Êíèãà: The Human Age
DNA’s Secret Doormen
Cyborgs and Chimeras
Meet My Maker, the Mad Molecule
DNA’s Secret Doormen
Swinging gamely among the fire-hose vines at the Toronto Zoo, Budi isn’t a cyborg or man-made chimera, and no human has reknit his DNA. He’s just a frisky orangutan kid, an emissary from the wild. But we’re starting to regard his physical nature (and our own) in radically new ways that connect and redefine us. Only the knowledge and what we can do with it are new. The rest is ancient as the family tree we share.
A YOUNG WOMAN with chestnut hair is seated in front of me in the cinema, slouched down, watching Stanley Kubrick’s 2001: A Space Odyssey. On the art-house screen, a vegetarian ape idly fingers the scattered bones of a fallen antelope. Slowly an idea begins to take shape. Picking up a bone, he raises it over his head and smashes it down on the rest of the skeleton, over and over, striking and shattering in an orgy of violence, while the vision of a tasty tapir flickers through his head and the pounding chords of Richard Strauss’s Thus Spake Zarathustra drive home the message: Man the Hunter is born. A day later, the ape man uses his weapon to kill the leader of a rival band of apes, while the Strauss soundtrack grows orgasmic with a new drama: the blow-by-blow chords of war. From there, Kubrick treats us to human evolution, artificial intelligence, alien life, and technological pageantry. Cascading into the spacefaring future, we find an astronaut vying with a sentient, mentally disturbed computer (which he subdues with a tool far subtler than an antelope bone). Reaching the apogee of his fate, he’s transfigured in a process that’s too advanced for us relative cavemen (in the cave of the movie theater, anyway) to distinguish from magic. As the credits roll like blankets of stars, rising houselights return us to Earth and a human saga and future that seem all the more epic.
When the chestnut-haired woman gets up to leave, one strand of hair remains on the back of her seat. From that tiny sample, someone could peruse the DNA and know if it belonged to a human female or an Irish setter or a fox, and find clues to her identity: ethnic background, eye color, likelihood of developing various diseases, even her probable life span. One would assume that she has little in common with a mouse or a roundworm, and yet they have a similar number of genes. She’s intimately related to almost every creature that walks, crawls, slithers, or flies, even the ones she’d find icky. Especially those. She shares all but a drop of her genetic heritage with spineless organisms. But that drop really counts.
Thanks to the Human Genome Project’s library of our roughly twenty-five thousand protein-coding genes, available via the Internet to anyone with a yen to peruse it, a micro-stalker could analyze the rungs of our redhead’s DNA, creeping up its spiral ladders, and discovering all sorts of juicy nuggets. Some of the micro-portrait he finds will be quite recent, because by hogging and restyling the environment we’ve altered plants, animals, single-celled organisms, and ourselves. Her DNA will show a panoply of revisions, indicative of our age, which we’ve either stage-managed or accidentally caused. Could the pollutants we use, and the wars we wage, really change our DNA and rewire the human species?
She knows they can, because in her college curriculum, Anthropocene Studies, she’s read research linking exposure to jet fuel, dioxin, the pesticides DEET and permethrin, plastics, and hydrocarbon mixtures to cancer, and not just in the person who had contact with it but for several generations. She’s learned how the arsenic-polluted drinking water in the Ganges delta in Bangladesh can lead to skin cancer, as can workplace exposure to cadmium, mercury, lead, and other heavy metals. Although she was tempted to spend her junior year abroad in Beijing, she’s having second thoughts now that a peer-reviewed PLOS ONE study ties life in smog-ridden cities to thickening of the arteries and heightened risk of heart disease. What clinches it is this headline in Mail Online: “China starts televising the sunrise on giant TV screens because Beijing is so clouded in smog.” Below it, a video shows a scarlet sunrise on an LED billboard in Tiananmen Square, completely encased by thick gray air, as if the sun were on display in a museum. Several black silhouettes are walking past it on their way to work, some wearing masks. As a daily jogger, she’d be inhaling a lot more pollution than most people, and she figures her genes have already been restyled just by growing up among the master trailblazers of the Human Age.
