The new scientific search for immortality
Goat testicle transplants. Elixirs of jade. Inhaling the breath of virgins. Injecting crushed dog gonads. Drinking radioactive waters.
These are just a few of the ways people have sought to lengthen their lives and renew their vitality. The oldest narrative to come down to us through the millennia—the Gilgamesh saga, from ancient Sumeria—describes a quest for immortality and perpetual youth. Enkidu, bosom buddy of the semi-divine King Gilgamesh, is killed for mocking the gods. The heartbroken king seeks the advice of Utnapishtim and his wife, the only two mortals to whom the gods have granted eternal life. Utnapishtim directs Gilgamesh to a certain waterweed that will restore his youth. Gilgamesh finds it but falls asleep, and a snake eats the weed. In the end, Gilgamesh realizes that the only immortality human beings can aspire to is making names for themselves as builders of cities.
This is, to say the least, unsatisfactory. As Woody Allen once put it, "I don't want to achieve immortality through my work. I want to achieve it through not dying." Modern biomedical researchers, in the quest for the equivalent of Gilgamesh's waterweed, have made great progress in unraveling the mystery of aging. Physical immortality may not be in the immediate offing, but the day may come when death is radically postponed, if not fully optional.
The barriers to this goal are not just biological but political. Believe it or not, some of our most influential contemporary intellectuals are opposed to the idea of long, healthy lives. "The finitude of human life is a blessing for every individual, whether he knows it or not," wrote Leon Kass, the president's favorite bioethicist, in the May 2001 issue of First Things. Francis Fukuyama warns in his new book Our Posthuman Future that young geezers will "refuse to get out of the way; not just of their children, but their grandchildren and great grandchildren."
And then there's Daniel Callahan, co-founder of the Hastings Center, the nation's leading bioethics think tank. "There is no known social good coming from the conquest of death," he declared at a March 2000 conference on aging and life extension. He added, "The worst possible way to resolve this issue is to leave it up to individual choice."
On the scientific front, though, there's good reason for optimism. "The prospects of dramatically increasing human longevity are excellent," declares Steven Austad, a biologist at the University of Idaho. "Don't expect them tomorrow, but there will be major advances within the next 50 years." Austad, author of the 1997 book Why We Age: What Science Is Discovering About the Body's Journey Through Life, expects 20- to 40-year jumps in longevity to occur later in this century.
"We see ourselves on the cusp of the second longevity revolution," agrees Jay Olshansky, a demographer at the University of Chicago and the author of The Quest for Immortality (2001). "Scientists are on the verge of discovering major secrets of aging." The first longevity revolution occurred in the early 20th century, as infant mortality declined and infectious diseases were conquered; as a result, more young people now enjoy the opportunity to become old. The next longevity revolution, by contrast, will actually postpone old age.
Of the two researchers, Olshansky can be considered the pessimist. He bet Austad $500 million that there will no 150-year-old person alive and in fairly good shape in 2150. The bet was set up as a trust fund endowed by $150 from each scientist. Given the math behind compound interest, the winner's heirs will get the $500 million payout on January 1, 2150.
Love and Death
Woody Allen might appreciate the science of longevity as well as the results. Sex and death, it turns out, are inextricably intertwined. "It doesn't pay to have a body that will last forever," notes Austad. "Evolution only cares about reproduction." Every body harbors a line of immortal cells: the germ cells that produce eggs and sperm. Germ cells migrate from body to body down the millennia, disposing of their worn-out carriers as they move on. Once your ovaries or testes are done with you, they couldn't care less whether you live.
Here, then, is the definitive an-swer to the eternal question: Which came first, the chicken or the egg? The egg did. A chicken is merely an egg's way of making more eggs.
In the case of human beings, evolution has selected for a set of genes that keep our bodies in pretty good shape long enough to mature sexually, produce progeny, and raise those progeny to sexual maturity. Time elapsed: about 40 years. The evolutionary insight here is that if a body invests a lot of energy in repairing itself, it will reduce the amount it can devote to reproduction. That may be good for individual bodies, but your germ cells have no interest in keeping you forever young.
