Physics of the Future_ How Science Will Shape Human Destiny... Part 8

One target for gene therapy is actually cancer. Almost 50 percent of all common cancers are linked to a damaged gene, p53. The p53 gene is long and complex; this makes it more probable that it will be damaged by environmental and chemical factors. So many gene therapy experiments are being conducted to insert a healthy p53 gene into patients. For example, cigarette smoke often causes characteristic mutations in three well-known sites within the p53 gene. Thus gene therapy, by replacing the damaged p53 gene, may one day be able to cure certain forms of lung cancer.

Progress has been slow but steady. In 2006, scientists at the National Inst.i.tutes of Health in Maryland were able to successfully treat metastatic melanoma, a form of skin cancer, by altering killer T cells so that they specifically targeted cancer cells. This is the first study to show that gene therapy can be successfully used against some form of cancer. And in 2007, doctors at the University College and Moorfields Eye Hospital in London were able to use gene therapy to treat a certain form of inherited retinal disease (caused by mutations in the RPE65 gene).

Meanwhile, some couples are not waiting for gene therapy but are taking their genetic heritage into their own hands. A couple can create several fertilized embryos using in vitro fertilization. Each embryo can be tested for a specific genetic disease, and the couple can select the embryo free of the genetic disease to implant in the mother. In this way, genetic diseases can gradually be eliminated without using expensive gene therapy techniques. This process is currently being done with some Orthodox Jews in Brooklyn who have a high risk of Tay-Sachs disease.

One disease, however, will probably remain deadly throughout this century-cancer.

COEXISTING WITH CANCER.

Back in 1971, President Richard Nixon, amid great fanfare and publicity, solemnly announced a war on cancer. By throwing money at cancer, he believed a cure would soon be at hand. But forty years (and $200 billion) later, cancer is the second-leading cause of death in the United States, responsible for 25 percent of all deaths. The death rate from cancer has dropped only 5 percent from 1950 to 2005 (adjusting for age and other factors). It is estimated that cancer will claim the lives of 562,000 Americans this year alone, or more than 1,000 people per day. Cancer rates have fallen for a few types of the disease but have remained stubbornly flat in others. And the treatment for cancer, involving poisoning, slicing, and zapping human tissue, leaves a trail of tears for the patients, who often wonder which is worse, the disease or the treatment.

In hindsight, we can see what went wrong. Back in 1971, before the revolution in genetic engineering, the causes of cancer were a total mystery.

Now scientists realize that cancer is basically a disease of our genes. Whether caused by a virus, chemical exposure, radiation, or chance, cancer fundamentally involves mutations in four or more of our genes, in which a normal cell "forgets how to die." The cell loses control over its reproduction and reproduces without limit, eventually killing the patient. The fact that it takes a sequence of four or more defective genes to cause cancer probably explains why it often kills decades after an original incident. For example, you might have a severe sunburn as a child. Many decades later, you might develop skin cancer at that same site. This means it probably took that long for the other mutations to occur and finally tip the cell into a cancerous mode.

There are at least two major types of these cancer genes, oncogenes and tumor suppressors, which function like the accelerator and brakes of a car. The oncogene acts like an accelerator stuck in the down position, so the car careens out of control, allowing the cell to reproduce without limit. The tumor suppressor normally acts like a brake, so when it is damaged, the cell is like a car that can't stop.

The Cancer Genome Project plans to sequence the genes of most cancers. Since each cancer requires sequencing the human genome, the Cancer Genome Project is hundreds of times more ambitious than the original Human Genome Project.

Some of the first results of this long-awaited Cancer Genome Project were announced in 2009 concerning skin and lung cancer. The results were startling. Mike Stratton of the Wellcome Trust Sanger Inst.i.tute said, "What we are seeing today is going to transform the way that we see cancer. We have never seen cancer revealed in this form before."