But she is tempted to read the book of her genes, and discover more about her lineage and genetic biases. For a truly personal profile, all our redhead would need is a vial of her blood and between $100 and $1,000. Such companies as Navigenics or 23andMe will gladly provide a glimpse of her future, a tale still being written but legible enough for genetic fortune-telling. She may have a slightly higher than normal risk of macular degeneration, a tendency to go bald, a gene variant that’s a well-known cause of blood cancer, maybe a different variant associated with Alzheimer’s, the family bane. If she read the report herself, she might not handle that information well. It could kindle needless worry about ailments that will never materialize, or it might warn of an impending but treatable illness, or predict a serious, disabling disease like Huntington’s. As a supposed calmative, such tests are usually marketed as a “recreational” exercise, to discover if you’re part Cherokee or African or Celt, or Neanderthal, or even related to Genghis Khan, as I may well be.
My mother always said I must be part Mongolian, because of my lotus-pale complexion and squid-ink-black hair. Something you’re not telling me? I was tempted to ask. But I knew she’d visited Mongolia with my father long after I was born. What I didn’t know is that one out of every two hundred males on Earth is related to Genghis Khan.
An international team of geneticists conducting a ten-year study of men living in what once was the Mongolian empire discovered that a surprisingly large number share the identical Y chromosome, which is passed down only from father to son. One individual’s Y chromosome can be found in sixteen million men “in a vast section of Asia from Manchuria near the sea of Japan to Uzbekistan and Afghanistan in Central Asia.”
The likeliest candidate is Khan, a warlord who raped and pillaged one town after another, killing all the men and impregnating the women, sowing his seed from China to Eastern Europe. Though legend credits Khan with many wives and offspring, he didn’t need to do all the begetting himself to ensure that his genes would flourish. His sons inherited the identical Y chromosome from him, as did their sons and their sons’ sons down a long, winding Silk Road of legitimate and illegitimate progeny. His equally warlike oldest son, Tushi, had forty legitimate sons (and who knows how many misbegotten), and his grandson Kublai Khan, who figured so large in Marco Polo’s life, had twenty-two.
Their genes scattered exponentially in an ever-widening fan, and the process really picked up speed in the twentieth century, when cars, trains, and airplanes began propelling genes around the planet and stretching the idea of “courting distance,” which used to be only twelve miles—how far a man could ride on horseback to visit his sweetheart and return home the same day. Now it’s commonplace to have children with someone from thousands of miles, even half a world, away.
Khan wasn’t trying to create a world in his image; his fiercest instincts had a mind of their own, and his savage personality spurred them on. Most people don’t run amok on murderous sprees, thank heavens, but history is awash with Khan-like wars and mayhem. In their wake, gene pools often change. One can only surmise that wiping out the genes of others and planting your own (what we call genocide) must come naturally to our kind, as it does to some other animals, from ants to lions.
Typically, wandering male lions attack a pride, drive off the other males, and kill their offspring. Then they mate with the females, ensuring that only the invaders’ genes will flourish. A colony of ants will slaughter millions of neighbors, provided they’re not family (somehow they can spot or whiff geographically distant kin they haven’t met before). Human history is riddled with similar dramas, but that doesn’t justify them. They were, and are, war’s legacy, an unconscious motive, not a blueprint for action.
Except once. During World War II, Hitler and his henchmen devised an agenda, both political and genetic, that was nothing less than the Nazification of nature. The human cost is well known: the extermination of millions while, in baby farms scattered around Europe, robust SS men and blond, blue-eyed women produced thousands of babies to use as seed stock for Hitler’s new master race. What’s little known is that their scheme for redesigning nature didn’t stop with people. The best soldiers needed to eat the best food, which Nazi biology argued could grow only from the purest of seeds. So, using eugenics, a method of breeding to emphasize specific traits, the Nazis hoped to invade the genetic spirals of evolution, seize control, and replace “unfit” foreign crops and livestock with genetically pure, so-called Aryan ones.
