I haven't been screwing off. Here is my report from the third conference for Strategically Engineered Negligable Senescence, the brainchild of cell biologist Aubrey DeGrey, as it appeared in the Times of London:
This summer two Cambridge undergraduates approached Aubrey de Grey, an outspoken expert on ageing, in his favourite pub, hoping for an informal chat. “Er, sorry, Dr de Grey?” one of them said. “I just wanted to say that I heard your lecture about antiageing medicine and that I thought it was brill . . .”
“Then what are you doing about it?” de Grey replied.
“What?” his student admirer said, clearly puzzled.
“What are you doing about it?” de Grey repeated, tapping his knuckles on the table before him. “Look, go to my website at Mprize.com and look under “what you can do”. There’s a list of six things you can do to help. Then if you have any more questions we can talk. All right?”
Dr de Grey is trying to end human ageing. End it, or, as he describes his mission, “to engineer huge gains in human life span”. Huge gains as in a 1,000-year life span, and a healthy 1,000 years at that. Huge gains as in the reversal of ageing in those already considered old. Huge gains as in the end of cancer, heart disease, stroke, diabetes and Alzheimer’s.
Predictably, his critics have had a field day ridiculing his science and even attacking him personally. Less predictably, he has encountered resistance among the general public. “People really go into a sort of pro-ageing trance when you start talking about radically extending life,” de Grey said at his Cambridge pub where I met him recently. “It’s as if they’d rather defend something they think they know – that life span is finite – than deal with ageing itself as a disease and as something to be defeated.” He sipped his beer and brushed aside his enormous hermit’s beard. “Isn’t that amazing? Can you believe it?”
But these days, with the demographics on ageing transforming the globe, de Grey is starting to gain some respect. He has just published a book, Ending Aging, which has earned good marks from some of his peers. He is constantly on the road, speaking far and wide to large audiences. This week he is holding his third conference on what he calls SENS, or “strategically engineered negligible senescence”, in Cambridge; it will be attended by some of the leading lights of modern gerontology, pathology and cell biology. And there is, finally, money. Last year Peter Thiel, the American founder of PayPal, the money transfer service, committed himself to a $3 million matching donation. The Methuselah Prize, that de Grey started a few years ago to reward anyone who could double the life span of a laboratory mouse, now stands at $4.4 million, much of it in the form of small cash gifts from around the world.
In de Grey’s world, that means only one thing: he’s begun to break the pro-ageing trance.
Like all of today’s PowerPoint visionaries, de Grey has a diagram that he insists you consider. Its simple lines depict what he sees as the basic architecture of modern ageing research. The bottom line represents the key ageing process – human metabolism. This constant burning of nutrients by the cell and its often poor processing of byproducts causes cell damage. Leave that damage to accumulate and you get pathology, disease and death. Fair enough, so far.
The top line shows where the main branches of ageing sciences tend to focus – gerontologists study the processes in metabolism that lead to damage, and geriatricians treat the disease consequence of that damage. In the middle of that line sits de Grey’s conceptual time bomb: the as-yet-unrealised role for “a pure engineering approach”, as he likes to call it. “You see,” he said, “this is all about a repair and maintenance effort. It’s not about trying to understand all the possible variables of human metabolism. We don’t need to do that to live a lot longer. We just have to identify the key damage and . . . eliminate it.”
The analogy that comes closest, he says, is that of the perfectly preserved vintage car. It wasn’t designed to run for 100 years, but it does so because of careful and constant repair and maintenance, using the best tools and materials available. The same with the human cell, de Grey argues. Focus on the rust that gathers on our fuel lines – the cellular plaque that gathers on and around our arteries – and get rid of it. Forget about interfering or altering the basic process that leads the body to produce it in the first place, the fixation of modern pharmacological science.
To advance this paradigm-buster, de Grey has identified seven principal domains of “cellular interventions” that, given the right scientific and economic support, will stop and even reverse the ageing process in human beings.
His logical tack in describing such interventions, while often zigzaggy, sails a fairly consistent pattern. First, identify a form of cellular breakdown. Start with, say, lyso-some dysfunction, in which a cell’s waste-burning organelle, or component, becomes overwhelmed and unable to do its job. That job, as he describes it, is burning up lipofuscin, a nearly indissoluble after-product of metabolism. Now look for the wide-ranging disease possibilities inherent in that breakdown. In the case of lysosome dysfunction, he says, this can range from atherosclerosis (because the immune cells that attack inflamed arterial plaque can’t process the waste and instead rupture and blow up), to macular degeneration (because of lipofuscin-like build-up behind the lens), to Alzheimer’s (wherein cells can’t keep up the policing of errant plaques and proteins that build up and impair neuronal health). Then ask: what would that lysosome need to be able to break down all that damaging waste? The answer, he says, would be more of the enzyme that it usually uses to do so, but has now been depleted. Find a new source for that enzyme and reintroduce it into the cell. Voila! Clean veins and clear vision and unfogged brain in the year 2500. “The goal is to wipe out the damage using any benign weapon available,” he says, “because it’s the damage that causes the disease.”
In the case of arterial plaques and amyloid, that weapon, he says, can be found in the bacteria of graveyard soil, which over the centuries has evolved enzymes that eat human lipofuscin. “I know it sounds far out, like Victor Frankenstein,” he says, noting how he sent a student to collect a soil sample in nearby Midsummer Common. “But when I approached the leading experts on the specific mechanisms I’m proposing, there was a lot of support. I’ve been quite encouraged.”