The UCLA biologist Michael Rose firmly established the evolutionary connection between sex and death by breeding fruit flies. Rose selected only those flies that reproduced late in life and bred them with one another. The longer it took the insects to reproduce, the longer they lived. Rose now has flies that live 130 days instead of the usual 40.
The connection was further bolstered this January by Cynthia Kenyon, a biologist at the University of California at San Francisco. Kenyon reported that she could double the life spans of nematode worms by removing their germline stem cells—the cells that produce eggs and sperm. Then there's Lawrence Donehower's recent research at Baylor Medical College. Donehower has found that the genes that are helpful in guaranteeing a robust youth are harmful in the long run. The tumor-suppressing p53 gene keeps us from developing cancers in early life, but at the cost of stimulating our immune systems to destroy over time the reserve of rapidly dividing stem cells that replenish our tissues. As our stem cells are killed off, our tissues deteriorate. The result of this "antagonistic pleiotropy" is aging.
Another example of antagonistic pleiotropy was discovered by the biologist Leonard Hayflick in 1961. Hayflick, now at U.C. San Francisco, found that human cells in vitro would divide only 50 to 80 times, then stop. For a while, some researchers thought this "Hayflick limit" might be the key to aging. What it appears to be is an evolved mechanism to prevent cancer. Cancer is the uncontrolled proliferation of cells, and as cells divide they often accumulate errors that predispose them toward becoming cancerous. If there is a limit on the number of times a cell can divide, such a limit prevents cells from eventually mutating into cancer cells.
How do cells know when to stop? Through telomeres, caps composed of repetitive DNA sequences at the ends of chromosomes. These function somewhat like the aglets on the ends of shoelaces that keep them from unraveling. Through a peculiarity in DNA replication, each time a cell divides, its daughter cells lose a tiny bit of their telomeres. Once the telomeres are gone, the cell stops dividing and becomes senescent.
Two types of cells do not suffer this problem. One is the germ cells that are the progenitors of sperm and eggs. Their telomeres are restored by an enzyme called telomerase, making them essentially immortal. The other group is cancer cells. They can divide without limit, which is what makes them so deadly.
Significant aging is a relatively new phenomenon. Over evolutionary history, once creatures began to falter in any way, they were eaten or dropped dead of disease—eaten by bacteria, as it were—so they never had a chance to get old. "As soon as an animal in the wild starts to slow down even a little bit, it's eliminated from the population very quickly," says Simon Melov, a researcher at the Buck Institute, a nonprofit organization devoted to aging research. "Aging is not a natural state for us either," he adds. "The evidence we have indicates that 10,000 to 20,000 years ago, most people didn't live much past 30." Today, the only creatures that actually experience aging are human beings and the animals they protect, such as pets and livestock.
The Roots of Aging
But what is aging, anyway? We all know it when we see it, but it's very hard to tease aging itself from the various diseases that accompany it. Michael Straight, a former editor of The New Republic, was asked when he was 80 what it felt like to be an old man. Straight replied, "I feel like a young man who's got something very bad wrong with him." In the language of gerontology, there are no good biomarkers for aging.
Even today, many things besides aging kill people—primarily, diseases and accidents. Then again, as we age we become increasingly vulnerable to the shocks and diseases that can kill us. In modern societies, disease plays a relatively small role in killing off younger people: If all the causes of death in the United States before age 50 were eliminated, average life expectancy would increase by only three and a half years. Meanwhile, Jay Olshansky has estimated that if all deaths from heart disease, cancer, and stroke were eliminated entirely the average life expectancy in the United States would increase to between 90 and 95. In the 19th century the insurance actuary Benjamin Gompertz pointed out that as people age, their chance of dying doubles every eight years or so. Thus, a 35-year-old is twice as likely to die at age 43 and four times as likely to die at age 51.
