Monday, October 24, 2005

The Man Who Would Murder Death

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From the issue dated October 28, 2005

The Man Who Would Murder Death
A Rogue Researcher Challenges Scientists To Reverse Human Aging


Cambridge, England

If you wish to be a prophet, first you must dress the part. No more silk ties or tasseled loafers. Instead, throw on a wrinkled T-shirt, frayed jeans, and dirty sneakers. You should appear somewhat unkempt, as if combs and showers were only for the unenlightened. When you encounter critics, as all prophets do, dismiss them as idiots. Make sure to pepper your conversation with grandiose predictions and remind others of your genius often, lest they forget. Oh, and if possible, grow a very long beard.

By these measures, Aubrey de Grey is indeed a prophet. The 42-year-old English biogerontologist has made his name by claiming that some people alive right now could live for 1,000 years or longer. Maybe much longer. Growing old is not, in his view, an inevitable consequence of the human condition; rather, it is the result of accumulated damage at the cellular and molecular levels that medical advances will soon be able to prevent - or even reverse - allowing people to go on living pretty much indefinitely. We'll still have to worry about angry bears and falling pianos, but aging,
the biggest killer of all, will cease to be a threat. Death, as we know it, will die.

Mainstream gerontologists do not agree and hate to even raise the topic in public. They shy away from talk about life extension or "curing" aging and prefer to focus on keeping older people healthy for as long as possible, a goal referred to in the discipline as "compression of morbidity" or "healthspan." Many of them write off Mr. de Grey as more beard than brain.

So ... is he crazy? Not in the sense that he is divorced from reality or just making things up as he goes along. Mr. de Grey is a serious, thoughtful, sincere, prolific, even brilliant researcher and thinker who seems to have devoted every last ounce of his intellect to conquering the single biggest medical menace facing mankind. Along the way, he has acquired plenty of supporters and detractors - and gained the respect of some of the top scientists in the world.

He even has a plan. It is, to say the least, ambitious, and it depends on a number of techniques and treatments that have yet to be developed (curing cancer, for instance, is one of the steps). His approach, which he has dubbed Strategies for Engineered Negligible Senescence, draws from different branches of science and medicine and is enough to spin the heads of specialists and nonspecialists alike. It has also caused a stir, something Mr. de Grey certainly knows how to do. "One hundred and fifty thousand people die every day, and two-thirds of those die of aging in one
way or the other," he says, while nursing a pint of fine English ale. "If I speed up the cure for aging by one day, then I've saved 100,000 people." He pauses thoughtfully for a moment. "Actually, I probably do that every week."

Seven Steps to Eternal Life

He made this bold pronouncement, and several more like it, late one evening during a recent conference here that could have been called "The Aubrey de Grey Symposium on Cheating Death." He organized it, chose each of the speakers, decided when and for how long they should speak, and helped coordinate travel arrangements. He could even be spotted handing out name tags at the sign-in desk. Sessions began at 8:30 a.m., and it wasn't unusual to hear Mr. de Grey arguing well past midnight about the moral imperative of curing aging.

The speakers were invited because their specialties all, in some way, fit into Mr. de Grey's seven-step plan to keep people from growing old. Each of the steps is related to the death of cells. For instance, Mr. de Grey recommends using stem-cell therapy to introduce new cells that can fill in the gaps left by dead ones. He also suggests that plaques that accumulate around cells - which may be responsible for diseases like Alzheimer's - can be dissolved with small molecules called "beta-breakers."

If that sounds a little vague, it is. Mr. de Grey is not saying he knows for certain how to fix these problems, only that these are the problems responsible for the physical breakdowns we experience as we grow older. Lick them, and you've licked aging, or so the thinking goes.

Among the speakers was Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine at Wake Forest University. Dr. Atala, a surgeon and a researcher, explained how he and his colleagues are growing new human tissue and organs - bladders, kidneys, blood vessels, cartilage - in the laboratory using a patient's own cells.

For example, a few healthy cells could be taken from a cancer-stricken bladder and used to a grow a new bladder, which could theoretically then be transplanted with a very low chance of rejection. In 1999, Dr. Atala's team became the first to successfully transplant a lab-grown organ - by placing  a new bladder in a beagle. Clinical trials will begin soon to see if thisprocedure also works in humans.

