Dr. Aubrey de Grey

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3BB8F5B6-ABAA-4243-800B-F142C82E31A5.jpgDr. Aubrey David Nicholas Jasper de Grey (born 20 April 1963 in London, England) is a British biomedical gerontologist educated at Cambridge University in the UK.

De Grey is the author of the Mitochondrial Free Radical Theory of Aging. He works on the development of engineered negligible senescence – a tissue-repair strategy intended to rejuvenate the human body and thereby allow an indefinite lifespan. To this end, he has identified seven tissue-damages caused by aging that need to be repaired medically before this can be done.[1]

De Grey has been interviewed in recent years in many news sources, including CBS 60 Minutes, BBC, the New York Times, Fortune Magazine, Free Talk Live, Prison Planet, Popular Science and The Colbert Report. His main activities at present are as chairman and chief science officer of the Methuselah Foundation[2] and editor-in-chief of the academic journal Rejuvenation Research.

Education

Aubrey de Grey was educated at Sussex House School, Harrow School and Trinity Hall, Cambridge. Prior to his work in cellular and molecular biology, he studied computer science. In 1985, he received a B.A. in Computer Science from the University of Cambridge and joined Sinclair Research Ltd as an AI/software engineer; in 1986, he co-founded Man-Made Minions Ltd[3] to pursue the development of an automated formal program verifier. Until 2006, he was in charge of software development at the University of Cambridge Genetics Department for the FlyBase genetic database.

During this time Cambridge awarded de Grey a Ph.D. by a mechanism available only to previous Cambridge undergraduates (of whatever discipline) — the “special regulations,” which require evidence of “…a significant contribution to scholarship,”[4] and are evaluated by the usual methods (examiners appointed; oral defence of the submitted work) but do not require an applicant to have been registered as a Ph.D. student while performing such work. The degree was granted in 2000[5] on the basis of de Grey’s book concerning the biology of one aspect of aging, The Mitochondrial Free Radical Theory of Aging (ISBN 1-58706-155-4), which he wrote in 1999. The book controversially claimed that obviating damage to mitochondrial DNA might by itself extend lifespan significantly, though it stated that it was more likely that cumulative damage to mitochondria is a significant cause of senescence, but not the single dominant cause. A February 8, 2007 search for “de Grey AD [au]” on PubMed [6] revealed 61 publications in 25 peer-reviewed journals, of which 19 are in Rejuvenation Research, the journal edited by de Grey.

Regarding his background as a computer scientist (and subsequently a bioinformatician in genetics), he states:

“There are really very important differences between the type of creativity involved in being a scientist and being a technical engineer. It means that I’m able to think in very different ways and come up with approaches to things that are different from the way a basic scientist might think.”[7]

Strategies

De Grey argues that the fundamental knowledge needed to develop effective anti-aging medicine mostly already exists, and that the science is ahead of the funding. He works to identify and promote specific technological approaches to the reversal of various aspects of aging, or as de Grey puts it, “the set of accumulated side effects from metabolism that eventually kills us,”[7] and for the more proactive and urgent approaches to extending the healthy human lifespan. Regarding this issue, de Grey is a supporter of life extension.

As of 2005, his work centered upon a detailed plan called Strategies for Engineered Negligible Senescence (SENS), which is aimed at preventing age-related physical and cognitive decline. He is also the co-founder (with David Gobel) and chief scientist of the Methuselah Foundation, a 501(c)(3) nonprofit organization based in Springfield, Virginia, United States. A major activity of the Methuselah Foundation is the Methuselah Mouse Prize,[8] a prize designed to hasten the research into effective life extension interventions by awarding monetary prizes to researchers who stretch the lifespan of mice to unprecedented lengths. Regarding this, de Grey stated in March 2005 “if we are to bring about real regenerative therapies that will benefit not just future generations, but those of us who are alive today, we must encourage scientists to work on the problem of aging.” The prize reached 4.2 USD million in February 2007. De Grey believes that once dramatic life extension of already middle-aged mice has been achieved, a large amount of funding will be diverted to this kind of research, which would accelerate progress in doing the same for humans.