Is there an upper limit on human lifespans? Researchers reported in the April 29 Science that life expectancy has been increasing at about two and a half years per decade for the last 160 years. Demographers like Olshansky, they note, have been consistently wrong in predicting an upper limit to human life expectancy. In 1928, for example, the demographer Louis Dublin predicted that average life expectancy in the United States would never exceed 64.75 years. Today it is 76.7.
At this rate of improvement, the authors of the Science report conclude, "record [average] life expectancy will reach about 100 in six decades." Still, as far as we know, the maximum human life span is the 122 years achieved by the cigarette-smoking French woman Jeanne Calment, who died in 1997.
Aging is accompanied by lots of simultaneous changes—graying hair, thinning bones, weakening muscles, failing immune systems. So far, researchers have not figured out whether those changes are aging itself or just symptoms of some more general process of decay.
Scientists are now in wide agreement that aging can largely be traced to the damage done to our cells by free radicals. A free radical is an atom or molecule that has at least one unpaired electron, causing it to be very chemically reactive. Lots of free radicals are created in cells as they produce energy. Free radicals disrupt a cell's DNA and protein synthesis and repair mechanisms. The Berkeley biologist Bruce Ames has calculated that oxygen radicals damage the DNA inside each cell some 10,000 times per day.
Each time a cell replicates, it copies all of the billions of DNA base pairs that comprise its genome. Cells are very crowded and chemically energetic places, so miscopying sometimes occurs. Fortunately, evolution has devised molecular machines that can rapidly read and then correct most of the copying mistakes, keeping the cells to a fantastically accurate rate of one error per billion nucleotide replications. However, each time the repair mechanisms miss a mistake, it becomes encoded in the DNA—and the next time duplication occurs, the miscopied DNA is treated as correct. As a result, errors accumulate over time. Miscopied genes lead to the production of distorted proteins, which are inefficient when they work at all. The accumulated molecular damage causes a 0.5 percent decline per year in overall physical capacity after age 30.
Increasingly, researchers are focusing their attention on the damage free radicals cause in the tiny energy-producing organelles called mitochondria. Like any other power plant, mitochondria produce not just energy but also wastes and pollution, including copious free radicals. As good as mitochondria are at mopping these up, some of them nevertheless get loose and damage the tiny DNA genomes at the heart of the mitochondria. Free radicals create a cellular death spiral by mutating mitochondrial DNA, which in turn degrades their energy production and increases the production of free radicals, refueling the cycle.
Other research points to another process linking free radicals to aging. Apparently, we are literally cooking ourselves to death. In cooking, sugars and proteins stick together to form tasty brown crusts like those on French toast. Our own metabolisms are a form of low-temperature cooking that causes sticky sugars such as glucose to cross-link with proteins to create advanced glycation end products (AGEs). AGEs are biological junk that accumulates in cells, interfering with their functions over time. For example, AGEs reduce the elasticity and flexibility of the collagen in our ligaments. They are also linked to diabetes and to cardiovascular disease.
In a related process, our cells' recycling centers, called lysosomes, become clogged with cross-linked proteins and other cellular rubbish. This cellular gunk is called lipofuscin. Lipofuscin-filled lysosomes slowly crowd and hinder other cellular functions.
Another process involving free radicals is inflammation. Inflammation occurs when our immune system cells drench invaders such as bacteria and viruses with free radicals to rip them apart. The problem is that sometimes the inflammatory attacks don't ratchet down when the threat is gone, and our immune cells keep pumping out free radicals. Chronic inflammation has been linked to many diseases associated with aging, including arthritis, atherosclerosis, diabetes, Alzheimer's, and cancer.
The free radical theory of aging is backed by more than seven decades of research on calorie restriction. In 1935 Clive McCay, a professor of nutrition at Cornell, noted that if laboratory rats are fed only about two-thirds of the food they would freely choose to eat, their life spans increase by 40 percent to 50 percent. This result has been confirmed many times since then. Researchers think that semi-starvation may make metabolic processes more efficient, producing fewer free radicals and also perhaps boosting cells' DNA repair systems, since the hungry organism may have to live longer in order to reproduce.