A few of Dr. Atala's PowerPoint slides show human organs that have never been inside a human. The images are at once disturbing and thrilling.

It may seem surprising that someone of Dr. Atala's stature was a featured speaker at an on-the-fringe conference. Although he declines to pass judgment on Mr. de Grey's more-extreme prognostications, he clearly respects him. "Aubrey is highly visionary and very selfless in his approach," Dr. Atala says. "It takes people like Aubrey to say 'Hey, look at this again. Maybe there is another way to do this.'"

Perhaps the biggest celebrity at the conference was Woo Suk Hwang, a South Korean researcher who has shocked the scientific world in the last few years with his laboratory's achievements. This summer Dr. Hwang and his colleagues at Seoul National University announced that they had cloned a dog, a feat researchers around the world had been trying to accomplish for years. Dogs are considered to be one of the trickiest animals to clone because of their unique reproductive system. Like a proud papa, Dr. Hwang showed a brief video of the cloned Afghan hound frolicking with several canine companions. "The dog is very cute," he said in careful, heavily accented English.

In May, Dr. Hwang announced that he had cloned human embryos and created 11 stem-cell lines that are genetically matched to 11 patients - a milestone that some believed would not be reached for years or possibly decades. Because his work often involves embryonic stem-cell lines and therapeutic cloning, Dr. Hwang has been criticized by opponents of cloning, and the Bush administration has even expressed concern over such research. At the moment there are few people in science generating more controversy or jealousy. As one conferencegoer put it: "Right now the man has to be walking on air."

And yet there he was, along with dozens of other well-regarded scientists who study anticancer therapies, immune-system disorders, or cellular aging. There were also less-mainstream researchers who look at topics like how to preserve tissue cryogenically. It was a strange hodgepodge of scientists who would probably never meet otherwise.

From Love, A Crusade

The man who brought them together began his career as a computer scientist, working for several years on programs that find bugs in other programs. He later received his Ph.D. in biology from the University of Cambridge and devoted himself, in a sense, to finding the bugs in human beings.

An important turning point in Mr. de Grey's personal and professional life occurred at a friend's party in 1990. That's when he met Adelaide Carpenter, who would later become Adelaide de Grey. When they met, Mr. de Grey was a computer scientist in his twenties and had never been married. His wife-to-be was in her forties and had been married twice before.  Despite the 19-year age difference, they fell for each other immediately and have been together ever since.

At the time, Ms. de Grey was on sabbatical from her position as a professor of genetics at the University of California at San Diego. She had already established her reputation in the discipline (and made some discoveries that are now in textbooks) and had a comfortable, tenured position. But she had grown tired of her research and her job. So, after she met Mr. de Grey, she decided to quit, move to Cambridge, and work as a technician in a fruit-fly laboratory. It was a big step down professionally, but she enjoyed her work and the company of her new husband.

The age difference was unimportant to Ms. de Grey: What mattered to her was intellectual compatibility. "I need my male partner to be smarter than I am," she explains. "And - I'm trying to be modest here - that narrows down the field quite a bit." Does her husband fit that bill? She nods vigorously. "Oh yes."

Ms. de Grey taught her husband genetics over the dinner table. She was amazed at how quickly he could absorb the concepts. "Very shortly we were able to have a conversation rather than a tutorial," she says. While talking about her academic career and her relationship, Ms. de Grey is puffing away steadily on an unfiltered Camel. Mr. de Grey would like her to quit, but she's been a smoker since she was a teenager and believes that nicotine is necessary to kick-start her brain. Unlike her husband, Ms. de Grey has no wish to live forever. She has not agreed to be cryogenically
frozen when she dies. (Mr. de Grey has, just in case medicine does not advance speedily enough to save him.)

"I don't think anyone would want to thaw me out," she says and smiles, revealing a mouth mostly devoid of teeth.

