Another possible explanation, though more theoretical, for the efficacy of food restriction is that a diet low in calories may influence the expression of certain genes by switching them on or off, and that these genes in some way determine the rate of aging, à la Kenyon and her worms. Whatever the mechanism, it is by now well known that dietary restriction works, at least in a variety of animals from flies to mice. Though no long-term study has yet been done in humans, there is preliminary evidence from at least one small group of obese adults studied for a relatively short period of time that the technique results in decreases in insulin levels, body temperature, thyroid hormone, and damage to DNA, and decreases in all of these areas are thought to be markers of longevity.
Of course, the key word in such restriction is “severe”—or even “extreme” or “drastic.” In laboratory animals, the amount of reduction is in the range of 50 percent, a figure that few men or women would tolerate for any significant period. At least for the present, such a regimen is a practical impossibility, but that situation could change. It may be that various drugs will be developed that by one or another mechanism make such a program tolerable for those willing to forgo the normative gustatory pleasures of life.
But whatever may happen in the far-off future, the one certainty with which no responsible scientist can disagree is that there is at present no medicine or pill of any value to combat aging, nor is there likely to be one soon, if ever. Even those optimistic researchers who, with dollar signs flashing in their eyes, have partnered themselves with investors and management teams to found companies with promising names that seem to ensure eternal youth and health cannot fairly claim that they are anywhere near their goals, whether in the laboratory or at the stock exchange. Some of our most experienced biogerontologists are convinced that no “aging gene” will ever be found. Others point out that manipulating telomeres has the frightening potential to unleash an uncontrolled torrent of cellular reproductive changes sufficient to vastly increase the frequency and severity of cancer at the same time that it leads us to as yet unpredictable influences on growth and development, not only in adults but in their offspring as well.
Though extreme caloric restriction would appear to have some real promise, it may very well be that the disadvantages associated with it will deter all but the most determined—or foolish—men and women from taking part in it. As for the present market in panaceas—ranging from growth hormone to injections of freeze-dried extracts derived from fetal cells—be assured that, the loud claims of irresponsible hucksters to the contrary, no modality now available has any usefulness, and some may be more than a little dangerous.
All of this has been heady stuff, but not heady enough for one remarkable man, whose vision reaches far beyond a mere few centuries of life. Aubrey de Grey thinks in terms of millennia, perhaps eternity. He believes that he has identified the molecular basis for aging; he believes that aging can be prevented with means that are at present barely—if at all—visible on the horizon but nevertheless not entirely impossible. De Grey would rearrange the responses of our bodies to the passage of time, to heredity, and to the biology of life, because he believes to the depths of his soul that none of us should have to die if we choose not to. At the very least, he believes the process of aging must be not only stopped but reversed. It is by his description “repulsive,” and the death that is its outcome is “barbaric.”
His choice of such vivid words reveals a great deal of what must be understood about de Grey, and about others so obsessed with the inevitability of death that they become zealots in their determination to thwart its designs. They would transcend biology, ecological imperatives, and the very nature of humanity all at once. To ponder the propositions of Aubrey de Grey is to ruminate on the entire philosophy of that small cadre of scientists who have convinced themselves that extreme life extension is a worthy endeavor—worthy of their talent, worthy of the vast amount of money that would have to be poured into it to the neglect of more immediate health concerns all over the globe, and worthy of the traditional aims of the scientific enterprise. In any study of aging, account must be taken of those who would seek to prolong our lives far beyond its species-determined length, and perhaps forever.
At the request of Jason Pontin, the editor of the MIT Technology Review, I traveled to Cambridge University in the fall of 2004, to spend the better part of two days with de Grey. The pages that follow are the story of my visit to England. I have since then spent more hours in de Grey’s company, at a conference in Spoleto, Italy, in the summer of 2005, where we spoke on opposing sides at a conference called “Altering Human Destiny.” Each time I hear him describe what to me seems the science fiction of his worldview and his conviction that life is a problem in engineering, I return to my own most deeply held certainty about the biology of our planet: the exquisitely delicate balance that allows it to exist—achieved over the course of 4.6 billion years for Earth itself and 3.5 billion for the living things that swarm on it—and is never entirely safe from going awry. There are immutable laws in nature that have allowed life to thrive, and we violate them at our own peril.
It was Sir Francis Bacon, the father of the scientific method of reasoning in the seventeenth century, who wrote, “Nature, to be commanded, must be obeyed.” But some fifty years earlier, Michel de Montaigne had already unknowingly fired off a preemptive response to the life-extending futurists who would appear in our much later era. He presciently cautioned his readers and posterity that men should not tamper with nature, because “she knows her business better than we do.”
Wandering through the quadrangles and medieval bastions of learning at Cambridge University one overcast Sunday afternoon shortly after my arrival to visit de Grey, I found myself ruminating on the role played by this venerable place as a crucible for the scientific revolution that changed humankind’s perceptions of itself and of the world in the seventeenth century. The notion of Cambridge as a source of grand transformative concepts was very much on my mind that day, because I had traveled to England to meet a contemporary Cantabrigian who aspires to a role in the history of science similar to those of Francis Bacon, Isaac Newton, and William Harvey. Aubrey David Nicholas Jasper de Grey is convinced that he has formulated the theoretical means by which our species might live thousands of years—indefinitely, in fact.