De Grey has published papers in this area in prominent journals with some of biogerontology’s foremost researchers, including Bruce Ames, Leonid Gavrilov and S. Jay Olshansky, as well as other thinkers such as Gregory Stock.[9] He has also received support from other prominent scientists, such as William Haseltine, the biotech pioneer of Human Genome Sciences, who in March 2005 stated regarding the Methuselah Mouse Prize “there’s nothing to compare with this effort, and it has already contributed significantly to the awareness that regenerative medicine is a near term reality, not an if.”[10]

In 2005, he was the subject of a critical article in MIT’s Technology Review.[9] See de Grey Technology Review controversy.

In 2007, de Grey wrote the book “Ending Aging” with the assistance of Michael Rae.[11] It summarizes the science, politics and social challenges of the entire SENS agenda.[12]

The seven types of aging damage proposed by de Grey

Main article: Strategies for Engineered Negligible Senescence

1. Cancer-causing nuclear mutations/epimutations:

These are changes to the nuclear DNA (nDNA), the molecule that contains our genetic information, or to proteins which bind to the nDNA. Certain mutations can lead to cancer, and, according to de Grey, non-cancerous mutations and epimutations do not contribute to aging within a normal lifespan, so cancer is the only endpoint of these types of damage that must be addressed.

2. Mitochondrial mutations:

Mitochondria are components in our cells that are important for energy production. They contain their own genetic material, and mutations to their DNA can affect a cell’s ability to function properly. Indirectly, these mutations may accelerate many aspects of aging.

3. Intracellular junk:

Our cells are constantly breaking down proteins and other molecules that are no longer useful or which can be harmful. Those molecules which can’t be digested simply accumulate as junk inside our cells. Atherosclerosis, macular degeneration and all kinds of neurodegenerative diseases (such as Alzheimer’s disease) are associated with this problem.

4. Extracellular junk:

Harmful junk protein can also accumulate outside of our cells. The amyloid plaque seen in the brains of Alzheimer’s patients is one example.

5. Cell loss:

Some of the cells in our bodies cannot be replaced, or can only be replaced very slowly – more slowly than they die. This decrease in cell number causes the heart to become weaker with age, and it also causes Parkinson’s disease and impairs the immune system.

6. Cell senescence:

This is a phenomenon where the cells are no longer able to divide, but also do not die and let others divide. They may also do other things that they’re not supposed to, like secreting proteins that could be harmful. Immune senescence and type 2 diabetes are caused by this.[citation needed]

7. Extracellular crosslinks:

Cells are held together by special linking proteins. When too many cross-links form between cells in a tissue, the tissue can lose its elasticity and cause problems including arteriosclerosis and presbyopia.[7]

Technology Review debate

Main article: De Grey Technology Review debate

A debate over the validity of the de Grey’s theories on ageing was published in MIT’s Technology Review. In the end, none of the challengers to de Grey were able to convince the judges that SENS was “so wrong that it is unworthy of learned debate.”

Scientific journal

* Rejuvenation Research (online reference) Editor: Aubrey de Grey. Publisher: Mary Ann Liebert, Inc. ISSN 1549-1684 – Published quarterly

Titles and positions

De Grey is a fellow of the Institute for Ethics and Emerging Technologies[13] and an advisor for the Singularity Institute.[14]

———————

The Invincible Man
Aubrey de Grey, 44 Going on 1,000, Wants Out of Old Age

By Joel Garreau
Washington Post Staff Writer
Wednesday, October 31, 2007

Aubrey de Grey may be wrong but, evidence suggests, he’s not nuts. This is a no small assertion. De Grey argues that some people alive today will live in a robust and youthful fashion for 1,000 years.

In 2005, an authoritative publication offered $20,000 to any molecular biologist who could demonstrate that de Grey’s plan for treating aging as a disease — and curing it — was “so wrong that it was unworthy of learned debate.”

Now mere mortals — who may wish to be significantly less mortal — can judge whether de Grey’s proposals are “science or fantasy,” as the magazine put it. De Grey’s much-awaited “Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime” has just been published.

The judges were formidable for that MIT Technology Review challenge prize. They included Rodney Brooks, then director of MIT’s Computer Science and Artificial Intelligence Laboratory; Nathan Myhrvold, former chief technology officer of Microsoft; and J. Craig Venter, who shares credit for first sequencing the human genome.

