The Future Is Coming
Ray Kurzweil is doing everything he can to live long enough to see the future. To get there, the fifty-six-year-old subjects himself to an unbelievably rigorous diet and health regimen, popping 250 supplements a day and washing them down with green tea. The author and inventor is constantly testing himself— measuring his progress with an array of tests, from reaction time, memory, tactile sensitivity, and such biochemical markers as hormone, vitamin, and nutrient levels in his body. When he first started testing himself seventeen years ago, Kurzweil says, he tested like someone who was thirty-eight. Now, he says, tests show he has the body of a forty-year-old. By his calculations, his biological age has advanced two years, while his chronological age has marched ahead seventeen years.
That’s just the beginning, according to Kurzweil, who invented the first reading machine for the blind and has been inducted into the National Inventors Hall of Fame. The futurist predicts if he lives ten to fifteen more years, he will be able to take advantage of the full flowering of the revolution in knowledge of the human body; maximum life expectancy, now around one hundred years, will start extending out decades and decades. Jeanne Calment, the Frenchwoman who made it to 122, will not be the exception. She won’t even be the rule. People in developed countries will routinely exceed her mark, with the help of scientific breakthroughs that are currently on the horizon.
Kurzweil has spent much of his life ahead of the curve. As a teenager in 1965, long before advent of the personal computer, he appeared on the Steve Allen show I’ve Got a Secret for writing a computer program that composed music. The MIT graduate, now the chairman of Kurzweil Technologies in Wellesley, Massachusetts, also invented the flatbed scanner and the first commercial speech-recognition software, among other things. Kurzweil is not alone among forward-thinking researchers in his belief that science will start increasing the human life span. But with his books and speaking engagements around the country, he is perhaps the most vocal. His two most recent books tout the coming revolution: The Singularity Is Near: When Humans Transcend Biology and Fantastic Voyage: Live Long Enough to Live Forever.
Kurzweil speaks to packed auditoriums about the longevity boom that’s right around the corner. Immortality, it seems, is a growing industry. Leading scientists have started companies with names like Elixir and Longevity. Investors, too, are buying into the possibility that the human life span can be radically altered with the help of research being done now and science not yet imagined.
Kurzweil envisions three bridges to radical life extension. We are in the midst of a biotechnology revolution, which is the first bridge. In ten to fifteen years, we will reach the second bridge and be able to reprogram our biology to avoid cancer, heart disease, diabetes—even aging itself. By the end of the teen years, say 2019, he says, we will cross the third bridge and begin using technology at a molecular level to extend our lives significantly. We started this voyage talking about practical immortality. Perhaps you thought it far-fetched. Kurzweil thinks it is right around the corner.
“The progress in this is exponential, not linear—that’s the important point,” he told me, adding that the rate of scientific progress is doubling every decade. He reminds me that “it took us fifteen years to sequence HIV. We sequenced SARS in thirty-one days.”
The human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), began spreading in the early 1980s. Severe acute respiratory syndrome (SARS) came along two decades later. SARS, too, is caused by a virus. The first known case occurred in China in 2002 and spread to more than two dozen countries before the outbreak was contained. The ability of researchers to decode the virus so much more quickly shows the tremendous advances science has made in genetic sequencing, Kurzweil says. “Ultimately, we’ll have very powerful tools to sort of reprogram our biology away from health and rejuvenate, really, all of our organs,” Kurzweil told me when I sat down with him a few months ago.
Kurzweil wears very mod glasses and has a stylish haircut. He wasn’t what I was expecting when I envisioned a radical scientist, although he did jump quickly from topic to topic, letting words hang mid sentence, which gave him a professorial demeanor. In Kurzweil’s brave new world, we will be the beneficiaries of personalized medicine, in which our genome will be scanned, looking for clues to future maladies. We will be able to replace our cells with younger versions of themselves. Perhaps his most outlandish prediction for the future involves microscopic robots, called nanobots, constantly circulating in our bloodstreams, reversing all known diseases and aging processes. And then there are the scientific advances coming that we can’t possibly predict, because science is moving so fast. Kurzweil himself says he expects to live at least one thousand years. If that sounds crazy, you haven’t sat down and listened to him.
“I think death is a tragedy. Many of our philosophies and religions have sought to rationalize that death is really a good thing. But our basic reaction is death is sad. That’s it’s a tremendous loss of knowledge and personality.”
Eventually, Kurzweil thinks we will be able to add more than a year of life expectancy for every chronological year that passes. That means Kurzweil thinks someday, humans will be able to live forever. Kurzweil uses the example of a house. Right now, we can repair everything that goes wrong with a house. We don’t have that sort of knowledge about our bodies—yet. Someday, though, he says we will be able to repair DNA and rejuvenate cells and organs the way we can fix all the systems of a house.
Unfortunately, we are far from having the same understanding of the human body as we do the systems in a house. Even unraveling the aging processes in worms and fruit flies has proven maddeningly difficult for some of the world’s brightest scientists.