What about cancer, a disease of uncontrolled cell growth? Answer: use nanotechnology to design molecular “Swiss army knives” to “unscrew” cancer-cell surface barriers to oncology drugs. Better still: delete the gene for telomerase, the enzyme that enables cellular division in the first place.
How about diabetes-producing visceral fat cells? Answer: stimulate the immune system selectively to target and kill those cells. What about muscle, skin and organ tissue loss? Replace them with stem cells that reproduce the lost tissue. And how about hardened arteries and weakened ligaments caused by so-called cross-linking extracellular proteins? Answer: after discovering a hyphenation-reducer, inject safe chemical agents that break apart the disease-causing links or use nanotechnology to design targeted “molecular buzzsaws”.
Needless to say, de Grey’s ideas have attracted criticism. The assaults, by some of the world’s leading scientists and science writers, have been fast and furious. Some have been personal. In an article for Technology Review, the physician-writer Sherwin B. Nuland noted that de Grey drinks a lot of beer and eats a lot of sweets, and that his wife (20 years his senior) lacks a full set of teeth and smokes a lot of cigarettes.
In the same issue, Jason Pontin, the editor, called de Grey a “troll”, noting that: “He dresses like a shabby graduate student and affects a Rip Van Winkle’s beard; he has no children; he has few interests outside the science of biogerontology; he drinks too much beer.”
Among the more substantial critiques, perhaps the most obvious is that without mainstream gerontology’s focus on disease processes de Grey would never have any “damage” targets in the first place. Worse, it is said that he picks and chooses disease theories to match his solutions.
The most obvious example is in the case of Alzheimer’s, de Grey singles out amyloid plaque for various forms of high-tech destruction. But the debate about such plaque’s role in the disease’s pathology is far from resolved, with many arguing that it is only an indicator of a disease process, not a cause of Alzheimer’s itself. Targeting amyloid would solve nothing, they say.
No wonder that in 2005, 25 of the world’s leading experts on ageing dubbed the SENS agenda a “farrago” and a “fantasy”. Writing in EMBO Reports, the journal of the European Molecular Biology Organisation, the scientists noted that nearly all of de Grey’s proposed interventions were deeply flawed, unreasonable and possibly dangerous. As for injections that target senescent cells for elimination, they wrote: “Senescence toxins do not yet exist.” Deleting the gene for telomerase to eliminate cancer “might have serious side-effects”. And engineered vaccines to improve immune response? They had “proved disastrous so far”. And finally, the ultimate academic put-down: de Grey, the EMBO writers said, was guilty of “clever marketing” that allowed him to “short-circuit” the traditional scientific channels of new ideas.
Not everyone in the scientific community, though, was so splenetic. Not long after the Technology Review article, the magazine and de Grey agreed to offer $20,000 for an essay that made a convincing case against SENS, proving that it “should not be discussed or taken seriously”. The Reviewfailed to find a winner. As the magazine was loath to admit: “SENS does not compel the assent of many knowledgeable scientists; but neither is it demonstrably wrong.”
What about the first generation of possible mille-generians? I ask. Won’t they be at the doctor’s office all the time for these repair and maintenance procedures? De Grey replies: “Probably a month in hospital every ten years with loads of things being done simultaneously. But I would not be surprised if after ten years it’s down to a day in hospital. Surgery will probably be involved at first, but diminishingly as the therapies are refined.”
Engineering-oriented technologies will prevail. If there is a schoolboy whizz-bang to it all, so be it.
De Grey’s pragmatic optimism has sprouted from two sources. One was the independence he developed in childhood. His father left home when he was 5 and he was brought up by his mother, an artist and poet. He went to Harrow School, where he says he was “insufferably arrogant”. The other formative source was the dinner-table education in genetics that he received from his wife, the American fruit-fly geneticist Adelaide Carpenter. By 1995 he had gained a PhD in cell biology from Cambridge.
At this week’s Sens3 scientists from around the world will be talking about everything from scar reversal to fighting obesity, using, at least in part, the SENS sensibility.
Even Caleb Finch, one of the world’s leading gerontology scholars and the author of the definitive Biology of Human Longevity, has come to value de Grey’s audacity. “Aubrey is a polemicist and monomaniac immortalist,” Finch says. “That being said, he has stimulated much new thought . . . to extending the health span that could conceivably allow for unprecedented longevity, as well as deeper understanding of the mysteries of ageing.”
“It’s an exciting time,” de Grey says. “No doubt about it.”
Just before our meeting, I had a chance to run de Grey’s vision past a group of highly educated, stylish Londoners gathered at a club to celebrate the birthday of a up-and-coming British comic.
“It’s greed. Just another example of how baby-boomers just can’t accept limits,” one young woman said.
“That’ll be good for the environment, won’t it?” said a marketing executive. “Just imagine another 50 million people a year on the planet and never effing leaving! Effing brilliant!”
Another said: “One thousand years! He’s got to be an American, right?”
Well, no, he’s British, but never mind that. As Aubrey de Grey would say: “They’re still in the pro-ageing trance.”
Greg Critser is the author of Fat Land, Generation Rx, and the forthcoming Eternity Soup: Inside the Quest to End Aging (Harmony/Random House)