In the end, they decided no scientist had succeeded in blowing de Grey out of the water. “At issue is the conflict between the scientific process and the ambiguous status of ideas that have not yet been subjected to that process,” Myhrvold wrote for the judges.

Well yes, that. Plus the question that has tantalized humans forever. What if the only certainty is taxes?

* * *

Dodging death has long been a dream.

Our earliest recorded legend is that of Gilgamesh, who finds and loses the secret of immortality.

The Greek goddess Eos prevails on Zeus to allow her human lover Tithonus to live eternally, forgetting, unfortunately, to ask that he also not become aged and frail. He winds up such a dried husk she turns him into a grasshopper.

In “It Ain’t Necessarily So,” Ira Gershwin writes:

Methus’lah lived nine hundred years
Methus’lah lived nine hundred years
But who calls dat livin’ when no gal’ll give in
To no man what’s nine hundred years.

Aubrey David Nicholas Jasper de Grey, 44, recently of Britain’s Cambridge University, advocates not myth but “strategies for engineering negligible senescence,” or SENS. It means curing aging.

With adequate funding, de Grey thinks scientists may, within a decade, triple the remaining life span of late-middle-age mice. The day this announcement is made, he believes, the news will hit people like a brick as they realize that their cells could be next. He speculates people will start abandoning risky jobs, such as being police officers, or soldiers.

De Grey’s looks are almost as striking as his ambitions.

His slightly graying chestnut hair is swept back into a ponytail. His russet beard falls to his belly. His mustache — as long as a hand — would have been the envy of Salvador Dali. When he talks about people soon putting a higher premium on health than wealth, he twirls the ends of his mustache back behind his ears, murmuring, “So many women, so much time.”

A little over six feet tall and lean — he weighs 147 pounds, the same as in his teenage years — de Grey shows up in a denim work shirt open to the sternum, ripped jeans and scuffed sneakers, looking for all the world like a denizen of Silicon Valley.

Not far from the mark. De Grey’s original academic field is computer science and artificial intelligence. He has become the darling of some Silicon Valley entrepreneurs who think changing the world is all in a day’s work. Peter Thiel, the co-founder and former CEO of PayPal — who sold it in 2002 for $1.5 billion, pocketing $55 million himself — has dropped $3.5 million on de Grey’s Methuselah Foundation.

“I thought he had this rare combination — a serious thinker who had enough courage to break with the crowd,” Thiel says. “A lot of people who are not conventional are not serious. But the real breakthroughs in science are made by serious thinkers who are willing to work on research areas that people think are too controversial or too implausible.”

At midday in George Washington University’s Kogan Plaza off H Street NW, you are surrounded by firm, young flesh. Muscular young men saunter by in sandals, T-shirts and cargo shorts. Young blond women sport clingy, sleeveless tops, oversize sunglasses and the astounding array of subtle variations available in flip-flops and painted toenails.

Is this the future? you ask de Grey.

“Yes, it is precisely the future,” he says. “Except without people who look as old as you and me.”

“Of course the world will be completely different in all manner of ways,” de Grey says of the next few decades. His speech is thick, fast and mellifluous, with a quality British accent.

“If we want to hit the high points, number one is, there will not be any frail elderly people. Which means we won’t be spending all this unbelievable amount of money keeping all those frail elderly people alive for like one extra year the way we do at the moment. That money will be available to spend on important things like, well, obviously, providing the health care to keep us that way, but that won’t be anything like so expensive. Secondly, just doing the things we can’t afford now, giving people proper education and not just when they’re kids, but also proper adult education and retraining and so on.

“Another thing that’s going to have to change completely is retirement. For the moment, when you retire, you retire forever. We’re sorry for old people because they’re going downhill. There will be no real moral or sociological requirement to do that. Sure, there is going to be a need for Social Security as a safety net just as there is now. But retirement will be a periodic thing. You’ll be a journalist for 40 years or whatever and then you’ll be sick of it and you’ll retire on your savings or on a state pension, depending on what the system is. So after 20 years, golf will have lost its novelty value, and you’ll want to do something else with your life. You’ll get more retraining and education, and go and be a rock star for 40 years, and then retire again and so on.”

The mind reels. Will we want to be married to the same person for a thousand years? Will we need religion anymore? Will the planet fill to overflowing?

But first — why are these questions coming up now? And why are we listening to answers from Aubrey de Grey?

