||Miércoles 3 de Octubre de 2007, Ip nº 210
The Queen's College, Cambridge dining hall is a Seventies version of the great dining hall of Hogwarts in Harry Potter. It's the summer holiday and delegates at the second SENS conference break bread on long beechwood tables under the oil-paint gazes of great kings and academics, now dead.
Among these diners are the wizards of the 21st century: molecular biologists who study the building blocks and mechanisms of the body - what keeps us alive, what kills us, in essence - in order that humans might gain greater control over their lives and deaths. The wizards have their different theories, sources of funding, loyalties and groups of acolytes. The world of biological research is in some ways a democratic world of shared humanistic aims, but it is also steeply hierarchical - from lab technicians at the bottom, up to Nobel prize winners - and much of the direction in which science travels is decided by the high-status personalities. These eminent men and women sit on public and private funding boards that decide where the money spent on health research and development ($126bn in 2003) should go. They build their reputations by publishing papers in journals and presiding over laboratories that make important breakthroughs, creating something where there was nothing, and changing our futures.
These are the titans of the biological revolution: that man over there in the suit is Professor Hwang Woo-suk, stem-cell scientist and, this summer, the first person to clone a dog - an Afghan hound named Snuppy. There's Professor Song Chang-hun, the Korean who made a paralysis victim of 19 years walk by injecting stem cells into her spine. And that one with the moustache is Professor Buddy Ratner; he's engineering a heart - yes, literally growing it out of cells on a mini-scaffold in a laboratory in Seattle.
Then, finally, there's Aubrey de Grey, a scruffy, self-taught, biomedical theorist who is currently creating something of a stir in the world of gerontology - the study of ageing. With long auburn hair and beard, and a spare frame hung with T-shirt and drainpipe jeans, the 43-year-old doesn't look the sort of person that Hollywood has led us to believe will save the human race from destruction, but that is what he is trying to do. He is devoting his professional life to convincing people that ageing is a disease that can and should be cured.
Over the past 100 years, life expectancy has been steadily increasing by two years every decade. One way of looking at this is that for every hour that passes you have gained 12 minutes more life. Some think this life 'dividend' will tail off, others that it can be sustained. Yet others - de Grey among them - argue it can be increased until we tip the balance and begin to gain more than 60 minutes for every 60 that pass. De Grey has created a detailed agenda and believes that, if followed, it will give us a chance of catching up with ageing in the next 25 years. Such notions put him squarely at odds with most of the gerontology establishment, who believe his claims are so wild they undermine their much less headline-grabbing research into how the body ages and what might be done to make the last years of life more comfortable.
SENS stands for Strategies for Engineered Negligible Senescence, which translates as 'strategies to prevent significant ageing'. It is important, de Grey says, to think about the difference between ageing and dying. At present most people die from illnesses that are caused, or made fatal, by the gradual decay of our bodies. For example, pneumonia kills many of the elderly people who catch it, but few of its young victims. Also, few young people suffer heart attacks or cancer because their bodies have deteriorated less. Identifying seven areas of cellular decay we need to tackle, SENS predicts that, through as yet un- or semi-developed processes (such as repairing or replacing worn-out body parts, flushing out the poisons that build up in our cells or preventing the growth of cancers) our bodies will no longer wear out in the way they currently do. Accidents, murder and suicide would still be able to kill us, but with actuaries calculating that a fatal accident comes our way on average once every 1,500 years, our life spans would be massively increased.
It's a balmy early autumn night, and de Grey is making his radical claims to me in the quad next to the Queen's College bar. Two days into the conference and 100-plus attendees from different disciplines, and from across the globe, mill around, swapping anecdotes and ideas. De Grey is engaging, funny, likeable and highly intelligent, but when he wants to ram his point home he can be extremely provocative. He begins with some maths: '150,000 people die every day worldwide and of those people, two-thirds die of ageing one way or another. Those are 30 World Trade Centres every day, and if I bring forward the cure for ageing by one day I've saved 100,000 lives.'
De Grey was born and brought up in Cambridge. He never knew his father. His mother was an artist who hothoused the young Aubrey in her weak points - science and mathematics. 'She did rather too good a job of it,' he recalls.