Then there is the debate about what lies at the root of aging. What does it mean when we talk about stopping the aging process or even slowing it? Earlier, I talked about aging as involving two components. One is more general and involves the accumulation of problems from the cells on up. Our cells stop dividing, get old, and die. Vital components in cells and tissues wear out. Our mitochondria, the power plants in our cells, become less efficient. Free radical oxygen attacks the components of our cells and causes damage. Our DNA accumulates mutations, which can lead to such serious health problems as cancer. Proteins bind together and disrupt cellular function.
The second way to look at aging is more specific. We develop heart disease. Tumors grow in our colons. Plaques and tangles accumulate in our brains. These are the signs of aging we in the medical profession try to treat when they appear. These are lumped into a category called age-related diseases. They are the kinds of problems we’d like to put off or avoid altogether, if possible.
Clearly, if we stop or postpone the diseases prevalent among the elderly, many of us would live healthier, longer lives. We would still be aging, though. The clock would still be ticking in our cells. We would risk winding up like the mythical figure Tithonus in the story dating back almost three thousand years. The god Zeus grants Tithonus eternal life, but not perpetual youth. As a result, Tithonus lives forever, old and incoherent, locked away in a room.
ON THE HORIZON
So the obvious goal in the quest for immortality is to reach very old age with vitality. This really strikes at the heart of what we’ve been exploring throughout this book. We’ve discussed some of the basic things we can do now to help fight aging and live longer, healthier lives. The future promises much more.
In much of science, researchers try to understand a biological process by looking at it in simpler organisms first. Investigators hoping to unlock the keys of aging have done this with the roundworm known as C. elegans, the fruit fly, and with genetically manipulated mice. In each of these organisms, investigators have found genes associated with longer life. These genes are able to confer greater longevity by affecting stress resistance, metabolism, insulin and blood sugar levels, cell growth and survival, free radical production, and other means. To be fair, the gains sometimes come with side effects, such as dwarfism, sterility, or increased cancer risk.
A gene called SIR2 has generated a lot of interest among researchers. Variants of the gene exist in all living organisms, from yeasts to humans. Adding a second copy of the SIR2 gene to a yeast cell increased its life span by 30 percent. Extra copies of the gene increased the life span of the roundworm by 50 percent. Researchers believe this gene, part of a family of genes called sirtuins, may help organisms survive adversity by regulating a survival mechanism.
SIR stands for silent information regulator. The SIR2 gene effectively silences other genes by rendering certain areas of the genetic code inaccessible. If it is activated over the long term, SIR2 staves off disease and prolongs life. Exactly how the gene does this is not known. Even armed with this knowledge, no one has created an immortal worm or fruit fly. Not yet, anyway.
Understanding SIR2 could someday lead to knowledge that will allow us to live longer, disease-free lives. That’s because humans and other mammals have a version of the gene, known as SIRT1. Studies in mice and rats suggest the protein encoded by SIRT1 allows some of the animals’ cells to survive stress and enhances cellular repair mechanisms.
Remember the calorie-restricted diets I talked about in chapter 2? It appears SIR2 is activated by calorie restriction. The stress of a calorie-restricted diet appears to cause SIR2 activity to go up, enhancing protective mechanisms in our bodies that may help us live longer. Restrict calories in yeast, worms, or fruit flies, and SIR2 activity increases. These organisms also live longer. If the SIR2 gene is removed, restricting calories in these organisms has no effect on longevity.
Resveratrol (discussed in chapter 3), the substance in red wine credited with helping the French live long lives despite a fatty diet and a relatively high prevalence of smoking, also activates SIR2. Giving resveratrol to yeast, worms, or fruit flies increases their life spans—even without calorie restriction. In fact, resveratrol-fed fruit flies can eat as much as they want and still enjoy the benefit of longer life.
Pharmaceutical companies are researching new ways to moderate appetite, which might well help slow the aging process. Already, the drug rimonabant is on the market in Europe under the brand name Acomplia as treatment for dangerously overweight patients. Acomplia is the first of a new class of drugs designed to block receptors responsible for giving marijuana users “the munchies.” FDA approval is expected sometime in 2007. Pharmaceutical companies are also investigating ways to regulate the appetite stimulating hormone, ghrelin. Even if these drugs succeed, they are not likely to be a magic bullet for weight loss. Acomplia is taken in conjunction with a diet and exercise program. Also, it is meant as a treatment for those whose weight puts them at risk for diabetes or heart disease, rather than for those who simply want to lose a few unwanted pounds.
Researchers also are studying the oldest Americans, looking for clues to their longevity on the twenty-three pairs of protein strands that form human chromosomes. They are using the latest scanning technology to look for longevity genes, something in our master code that tells our bodies not to get old, or to at least take its sweet time getting there. Although genes account for only 30 percent of our expected life span, finding a gene that could influence how long we live—or what age we get an age-related ailment, like heart disease—would be an enormous advance in living out life to its potential maximum. Understanding the genes of the very old could help drug makers produce compounds that manipulate the processes governing the aging process itself.