Appalled at the Carnage

De Grey became the archenemy of aging in two steps.

“The first stage happened when I was probably 8 or 9 years old. My mother wanted me to practice the piano, and I would resist it.

“She’d already somehow brought me up to be very analytical and introspective. So I realized it was very straightforward. The best possible outcome of my putting in this enormous time at the piano is that I would become a good pianist. That wasn’t good enough. I would make a minimal difference in the world, because there were plenty of other very good pianists already. Well, that won’t do. What I actually wanted to do with my life is make a difference to the world. That led me into science very quickly.”

In his teens he heard the siren song of the the first British microcomputers, the Sinclairs and Acorns, and never looked back. Computer science filled his undergraduate years at Cambridge and became the field in which he spent more than a decade.

The second stage started when he was 26. De Grey fell in love with and married a geneticist, Adelaide Carpenter, who is 19 years his senior.

He learned a lot of biology over the dinner table, he says, and gradually became driven by the notion that “aging is responsible for two-thirds of all death — now that means worldwide 100,000 people every single day — and in the industrialized world, it is something like 90 percent.”

The further he got into Carpenter’s world and that of her senior colleagues, the more incensed he became that biologists and gerontologists just accept this carnage.

“I was appalled. Utterly appalled. I began to realize the profound difference of motivation and mind-set between scientists on the one hand and technologists and engineers on the other hand.”

In his world of information technology, the norm is making the world new. Try something and if it doesn’t work, try something else. Science doesn’t pave the way for engineering, it’s the other way around. Intel figures out a way to make wires only a few molecules thick. Why the circuits function is at best of passing interest — as long as they do. Science can take years if not decades to catch up with an adequate explanation of the device’s quantum mechanics. It is the final triumph of Edison over Einstein.

The idea of bringing pragmatism to biology made de Grey think “I might be able to make a contribution. I became very aware by this time that biology was critically short of synthesizers — people who brought ideas together from disparate fields who came up with new ideas for experimentalists to do.” So he got his PhD in biology from Cambridge and started scattering ideas like viruses.

Aging consists of seven critical kinds of damage, according to de Grey. For example, unwholesome goo accumulates in our cells. Our bodies have not evolved means quickly to clean up “intracellular aggregates such as lipofuscin.” However, outside our bodies, microorganisms have eagerly and rapidly evolved to turn this toxic waste into compost. (De Grey made this connection because he knew two things: Lipofuscin is fluorescent and graveyards don’t glow in the dark.)

By taking soil samples from an ancient mass grave, de Grey’s colleagues in short order found the bacteria that digest lipofuscin as easily as enzymes in our stomachs digest a steak. The trick now is getting those lipofuscin-digesting enzymes into our bodies. That has not yet been done. But, de Grey says, comparable fundamental biotechnology is already in clinical use fighting diseases such as Tay-Sachs. So he sees it as merely an engineering problem.

Examples like this make up the 262 pages at the center of “Ending Aging.”

“It’s a repair and maintenance approach to extending the functional life span of a human body,” de Grey says. “It’s just like maintaining the functional life span of a classic car, or a house. We know — because people do it — that there is no limit to how long you can do that. Once you have a sufficiently comprehensive panel of interventions to get rid of damage and maintain these things, then, they can last indefinitely. The only reason we don’t see that in the human body now is that the panel of interventions we have available to us today is not sufficiently comprehensive.”

By 2005, his ideas had attracted enough attention as to no longer be merely controversial. De Grey was being pilloried as a full-blown heretic.

“The idea that a research programme organized around the SENS agenda will not only retard ageing, but also reverse it — creating young people from old ones and do so within our lifetime, is so far from plausible that it commands no respect at all within the informed scientific community,” wrote 28 biogerontologists in the journal of the European Molecular Biology Organization. Their recommendation: more of the patient, basic scientific research that is their stock in trade.

“Each idea that we decide to pursue will cost years of work and a great deal of money, so we spend a lot of time — at meetings, seminars and in the library — trying to search for and weigh alternatives, and looking for loopholes in our chain of arguments before they are pointed out to us either by peer reviewers or experimental results.