To that end, they created an SS commando unit for botanical collection, which was ordered to raid the world’s botanical gardens and institutes and steal the best specimens. Starting with Poland, they planned on using slave labor to drain about a hundred thousand square miles of wetlands so that they could farm it with Aryan crops. Draining the marshes might well lower the water table and create a dust bowl, and it would certainly kill the habitat of wolves, geese, wild boar, and many other native species, but despoilers rarely see downstream from events.
Elsewhere, the Nazis proposed planting forests of oak, birch, beech, yew, and pine to sweeten the climate so that it was more favorable for their own oats and wheat, and they spoke openly about reshaping the landscape to better suit Nazi ideals. That revision included people, railways, animals, and land alike, even the geometry of farm fields (no acute angles below 70°), and the alignment of trees and shrubs (only on north-south or east-west axes). Today, though we deplore genocide it stubbornly persists, and we may have our work cut out for us because it seems to tap a deeply rooted drive. It’s bone-chilling how close the Nazis came to a feat of genetic domination that dwarfs all of Genghis Khan’s exploits.
The human DNA that Olivine finds in future days will show some lineages, like Khan’s, triumphing through war, and others succeeding because of geography, religion, politics, fashionable ideals of beauty, and elements native to our age such as giant factories and workplaces, cars, jet travel, Internet and social media, the jammed crossroads of megacities, and widely available birth control and infertility treatments.
When my mother teased about my being part Mongolian, she may have been right, since Genghis Khan and his clan reached into Russia. But I like knowing that the farther back one traces any lineage the narrower the path grows, to the haunt of just a few shaggy ancestors, with luck on their side, little gizmos in their cells, and a future storied with impulses and choices that will ultimately define them.
The noble goal of the Human Genome Project is to use such knowledge to find new ways to understand, treat, and cure illness. In that sense, it’s a group portrait of us as a species, realized at last, a mere fifty years after Crick, Watson, and Franklin decoded the double-helix design of DNA. The only thing more unlikely than DNA itself, nature’s blueprint for building a human being, is our ability to decode it. Thus far, it’s our greatest voyage of discovery, and we’re still scouting its spiral coves.
IN NORRBOTTEN, THE northernmost province of Sweden, the reindeer outnumber humans, and shimmery green veils of northern lights spiral up from the horizon like enchanted scarves. In summer, crops ripen under a ceramic sun; moon-shadows haunt the ice-marbled winter nights. Although the citizens can travel by car today, in the past they relied on foot or horse power to carry them to grace at an early-fifteenth-century church in the ancient settlement of Gammelstad, where they eased their isolation and replenished hope.
Getting there was only half the pilgrimage. Needing rest before the formidable trek home, each family retired to their tiny wooden house near the church, painted red with windows and doors picked out in white. Some bore grass roofs. Delicate lace curtains hemmed the frost-curled windows, and stout shutters sealed out the warring tempests. Doors were adorned with a pyramid motif, a legacy from pagan antiquity admired for its stark symmetry, and reinterpreted as a Christian altar lit by sacrificial fire.
In such a remote frontier, the human population thinned to only about six people per square mile, and farmers crafted what they needed, from harnesses to nails. Neighbors helped neighbors, and married neighbors. But if the harvest failed—as it did with alarming frequency—rescue lay too far away. Railways didn’t venture that far north, even at the height of the Industrial Age when iron horses snorted soot across many frontiers, and in any case locals spoke a dialect unintelligible to other Swedes.
Gammelstad’s church, plus the rows of red bungalows clustered behind it, are part of a World Heritage Site that also includes the remains of a six-thousand-year-old Stone Age settlement in the heart of town. Tourists are today’s pilgrims, closely followed by geneticists. It’s an unlikely setting to be at the center of a revolution in medicine, and yet it holds an important key to the health and longevity of everyone on Earth.
In the nineteenth century, Norrbotten’s fickle climate bred many lopsided years of surfeit or famine, with no way to foretell the fate of the crops. People either nearly starved or died. For example, 1800, 1812, 1821, 1836, and 1856 all were years of deprivation, when crops totally failed (including staples like potatoes and grains for porridge), farm animals died, families suffered pounding hunger and malnutrition, and underweight babies entered a lean world with even leaner prospects. But in 1801, 1822, 1828, 1844, and 1863, on the other hand, the weather sweetened and food leapt from the soil in such abundance that families thrived, the economy bloomed, and for many people overeating became a pastime.