Looking for Longevity
Today, one in ten thousand people make it to one hundred, most of them women. The lucky few who reach the century mark often do so in remarkably good health. For starters, many often don’t look their hundred years. Somehow the sands of time have moved more slowly for them. Second, many get heart disease or some other age-related disease decades later than their peers. The obvious question is why. Do they have some genetic advantage? Are they eating something with life-giving properties?
In 1998, Dr. Nir Barzilai began the Longevity Genes Project at the Albert Einstein College of Medicine in New York. Barzilai had been working with calorie-restricted animals, but he became curious about the genetic influence on life span. Barzilai and his team study Ashkenazi Jews who are 95 and older. He picked Ashkenazi Jews, because they are relatively genetically homogenous. Plagues, wars, and anti-Semitic persecution reduced their population to an estimated few hundred thousand by the seventeenth century. This relatively small group (from a demographic point of view) then experienced a rapid population growth. This small number of “founders” makes it easier to find genetic differences among Ashkenazi Jews. The genes for ovarian and breast cancer were originally discovered in studies of Ashkenazi women.
Barzilai is now looking for genetic markers for longevity in long-lived Ashkenazi Jews who are healthy and living independently. The Israeli-born doctor says he is not after the fountain of youth. He is simply trying to find ways for each of us to make the most of what we have. He thinks science and medicine have a role to play, and points to his own family as an example of how the advance of knowledge can lengthen life. His grandfather had a heart attack when he was 68 and died. His father had a heart attack at exactly the same age. Thanks to better medical care, he lived. When we spoke to Barzilai, his father was 83. Barzilai thinks humans have the potential to remain healthy past 100, possibly to 120, if he and others can figure out how to slow the aging process.
To search for genetic clues to aging, Barzilai and his team arrange for “family reunions” of those 95 and older, their children, and their children’s husbands and wives. When they get family members together, they do a short physical exam and a mental test; they take measurements of height, weight, body fat, and temperature; and then they draw a blood sample. Barzilai has collected data on close to four hundred families. Blood from these families is now stored in small vials in an oversized freezer next door to his lab at Albert Einstein, in the Bronx.
What Barzilai has found is that such age-related diseases as hypertension, diabetes, heart attack, and stroke have been delayed by about thirty years in centenarians, and he is convinced genes play an important role in this delay. In fact, he says the older you get, the bigger role genes play. By the age of 100, he says, genetics is more important than environment. He has found centenarians who were obese in middle age. He has found others who smoked for more than 90 years. Literally two packs a day for more than 90 years. He has found other unhealthy behaviors these 100-year-olds somehow overcame to achieve very long life. They have defied the odds. They have avoided death and dodged disease. If their genes somehow protect them, then they should pass on those genes to their offspring. The children of the very old should also be more likely to live a long time. As you might guess, that’s true. Barzilai has found the children of centenarians are generally healthier than their spouses, with whom they usually share diet and lifestyle. The New England Centenarian Study, in a separate, ongoing study of 100-year-olds, has found that centenarians are four times more likely to have a sibling who lived past 90 than is someone with an average life span.
What’s behind this? Barzilai has uncovered some clues. Longevity appears to be linked to high levels of HDL (“good”) cholesterol and low levels of LDL (“bad”) cholesterol. Long life is more likely among those with larger HDL and LDL molecule sizes, which he says results in lower incidences of cardiovascular disease, hypertension, and insulin resistance. LDL cholesterol attaches to the vessel walls, where it can harden and turn into plaque. Over time, plaque can cause narrowing of blood vessels, raising the risk for heart disease and stroke. HDL appears to have the opposite effect, cleaning out the blood vessels. “Good” cholesterol levels typically drop with age, but not in the centenarians. Barzilai has encountered levels three times as high as expected. High levels of HDL cholesterol also appear to be linked with mental ability in very old age.
If you are interested in raising your own levels of good cholesterol, you can try drinking a moderate amount of wine, but that will cause only a very small increase in HDL, nothing at all like the levels found in Barzilai’s centenarians.
In addition to what he’s learned about good cholesterol levels in the very old, Barzilai has also found three genes that are overrepresented in centenarians. About 8 to 12 percent of 65-year-olds have these genes. Some 24 to 32 percent of centenarians do. Of course, this doesn’t prove the genes are the cause of the longevity, but they are certainly linked with people who have achieved an extraordinary life span. People who have one of the genes appear to live four years longer than those who don’t, on average. That is a huge number. If you could reproduce that gene’s protective power in a pill, it would have more of an effect than would curing heart disease, he says.
Researchers conducting the New England Centenarian Study, which is also looking at genetic links to long life, pinpointed a region on chromosome 4 they believe holds at least one longevity-enabling gene. They made this discovery after scanning the genes of 137 sets of long-lived siblings.
Because women live longer, there may be a spot on the X chromosome that gives women an edge. Women have two X chromosomes; men have only one.