Besides free radicals and telomere shortening, re-searchers have long noted that as our bodies age the levels of several key hormones begin to decline—testosterone for men, estrogen in women, DHEA and growth hormone for everyone. Boosting the levels of these hormones has become the stock in trade for the growing business of longevity clinics.
So what are your chances of living forever? First the bad news. As U.C.San Francisco's Leonard Hayflick recently told The Washington Post, "There is no intervention that has been proven to slow, stop, or reverse aging. Period."
Now the good news: Despite that, researchers are making a lot of progress.
Probably the most promising immediate thing you can do to increase your chances of seeing your great-grandchildren is to stop eating so much. Calorie restriction is the only known technique for increasing the life spans of many different organisms. The foremost advocate of this approach is probably the UCLA biologist Roy Walford, whose Web site offers menus for those who want to pursue longer life by dieting themselves nearly to death. Calorie restriction may not make your life longer, but it will certainly make it feel that way.
Barbara Hansen, a diabetes researcher at the University of Maryland, has spent 20 years investigating the effects of calorie restriction on rhesus monkeys. The experiment has not run long enough to determine if the ultimate life spans of the calorie-restricted monkeys will be increased. But on several related issues, her findings are unequivocal: When she compares old calorie-restricted monkeys to old monkeys that eat what they want, the calorie-restricted ones do not have heart disease, diabetes, or hypertension, and their cholesterol is lower. They're healthier.
There is no question that maintaining a reasonable weight prevents the onset of many illnesses associated with aging. But what if you find the notion of living without foie gras and pepperoni pizza unbearable? Is there hope for you?
There may be. Hansen hopes that by starving monkeys she can pave the way to a pill providing all the health benefits of calorie restriction while allowing you to inhale all the ice cream and beer you want. She has identified a compound that affects the PPAR-Delta receptor, which improves the body's response to insulin and glucose, mimicking the benefits of calorie restriction. It is now in early testing by Glaxo.
Calorie restriction research could also help us discover aging's elusive biomarkers. With the sequencing of the human genome and the advent of chip gene technologies, researchers can monitor the simultaneous actions of thousands of genes in tissues. The aim is to characterize the differences between the gene activity in tissues from old people and the gene activity in tissues from young people. Already, chip tests have found that the gene expression of tissues taken from old, calorie-restricted mice is similar to that found in young mice.
Among other benefits, finding such biomarkers would be a major advance in testing interventions for their effectiveness in slowing aging. Right now, the only way to see whether a proposed longevity treatment works is to wait for people to die.
Cloning for Longevity
If calorie restriction isn't your cup of tea, regenerative medicine is the next best bet for near-term success. The most promising path to regenerative medicine is the controversial process known as therapeutic cloning. If you need a new heart or liver, it might be possible to grow a new perfect transplant using your own cells. The process would involve transferring the nucleus of one of your skin cells to an enucleated human egg, which would then grow in a petri dish to the blastocyst stage. Stem cells would be harvested from the blastocyst and transformed into the desired tissues for transplant.
Stem cells have been found in adult tissues, in umbilical cord blood from newborns, and in embryos. All have shown some promise. William Haseltine, the CEO of Human Genome Sciences, recently predicted in The Washington Post that it will one day be possible to "reseed the body with our own cells that are made more potent and younger, so we can repopulate the body." But stem cell transplants are at least 10 years away—or even longer, if Leon Kass and his allies succeed in banning therapeutic cloning. Since the chorus calling for a ban includes President Bush, the prospects for research in this area are not as bright as they ought to be.
Another problem: Regenerative medicine does not stop or slow aging. It just fixes the problems and diseases that accompany aging. In a sense, it's just a better form of conventional medicine. Continually trading in your old, worn-out organs for new ones is certainly better than the alternative, but it would be ever so much more pleasant if you could just stay young forever.