Cells from a lung cancer cell had an astounding 23,000 individual mutations, while the melanoma cancer cell had 33,000 mutations. This means that a typical smoker develops one mutation for every fifteen cigarettes he or she smokes. (Lung cancer kills 1 million people every year around the world, mostly from smoking.) The goal is to genetically a.n.a.lyze all types of cancers, of which there are more than 100. There are many tissues in the body, all of which can become cancerous; many types of cancers for each tissue; and tens of thousands of mutations within each type of cancer. Since each cancer involves tens of thousands of mutations, it will take many decades to isolate precisely which of these mutations causes the cell mechanism to go haywire. Scientists will develop cures for a wide variety of cancers but no one cure for all of them, since cancer itself is like a collection of diseases.

New treatments and therapies will also continually enter the market, all of them designed to hit cancer at its molecular and genetic roots. Some of the promising ones include: *antiangiogenesis, or choking off the blood supply of a tumor so that it never grows *nanoparticles, which are like "smart bombs" directed at cancer cells *gene therapy, especially for gene p53 *new drugs that target just the cancer cells *new vaccinations against viruses that can cause cancer, like the human papillomavirus (HPV), which can cause cervical cancer

Unfortunately, it is unlikely that we will find a magic bullet for cancer. Rather, we will cure cancer one step at a time. More than likely, the major reduction in death rates will come when we have DNA chips scattered throughout our environment, constantly monitoring us for cancer cells years before a tumor forms.

As n.o.bel laureate David Baltimore notes, "Cancer is an army of cells that fights our therapies in ways that I'm sure will keep us continually in the battle."

GENE THERAPY.

Despite the setbacks in gene therapy, researchers believe steady gains will be made into the coming decades. By midcentury, many think, gene therapy will be a standard method of treating a variety of genetic diseases. Much of the success that scientists have had in animal studies will eventually be translated into human studies.

So far, gene therapy has targeted diseases caused by mutations in a single gene. They will be the first to be cured. But many diseases are caused by mutations in multiple genes, along with triggers from the environment. These are much more difficult to treat, but they include such important diseases as diabetes, schizophrenia, Alzheimer's, Parkinson's, and heart disease. All of them show definite genetic patterns, but no single gene is responsible. For example, it is possible to have a schizophrenic whose identical twin is normal.

Over the years, there have been a number of announcements that scientists have been able to isolate some of the genes involved in schizophrenia by following the genetic history of certain families. However, it is embarra.s.sing that these results are often not verifiable by other independent studies. So these results are flawed, or perhaps many genes are involved in schizophrenia. Plus, certain environmental factors seem to be involved.

By midcentury, gene therapy should become a well-established therapy, at least for diseases caused by single genes. But patients might not be content with just fixing genes. They may also want to improve them.

DESIGNER CHILDREN.

By midcentury, scientists will go beyond just fixing broken genes to actually enhancing and improving them.

The desire to have superhuman ability is an ancient one, rooted deeply in Greek and Roman mythology and our dreams. The great hero Hercules, one of the most popular of all the Greek and Roman demiG.o.ds, got his great powers not from exercise and diet but by an injection of divine genes. His mother was a beautiful mortal, Alcmene, who one day caught the attention of Zeus, who disguised himself as her husband to make love to her. When she became pregnant with his child, Zeus announced that the baby would one day become a great warrior. But Zeus's wife, Hera, became jealous and secretly schemed to kill the baby by delaying his birth. Alcmene almost died in agony during a prolonged labor, but Hera's plot was exposed at the last minute and Alcmene delivered an unusually large baby. Half man and half G.o.d, Hercules inherited the G.o.dlike strength of his father to accomplish heroic, legendary feats.

In the future, we might not be able to create divine genes, but we certainly will be able to create genes that will give us superhuman abilities. And like Hercules' difficult delivery, there will be many difficulties bringing this technology to fruition.

By midcentury, "designer children" could become a reality. As Harvard biologist E. O. Wilson has said, "h.o.m.o sapiens, the first truly free species, is about to decommission natural selection, the force that made us.... Soon we must look deep within ourselves and decide what we wish to become." the first truly free species, is about to decommission natural selection, the force that made us.... Soon we must look deep within ourselves and decide what we wish to become."