Barzilai believes there may be 100 longevity genes in all. Some of them might be necessary but not sufficient to promote longevity by themselves. Barzilai is currently searching centenarians’ genome at 500,000 different places. By doing this, he will see which genotypes are overrepresented. There are two ways genes can help us live longer. They can slow the aging process itself, or they can protect against age-related diseases.
New Drugs
Science is also moving forward in other areas that may have profound consequences as we chase life. Something called RNA interference (RNAi) could revolutionize the way drugs work. Scientists believe it might be used someday to treat a wide range of disease and conditions, including HIV infection, cancer, hepatitis, macular degeneration, and high cholesterol.
Most medicines work by binding to the active site of a protein. This stops a chemical pathway that produces some unwanted result. Let’s take the example of antidepressants such as Prozac or Zoloft. These drugs bind to receptor sites in the brain, blocking the absorption of the mood-enhancing chemical serotonin. You may have heard of these drugs referred to as SSRIs. That stands for selective serotonin reuptake inhibitors. The drugs stop the reuptake of serotonin, keeping the levels of the chemical in the brain higher.
Finding molecules that bind to the active site of a protein is difficult, and some processes cannot be blocked in the traditional way. In some cases, it would be more desirable to destroy the protein than disrupt it. That’s where RNAi comes in. RNA is the single-stranded cousin of DNA. It is the molecule that directs the middle steps of protein production. By introducing the right bits of RNA into a cell, a protein could be destroyed. Since genes are chemical instructions calling for the cell to produce a protein, RNAi would essentially give physicians the power to turn off a gene. That would be an enormous tool for physicians.
Already, Swiss researchers have used RNAi to slow the progression of amytrophic lateral sclerosis, better known as Lou Gehrig’s disease, in mice. The technique has also been used successfully in monkeys, turning off a gene that is critical to the metabolism of cholesterol. As a result, the monkeys’ cholesterol levels were cut by two-thirds, according to the online version of the journal Nature. As I write this, human trials are underway for a pair of RNAi drugs to treat macular degeneration, the most common cause of blindness in adults. The drugs are designed to block production of proteins that trigger the disease. Needless to say, if the trials are successful, it would be a huge boost not only for those suffering from macular degeneration but for medicine in general. RNAi could be a powerful tool in modern medicine’s arsenal of weapons to fight diseases and of course aging.
Because genes code for proteins, each longevity gene Barzilai finds may offer the chance for a pharmaceutical intervention to help ward off the ravages of time.
“Everything we’ve found so far can be a target of drug therapies,” he says. Unfortunately, drug companies have not shown much interest. “The problem with aging is you don’t show results the next day. It takes eight to ten years.” Therefore, the cost to test a potential antiaging drug is around $500 million.
That isn’t to say drug companies are not interested in coming up with drugs to help people live longer. One drug company is already producing a drug that raises HDL, and Business Week reports that Pfizer spent $800 million to develop a pill that combines an HDL-raising pill with its blockbuster drug atorvastatin (Lipitor), which lowers LDL cholesterol. Unfortunately, the trial failed.
Befriending Bacteria
Researchers are dreaming up other novel ways to keep us healthy in the twenty-first century. Bacteria are generally not considered our friends. After all, they are the cause of a host of illnesses, from food poisoning to strep throat. Researchers are developing ways to manipulate bacteria to use them as ways to fight cancer and tumors. Here’s how. Salmonella is famous for its power to cause food poisoning and the misery that goes with it. The bacterium also thrives in human tumors. Human trials are under way with Salmonella that has been modified to destroy tumor cells. Investigators have started animal studies to determine whether the toxin-producing bacterium Clostridium novyi could be used to melt the dead interiors of tumors. And they are looking at altering Listeria monocytogenes, the cause of a deadly form of food poisoning, to make it appear more like tumor molecules as a way to trick the body’s own defenses into attacking tumors.
Using the bacteria already living in our bodies to promote our health has also attracted attention among researchers. Jeffrey Gordon, director for the Center for Genome Sciences at Washington University in St. Louis, thinks we might be able to use the bacteria in our guts to adjust our metabolism in a way that will keep us from gaining weight. Prebiotics and probiotics are very sterile sounding names for ways to manipulate our gut bacteria. The human gut is home to 10 trillion to 100 trillion microbes, from five hundred to one thousand species. Together, these bacteria, archaea (bacterialike creatures that live in extreme environments), and viruses outnumber our own cells by a factor of ten, but until recently, very little was known about them.
These species of bacteria—together known by the pleasant-sounding name microflora—are more than parasites, though. They break down otherwise indigestible plant fibers into nutrients we can use. For example, microbes in our bodies break down polysaccharide, a carbohydrate in foods ranging from breads to pasta. Microbes also help us store fat.
All of us do not have the same bacteria in our guts, though. We are microbe-free in the womb, but start acquiring bacteria from the moment we head down the birth canal. We wind up with a unique combination of microflora, though there is a constant flux in our microscopic squatters. If these bacteria are particularly good at breaking down food and storing it as fat, then we might be more prone to obesity. By one estimate, differences in the bacteria in people’s digestive tracts may allow some people to eat 30 percent more calories daily than another without gaining weight.