When the software project Mr. de Grey had been working on didn't pan out, he got a part-time job designing a database for fruit-fly researchers at the lab where his wife worked. It is a position he still holds; as it turns out, being a prophet is not a sufficiently remunerative profession. In 1995, after having absorbed a great deal of genetics, Mr. de Grey moved on to gerontology, a subject that had always intrigued him. For two months he immersed himself in the literature. He emerged with an insight into the mechanics of mitochondrial mutations, wrote a paper on what he thought, and submitted it to a respected journal.

It was accepted. He was off to a good start.

Mr. de Grey continued reading widely on the subject and soon came to the conclusion that not much was being done. "I assumed that everyone was beavering away on aging," he says. "But it gradually occurred to me that I might be wrong about that." The field, he believed, needed him. "Gerontology has more than its share of not terribly bright people," he says. That's because, according to Mr. de Grey, progress is incremental, so there's less chance for a young researcher to make a big splash, and consequently, the best minds go elsewhere.

One will not find Mr. de Grey in the laboratory hovering over petri dishes or test tubes. He readily acknowledges that he lacks the qualifications to perform experiments. What some might view as a handicap, he sees as a strength: Rather than spending his time behind a microscope, he reads the literature and searches for connections that a specialist may have missed.
Buoyed by his early success, Mr. de Grey started thinking bigger. He came to believe that most people in the world, including most scientists, are in a "pro-aging trance." That is, they believe that getting old is awful but inevitable and therefore it is best not to think about it. But what if aging were preventable? What if death were not a foregone conclusion?

He is not the first person to propose such an idea. But a couple of things set Aubrey de Grey apart from other eternal-life prophets. For starters, he is a bona fide scholar. Other researchers can, and often do, disagree with his conclusions, but they also acknowledge that he knows what he is talking about.

Also, Mr. de Grey is not hawking a product or hustling investors for some biotech start-up. He does raise money to fund the Methuselah Foundation, which among other things is responsible for the Methuselah Mouse Prize (awarded to the scientific research team that develops the longest-living mouse), and for the Institute of Biomedical Gerontology, which at this stage is just a proposal. But he's not trying to get rich. And the apparent purity of his motives, along with a genuine grasp of the science, is part of his appeal.

A Bounty on His Theory

He also has a talent for drumming up publicity. His eccentricities (the long beard, the thrift-store clothes, the pub crawling) appeal to journalists looking for a colorful feature subject. There is also his
willingness - eagerness, in fact - to explain his plan for fighting aging to any reporter with a notebook and time to kill. More publicity, he hopes, will lead to more donations. The donations can then be used to help finance the kinds of research Mr. de Grey believes are most important.

Not every article, however, has taken a gee-whiz tone. In February, Technology Review, which is owned by the Massachusetts Institute of Technology, published an article about Mr. de Grey along with an editorial written by Jason Pontin, the magazine's editor. The article, by Sherwin Nuland, a clinical professor of surgery at Yale University's School of Medicine and the author of How We Die, concluded that Mr. de Grey was "neither a madman nor a bad man" but that his plan "will almost certainly not succeed." And, even if it did, Mr. de Grey "would surely destroy us in attempting to preserve us" because living for such long periods would undermine what it means to be human.

The editorial took a more ad hominem approach. Mr. Pontin wrote that Mr. de Grey "drinks too much beer" and that even though he's just in his early 40s"the signs of decay are strongly marked on his face." He also called the potential social consequences of extending life indefinitely "terrible" and wrote that Mr. de Grey "thinks he is a technological messiah."

The response to the article and the editorial was extraordinary and extremely negative. Mr. Pontin says he has received thousands of e-mail messages, many of them from "enraged" readers. "It was as if I was personally depriving them of the possibility of immortality," he says. The online version of the article has been clicked on nearly a million times, making it by far the most-read article in the history of the magazine.

Readers criticized the magazine for dismissing Mr. de Grey's ideas as ludicrous without ever fully engaging with them. Because of the enormous and unexpected reaction, Mr. Pontin decided to do something unusual: He commissioned Cynthia Kenyon, a professor of biochemistry and biophysics at the University of California at San Francisco and director of the Hillblom Center for the Biology of Aging, to review Mr. de Grey's ideas and write a follow-up. Ms. Kenyon is well-known among gerontologists and has made some important discoveries of her own. By altering a gene in a roundworm, she extended its life span from two weeks to 20 weeks, which may or may not have implications for humans.