Already, scientists are teasing apart the genes that control basic functions. For example, the "smart mouse" gene, which increases the memory and performance of mice, was isolated in 1999. Mice that have the smart gene are better able to navigate mazes and remember things.

Scientists at Princeton University such as Joseph Tsien have created a strain of genetically altered mice with an extra gene called NR2B that helps to trigger the production of the neurotransmitter N-methyl-D-aspartate (NMDA) in the forebrain of mice. The creators of the smart mice have christened them Doogie mice (after the TV character Doogie Howser, MD).

These smart mice outperformed normal mice on a variety of tests. If a mouse is placed in a vat of milky water, it must find a platform hidden just beneath the surface where it can rest. Normal mice forget where this platform is and swim randomly around the vat, while smart mice make a beeline to it on the first try. If the mice are shown two objects, one an old one and one a new one, the normal mice do not pay attention to the new object. But the smart mice immediately recognize the presence of this new object.

What is most important is that scientists understand how these smart mice genes work: they regulate the synapses of the brain. If you think of the brain as a vast collection of freeways, then the synapse would be equivalent to a toll booth. If the toll is too high, then cars cannot pa.s.s through the gate: a message is stopped within the brain. But if the toll is low, then cars can pa.s.s and the message is transmitted through the brain. Neurotransmitters like NMDA lower the toll at the synapse, making it possible for messages to pa.s.s freely. The smart mice have two copies of the NR2B gene, which in turn helps to produce the NMDA neurotransmitter.

These smart mice verify Hebb's rule: learning takes place when certain neural pathways are reinforced. Specifically, these pathways could be reinforced by regulating the synapses that connect two nerve fibers, making it easier for signals to cross a synapse.

This result may help to explain certain peculiarities about learning. It's been known that aging animals have a reduced ability to learn. Scientists see this throughout the animal kingdom. This might be explained because the NR2B gene becomes less active with age.

Also, as we saw earlier with Hebb's rule, memories might be created when neurons form a strong connection. This might be true, since activating the NMDA receptor creates a strong connection.

MIGHTY MOUSE GENE.

In addition, the "mighty mouse gene" has been isolated, which increases the muscle ma.s.s so that the mouse appears to be musclebound. It was first found in mice with unusually large muscles. Scientists now realize that the key lies in the myostatin gene, which helps to keep muscle growth in check. But in 1997, scientists found that when the myostatin gene is silenced in mice, muscle growth expands enormously.

Another breakthrough was made soon afterward in Germany, when scientists examined a newborn boy who had unusual muscles in his upper legs and arms. Ultrasound a.n.a.lysis showed that this boy's muscles were twice as large as normal. By sequencing the genes of this baby and of his mother (who was a professional sprinter), they found a similar genetic pattern. In fact, an a.n.a.lysis of the boy's blood showed no myostatin whatsoever.

Scientists at the Johns Hopkins Medical School were at first eager to make contact with patients suffering from degenerative muscle disorders who might benefit from this result, but they were disappointed to find that half the telephone calls to their office came from bodybuilders who wanted the gene to bulk themselves up, regardless of the consequences. Perhaps these bodybuilders were recalling the phenomenal success of Arnold Schwarzenegger, who has admitted to using steroids to jump-start his meteoric career. Because of the intense interest in the myostatin gene and ways to suppress it, even the Olympic Committee was forced to set up a special commission to look into it. Unlike steroids, which are relatively easy to detect via chemical tests, this new method, because it involves genes and the proteins they create, is much more difficult to detect.

Studies done on identical twins who have been separated at birth show that there is a wide variety of behavioral traits influenced by genetics. In fact, these studies show that roughly 50 percent of a twin's behavior is influenced by genes, the other 50 percent by environment. These traits include memory, verbal reasoning, spatial reasoning, processing speed, extroversion, and thrill seeking.