What if we could manipulate the microbes? Could we change the microflora in a way that would reduce the number of calories stored as fat? Would we be less prone to gaining weight? These are questions that have researchers excited, and they bring us back to probiotics and prebiotics.
Probiotics contain live bacteria and other microbes that are designed to be beneficial to our health. You may never have consciously consumed a probiotic, but you almost certainly have done just that. That’s because yogurt contains the live bacterium Lactobacillus acidophilus. Probiotics live in other fermented dairy products as well. Yogurt has been touted for years as a food linked to long life, and L. acidophilus has been shown to enhance the body’s immune response and raise levels of cytokines, messenger molecules that help regulate the activities of the immune system. Proponents of probiotics say we should be particularly concerned about having low levels of friendly bacteria in our guts after taking a course of antibiotics, if we have been eating poorly, or if we have been suffering from diarrhea.
Prebiotics are nonliving dietary supplements that selectively promote the growth of bacteria in your colon. You are essentially feeding the bacteria in your intestine the way you would feed a pet. Of course, we still don’t know a whole lot about the creatures inside us. We do know microbial genes outnumber our own by a factor of one hundred. That’s why Gordon likes to refer to these gut dwellers as “this vast community.” He talks about them the way you or I might talk about a sprawling suburb you’d visited only once or twice. He also likes to talk about the human body as a “superorganism,” because we are a combination of species (bacterial and human) sharing the same body.
Because they are so integral to the digestive process, Gordon thinks we might be able to enlist these microbes in our battle of the bulge. Gordon has been raising germ-free mice in a sterile lab. Without the benefit of gut bacteria helping them digest food, the germ-free mice are slim compared to genetically identical mice that are not kept in the sterile environment. In fact, these germ-free mice are able to gorge themselves and not get fat. When they are returned to a normal, germ-filled environment, however, they gain weight as readily as the other mice. Gordon thinks the role of the bacteria goes beyond digestion. He says gut bacteria also suppress a key gene in mice. The gene, which goes by the acronym FIAF, inhibits fat storage. Suppressing the FIAF (fasting-induced adipocyte factor protein) allows more fat to be stored. Germ-free mice do not suppress this protein, which means they are able to stay thin.
“We are at an amazing time for the understanding of self,” Gordon says. “We’re entering a phase of personalized nutrition.”
Gordon says we might someday be able to manipulate “the microbial community or use microbes as teachers to see how they manipulate our biology, use them as a way to set up therapeutic targets.” In other words, if we can’t train them to digest our food in a way that doesn’t promote fat storage, we might be able to learn from them to mimic what the more beneficial microbes are doing.
Converting Viruses
Viruses, too, may someday be enlisted as friends rather than foes. Researchers are investigating ways to use modified viruses as a potent delivery system to fight cancer. In 1997, British doctors received special permission from the United Kingdom’s medical authorities to inject live herpes simplex virus in the brain of a twenty-one-year-old man with an aggressive form of brain cancer called a glioma. The treatment had never been tried anywhere in the world. It worked. The tumor went away, and the man who had been given four months to live was reportedly alive and well at this writing.
S. Moira Brown, who headed the University of Glasgow team that pioneered treatment with HSV1716, started a company to capitalize on the research, Crusade Laboratories. The U.K. company removes a protein from the herpes virus that causes it to grow. When it’s injected, the virus steals this same protein from cancer cells, which ultimately causes the tumor to shrink and sometimes disappear. The goal is to kill the cancer cells. When the herpes virus reaches healthy cells, which do not have this growth driver, the virus stops spreading.
Crusade Laboratories has received approval in Europe to use the herpes simplex virus in treating gliomas. Crusader also has clinical trials under way in which they are using the virus in treating ovarian and other cancers. Researchers in the United States are also working on what are called virotherapies for brain and liver cancers.
Virotherapy holds promise because viruses are able to target cancer cells with pinpoint accuracy and cause few side effects. The ability to destroy cancer cells and leave healthy cells alone sets virotherapies apart from chemotherapy and radiation therapy, which are far less precise. By one estimate, chemotherapy agents kill about six cancer cells for every healthy cell killed. By comparison, viruses kill more than one thousand cancer cells for every healthy cell killed.
Replaceable You
Ray Kurzweil is among those who are thinking bigger. They believe we will someday be able to use our own cells to build replacement organs. When our heart or liver or kidneys or lungs become old, he and others believe we will someday be able to replace them. Dr. Anthony Atala at Wake Forest University in Winston-Salem, North Carolina, made history recently by growing a new bladder using a patient’s own cells. By doing so, he became the first scientist to grow a human organ in a laboratory and transplant it into a human.
