student any biology professor is likely to have. Adelaide stayed on at Cambridge, contentedly working below her rsum, currently as a postdoc in the genetics department. Over the course of the next two years, de Grey would hit his own career wall in computer science, failing to bring to fruition an entrepreneurial software venture. So he was more than available in 1992 when Adelaide’s boss at the time needed someone versed in computers and biology to take over the running of a large database on fruit flies. That, as it turned out, was all the institutional purchase de Grey needed to launch his career as longevity theorist without (conventional) portfolio.
Here at the Eagle, de Grey is consuming another liquid lunch. He says his more typical afternoon repast consists of “a couple Mars bars, crisps and sandwiches” (though one anagram of his name, he notes, is “Ready Beer Guy”). The de Grey diet does not seem ideal for a man who’s planning on inhabiting his corporeal being for several millennia. But that’s the beauty, I guess, of the bioengineering approach–no need for undue discipline or willpower to keep our bodies healthy, when the right cellular interventions can repair any insult.
The meal over, our band of four strikes out on a walking tour of the Cambridge campus: de Grey, Adelaide, myself, and Ben Zealley, a 19-year-old first-year biology student and de Grey protg who, with characteristic earnestness, is attempting to launch an undergraduate longevity society. We enter the courtyard of Trinity Hall, de Grey’s alma mater, where an ancient guard inquires whether we have the proper ID. “Aubrey, he’s asking you to justify your existence,” Adelaide says. Our next stop, the Great Court of Trinity College, is even grander; it’s where, in 1927, future Olympic hero David George Burghley made university history (and provided grist for the movie Chariots of Fire) by sprinting 400 yards around the cobblestoned rectangle before the last of the 24 chimes of the Trinity clock had sounded. By the time de Grey was a Cambridge undergrad in the early 1980s, standards had slackened a bit. “I was once induced to do the Great Court run at midnight, after a party, with no clothes on,” he recalls. “I got more than two thirds of the way around, which wasn’t too bad a showing. However, I did slip on some fairly nasty cobbles, and I got these massive black eyes, so for a while I was known as Aubrey Aubergine.”
Adelaide wanders off to her lab, and de Grey, Ben and I settle down among the buttercups on a cow-munched field beyond the university, whose flag-festooned battlements in the distance look like a Hollywood treatment of Camelot. We’re playing Othello, a Go-like board game–or rather, I am watching as de Grey makes mincemeat of his young acolyte. Ben, who is given to pronouncements like “I plan to be either the last generation to die or the first not to die,” takes it well. He and de Grey met through the Internet, both being devotees of the “transhumanist” Web sites and blogs that have recently flourished, especially in the U.K., sites with names such as Betterhumans and The Immortality Institute. Transhumanists are science (and science-fiction) enthusiasts entranced by the prospect that futuristic technology will allow us to modify our bodies–wings, anyone? infrared vision?–and also to live a really, really long time (if not in our own bodies, then in robotic ones governed by our own downloaded brains). Most any gerontologist of repute would dive under the desk if a transhumanist came calling, but de Grey enjoys passing between the worlds of the professional scientist and the amateur crank.
In due course, de Grey takes over the crucial corner positions on the Othello board (“I’m doing something really evil,” he chortles). In the meantime he tells us of his plan to combat cancer, perhaps the most pernicious of the Seven Deadly Sins. The chink in cancer’s armor, de Grey believes, is the telomeres, strands of DNA at the ends of our chromosomes that must be maintained in order for a cell to continue to divide. When scientists started intensively investigating telomeres in the 1990s, the buzz went as follows: If we could turn on the enzyme telomerase, which maintains the telomeres, thereby keeping them, and cell division, going indefinitely, was this not the molecular fountain of youth? It was not. Researchers have since concluded that short, unrepaired telomeres don’t impose an absolute limit on human life. Our bodies have considerable cell reserves, and some of the most crucial types of cells, in the brain
and heart, divide rarely or not at all. Cancer cells, however, do require well-
maintained telomeres if they are to keep lethally multiplying, which is why cancer is most commonly found in the oft-dividing cells of the gut, the reproductive system, the skin and the blood, cells that are actively producing telomerase. (It’s also why Mike West and others are pursuing anti-cancer drugs based on telomerase.)
De Grey, as is his wont, takes the strategy a few steps further, even if the end result bears little resemblance to medical reality as we know it. He has devised a plan to make people essentially immune to cancer. Stem cells from the cancer-prone organ systems would be removed and, in a process not yet developed, reproduced in the lab after they had been genetically modified to turn off their production of telomerase. The stem cells would then be reintroduced into the body, but not before they had been genetically modified a second time to make them more resistant to cancer-fighting chemotherapy drugs. So now people could be bombarded with ultrapowerful doses of chemo to kill any potential cancers, and their newly modified stem cells would shake off the insult. Over time, as people returned to the doctor for periodic stem cell “reseedings” (necessary because without telomerase, cells won’t divide normally), their cells would become progressively less capable of letting cancers grow.
“This is an extraordinarily radical idea,” de Grey allows. “But when we’re living a long time, the short-term anti-cancer stuff we do now isn’t going to work.” When he has presented the idea at scientific conferences, it’s been met with something less than the tentative interest his lysosomal-enhancement concept receives. “But I haven’t been thrown out of any rooms yet,” he says.
By now de Grey has both trounced Ben at Othello and cured cancer (in
theory), and time has flown in the luminous English springtime. I notice that it’s 7:10 p.m. “F***in’ hell!” de Grey exclaims, and furiously pulls together his things. “I’m 10 minutes late for dinner, and I’m never late for dinner!” He takes off for home and Adelaide through the high grass, his long arms and legs flapping, looking for all the world like a startled, aristocratic gazelle.
My last day in Cambridge, I am being ferried by de Grey up the River Cam, which, as he talks indefatigably about the relative imminence of near-immortality, seems more and more like the river of time. We rented our flat-bottomed punt at Scudamore’s Punting Co., Est. 1910, and de Grey, with remarkable felicity, is now poling the boat through the congested stretch of river that runs by the university. Soon, though, we’re in Elysian countryside, skimming by lush, overhanging willow trees and other riverine flora that de Grey, no all-purpose biologist, can’t name. He cuts a remarkable figure, one hand on the punter’s pole, another wrapped around a tallboy of John Smith ale, his voluminous beard flowing behind his shoulders in the mild breeze like a scarf. De Grey never successfully learned to drive a car, too intimidated by the speed and potential lethality. But in his first year at university, he discovered he was a punting natural, and even made good money one summer taking tourists up and down the Cam in his second-
hand boat, tossing off outrageous lies about the local history and architecture.
As de Grey handles the boat work, my exercise, purely intellectual, is to imagine the world he’s advocating. Even if research science disappoints him and we blunder our way to a measly life span of 150 years sometime in the next century–something that’s not guaranteed but isn’t a bad bet either–society as we know it will be turned on its head. And if de Grey turns out to be closer to the mark, some obvious elephant-in-the-room questions present themselves.
For one thing, who is going to have access to fabulously pricey life-extension technology? Will the rich get older as well as richer? As the two of us slip through a landscape that looks as if it’s been lifted from a Jane Austen novel, de Grey conjures up a rather unpersuasive argument to the effect that life-extension technology will diffuse globally, rapidly and
fairly, because the developed world, the haves, will be too frightened of 9/11-style resentment from the have-nots. And where will the money for this democratic approach to long-livedness come from? The longevity dividend, de Grey says, that will accrue when people, indefinitely vigorous, don’t retire from the workforce
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