The true fountain of youth will involve stopping those pesky free radicals that are wrecking your DNA and cooking your tissues to death. The most popular anti-aging regimen, practiced by millions of Americans, is to pop anti-oxidant vitamin and mineral pills. There is no firm scientific evidence that gobbling down such supplements actually increases life spans. Simon Melov of the Buck Institute for Aging Research notes that the effects of anti-oxidant pills are fairly weak, since most of the nutrients don't get inside the cells where the free radical damage is occurring. Jay Olshansky dismisses megadose vitamin supplements as "a way to make expensive urine."
On the other hand, Olshansky admits that some people can benefit from vitamin supplements. Epidemiological studies show that vitamin E supplements might help 12 percent of the population. The problem is, each individual has no way of knowing now whether he or she is part of that 12 percent. Nevertheless, many of us cover our bets by taking supplements anyway.
A recent study conducted by Bruce Ames' team at Berkeley found that lethargic old rats are perked up by l-carnitine and alpha lipoic acid. Their mitochondrial function improves, they become more active, and their memories get better. A company called Juvenon, founded by Ames and others, is testing the supplements in people with the goal of finding an effective human dose.
Meanwhile, Thomas Perls of Harvard is hunting for longevity genes. Perls noticed a decade ago that people who live to be 100 are often in remarkably good shape. Today, he runs the New England Centenarian Project, whose participants must be 100 years old and have siblings who lived to be over 90. By looking at DNA taken from some 600 participants so far, Perls has found that a region on chromosome four appears to help its carriers become healthy geezers.
Perls and his colleagues have formed a company called Centagenetix to narrow the search for the longevity gene. Once it's identified, Centagenetix will try to produce a Methuselah pill that mimics the activity of the proteins made by the longevity gene.
The M.I.T. biologist Leonard Guarente recently showed that nematode worms with more than one copy of a gene called SIR2 live 50 percent longer than normal worms. This may explain why calorie restriction increases life span, because SIR2 slows down gene activity when a cell is being starved. Guarente and Cynthia Kenyon have already identified genes and enzymatic pathways that increase the life spans of invertebrate species. They believe that these same mechanisms will be found in people, giving them targets at which to aim anti-aging drugs. Guarente and Kenyon have created a company called Elixir, which will try to develop such pharmaceuticals.
Eurkarion, a privately held biotech start-up in Massachusetts, is working with the Buck Institute's Melov to test its novel small-molecule anti-oxidant compounds. Melov has genetically engineered mice that don't produce superoxide dismutase, the oxygen-scavenging enzyme that protects mitochondria from free radicals.
Such mice typically die within a week after birth. They suffer from enlarged hearts, damaged livers, and a spongiform brain ailment that looks very much like mad cow disease. But when these mice are injected with compounds that mimic the effects of superoxide dismutase and catalase (a compound that transforms hydrogen peroxide into water), they live four times longer. Eukarion is currently testing one of its compounds as a topical application to heal skin damaged by radiation treatments. It plans to test further compounds as treatments for degenerative neurological diseases in human beings.
As for the gunk built up in our cells, researchers are testing some compounds that break apart AGEs, enabling cells to get rid of them. In preliminary testing, a compound called Pimagedine has improved cardiac function in rats, dogs, and primates. It is also being tested for efficacy in treating kidney failure associated with diabetes. Another anti-AGEing compound, ATL-711, has shown some promise as a treatment to reverse age-related and diabetes-related cardiovascular diseases and restore function to the cardiovascular system.
What about lengthening telomeres? Remember, our immortal germ cells activate the gene that produces the enzyme telomerase, which restores the ends of their telomeres whenever they divide. Cancer cells also stimulate production of the enzyme. The Geron Corporation is conducting research into how to use telomerase to fight cancer. The idea is that if you can turn off telomerase in the cancer cells they will stop dividing and commit cellular suicide, called apoptosis.
Some researchers have suggested that it might be possible to make normal cells immortal by getting them to produce telomerase, which could prevent the shortening of their protective telomeres. It seems logical that if telomere shortening causes cells to become senescent, lengthening them should rejuvenate them and the tissues in which they reside. Still, according to Barbara Hansen, there is little evidence that telomere shortening causes senescence on the organism level.