If we jump to the 1980s and step across the North Sea to London, we find the prestigious medical journal The Lancet publishing studies that highlighted the importance of womb-time, linking a mother’s poor diet during pregnancy with her child’s higher risk of heart disease, diabetes, obesity, and related illnesses. This was a revelation to the medical community and a warning to parents.
According to Darwin’s theory of natural selection, a child is born with a genetic blueprint that has evolved over millennia. All the hard-luck times its parents faced might be taught as life lessons, but they aren’t hereditary; they won’t alter a child’s chemistry. Thinking otherwise was a delusion mocked and dismissed in the eighteenth century, when the naturalist Jean-Baptiste Lamarck (the man who coined the word “biology”) posed a theory that parents could pass along acquired traits to their offspring. In his most famous example, a giraffe reaches achingly high into the treetops each day to feed on tasty leaves, which ultimately lengthens its neck, and then its offspring inherit longer necks and stretch them even more by mimicking the parent’s behavior. Smart, keen-eyed, and right about many aspects of botany and zoology, including the dangerous idea that new species arise naturally through evolution, Lamarck was wrongheaded about giraffe necks and heritable traits. According to his logic, if a blacksmith grew anvil-hard arms from a lifetime of heavy hammering, his offspring would inherit equally burly muscles. It’s fun to think what such a world would look like—a mismatched crowd of animals within each species and the enviable ability to will traits to one’s offspring. Practice wouldn’t be needed—you could inherit your pianist dad’s spiderlike dexterity with his fingers or your bicycling mom’s loaflike quadriceps.
Darwinian evolution teaches us that genetic changes in DNA unfold with granular slowness over millennia; no individual can erase or rewrite them in his lifetime. Genetic mutations come and go, and if one is harmful or useless for survival, it tends not to linger. But if it’s beneficial it equips the animal with an edge, a better chance at surviving long enough to breed, and then the mutation empowers the animal’s offspring and their offspring in turn, passing the winning trait along to future generations in quite a sloppy way, all things considered. In time this fluky mechanism leaves the world with only those animals best suited to their different habitats.
That’s the accepted theory, proven in countless experiments, and there’s no reason to doubt it. But what if that isn’t the whole story? Eclipsed by Darwin, Lamarck seems to have been right at least in spirit, a reality that has stunned much of the scientific world. What makes a paradigm shift so shifty is that you don’t see it coming. Then it suddenly pulls a mental ripcord and your mind plummets at speed. A new paradigm blossoms overhead, the freefall slows to float, and the world becomes visible once again, but from a new perspective. “Creative insight,” we call this parachute flare with discovery.
After Lars Olov Bygren, of the Karolinska Institute in Stockholm, read the Lancet articles, he began to wonder about the nineteenth-century children of Norrbotten who had alternately starved and binged. The people of that region seemed ideally isolated for a genetics study. Certainly the children would have been influenced by their mothers’ nutrition during pregnancy, but what about all the earlier feasts and famines their parents endured—could those blemish the children’s health? This was a daring question to ask, let alone pursue, since it flew in the face of Darwinian fashion. But it nagged at him until he finally decided to focus on ninety-nine children born in ?verkalix in 1905, relying on a wealth of historical data. Why choose those mountain bluffs and chanting shores?
“I grew up in a small forested area, ten miles north of the Arctic Circle,” Bygren explains.
A slender man with gray hair and round glasses, he walks thoughtfully among the headstones in the church cemetery, where tall stalks of sunlit grass surround some of the young who died for lack of grain a hundred years before. The headstones bear such familiar names as Larssen and Persson, the English equivalent of Smith and Jones; Bygren probably played with some of their relatives as a boy. Bluebells and daisies flower naturally between the stones, and some graves are adorned with gaudier store-bought flowers.
“We have an expression,” he says with a laugh. “Dig where you stand!”