Even behaviors once thought to be complex are now revealing their genetic roots. For example, prairie voles are monogamous. Laboratory mice are promiscuous. Larry Young at Emory University shocked the world of biotechnology by showing that the transfer of one gene from prairie voles could create mice that exhibited monogamous characteristics. Each animal has a different version of a certain receptor for a brain peptide a.s.sociated with social behavior and mating. Young inserted the vole gene for this receptor into the mice and found that the mice then exhibited behaviors more like the monogamous voles.

Young said, "Although many genes are likely to be involved in the evolution of complex social behaviors such as monogamy...changes in the expression of a single gene can have an impact on the expression of components of these behaviors, such as affiliation."

Depression and happiness may also have genetic roots. It has long been known that there are people who are happy even though they may have suffered tragic accidents. They always see the brighter side of things, even in the face of setbacks that may devastate another individual. These people also tend to be healthier than normal. Harvard psychologist Daniel Gilbert told me that there is a theory that might explain this. Perhaps we are born with a "happiness set point." Day by day we may oscillate around this set point, but its level is fixed at birth. In the future, via drugs or gene therapy, one may be able to s.h.i.+ft this set point, especially for those who are chronically depressed.

SIDE EFFECTS OF THE BIOTECH REVOLUTION.

By midcentury, scientists will be able to isolate and alter many of the single genes that control a variety of human characteristics. But this does not mean humanity will immediately benefit from them. There is also the long, hard work of ironing out side effects and unwanted consequences, which will take decades.

For example, Achilles was invincible in combat, leading the victorious Greeks in their epic battle with the Trojans. However, his power had a fatal flaw. When he was a baby, his mother dipped him into the magic river Styx in order to make him invincible. Unfortunately, she had to hold him by the heel when she placed him into the river, leaving that one crucial point of vulnerability. Later, he would die during the Trojan War after being hit in the heel by an arrow.

Today, scientists are wondering if the new strains of creatures emerging from their laboratories also have a hidden Achilles' heel. For example, today there are about thirty-three different "smart mouse" strains that have enhanced memory and performance. However, there is an unexpected side effect of having enhanced memory; smart mice are sometimes paralyzed by fear. If they are exposed to an extremely mild electric shock, for example, they will s.h.i.+ver in terror. "It's as if they remember too much," says Alcino Silva of UCLA, who developed his own strain of smart mice. Scientists now realize that forgetting may be as important as remembering in making sense of this world and organizing our knowledge. Perhaps we have to throw out a lot of files in order to organize our knowledge.

This is reminiscent of a case from the 1920s, doc.u.mented by Russian neurologist A. R. Luria, of a man who had a photographic memory. After just a single reading of Dante's Divine Comedy, Divine Comedy, he had memorized every word. This was helpful in his work as a newspaper reporter, but he was incapable of understanding figures of speech. Luria observed, "The obstacles to his understanding were overwhelming: each expression gave rise to an image; this, in turn, would conflict with another image that had been evoked." he had memorized every word. This was helpful in his work as a newspaper reporter, but he was incapable of understanding figures of speech. Luria observed, "The obstacles to his understanding were overwhelming: each expression gave rise to an image; this, in turn, would conflict with another image that had been evoked."

In fact, scientists believe that there has to be a balance between forgetting and remembering. If you forget too much, you may be able to forget the pain of previous mistakes, but you also forget key facts and skills. If you remember too much, you may be able to remember important details, but you might be paralyzed by the memory of every hurt and setback. Only a trade-off between these two may yield optimal understanding.

Bodybuilders are already flocking to different drugs and therapies that promise them fame and glory. The hormone erythropoietin (EPO) works by making more oxygen-containing red blood cells, which means increased endurance. Because EPO thickens the blood, it also has been linked to strokes and heart attacks. Insulin-like growth factors (IGF) are useful because they help proteins to bulk up muscles, but they have been linked to tumor growth.