Hormone replacement therapy is second only to vitamin supplements in popularity among those seeking the fountain of youth. The aim here is to restore the hormones that decline with age to their youthful levels. The most popular hormones involved are DHEA, human growth hormone, melatonin, testosterone, and estrogen.
The notion that hormones could restore youth has a long and disreputable history. In the late 19th century the noted French physiologist Charles Edouard Brown-Sequard injected himself and his patients with extracts from the testicles of young dogs and guinea pigs, then declared that the treatments had restored his physical vigor and mental acuity. In the early 20th century the American John Brinkley claimed to restore men's vitality by transplanting goat testicles into them. He performed over 16,000 transplants before he died, though his medical license was revoked after some of his customers claimed a new compulsion "to chew sprouts."
More recently, hormone replacement therapies took off after the endocrinologist Daniel Rudman reported in 1990 that a dozen older men he had injected with growth hormone three times a week had more muscle mass, less fat, tauter skin, and lower cholesterol levels. Subsequent studies have shown that these quality-of-life benefits are real but slight. In fact, regular exercise is more effective in obtaining most of the gains achieved from injecting growth hormone.
Furthermore, there is no evidence that growth hormone treatments increase longevity. Indeed, mice that overproduce growth hormone die sooner than normal mice, and fruit flies that underproduce growth hormone live longer than normal flies. In addition, some researchers suspect that supplementary growth hormone may increase the risk of cancer.
DHEA is the most abundant steroid in the body, yet nobody knows much about what it does. It is clear that DHEA levels peak in a person's early 20s and decline as he or she ages. Interestingly, feeding DHEA to mice, which produce very small quantities of this hormone naturally, increases their life spans by 40 percent. In Why We Age, Steve Austad notes that in the few scientifically valid human trials involving DHEA supplementation, the hormone produced "some improvement in immune response, muscle strength, and sleep patterns among the elderly." Still, not much is known about the effects of the long-term use of this hormone, so most researchers advise caution.
Much has also been made of the so-called "melatonin miracle." But rigorous testing of melatonin's effects on human beings has not been done yet. Mice that are fed melatonin live 5 percent longer but are at a greater risk of developing tumors. Again, most researchers advise caution.
So far, estrogen replacement therapy is the most effective hormone treatment. Epidemiological evidence suggests that supplemental estrogen after menopause helps prevent osteoporosis. But recent research has undercut claims that estrogen therapy reduces the risk of heart disease and dementia. Using estrogen does slightly increase the risk of ovarian cancer and promotes the growth of existing breast tumors. Estrogen may delay the onset of certain diseases that become more common as women grow older, but there is no evidence that it increases users' life spans.
Testosterone levels generally drop in men as they age. Research on testosterone has lagged behind estrogen research, perhaps because of the unsavory treatments of the past and perhaps because of steroid abuse among athletes. There are some indications that testosterone replacement can provide benefits to older men, including increasing muscle tone, overcoming erectile dysfunction, and improving their overall sense of well-being. On the other hand, it might promote the growth of any pre-existing prostate tumors. There are other unwelcome side effects, including increased hairiness and acne. And there is no evidence that testosterone supplementation will increase longevity.
The Genetic Imperative
Looking further down the road, once the genes that promote disease (Alzheimer's, diabetes, cardiovascular problems) and those that promote longevity are identified, it will become possible for parents to select favorable genes for their progeny. Already, more than 1,000 healthy children have been born after their parents used pre-implantation genetic diagnosis to select among eight-cell embryos to find the ones that were free of disease genes. In the future, parents might also select embryos that bear longevity-promoting genes and implant those. Further in the future, parents will be able to add genes that improve their progeny's immune systems, mental acuity, and athletic abilities by installing artificial chromosomes.
The Cambridge gerontologist Aubrey de Grey wants to genetically engineer mitochondrial genes into the nuclei of cells, where they would be better protected from the ravages of free radicals. He believes that once those genes are better protected they will not be so quickly mutated into the free radical death spiral. Once the vicious circle of mitochondrial mutations producing ever more free radicals is broken, longer life should result, he argues.