One curious fact struck the young de Grey: 'It was completely obvious to me that ageing was a bad thing, and also that ageing must, in principle, be fixable. But the people I came into contact with seemed to think that there might be something good about ageing, that it would be dangerous to mess with it, or, even worse, that it was completely inevitable. I disagree. We are machines, and ageing is the wearing out of a machine, the accumulation of damage to a machine, and hence potentially fixable.' After studying computer science, de Grey became a software engineer and went into artificial intelligence research. But when he met and married a professor of biology, Adelaide Carpenter, his interest in ageing was reawakened.
In 1995 he made himself the first gerontological 'theorist' by reading the field's journals and textbooks and attending conferences. He did no lab work and did not apply for grants; he simply observed the subject. This position is common in physics - Stephen Hawking and Einstein are examples - but less so in biology. Two months after he began teaching himself, de Grey wrote a speculation on the accumulation of mutations in the mitochondria (the generators that power our cells, which produce the free radicals that contribute to much of the deterioration of our bodies). His paper cleared up a problem that had frustrated researchers for years. Mitochondria have their own DNA - separate from the chromasomes which reside in the nucleus - and these suffer mutations. For years researchers believed the mutations were responsible for cellular decay, but couldn't make the experimental evidence tally with the theory. De Grey's paper brought the two together. 'There's a long tradition of people coming in from a different field unencumbered by conventional wisdom and making real breakthroughs quickly,' he says.
De Grey's Norman name and hippyish figure became well known on the gerontology circuit of journals, meetings and conferences. Despite being patronised for not having done any lab work ('He doesn't know one end of a pipette from another,' one anonymous declaimer told me) his comments were still relevant and intelligent. Cambridge University awarded him a PhD in biology in 2000. He became an accepted, if fringe, member of the scene.
The process of ageing has three stages. The state of chemical flux of our bodies (metabolism) gradually causes damage to the 100,000bn cells in our bodies (deterioration) which leads to pathology (disease and illness). Most attempts to combat the ageing process either tackle the metabolism stage of things (for example, eating well or exercising) or the pathological stage (antibiotics or surgery to counter the effects of disease). One of the world's leading gerontologists, Professor Rich Miller of the University of Michigan, works on the metabolism stage of ageing. Like de Grey, he is certain that ageing isn't fixed. 'It's no longer respectable to say ageing is immutable,' he has said.
At his laboratories in Ann Arbor, Michigan, Miller works with mice and rats - two species he has managed to keep alive for impressive lengths of time. Two different diets - one restricting calories, the other restricting the amino acid methionine - have extended the life span of mice to 30 or 40 per cent longer than is usual. Not only did they live longer, but these extra months of life were healthy. Cancers and organ deterioration were delayed until the end of their lives, and the 'doctored' animals were much more active than the placebo group. 'Our special mice were running 5km on a wheel a day, months after their placebo equivalent were dead,' Miller tells me. 'If I had to bet whether it may some day be possible to extend the human life span by 30 to 40 per cent - to, say, 120 years, I'd bet yes. But it's a safe guess that I wouldn't be around to collect the winnings.'
Such extraordinary results are not sufficient to placate de Grey though, who had a 'eureka' moment in a hotel room in LA in 2000 which has taken him in a different direction to Miller. 'I suddenly had the realisation that if you focus on fixing the damage rather than on pre-empting the damage, you've got a much more feasible approach. If you look after a car very well, use lots of oil, drive it carefully and only drive on smooth roads, it's still going to deteriorate and eventually break down, whereas if you replace the parts it can go on for ever.'
One effect of the 'repairing' or 'fixing' damage route is that, if successful, it could be made to help people who have already lived a long time. For many of us it is too late to start a special diet or have our genes tampered with in such a way that would meaningfully extend our lifespan: we've simply seen too much metabolism wash under the bridge. But if the damage already laid down by this metabolism was fixed we might, theoretically, be able to arrest the ageing process in its tracks - even reverse it. According to de Grey, the therapies of the future would be of a rejuvenating nature so that 'people will be able to permanently oscillate between the physical appearance of 20 and 25'. To take this extraordinary futurism to its logical conclusion, chatting up someone in a bar in 200 years' time we would be uncertain if the beautiful person opposite was 25 or 250 years old. But de Grey is in bad company when it comes to predicting a significant extension in life span. Over the centuries a long line of charlatans, hucksters and optimists have propounded as diverse methods of postponing death as drinking from the fountain of youth or implanting goats' testicles. The one thing they have in common is that they are all dead.