Perhaps “theoretical” is too small a word. De Grey has mapped out his proposed course in such detail that he believes it may very well be possible for his objective to be achieved within as short a period as perhaps thirty-five years from now, in time for many people now alive to avail themselves of its formulations—and, not incidentally, in time for his forty-one-year-old self as well. Like Bacon, de Grey has never stationed himself at a laboratory bench to attempt a single hands-on experiment, at least not in human biology. He is without qualifications for that, and makes no pretensions to being anything other than what he is, a computer scientist who has taught himself natural science. Aubrey de Grey is a man of ideas, and he has set himself toward the goal of transforming the very basis of what it means to be human.
For reasons that memory cannot retrieve, de Grey has been convinced since childhood that aging is, in his words, “something we need to fix.” Having become interested in biology after marrying a geneticist in 1991, he began poring over texts, and taught himself until he had mastered the subject far beyond the field’s mere essentials. The more he learned, the more he became convinced that the postponement of death was a problem that could very well have some real solutions, and given enough time, he might be just the person to find them. As he reviewed the possible reasons why so little progress in “fixing” aging had been made, in spite of the remarkable molecular and cellular discoveries of recent decades, he came to the conclusion that the nut might be far less difficult to crack than some thought. The lack of progress seemed to him related to a factor too often brushed under the table when the motivations of scientists are discussed, namely, the small likelihood of achieving
promising results within the period required for academic advancement—careerism, in a word. As he puts it, “High-risk fields are not the most conducive to getting promoted quickly.”
De Grey began reading the relevant literature in late 1995 and after only a few months had learned so much that he was able to explain previously unidentified influences affecting mutations in mitochondria, which are the intracellular structures within which certain chemical processes release energy for the cell’s functioning. Having contacted an expert in this area of research who told him that he had indeed made a new discovery consistent with available data, de Grey published his first biological research paper in 1997, in the peer-reviewed journal BioEssays (“A Proposed Refinement of the Mitochondrial Free Radical Theory of Aging,” BioEssays 19(2):161–66, 1997). By July 2000, further assiduous application had brought him to what some have called his “Eureka moment,” the insight to which he refers as his realization that “aging could be described as a reasonably small set of accumulating and eventually pathogenic molecular and cellular changes in our bodies, each of which is potentially amenable to repair.” This concept became the theme of all theoretical investigation he would do after that time; it is the leitmotif of his life. He became determined to approach longevity as what can only be called a problem in engineering. If it were possible to know all the components of the variety of processes that cause animal tissues to age, he reasoned, it might also be possible to design remedies for each of them.
All along the way, de Grey would be continually surprised at the relative ease with which the necessary knowledge could be mastered—or at least he himself found it so. And here a caveat must be issued, a variant of those seen in television commercials featuring some daredevil and seemingly impossible automotive stunt: “Do not attempt this on your own. It is extremely hazardous and requires special abilities.” For if there is a single impression that can be taken away from spending even a modicum of time with Aubrey de Grey, it is the indubitable one that he is the possessor of special abilities.
As he surveyed the literature, de Grey reached the conclusion that there are seven distinct ingredients in the aging process, and that emerging understanding of molecular biology shows promise of one day providing appropriate technologies by which each of them might be manipulated. His certainty that there are only seven such factors—and that others are unlikely to be found—is based on the lack of discoveries of any new ones in some twenty years despite the flourishing state of research in the field that has come to be known as biogerontology, the science of aging. His certainty that he is the man to lead the crusade for endless life is based on his conception that the qualification needed to accomplish it is the mind-set he brings to the problem: the goal-driven orientation of an engineer rather than the curiosity-driven orientation of the basic scientists who have made and will continue to make the laboratory discoveries that he intends to employ. He sees himself as the applied scientist who will bring the benisons of molecular biology to practical use. In the analogous terminology often used by historians of medicine, he is the clinician who will bring the laboratory to the bedside.
And so, in order to achieve his goal of transforming our society, de Grey has transformed himself. His “day job,” as he described it to me, is relatively modest; at the time we met, he was working as the computer support for a genetics research team, and his entire official working space was a corner of its small lab. And yet, he has achieved international renown and more than a little notoriety in the field of aging, not only for the boldness of his theories, but also because of the forcefulness of his proselytizing for them. His stature has become such that he is a factor to be dealt with in any serious discussion of the topic, to which he has documented his contributions through scores of articles in the scientific literature. De Grey has published in an impressive array of peer-reviewed journals, including those of the quality of Science, Biogerontology, Trends in Biotechnology, Annals of the New York Academy of Sciences, and the aforementioned BioEssays, among others.