After a moment, Bygren adds, “We are really data rich.” Data rich even when crop poor. “Everything happening in the family was recorded.”
Ever since the sixteenth century, the clergy has kept a fastidious ledger of births and deaths (with causes), as well as land ownership, crop prices, and harvests. Thanks to the clergy’s meticulous record-keeping, Bygren was able to gauge how much food was on hand when parents and grandparents were children. ?verkalix provided a natural experiment where he could follow isolated families as they tumbled forward in time.
Common sense hints that if you’re creased by trauma, are a junk food junkie, or spend your days staring at lit screens while spring offers the likes of pink-petaled magnolias ruffling their flamingo feathers in the breeze, it may make you miserable and unhealthy, but it won’t affect the DNA of your unborn children. They may inherit your curly hair, gray eyes, musical ear reliable as a tuning fork, thin porcelain skin, or risk of a genetic disease such as Huntington’s, but they won’t suffer from your accidents and misdeeds. Their DNA won’t be damaged by your rotten choices in lifestyle, nor can you pass on all the wonderful feats you’ve accomplished, the wonders your senses have soaked in, the perils you’ve avoided. In that sense, they’re born with a clean slate and will become entangled in their own dramas and make their own questionable choices. Certainly they won’t be obese, get diabetes, or die young just because a grandparent binged during one tantalizingly rich harvest season after a year of brutal gourd-bellied hunger. Evolution doesn’t work that way or that fast—end of story. Or is it?
What Bygren found was quite different. He and the geneticist Marcus Pembrey, of University College London, began collaborating on groundbreaking studies that raised eyebrows and led to such headlines as “You Can Traumatize Your DNA,” “You Are What Your Grandparents Ate,” “Nurture Matters,” and “The Sins of Our Fathers” (in Exodus, God speaks of “visiting the iniquity of the fathers on the children and the children’s children”).
The ultimate immigrants, babies arrive in this world from a far country with no dry land, lugging helical clouds of ancient DNA, primed for survival, but seemingly ill equipped to face sudden changes in the environment. Yet it is possible to warn children and grandchildren about recent dangers. Episodes of near-starvation—or other extreme changes in the environment—tag the DNA in children’s nascent eggs and sperm. Then years later, when they have children of their own, new traits emerge, not because the traits serve the species well, but because of the parents’ specific stresses long before their children were conceived.
When Bygren looked at the children of ?verkalix, he was surprised to discover that boys between the ages of nine and twelve who gorged during a bountiful season, inviting diabetes and heart problems, produced sons and grandsons with shorter life spans. And not by a negligible amount. Both sons and grandsons lived an average of thirty-two years less! In contrast, the boys who suffered a hunger winter, if they survived and grew up to have sons of their own, raised boys with health benefits—four times less diabetes and heart disease than their peers and life spans that averaged thirty-two years longer. Later studies found similar results among the girls, though at a younger age, since girls are born with a bevy of eggs and boys develop sperm in the prelude to puberty. During these growth windows, ripening eggs and sperm seem to be especially vulnerable to intel about the environment. Like a computer’s binary code, the marks tell switches to turn on or off in the cells. Then eggs and/or sperm ferry the message to the next generation, where they may indeed be lifesaving. On the other hand, they could usher in the onset of disease by equipping someone for a world that no longer exists. Problems detonate when one is biologically prepared for a radically different environment.
“The results are there,” Bygren says, solid as the iron ore enriching the folds of Norrbotten. “The mechanisms are not so clear.”
Shocking though the idea was, the evidence plainly showed that it only took a single generation to make indelible changes. That year of gluttony as a child set in motion a biological avalanche in the cells, dooming the children’s as yet unimagined grandchildren to a host of illnesses and vastly shorter lives than their peers. It’s as if they had inherited a genetic scar.
How and why this evolutionary sidestep happens is the focus of epigenetics, a new science that puts all the old-fashioned college debates about nature or nurture on the Anthropocene scrap heap of outmoded ideas. It also lays a heavier burden on the shoulders of would-be parents. Apparently, it’s never too soon to begin worrying about the health of your grandchildren.