'First it's scientifically absurd and secondly it's scientifically irresponsible,' Professor Tom Kirkwood says of the SENS agenda when we talk some weeks later. One of the UK's most respected bio-gerontologists, Kirkwood runs an institute and several laboratories at the University of Newcastle. The institute focuses on science that will improve the lives of the elderly. His short dark hair frames a melancholy face. In his suit he resembles a bank manager. If you were going to entrust your pension to either Kirkwood or de Grey, you'd choose Kirkwood. Not that Professor Kirkwood is a stranger to pushing back the boundaries of science.
'When I started 30 years ago I was really challenging the dogma that ageing was simply programmed into us, that there was nothing we could do about it.' In 1977 he developed the radical Disposable Soma Theory, which has been widely accepted by gerontologists ever since. The theory concluded that 'maximum life span is not clock-driven but malleable'.
Kirkwood's theory argues that ageing results from the accumulation during life of damage in cells and tissues, and that our maintenance systems have evolved during the aeons of our prehistory to cease repairing the body beyond the ages when we were likely to be dead - killed, say, by a sabre-toothed tiger - or to have become infertile. So, from what we now call middle-age, our bodies no longer try to keep us healthy to the same extent.
Prior to Kirkwood's breakthrough it had generally been thought that our bodies actively die. Now we know our bodies just stop being so proactive about living. Thus there is, theoretically, no reason why by reducing exposure to damage and enhancing the parts of the body that maintain cells we can't increase life span.
Kirkwood believes we are at a particularly tantalising time in gerontology. 'Until recently a lot of people thought ageing was too complicated to ever get a real handle on,' he says. 'Someone described it rather graphically as like a car crash - everything just gets wrecked. The exciting thing about the current science is that we are becoming like sophisticated accident investigators. We can actually understand what influences the process of ageing and what parts of the body work most successfully to keep us in good health for as long as they do. The research is moving forward fast.'
Fast is one thing; the idea of a human living for 150 years another. As for the idea of the first human millenarian already existing? 'I think that Aubrey's making assumptions that are very largely fantasy,' he says.
In Gulliver's Travels, written when the average life expectancy was 40, Gulliver, shipwrecked yet again, hears of a race of immortal humans named the Struldbruggs. Initially, he is overjoyed at the thought of freedom from 'the continual apprehension of death', but his joy soon turns to ashes when he learns that while they never die, they continue ageing. 'At 90 they lose their teeth and hair, they have at that age no distinction of taste, but eat and drink whatever they can get, without relish or appetite ... In talking they forgot the common appellation of things, and the names of persons, even... their nearest friends and relations.'
The plight of the Struldbruggs in many ways chimes with that of old people today. Deborah Dunn Walters is a senior lecturer in immunology at King's College, London. She is interested in the deterioration in our immune systems as we get older, which leaves us so much more susceptible to infection, and is all too aware of the way the body breaks down as we age. 'Most people I know working in this area are not working for life extension, they're working towards a better quality of life for elderly people,' she says. 'Infection, Parkinson's, Alzheimer's, angina - a lot of people are not fit enough to enjoy their retirement.'
Professor Kirkwood was the specialist adviser to a House of Lords report into the science of ageing which found that the over-65s now make up 18 per cent of the population, and that on average old people suffer between eight and 11 years of general ill health at the end of their lives. The report made recommendations to help increase life span and decrease the period of ill health at the end of it. There are not only humanitarian but economic reasons to do this - we want our burgeoning elderly population to cost us as little as possible. The aim is summed up as 'live longer, die faster'. The recommendations show the simplicity of much that could be done to improve the lives of the older population: more exercise, better nutrition, better oral health, better housing stock, access to the internet to counter isolation.
The report was submitted last summer to the government, whose response was 'intensely disappointing', according to Kirkwood. It is understandable in the face of this political apathy towards the elderly that Kirkwood is exasperated by the amount of attention de Grey gets. 'What we have at the moment,' he says, 'is a world in which life expectancy is increasing year by year, generating significantly increased numbers of older people; and we are aware that the extra years of life that we are gaining are not always of as high a quality as we might wish. The danger of [the SENS] agenda is that for people grappling with the realities of the ageing process it suggests that the major challenges people face in their lives today are an ephemeral problem.'