De Grey has been indefatigable as a missionary in his own cause, joining the appropriate professional societies and evangelizing in every medium available to him, including one of his own making, the sponsoring of an international symposium. Though he and his ideas may be sui generis, he is hardly an isolated monkish figure content to harangue the heavens and desert winds with his lonely philosophy. In addition to everything else, he seems to have a remarkable talent for organization and even for his own unique brand of fellowship. The sheer output of his pen and tongue is staggering, and every line of that bumper crop, whether intended for the most scientifically sophisticated or for the general biology-interested reader, is delivered in the same linear, lucid, point-by-point style that characterizes his writings on life prolongation. Like a skilled debater, he replies to arguments before they arise and hammers at his opposition with a forceful rhetoric that has just enough dismissiveness—and sometimes even castigation—to betray his impatience with stragglers in the march toward extreme longevity.
De Grey’s is a familiar figure at meetings of certain kinds of scientific societies, where he has earned the respect of many gerontologists and that new variety of theoreticians to which the press has given the name “futurists.” Not only has his work put him at the forefront of a field that might best be called theoretical biogerontology, but he swims close enough to the mainstream that some of its foremost champions and researchers have willingly agreed to have their names on his papers, despite not being in agreement with the full range of his thinking. Among the most prominent are such highly regarded figures as Bruce Ames of the University of California, the University of Chicago’s Leonid Gavrilov, and S. Jay Olshansky from the University of Illinois at Chicago. Their attitude toward him is perhaps best expressed by Olshansky, who is a senior research scientist in epidemiology and biostatistics: “I’m a big fan of Aubrey; I love debating him. We need him. He challenges us and makes us expand our way of thinking. I disagree with his conclusions, but in science that’s okay. That’s what advances the field.” De Grey has by his vigorous efforts brought together a kind of cohort of responsible scientists who see just enough theoretical value in his work to justify not only their engagement but also their cautious encouragment. As Gregory Stock, a futurist of biologic technology currently at Princeton, has pointed out to me, de Grey’s proposals create scientific and public interest in every aspect of the biology of aging. Stock, too, has lent his name to several of de Grey’s papers.
De Grey enjoys popular fame as well. He is often called upon when journalists need a quote on anti-aging science, and he has been the subject of profiles in publications as varied as Fortune, Popular Mechanics, and the London Daily Mail, and, more recently, the subject of television documentaries. His tireless efforts at thrusting himself and his theories into the vanguard of a notion that has been eternally fascinating to the human mind have put him among the most prominent proponents of anti-aging science in the world. And his timing is perfect. With the baby boomers—perhaps the most determinedly self-improving (and self-absorbed) generation in history—now approaching or having reached their early sixties, there is a plenitude of eager seekers after such death-defying panaceas as he promises. De Grey has become almost more than a man; he is an entire movement. And that movement epitomizes the ancient and perennial yearning for eternal life.
I should declare here that I have no desire to live beyond the life span that nature has granted to our species. For reasons that are pragmatic, scientific, demographic, economic, political, social, emotional, and secularly spiritual, I am committed to the notion that both individual fulfillment and the ecological balance of life on this planet are best served by dying when our inherent biology decrees that we do. I am equally committed to having that age be, as close as modern biomedicine will allow, our biologically probable maximum of approximately 120 years, and I’m also committed to efforts at decreasing and compressing the years of morbidity and disabilities now attendant on
extreme old age. But I cannot imagine that the consequences of doing a single thing beyond this will be anything but baleful, not only for each of us as an individual, but for every other living creature in our world. Another action I cannot imagine is enrolling myself—as has de Grey—with Alcor, the cryogenics company that will, for a price, preserve a customer’s head or more until that hoped-for day when it can be brought back to some form of life.
With this worldview, is it any wonder that I would be intrigued by an Aubrey de Grey? What would it be like to come face-to-face with such a man? Not to debate him—as a clinical surgeon I would be scientifically unqualified—but just to sound him out, to see how he behaves in an ordinary situation, to speak of my concerns and hear his responses—to take his measure. To me, his philosophies are outlandish. I would in time discover that, to him, mine are equally so.
With all of this in mind, I contacted de Grey via e-mail in the fall of 2004, and received a response that was both gracious and welcoming. Addressing me by first name, he had no hesitation in offering to give up the better part of two days to speak with me, and moreover suggested that we spend them close to the lubricating effects of invigorating fluids, as follows:
I hope you like a good English beer, as that is one of the main (open) secrets of my boundless energy as well as a good part of my intellectual creativity (or so I like to think…). A good plan (by which I mean a plan that has been well tested over the years!) is to meet at 11:00 A.M. Monday 18th in the Eagle, the most famous pub in Cambridge for a variety of reasons which I can point out to you. From there we may (weather permitting) be able to go punting on the Cam, an activity with which I fell in love at first sight on arriving here in 1982 and which all visitors seem to find unforgettable. We will be able to talk for as long as you like, and if there is reason to meet again on the Tuesday, I can arrange that too.
The Art of Aging Page 17