To investigate, we talked to one of his patients, a sixteen-year-old named Kaitlyne McNamara. She was born with spina bifida, a rare birth defect that stunts brain and spinal cord development. As she grew, McNamara’s parents realized her bladder was not functioning properly. It turned out her bladder was about the size of a thimble and could not hold normal amounts of fluid. What didn’t fit in her bladder flowed back toward her kidneys. Eventually, she would experience a bladder burst, resulting in embarrassing accidents she could not control. To make matters worse, her kidneys were becoming damaged. Doctors gave her the option of forming a new bladder out of a piece of intestine, a surgery with potential complications, or trying an experimental procedure and growing a new bladder using her own cells. She went with Atala, one of seven patients to try the new technique. All seven report their bladders hold more fluid, and they have fewer problems with incontinence.
Atala takes a small piece of the patient’s bladder—less than the size of a postage stamp—and teases out muscle and bladder cells, which he grows in a petri dish. When there are enough cells, they are layered onto a three-dimensional mold shaped like a bladder and allowed to grow. Several weeks later, the cells have produced a bioengineered bladder, which is grafted onto the patients’ own bladder. Atala is by no means alone in this field. Cartilage cells are being taken from patients, grown, and reimplanted. So are pieces of skin for burn victims. And this is just the beginning.
There is plenty of research still to be done before organs more complicated than the bladder are grown in the lab. Also, even with his remarkable feat in bioengineering, we need to remember that Atala did not replace the patient’s entire bladder, which would require sophisticated surgery to attach the bladder to the ureters, the tubes that carry urine from the kidneys to the bladder. He took the new bladders and grafted them onto the existing ones.
The true holy grail is the creation of entirely new organs and tissue using the patients’ own stem cells. These are the generic balls of cells smaller than a grain of rice that develop a few days after conception and are capable of becoming any of the two hundred or so kinds of cells in the body. Skin, bone, heart, lung, and brain all emerge from these versatile, virgin cells—essentially the body’s master cells. Growing a new heart or kidney or liver from stem cells would result in a new organ free of any risk of rejection.
To do this, scientists would take a single cell from your arm or somewhere else on your body, remove the DNA-containing nucleus, and implant it in a donor egg cell that has had the nucleus removed. It would be grown for five to seven days, until the embryonic cells form. From there, the cells would be given specific nutrients and growth factors to create the desired type of cells. Creating an embryo simply for using its cells is something President Bush and others find morally objectionable, but scientists around the world are moving forward with the research. Given all the publicity and promise of stem cells, it’s hard to believe human embryonic stem cells were only discovered in 1998.
An embryo is not the only place to harvest stem cells, though. They also come from bone marrow, the umbilical cord, and other tissues, but these alternatives appear to be more limited than embryonic stem cells in their ability to develop into different types of cells. Stem cells have been at the center of a great deal of hope and hype, clinical research, and controversy in recent years, but stem cell therapy is nothing new. It has been around and saving the lives of cancer patients for thirty years. It’s called the bone marrow transplant, used in patients whose marrow tissue has been destroyed by chemotherapy or radiation therapy.
Stem cells’ power to rejuvenate has come into sharp focus recently. There is hope stem cell treatments can be used for people suffering from the devastating and progressive Parkinson’s disease. Others envision using stem cells to cure type 1 diabetes, which is caused by the loss of insulin-producing cells in the pancreas called islets. There is also the hope that stem cells could help people paralyzed by spinal cord injuries walk again. Already, researchers at the University of California, Irvine have reported that paralyzed rats treated with a stem cell therapy were able to walk. Stem cells have also shown promise in treating diabetic mice and helping rats and mice with conditions mimicking Alzheimer’s and Parkinson’s.
As I write this, Geron, a California biopharmaceutical company, claims to be close to filing for permission to conduct the first human trials on an embryonic stem cell therapy for spinal tissue repair. Other American researchers also say they are close to asking the FDA for permission to begin testing stem cell–based therapies for macular degeneration, heart muscle repair, and regenerating damaged skin. Others have “trained” embryonic stem cells to become most of the cell types affected by Parkinson’s.
Other uses envisioned for stem cells include giving cystic fibrosis sufferers new lung tissue, the blind new cornea or retina tissue, the deaf new hair cells in the inner ear, the bald new hair follicles, type 2 diabetics new insulin-producing cells in the pancreas. The elderly could benefit from replacing diseased or worn-out brain cells, muscle, bone, cartilage, and skin. The possibilities are legion. There is even talk that stem cells could be used to grow new teeth.
Probably the boldest prediction of all is the potential for stem cells to create entirely new organs. If you suffer from heart disease, a new heart could be grown from your own cells. This would bring us closer to Ray Kurzweil’s analogy of fixing problems in the body the way we are now able to fix problems in a house. It would solve the problem of one organ in your body aging faster than the rest of you. It squarely puts us in the realm of practical immortality.
Despite the enormous amount of media attention surrounding stem cell research, we are probably years away from any homegrown organs, or any of the other potential medical uses for stem cells for that matter. Still, early research offers a glimpse at the potential of stem cells. For example, embryonic stem cells can be made in a laboratory dish to grow into heart muscle cells that clump together and beat in unison. Taking that heart tissue and implanting it in a way that helps a patient with a diseased heart adds layers of complexity to the challenge, though.