Even if laws are pa.s.sed banning genetic enhancements, they will be difficult to stop. For example, parents are genetically hardwired by evolution to want to give every advantage to their children. On the one hand, this might mean giving them violin, ballet, and sports lessons. But on the other hand, this might mean giving them genetic enhancements to improve their memory, attention span, athletic ability, and perhaps even their looks. If parents find out that their child is competing with a neighbor's child who is rumored to have been genetically enhanced, there will be enormous pressure to give the same benefit to their child.

As Gregory Benford has said, "We all know that good-looking people do well. What parents could resist the argument that they were giving the child a powerful leg up (maybe literally) in a brave new compet.i.tive world?"

By midcentury, genetic enhancements may become commonplace. In fact, genetic enhancements may even be indispensable if we are to explore the solar system and live on inhospitable planets.

Some say that we should use designer genes to make us healthier and happier. Others say that we should allow for cosmetic enhancements. The big question will be how far this will go. In any event, it may become increasingly difficult to control the spread of "designer genes" that enhance looks and performance. We don't want the human race to split into different genetic factions, the enhanced and the unenhanced, but society will have to democratically decide how far to push this technology.

Personally, I believe that laws will be pa.s.sed to regulate this powerful technology, possibly to allow gene therapy when it cures disease and allows us to lead productive lives, but to restrict gene therapy for purely cosmetic reasons. This means that a black market might eventually develop to skirt these laws, so we might have to adjust to a society in which a small fraction of the population is genetically enhanced.

For the most part, this might not be a disaster. Already, one can use plastic surgery to improve appearance, so using genetic engineering to do this may be unnecessary. But the danger may arise when one tries to genetically change one's personality. There are probably many genes that influence behavior, and they interact in complex ways, so tampering with behavioral genes may create unintended side effects. It may take decades to sort through all these side effects.

But what about the greatest gene enhancement of all, extending the human life span?

REVERSING AGING.

Throughout history, kings and warlords had the power to command entire empires, but there was one thing that was forever beyond their control: aging. Hence, the search for immortality has been one of the oldest quests in human history.

In the Bible, G.o.d banishes Adam and Even from the Garden of Eden for disobeying his orders concerning the apple of knowledge. G.o.d's fear was that Adam and Eve might use this knowledge to unlock the secret of immortality and become G.o.ds themselves. In Genesis 3:22, the Bible reads, "Behold, the man is become as one of us, to know good and evil: and now, lest he put forth his hand, and take also of the tree of life, and eat, and live for ever."

Besides the Bible, one of the oldest and greatest tales in human civilization, dating back to the twenty-seventh century BC, is The Epic of Gilgamesh, The Epic of Gilgamesh, about the great warrior of Mesopotamia. When his lifelong, loyal companion suddenly died, Gilgamesh decided to embark upon a journey to find the secret of immortality. He heard rumors that a wise man and his wife had been granted the gift of immortality by the G.o.ds, and were, in fact, the only ones in their land to have survived the Great Flood. After an epic quest, Gilgamesh finally found the secret of immortality, only to see a serpent s.n.a.t.c.h it away at the last minute. about the great warrior of Mesopotamia. When his lifelong, loyal companion suddenly died, Gilgamesh decided to embark upon a journey to find the secret of immortality. He heard rumors that a wise man and his wife had been granted the gift of immortality by the G.o.ds, and were, in fact, the only ones in their land to have survived the Great Flood. After an epic quest, Gilgamesh finally found the secret of immortality, only to see a serpent s.n.a.t.c.h it away at the last minute.

Because The Epic of Gilgamesh The Epic of Gilgamesh is one of the oldest pieces of literature, historians believe that this search for immortality was the inspiration for the Greek writer Homer to write the is one of the oldest pieces of literature, historians believe that this search for immortality was the inspiration for the Greek writer Homer to write the Odyssey, Odyssey, and also for Noah's flood mentioned in the Bible. and also for Noah's flood mentioned in the Bible.