Even further in the future, another method to improve how human cells protect themselves from the ravages of free radicals might be possible. Some animals, such as birds, have more effective anti-oxidant protective mechanisms. Using them as a model, we might tweak our own genes. This could be the moral equivalent of replacing human anti-oxidant genes with similar but more effective genes from birds.
An even more visionary approach has been suggested by Robert Bradbury, whose startup Robiobotics is investigating the possibility of repairing whole genomes by using bacteria to ferry artificial chromosomes into human cells. The genetically engineered bacteria would infect billions of a patient's cells and deliver artificial chromosomes carrying a suite of hundreds of genes specifically aimed at repairing the damage done by free radicals. Some genes on the artificial chromosomes might be replacements for damaged genes; others would be designed to enhance cellular DNA repair. Skeptics point out that our immune systems would likely do in Robiobotics' designer bacteria, but Bradbury suggests that the problem might be dealt with by using a transitory immunosuppressive therapy that would give the genetically engineered bacteria an opportunity to reach their desired cellular targets.
But this focus on biological interventions may be wrongheaded. After all, some argue, we don't fly because we sprouted wings, so neither will we live longer because we've fiddled with our genomes. Why not make machines that hunt down harmful disease organisms and repair damaged cells? That is the ambitious aim of nanomedicine.
Nanotechnology is the science and technology of building devices using single atoms and molecules. A nanometer is a billionth of a meter, a length that is just over the diameter of many atoms. Conceptually, nanotechnology and biotechnology are not all that distinct. In the words of Rita Colwell, the director of the National Science Foundation, "Life is nanotechnology that works."
Proponents of medical nanotechnology—such as Ralph Merkle, a former research scientist at Xerox's Palo Alto Research Center and now a fellow at the Texas nanotech company Zyvex—outline an ambitious vision. "Nanotechnology will let us build fleets of computer-controlled molecular tools much smaller than a human cell and with the accuracy and precision of drug molecules," Merkle declared in the Winter 1999 issue of the Anti-Aging Medical News. He added, "These machines could remove obstructions in the circulatory system, kill cancer cells or take over the function of subcellular organelles." Robert Freitas, author of the 1999 book Nanomedicine, foresees a day when oxygen-carrying red blood cells could be supplemented by artificial respirocytes made of carbon that would be 200 times more efficient.
If that isn't wild enough, Freitas recently unveiled a scheme that would replace your entire circulatory system with a sapphire vasculoid weighing two kilograms. No heart, no blood—just a system of nanotech machines that would ferry oxygen, carbon dioxide, nutrients, and immune protective machines throughout your body, all encased in nearly unbreakable sapphire that would line your old-fashioned veins and arteries. Since 80 percent of what kills most people can be traced to the circulatory system—heart attacks, strokes, wounding, metastasizing cancer—such a vasculoid would dramatically increase one's life span. Freitas thinks the first models will be available in 40 years.
"With nanotechnology we could someday be rebuilding our own bodies, regenerating organs, slowing down aging," a bullish Samuel Stupp, professor of materials science and medicine at Northwestern University, predicted at a National Science Foundation conference earlier this year.
Pharmaceutical manufacturers are already building new drugs—atom by atom, essentially—to treat diseases. Merkle believes that it will be another 20 to 30 years before the visionary technologies he foresees will be available. In the medical arena, nanotechnology and biotechnology may well be destined to meld together.
Nanotechnology also plays a role in what some consider the second best alternative to living forever: cryonics. Cryonicists freeze people in liquid nitrogen with the idea that future technologies will be sufficiently advanced that the patients can be thawed out, revived, and cured of whatever ailments, including old age, afflicted them before they entered the deep freeze.
One problem facing cryonics enthusiasts is that no animal larger than a microscopic human embryo or a tiny tardigrade—an insect that measures only a couple hundred microns across—has yet been frozen and successfully revived. Freezing causes water in cells to expand, which disrupts them. But some researchers have developed a preservation technique called vitrification, essentially glassifying cells. This approach, it is claimed, causes far less disruption to cellular organization and destruction of cell walls. Scores of people have chosen to have either their full bodies or just their heads cryonically "suspended."