Grow Your Own
There is another possible way to replace digits and limbs and maybe even portions of damaged organs that has been largely overlooked because of all the hoopla over stem cells—regrow our own. It can be done. Humans can regrow the liver even if most of it is removed in surgery. We can also regenerate blood and the outermost layer of skin. Children can even regrow the tip of a finger, from the base of the nail up. Of course, this is nothing compared with the salamander, which can regrow entire limbs. Amphibians like the salamander and certain fish can regrow other body parts, too, like the intestine or the spinal cord, even part of the heart. They do this by converting mature cells at the site of the injury to immature cells, which clump together into something called a blastema. The blastema, in turn, starts regrowing the missing body part.
Humans and other mammals scar at the site of a wound instead of converting mature cells to immature ones and regenerating tissue. Some scientists think we evolved this way because it reduces the chances of developing cancer and allows us to have a more robust immune system. But researchers are now studying the chemical processes that cause organs to grow in embryos. They think if they are able to develop a drug therapy that mimics the chemical signals orchestrating organ growth in embryos, then adults with kidney failure, for example, would be able to grow a new kidney. Tests of one such protein, named bone morphogenic protein-7, suggest it could potentially reverse tissue damage and scarring and improve function in patients with kidney disease.
The notion that mammals could potentially regrow organs received a boost in 2005, when a strain of lab mouse known as MRL showed the ability to grow back amputated digits and even portions of the heart, liver, and brain. Even more astonishing, injecting cells from the MRL mice into normal mice gave the previously unremarkable mice the power to regenerate tissue. So we are one step closer to achieving practical immortality and chasing life.
Slowing the Clock
Some investigators think we need to dig deeper to determine how to chase life by slowing the aging process. They think the root cause of aging lies in oxidative damage to the mitochondria, the cells’ sausage-shaped power plants. Rejuvenating the mitochondria will turn back the hands of time, they reason. Here’s why: Each mitochondrion has its own DNA, separate from the DNA in the nucleus of the cell. Because this small, circular strand of DNA is where energy is being produced in the cell, it is subject to point-blank exposure to free radicals and the mutations they cause. To make matters worse, mitochondria do not have the same elaborate mechanisms for repairing DNA damage as the cell’s nucleus; they are copied more frequently than nuclear DNA, and they are replicated by an enzyme that is more error prone than its counterpart in the nucleus. It shouldn’t be a surprise, then, that mutations accumulate quickly in mitochondrial DNA. The elderly generally have an array of mutations in their mitochondrial DNA. Scientists have even tested the same people fifteen years apart and shown the buildup of mitochondrial mutations. When mutations hit a critical level, energy production in the cells falls and finally, the cells self-destruct. When cells start dying off faster than they are replaced in the brain or heart or some other organ, the result is the loss of function that most of us think of as aging.
Researchers have started trying to manipulate the mitochondria. They’ve created mice more prone to developing mutations. As a result, these mice die young and develop many of the telltale signs of aging at a relatively early age, such as hair loss, stooped posture, hearing loss, and osteoporosis. That alone doesn’t prove mitochondrial damage from free radicals causes aging. What researchers did next, though, certainly adds weight to their argument. Remember catalase (chapter 3), the enzyme that fights free radicals? When the gerontologist Peter Rabinovich and his team at the University of Washington got more catalase to the mitochondria, the mice lived 20 percent longer, and such age-related problems as heart disease developed later than normal. For now, delivering catalase to the mitochondria is incredibly difficult, and we are unlikely to be taking any sort of catalase treatment to boost our mitochondria anytime soon.
Cracking the Code
At each end of twenty-three pairs of chromosomes is a string of DNA that for years scientists assumed was genetic gibberish. These are called telomeres. Telomere sequences are repeated over and over, comprising ten thousand nucleotides. Telomeres cap the end of each chromosome, which contains our body’s DNA. Each time the cells divide, the telomere sequence shortens. Telomere loss is steady over time. When they get short enough, the DNA cannot fold properly, and the cells stop dividing. This takes 290 or so days in the somatic cells in the body (the cells that are not involved in reproduction). All it takes is a single telomere on one chromosome becoming too short, and that’s the end of cell division. Also, the distance from the gene to the end of the telomere appears to affect how the gene acts—and may play a role in aging.
The length of the telomeres on our chromosomes is linked to longevity. On average, people with longer telomeres live longer than those with shorter telomeres. Not surprisingly, women lose telomeres at a slower rate than men. They also live longer. People with coronary artery disease, in general, have shorter telomeres. Women with chronically ill children have shorter telomeres than other women. Because we lose telomeres at a predictable rate, these women’s cells were said to be nine to seventeen years older than that of other women under less stress. Having shorter telomeres also appears to increase the risk of infection.