But there's another issue that troubles Kirkwood: 'By making claims about significant jumps in human life expectancy, Aubrey draws what space is available in the media for discussion of the real challenges of ageing to discussion of a complete non-issue. If he seems to be speaking on behalf of the research community on ageing he makes that community appear by association to be wildly unrealistic in its promises. We don't want people making predictions that will leave us showered in ridicule,' he says.
Fortunately for de Grey, his ideas do appeal to several affluent individuals. He has set about sidestepping traditional sources of funding by setting up the Methuselah Mouse Prize, which appeals for donations to a fund that will be offered as a prize to anti-ageing researchers, and tempt them into tackling ageing in de Grey's way. De Grey spends a few days a month fundraising in the Bay area of California, 'where most of the world's visionary billionaires can be found'. Many of them are hitting middle age and share an enthusiasm for changing the future.
As I talk to Kirkwood beside the quad, a woman comes over to tell us that 'Eric's in Baikonur launching a Proton,' and wanders over to a laptop on a garden table. The simple fact of sitting at a tiny wireless computer in Cambridge and watching a rocket being launched out of the earth's atmosphere from Kazakhstan is a breathtaking example of what humankind is capable of creating in a short space of time. When de Grey and his champions want to attack his critics they talk about Lord Kelvin dismissing the possibility of 'heavier-than-air flying machines' in 1895. Of how the X-prize - where Nasa offered $10m to the first private company to take a craft out of the earth's atmosphere twice in a week - defied the naysayers by being claimed within 10 years. In return, his detractors mention Herb Simon's 40-year-old prediction that computers would be doing all our work in 20 years' time, and Richard Nixon's 1971 declaration that his government would declare 'war on cancer'.
Thirty-six years after Nixon gave his famous speech, cancer has in no sense been eradicated as a threat - even with an estimated $25bn spent in the US alone on the disease. The result is more mixed, according to Dr Maria Blasco, an award-winning cancer scientist from Madrid. 'Certainly there are tumours that can be completely cured nowadays which used to be lethal,' she says. 'But cancer is just a common term for more than 300 diseases that have to be cured one at a time.' Curing cancer is one of the seven strands of de Grey's SENS agenda and, he concedes, the one we're furthest from sorting out. But according to Kirkwood, 'at the level of scientific understanding that Aubrey's talking about, we've known how to cure cancer for a very long time. We know broadly speaking what goes wrong; we also know very clearly what we need to do to cure cancer tomorrow: we need to be able to target an agent to kill cells that shouldn't be dividing and re-dividing and we want to spare the cells that we want to spare. But can we do it? The tragic reality is that we have large numbers of people dying well before their time.' But de Grey feels that making overly optimistic predictions does not necessarily damage the reputation of a field. 'Nixon's famous speech can now be seen to have been hasty, but has that stopped people putting funding into cancer research? No, it has not.'
While everyone is convinced that diseases like cancer should be combated, the same can not be said about ageing - research into which receives just 0.06 per cent of the US biomedical budget. Ageing is generally considered unfixable, and increasing life spans would have problematical knock-on effects. There are already serious worries about dwindling water and food resources for an expanding global population, and about global warming affecting our habitats. People worry that life extension of a dramatic sort would create an even bigger gulf between the long-lived rich and the short-lived poor. Then there is the idea that our life cycle is central to our social and moral codes.
Francis Fukuyama considers the goal of defeating ageing as 'the world's most dangerous idea'. 'What is ultimately at stake with biotechnology,' he declares in his book Our Posthuman Future, 'is the very grounding of the human moral sense.' De Grey has answers to all of these worries and more. On population: people will stop having children; we can develop colonies on the moon and Mars. On food, water, habitats: that inevitable death is a major reason why we don't sort out such problems. On morality: well, there is a trump card - de Grey will be saving 150,000 lives a day.
It's a rare medical innovation that hasn't been dubbed the 'holy grail of medicine' at some point in its life, but stem cells have probably attracted that description more than any other. Stem cells have the extraordinary ability to turn into any one of the 210 cell types we have in our body (hair, kidney, retina, blood and so on). Advances in harvesting and manipulating stem cells have conjured up the vision of growing brand new, personalised body parts, free from the risk of rejection from a patient's body. Last year, Professor Anthony Atala's lab in North Carolina grew bladders from patients' stem cells and transplanted them into their bodies.