Ms. Kenyon agreed to write the article and then, three months later, she backed out. Why she did this remains unclear. She declined a telephone interview with The Chronicle, citing a hectic travel schedule, but in an e-mail message wrote that she was "overwhelmed with other commitments then and didn't have time to do a good job."

Mr. Pontin then decided to put a bounty of sorts on Mr. de Grey, offering $10,000 to any gerontologist who could prove to an independent review panel that his ideas about radical life-extension had no merit. Mr. de Grey then upped the ante, matching the $10,000 through his Methuselah Foundation, making the prize for debunking him a generous $20,000.

You might think researchers would be lining up. In fact, no: So far Mr. Pontin has had no takers. He has also had trouble finding scientists willing to sit on the independent panel. Mr. de Grey sees the entire episode as a giant victory, particularly the fact that a prominent scientist such as Ms. Kenyon took up the project, then abandoned it. This is proof, he says, that "they can't ignore me any longer."

For Mr. Pontin, it is all somewhat exasperating. "People want to stay as far away from this as possible," he sighs. "If he's as crazy as people say, then even in lieu of experimental data, it should be possible to get someone to say why he's crazy."

Outrunning Death

"Aubrey's always arguing against people who tell him he's crazy," says Graham Pawelec, a professor of experimental immunology at the University of Tübingen in Germany. "I have never heard him lose an argument."

Mr. Pawelec is one of Mr. de Grey's staunch supporters. He quotes him often, beginning sentences by saying "Remember what Aubrey tells us ... ." He puts a lot of stock in Mr. de Grey's "escape velocity" theory. This is, in short, the idea that in the next 10 or 20 years science will have advanced sufficiently to allow people to live for, say, 150 or 200 years. And then by the time those people turn 200, science will have figured out how to allow them to live to 500. It is not that the battle against aging will be over shortly, but that there will be enough steady progress so that we can all live forever. More or less.

"In 10 years, we will have proof that we can cure these seven things and therefore beat aging," says Mr. Pawelec, who spoke at the conference on "immunorejuvenation" in the elderly. "All of my mainstream colleagues will be up there saying Aubrey was right. And then the general public will believe it."

But, even at Mr. de Grey's own conference, there was no shortage of doubters. Among them was David Finkelstein, program administrator for the Metabolic Regulation Program at the National Institute on Aging. He came to the conference, he says, because it attracts "some of the most creative scientists around." But he is definitely not one of Mr. de Grey's acolytes. "Is there a kernel of truth in what Aubrey says? Absolutely. Will it happen in the short term?" Mr. Finkelstein shakes his head. "To say if we solve these seven things we'll live to 1,000? That's hyperbole. I don't like

Mr. Finkelstein has little respect for Mr. de Grey's own research contributions. "I am very underwhelmed," he says. The fact that Mr. de Grey does not set foot inside a laboratory also bothers him: "Look, you either work at the bench, or you don't work at the bench," he says.

Some of Mr. de Grey's more extreme statements make it hard to take him seriously, according to Mr. Finkelstein: "There are people who say that if Aubrey says it must be right then it must be wrong." At the same time, despite his criticism, Mr. Finkelstein has some appreciation for Mr. de Grey's role as provocateur. "I like him," he says. "He ruffles feathers. He has the balls to say stuff."
The question is whether that stuff will prove to be true. Gregory M. Fahy, a biologist and vice president and chief scientific officer of 21st Century Medicine, a biomedical research company, was very skeptical at first. While they still do not agree on everything, Mr. Fahy has been largely won over. And, like Mr. Finkelstein, he respects Mr. de Grey for his courage in the face of ridicule. "If you think you're right, you have to stand up and say what you believe even if people think you're nuts," says Mr. Fahy. "Now, if they prove you're nuts, you have to shut up. But that hasn't happened yet."
Section: Research & Publishing
Volume 52, Issue 10, Page A14


Copyright © 2005 by The Chronicle of Higher Education



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