Many early kings-like Emperor Qin, who unified China around 200 BC-sent huge fleets of s.h.i.+ps to find the Fountain of Youth, but all failed. (According to mythology, Emperor Qin gave instructions to his fleet not to come back if they failed to find the Fountain of Youth. Unable to find the fountain, but too afraid to return, they founded j.a.pan instead.) For decades, most scientists believed that life span was fixed and immutable, beyond the reach of science. Within the last few years, this view has crumbled under the onslaught of a stunning series of experimental results that have revolutionized the field. Gerontology, once a sleepy, backwater area of science, has now become one of the hottest fields, attracting hundreds of millions of dollars in research funds and even raising the possibility of commercial development.

The secrets of the aging process are now being unraveled, and genetics will play a vital role in this process. Looking at the animal kingdom, we see a vast variety of life spans. For example, our DNA differs from that of our nearest genetic relative, the chimpanzee, by only 1.5 percent, yet we live 50 percent longer. By a.n.a.lyzing the handful of genes separating us from the chimpanzees, we may be able to determine why we live so much longer than our genetic relative.

This, in turn, has given us a "unified theory of aging" that brings the various strands of research into a single, coherent tapestry. Scientists now know what aging is. It is the acc.u.mulation of errors at the genetic and cellular level. These errors can build up in various ways. For example, metabolism creates free radicals and oxidation, which damage the delicate molecular machinery of our cells, causing them to age; errors can build up in the form of "junk" molecular debris acc.u.mulating inside and outside the cells.

The buildup of these genetic errors is a by-product of the second law of thermodynamics: total entropy (that is, chaos) always increases. This is why rusting, rotting, decaying, etc., are universal features of life. The second law is inescapable. Everything, from the flowers in the field to our bodies and even the universe itself, is doomed to wither and die.

But there is a small but important loophole in the second law that states total total entropy always increases. This means that you can actually reduce entropy in one place and reverse aging, as long as you increase entropy somewhere else. So it's possible to get younger, at the expense of wreaking havoc elsewhere. (This was alluded to in Oscar Wilde's famous novel entropy always increases. This means that you can actually reduce entropy in one place and reverse aging, as long as you increase entropy somewhere else. So it's possible to get younger, at the expense of wreaking havoc elsewhere. (This was alluded to in Oscar Wilde's famous novel The Picture of Dorian Gray. The Picture of Dorian Gray. Mr. Gray was mysteriously eternally young. But his secret was the painting of himself that aged horribly. So the total amount of aging still increased.) The principle of entropy can also be seen by looking behind a refrigerator. Inside the refrigerator, entropy decreases as the temperature drops. But to lower the entropy, you have to have a motor, which increases the heat generated behind the refrigerator, increasing the entropy outside the machine. That is why refrigerators are always hot in the back. Mr. Gray was mysteriously eternally young. But his secret was the painting of himself that aged horribly. So the total amount of aging still increased.) The principle of entropy can also be seen by looking behind a refrigerator. Inside the refrigerator, entropy decreases as the temperature drops. But to lower the entropy, you have to have a motor, which increases the heat generated behind the refrigerator, increasing the entropy outside the machine. That is why refrigerators are always hot in the back.

As n.o.bel laureate Richard Feynman once said, "There is nothing in biology yet found that indicates the inevitability of death. This suggests to me that it is not at all inevitable and that it is only a matter of time before biologists discover what it is that is causing us the trouble and that this terrible universal disease or temporariness of the human's body will be cured."