The vision of armies of stem cells marching across the battlefields of our bodies and repairing them as new prompted large numbers of biotech start-up companies in the US to make promises they couldn't keep. From the late Nineties, a stream of bankruptcies ensued.
Then there was the case of Professor Hwang Woo-suk, who achieved incredible results with somatic cell nuclear transfer, which made him a national hero in his home country of South Korea - his face was even emblazoned on postage stamps and planes. But after appearing at the SENS conference his results began to unravel, until whistle-blowers exposed them as a series of elaborate fictions. Now considered a national pariah, he was indicted for embezzlement and breach of the country's bioethics.
Open conflicts in science are rare. Public disagreement is kept to a minimum - seen as ungentlemanly and bad for business. For several years those scientists who were perturbed by de Grey's provocations tried to ignore him into obscurity. But eventually his success in getting media attention, and a starring role at major conferences, proved too much. There was an uncharacteristically personal attack written in the respected MIT Technology Review magazine, by editor Jason Pontin. 'He dresses like a shabby graduate student and affects Rip Van Winkle's beard; he has no children; he has few interests outside the science of biogerontology; he drinks too much beer. Although he is only 41, the signs of decay are strongly marked on his face.' The editorial elicited thousands of complaints from readers shocked by the personal and 'unscientific' nature of the criticism.
Pushed to provide a reason for the attack, a somewhat chastened Pontin admitted that 'while a number of biologists have criticised SENS to me privately, none has been willing to do so in public'. In an attempt to make amends he set up a prize - in conjunction with de Grey - offering $20,000 to any molecular biologist who can submit 'an intellectually serious argument that SENS is so wrong that it is unworthy of learned debate'. A high-profile judging panel, including Craig Venter of Human Genome Project fame, considered five submissions last summer, but concluded that they 'have not demonstrated that SENS is unworthy of discussion, [although] the proponents of SENS have not made a compelling case for it'. Following the Technology Review furore, Kirkwood, Miller and 22 other gerontologists signed an open letter to the journal Embo Reports, rubbishing the SENS agenda.
De Grey was allowed to respond in the same issue, pointing out that 'engineering - of which life extension is an example, as all medicine is - differs profoundly from science in its goals, methods and skills.' On the charge of the SENS components' lack of efficacy he argued that the individual components of a car engine do not move on their own, and on the charge that SENS 'commands no respect at all within the scientific community', he cited 'a list of equally eminent individuals who have let me know they were asked to be co-authors [to the letter] but declined'. Two weeks later SENS received a donation of $1m; and last year PayPal founder Peter Thiel donated $3.5m. The combined funds now stand at $10m, with labs in Cambridge, Houston and Phoenix working on two of the strands that de Grey advocates in SENS.
In March I catch up with de Grey at a conference in Oxford. De Grey, Miller and Kirkwood all give talks before a break-out session to discuss 'Immortality: good idea or dangerous delusion'. After receiving the usual polite verbal beating, de Grey tells the group, 'I have essentially engineered this public and somewhat acrimonious debate between myself and the gerontology establishment, despite the fact that I'm not enjoying it any more than my critics. I'm going to carry on doing this either until scientific rebuttals of my proposals are provided or until people realise they don't exist.'
Kirkwood refuses to be drawn on hypotheticals about the SENS agenda and admits that he admires people who battle against the odds, 'but when it's soundly based and can be subjected to the real rough and tumble of scientific peer review. My concern,' he says, 'is that when people a couple of years down the line say, "You know, there was this long-bearded guy from Cambridge telling us all we're going to live to 5,000 years or something, what became of that?", our credibility may be damaged.'
During the conference I wander over to King's College to visit a friend struggling into his eighties with bronchitis, sciatica and other health problems. I feel a little embarrassed telling him about de Grey's theories, which shows how intoxicated I've become by the notion of a future where he will die soon and younger people will live for an extraordinarily long time. He listens patiently then recites the prayer to serenity: 'Give us the grace to accept the things that cannot be changed, courage to change the things that should be changed, and the wisdom to distinguish the one from the other'.
|| 16/09/2007. The Observer.