Now researchers are measuring telomeres for signs how far our biological clocks have wound down. For example, Tim Spector of St. Thomas’ Hospital in London measured the length of the telomeres at the end of chromosomes in the white blood cells of 1,122 women whose ages ranged from eighteen to seventy-six. Spector found the telomeres of the youngest women were about 7,500 base pairs long. Their length declined by an average of twenty-seven base pairs a year, but lifestyle could dramatically speed up the “clock.” Spector used these measurements as his timetable for aging and concluded, for example, that smokers were biologically older than nonsmokers by 4.6 years on average, while the obese were 8.8 years older than those women who were lean. An obese smoker was, by Spector’s reckoning, at least ten years older than a lean nonsmoker. One day, researchers hope that an enzyme, appropriately named telomerase, will allow them to reverse the process and cause the telomeres to maintain or grow in length. This could allow the creation of the perfect immortal cell and be the key to chasing life.
In the future, scientists will attempt to alter the cells’ clocks by lengthening the telomeres to extend the life of the cells. The goal is to make an immortal cell, but we should be wary of freeing cells from their own natural life spans. We are all familiar with cells that are immortal. They are called cancer cells. The trick will be how to rejuvenate our cells selectively without unleashing “the beast.” Because we have so many cells relative to most other species and because we live so long, we may need telomere shortening to counteract cancer.
Nanotechnology
As I mentioned, the final bridge in Ray Kurzweil’s vision of future immortality is nanotechnology. This is the stuff science fiction is made of. He and others see atomic-scale engineering as a way to reprogram systems in our bodies. Microscopic nanobots will navigate through our bloodstreams, combating pathogens, correcting DNA mutations, and reversing the aging processes. They will also replace our digestive system and our heart, taking over the job of moving oxygen and carbon dioxide around our bodies. He even predicts nanobots will circulate in our brains, making us smarter. Kurzweil refers to this transformation as replacing version 1.0 of the human body with version 2.0.
Already, scientists have developed nanotechnologies that deliver insulin to diabetic rats via capsules with pores only 7 nanometers across, inject drugs to small tumors via microscopic spinning screws, and capture individual cells in microteeth. They have even crafted a micromachine that is part muscle tissue, part machine and is fueled by glucose. There are dozens of companies and research labs devoted to nanomedicine, and new breakthroughs emerge almost daily.
In one example of Kurzweil’s predictions moving toward reality, researchers at the Massachusetts Institute of Technology have developed a technique that allows nanoparticles to group together inside tumors. The mass of nanoparticles is large enough to be detected by an MRI machine.
The Big Freeze
Of course, if you don’t think any of this is going to work out, you can always try to call the biological equivalent of a time-out. Make arrangements to have your body frozen, with instructions to thaw you out when science has advanced enough to bring you back to life and keep you alive indefinitely.
For a news story, we talked to Brian Harris, a twenty-nine-year-old father who has made arrangements to have his body frozen when he dies. Harris told me he is looking forward to meeting his great, great, great, great, great-grandchildren. Harris is one of a small group of people, perhaps numbering one thousand, who call themselves cryonicists. As soon as they are legally dead, the freezing process begins. Ideally, the process would begin within minutes of death. The goal is to keep the tissue alive. With that in mind, the body’s blood and much of its water are replaced to prevent tissue-destroying ice crystals from forming. When the freezing process is complete, the bodies—or sometimes just the head—are stored in liquid nitrogen in containers that resemble giant thermos bottles. This is not cheap. At Alcor Life Extension Foundation in Arizona, which may be the largest company catering to cryonicists, it costs $150,000 to store the whole body; $80,000 for the head and brain. More than seven hundred people have signed on with Alcor to be cryopreserved when they die. Among Alcor’s seventy-three current clients is Ted Williams, the baseball great, who died in 2002. A similar company with the optimistic name Suspended Animation Inc. opened in Florida in 2005.
Surgeons are now exploring ways to place cooled patients into suspended animation—heart stopped, blood drained from the body, no electrical activity in the brain. Already, as neurosurgeons we are able to induce comas in patients and have even stopped their hearts and brains using a combination of medications and induced hypothermia. This is useful if the neurosurgeon is, for example, clipping a hard-to-reach brain aneurysm. There is no blood flowing through the brain, so there will be no bleeding as the surgeon performs the operation. The ability to stop all activity in the body is still a work in progress, currently being tested on pigs. If surgeons are able to slow all metabolic activity to a crawl for hours while they repair wounds and other injuries, what about taking it to the next level and suspending that life indefinitely—or until science catches up with whatever ails the patient?
Of course, technology is nowhere near ready to revive those who are dead and frozen. Most organs donated for transplant can only be preserved for twenty-four hours—less for hearts and more complex organs—and they are not frozen and revived. Still, hope—if not the cryonicists themselves—springs eternal.
“I think that reviving people that are cryopreserved is almost inevitable in some way or another, just like going to Mars is inevitable,” Dr. Steve Harris, Alcor’s medical director, told us. Some believers in cryonics have even made financial plans for the future by setting up “personal revival trusts,” nest eggs for their reanimation.
Despite everything you have just read, I am not recommending you pull out your checkbook or start a cryonics savings account. While I do have faith in the future and the promise of science, I think we have a long way to go with simply realizing and harvesting our own potential. If you can do that, then your future is already here.