The second law can also be seen by the action of the female s.e.x hormone estrogen, which keeps women young and vibrant until they hit menopause, when aging accelerates and the death rate increases. Estrogen is like putting high-octane fuel into a sports car. The car performs beautifully but at the price of causing more wear and tear on the engine. For women, this cellular wear and tear might be manifested in breast cancer. In fact, injections of estrogen are known to accelerate the growth of breast cancer. So the price women pay for youth and vigor before menopause is possibly an increase in total entropy, in this case, breast cancer. (There have been scores of theories proposed to explain the recent rise in breast cancer rates, which are still quite controversial. One theory says that this is in part related to the total number of menstrual cycles a woman has. Throughout ancient history, after p.u.b.erty women were more or less constantly pregnant until they hit menopause, and then they died soon afterward. This meant they had few menstrual cycles, low levels of estrogen, and hence, possibly, a relatively low level of breast cancer. Today, young girls reach p.u.b.erty earlier, have many menstrual cycles, bear an average of only 1.5 children, live past menopause, and hence have considerably more exposure to estrogen, leading to a possible rise in the occurrence of breast cancer.) Recently, a series of tantalizing clues has been discovered about genes and aging. First, researchers have shown that it is possible to breed generations of animals that live longer than normal. In particular, yeast cells, nematode worms, and fruit flies can be bred in the laboratory to live longer than normal. The scientific world was stunned when Michael Rose of the University of California at Irvine announced that he was able to increase the life span of fruit flies by 70 percent by selective breeding. His "superflies," or Methuselah flies, were found to have higher quant.i.ties of the antioxidant superoxide dis.m.u.tase (SOD), which can slow down the damage caused by free radicals. In 1991, Thomas Johnson of the University of Colorado at Boulder isolated a gene, which he dubbed age-1, that seems to be responsible for aging in nematodes and increases their life spans by 110 percent. "If something like age-1 exists in humans, we might really be able to do something spectacular," he noted.

Scientists have now isolated a number of genes (age-1, age-2, daf-2) that control and regulate the aging process in lower organisms, but these genes have counterparts in humans as well. In fact, one scientist remarked that changing the life span of yeast cells was almost like flicking on a light switch. When one activated a certain gene, the cells lived longer. When you deactivated it, they lived shorter lives.

Breeding yeast cells to live longer is simple compared to the onerous task of breeding humans, who live so long that testing is almost impossible. But isolating the genes responsible for aging could accelerate in the future, especially when all of us have our genomes on a CD-ROM. By then, scientists will have a tremendous database of billions of genes that can be a.n.a.lyzed by computers. Scientists will be able to scan millions of genomes of two groups of people, the young and the old. By comparing the two sets, one can then identify where aging takes place at the genetic level. A preliminary scan of these genes has already isolated about sixty genes on which aging seems to be concentrated.

For example, scientists know that longevity tends to run somewhat in families. People who live long tend to have parents who also lived long. The effect is not dramatic, but it can be measured. Scientists who a.n.a.lyze identical twins who were separated at birth can also see this at the genetic level. But our life expectancy is not 100 percent determined by our genes. Scientists who have studied this believe that our life expectancy is only 35percent determined by our genes. So in the future, when everyone has their own $100 personal genome, one may be able to scan the genomes of millions of people by computer to isolate the genes that partially control our life span.

Furthermore, these computer studies may be able to locate precisely where aging primarily takes place. In a car, we know that aging takes place mainly in the engine, where gasoline is oxidized and burned. Likewise, genetic a.n.a.lysis shows that aging is concentrated in the "engine" of the cell, the mitochondria, or the cell's power plant. This has allowed scientists to narrow the search for "age genes" and look for ways to accelerate the gene repair inside the mitochondria to reverse the effects of aging.

By 2050, it might be possible to slow down the aging process via a variety of therapies, for example, stem cells, the human body shop, and gene therapy to fix aging genes. We could live to be 150 or older. By 2100, it might be possible to reverse the effects of aging by accelerating cell repair mechanisms to live well beyond that.

CALORIC RESTRICTION.

This theory may also explain the strange fact that caloric restriction (that is, lowering the calories we eat by 30 percent or more) increases the life span by 30 percent. Every organism studied so far-from yeast cells, spiders, and insects to rabbits, dogs, and now monkeys-exhibits this strange phenomenon. Animals given this restricted diet have fewer tumors, less heart disease, a lower incidence of diabetes, and fewer diseases related to aging. In fact, caloric restriction is the only only known mechanism guaranteed to increase the life span that has been tested repeatedly, over almost the entire animal kingdom, and it works every time. Until recently, the only major species that still eluded researchers of caloric restriction were the primates, of which humans are a member, because they live so long. known mechanism guaranteed to increase the life span that has been tested repeatedly, over almost the entire animal kingdom, and it works every time. Until recently, the only major species that still eluded researchers of caloric restriction were the primates, of which humans are a member, because they live so long.