When it comes time to revive patients, the plan goes, nanotech machines will race through the patients' bodies, repairing the damage they have suffered from disease and freezing. Will it work? Who knows? Cryonicists put it this way: "The clinical trials are in progress. Come back in a century and we'll give you a reliable answer." Cryonicists divide the world into two groups, those who are experimenting with cryonics by being frozen vs. those who just die and are buried. Which would you rather be in, they ask: the control group or the experimental group?
The defining political conflict of the 21st century will be the battle over life and death. On one side stand the partisans of mortality, who counsel humanity to quietly accept our morbid fate and go gentle into that good night. On the other is the party of life, who rage against the dying of the light and yearn to extend the enjoyment of healthy life to as many as possible for as long as possible.
The most moderate critics of longevity simply worry that immortality would cause massive overpopulation. Worry not, says demographer Olshansky. If everyone on the planet were made immortal tomorrow, while maintaining the current projected trends in human fertility, world population would rise to around 13 billion by 2100. That, he notes, is the same number that alarmists like Paul Ehrlich used to predict for the middle of this century. Olshansky thinks that 100 years will give human society plenty of time to adjust to longer, healthier lives.
Death to Radical Mortalists!
Then there are the more radical mortalists, such as Fukuyama, Callahan, and Kass. Writing in the aforementioned issue of First Things, Leon Kass asserts that "to argue that human life would be better without death is, I submit, to argue that human life would be better being something other than human." Without the sound of time's winged chariot rushing at our backs, Kass claims, humanity would become frivolous, frittering away eternity with meaningless pastimes. Apparently, if we live longer, we'll just watch more Baywatch reruns and revisit Disney World.
For Kass, the sting of death makes for stronger friendships, greater loves, more ardent learning, and nobler deeds. But the fact of human mortality has also led people to commit all manner of villainy, cowardice, and crime. If one man nobly sacrifices his life to save his family and friends from invaders, it is because those invaders have themselves overcome their fear of death to seek glory, goods, and dominion. Gilgamesh wanted to avoid the oblivion of eternity, so he built a city, fought wars, and sought glory so that his name would ring down the ages.
Meanwhile, the names of all those thousands crushed under his tyranny—those who labored to build the walls and temples of his city—are lost for all time. The certainty of death may cause us to aspire, but not necessarily to the fulfillment offered by the gentler virtues.
Kass also points to the "undesired consequences of medical success in sustaining life, as more and more people are kept alive by artificial means in greatly debilitated and degraded conditions." Here he is engaged in what might be called Struldbruggism, after an episode in Gulliver's Travels. Gulliver visits the land of the Luggnuggians, among whom are occasionally born immortals called Struldbruggs. This is no blessing, since the immortals still grow older, weaker, and sicker.
But the goal of research on aging is not to turn us into a race of miserable Struldbruggs. As Olshansky puts it, "We don't want to make ourselves older longer, we want to make ourselves younger longer." Characteristically, Kass ignores the real goals of anti-aging research, misleading readers with a gruesome scenario in hopes of frightening them into embracing his pro-death dogma.
Future generations will look back at the beginning of the 21st century and marvel that intelligent people actually tried to stop biomedical progress just to protect their cramped and limited vision of human nature. But the chances that the Kassians will actually hold back longevity seem small. "It's too alluring," says Olshansky. "It's been the dream of humanity forever. How can we not?" Austad agrees. "People want this so badly, it's going to happen no matter what the government does," he predicts. "The government can help or it can hinder this research, but it will happen."
"A dramatic increase in lifespan is inevitable," Aubrey de Grey said in the British Sunday Times two years ago. "We understand aging at the molecular level sufficiently to not just imagine interventions to retard aging, but enough that we can describe them. It's an engineering project now, not a scientific one. We just don't know how long it will take."
To which I say: Hurry up! The 22nd century looks too interesting to miss.