“Presented by an articulate, witty and colourful proponent, a flashy research agenda might catch the eye of a journalist or meeting organizer who is hunting for attention, publicity and an audience; however, the SENS agenda is easily recognized as a pretence by those with scientific experience.

“Why not simply debate with de Grey and let the most convincing arguments win? It is . . . our opinion that pretending that such a collection of ill-founded speculations is a useful topic for debate, let alone a serious guide to research planning, does more harm than good both for science and for society.”

The resulting uproar was followed by the put-up-or-shut-up smack-down in MIT Technology Review. The upshot was intriguing.

“In our judgment none of the ‘refutations’ succeeded,” Myhrvold, one of the judges, writes in an e-mail.

“It was a bit ironic because they were mostly the work of established scientists in mainstream gerontology who sought to brand de Grey as ‘unscientific’ — yet the supposed refutations were themselves quite unscientific.

“The ‘refutations’ were either ad hominem attacks on de Grey, or arguments that his ideas would never work (which might be right, but that is what experiments are for), or arguments that portions of de Grey’s work rested on other people’s ideas. None of these refute the possibility that he is at least partially correct.

“This is not to say that the MIT group endorsed de Grey,” Myhrvold emphasizes, “or thinks he has proven his case. He hasn’t, but admits that upfront. All of science rests on ideas that were either unproven hypotheses or crazy speculations at one point. . . . The sad reality is that most crazy speculations fail. . . . We do not know today how to be forever young for 1,000 years, and I am deeply skeptical that we will figure it out in time for me!”

No Point in Being Miserable

Off the J Street food court at GWU, there is a cafe so metabolically correct that it features not only a vegan service bar, but, separately, a vegetarian service bar, which is not to be confused with the salad bar.

Seems like a good place for lunch with a man intent on immortality.

Not so much.

“I’m getting damn thirsty,” de Grey announces.

What appeals to him is the Froggy Bottom Pub on Pennsylvania Avenue. “I like good beer, but I’m not really a snob about beer. I’m perfectly happy to drink Sam Adams, if that’s what they have.”

Aubrey de Grey is not interested in spending his next centuries miserable. He cheerfully chows down on french fries, heavily crusted deep-fried chicken and two dark beers.

So beyond the question of whether immortality is feasible, is it a good idea? For every Woody Allen who says, “I don’t want to achieve immortality through my work; I want to achieve it through not dying,” isn’t there a Ralph Waldo Emerson who asks, “What would be the use of immortality to a person who cannot use well a half an hour?”

Why is it, when you bring up the idea of living forever — even if robust and healthy, not drooling on your shoes — some people just recoil viscerally?

“It’s probably the majority that recoils viscerally,” de Grey says. “It’s what I call the pro-aging trance.

“Since the beginning of civilization, we have been aware that aging is ghastly and that aging is utterly inevitable. . . . So we have two choices. Either we spend our lives being preoccupied by this ghastly future or we find some way to get on with our miserably short lives and make the best of it.

“If we do that second thing, which is obviously the right thing to do, then it doesn’t matter how irrational that rationalization might be. . . . It could be, well, we’re all going to go to heaven. Or it could be, we’re going to have overpopulation. Or it could be, it will be boring. Or, dictators will live forever.

“It doesn’t matter what the answers are. It’s so important for them to maintain their belief that aging is actually not such a bad thing, that they completely suspend any normal rational sense of proportion.”

But if people don’t die, won’t we indeed fill the planet shoulder to shoulder?

“The birthrate is going to have to go down by an order of magnitude,” de Grey acknowledges. “But even if that is going to be a severe problem, the question is not, do problems exist? The question is, are they serious enough to outweigh the benefits of saving 100,000 lives a day? That’s the fundamental question. If you haven’t got an argument that says that it’s that serious that we shouldn’t save 30 [bleeping] World Trade Centers every [bleeping] day, don’t waste my time. It’s a sense of proportion thing.”

So de Grey soldiers on, not that it is anywhere written that anything he advocates will work. His approach, however, does have echoes in history.

On Oct. 9, 1903, the New York Times wrote:

“The flying machine which will really fly might be evolved by the combined and continuous efforts of mathematicians and mechanicians in from one million to ten million years.”

On the same day, on Kill Devil Hill, N.C., in his diary, a bicycle mechanic named Orville Wright wrote:

“We unpacked rest of goods for new machine.”

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