Scientists were especially anxious to see the results of caloric restriction on rhesus monkeys. Finally, in 2009, the long-awaited results came in. The University of Wisconsin study showed that, after twenty years of caloric restriction, monkeys on the restricted diet suffered less disease across the board: less diabetes, cancer, heart disease. In general, these monkeys were in better health than their cousins who were fed a normal diet.

There is a theory that might explain this: Nature gives animals two "choices" concerning how they use their energy. During times of plenty, energy is used to reproduce. During times of famine, the body shuts down reproduction, conserves energy, and tries to ride out the famine. In the animal kingdom, the state of near starvation is a common one, and hence animals frequently make the "choice" of shutting down reproduction, slowing metabolism, living longer, and hoping for better days in the future.

The Holy Grail of aging research is to somehow preserve the benefits of caloric restriction without the downside (starving yourself). The natural tendency of humans apparently is to gain weight, not lose it. In fact, living on a calorically restricted diet is no fun; you are fed a diet that would make a hermit gag. Also, animals fed a particularly severe, restricted diet become lethargic, sluggish, and lose all interest in s.e.x. What motivates scientists is the search for a gene that controls this mechanism, whereby we can reap the benefits of caloric restriction without the downside.

An important clue to this was found in 1991 by MIT researcher LeonardP. Guarente and others, who were looking for a gene that might lengthen the life span of yeast cells. Guarente, David Sinclair of Harvard, and coworkers discovered the gene SIR2, which is involved in bringing on the effects of caloric restriction. This gene is responsible for detecting the energy reserves of a cell. When the energy reserves are low, as during a famine, the gene is activated. This is precisely what you might expect in a gene that controls the effects of caloric restriction. They also found that the SIR2 gene has a counterpart in mice and in people, called the SIRT genes, which produce proteins called sirtuins. They then looked for chemicals that activate the sirtuins, and found the chemical resveratrol.

This was intriguing, because scientists also believe that resveratrol may be responsible for the benefits of red wine and may explain the "French paradox." French cooking is famous for its rich sauces, which are high in fats and oils, yet the French seem to have a normal life span. Perhaps this mystery can be explained because the French consume so much red wine, which contains resveratrol.

Scientists have found that sirtuin activators can protect mice from an impressive variety of diseases, including lung and colon cancer, melanoma, lymphoma, type 2 diabetes, cardiovascular disease, and Alzheimer's disease, according to Sinclair. If even a fraction of these diseases can be treated in humans via sirtuins, it would revolutionize all medicine.

Recently, a theory has been proposed to explain all the remarkable properties of resveratrol. According to Sinclair, the main purpose of sirtuin is to prevent certain genes from being activated. A single cell's chromosomes, for example, if fully stretched, would extend six feet, making an astronomically long molecule. At any time, only a portion of the genes along this six feet of chromosomes are necessary; all the rest must be inactive. The cell gags most of the genes when they are not needed by wrapping the chromosome tightly with chromatin, which is maintained by sirtuin.

Sometimes, however, there are catastrophic disruptions of these delicate chromosomes, like a total break in one of the strands. Then the sirtuins spring into action, helping to repair the broken chromosome. But when the sirtuins temporarily leave their posts to come to the rescue, they must abandon their primary job of silencing the genes. Hence, genes get activated, causing genetic chaos. This breakdown, Sinclair proposes, is one of the chief mechanisms for aging.

If this is true, then perhaps sirtuins can not only halt the advance of aging but also reverse it. DNA damage to our cells is difficult to repair and reverse. But Sinclair believes that much of our aging is caused by sirtuins that have been diverted from their primary task, allowing cells to degenerate. The diversion of these sirtuins can be easily reversed, he claims.