The implications are staggering. Up until now, inheritance was a tale told by DNA; it lay exclusively in the genes. In the watch-how-you-step, deep-nurture world of epigenetics, proteins tag DNA by coiling around it, pythonlike, squeezing some genes tighter and loosening others, in the process switching them on or off, or leaving them on but turning the volume up or dialing it down to a whisper.
Changes in our genome took millions of years, but the epigenome can be changed quickly, for example, by simply adding a tiny methyl group (three hydrogen atoms glued to one carbon atom) or an acetyl group (two carbons, three hydrogens, and an oxygen). This “methylation” turns a gene off, and “acetylation” turns a gene on. Environmental stresses flip the switch, which makes sense, since in theory it prepares offspring for the environment they’re going to find. Diet, stress, prenatal nutrition, and neglect create especially strong marks, whose influence can be either good or bad. How the marks fiddle with your genes may be deadly in the long run, or may prolong your life. Exercise and good nutrition leave beneficial tags, smoking and high stress pernicious ones.
What changes isn’t the tool but how it’s used. It’s like the difference between wielding a hammer to tap in a picture nail or to smash a hole in a wall. Nature is thrifty, recycling the basics. It’s as if DNA were a tonal language using the same consonants and vowels, but speaking them with different inflections. In Mandarin Chinese, the world’s most widely spoken tonal language, how you voice the word “man” determines whether you mean “slow” or “deceive.” Exactly the same DNA funds heart, pancreas, and brain cells, yet they finesse different tasks. As genes are switched on and off, made to shout or whisper, their meaning and purpose shift. That’s why it’s merely an embarrassment that we have fewer genes than plants and nearly the same genes as chimpanzees. Gifted with the same libretto of genes, life forms intone them differently, and our own cells morph into skin, bone, lips, liver, blood. Epigenetics is providing clues to how this tonal magic is performed.
Pembrey’s fascinating hypothesis is that the Industrial Age ushered in a flood of rapid-fire environmental and social changes, and while genetic evolution struggled to keep up with them, it couldn’t adapt that fast. The speed of change was unprecedented, and our genes don’t evolve in just a few generations. But certain “epigenetic tags” clinging to those genes could. So the pesticides or hydrocarbons your great-grandmother was exposed to when she was pregnant may heighten the risk of ovarian disease in you, and you in turn might pass that risk on to your grandchildren. Ovarian cancer has been increasing to affect more than 10 percent of women over the past few decades, and environmental epigenetics offers a plausible reason why.
We only exist in relation to others and the world. This dialogue, a three-ring circus among the genes, a perpetual biological tango performed by multitudes, deserves a better name than the unwieldy crunch of “epigenetics,” but the word is springing from many more lips as doctors search for clues in both a patient’s environmental exposure history and that of his parents.
“We’re in the midst of probably the biggest revolution in biology,” says Mark Mehler, chair of the Department of Neurology at Albert Einstein College of Medicine. “It’s forever going to transform the way we understand genetics, environment, the way the two interact, what causes disease. It’s another level of biology, which for the first time really is up to the task of explaining the biological complexity of life.”
“The Human Genome Project was supposed to usher in a new era of personalized medicine,” Mehler told the American Academy of Neurology at its annual meeting in 2011. “Instead, it alerted us to the presence of a second, more sophisticated genome that needed to be studied.”
Despite the DNA of twins, for example, they’re never perfect matches. If one has schizophrenia, the odds of her twin developing it are only 50 percent, not 100 percent as one might assume since they have identical genes. Twins have become an important part of epigenetic studies. So have children of Holocaust survivors, Romanian orphans who weren’t held and comforted enough, and children with stress-rattled or neglectful caregivers. From psychiatric epigenetics we’re learning how important a mother’s mood is to the fate of her fetus. The chemicals that swaddle and seep through a fetus can influence its future health, mood, and life span.
In 2004, Michael Meaney, whose lab at McGill University was studying maternal behavior, published his findings in Nature Neuroscience. Good mother rats, who licked their fourteen to twenty pups often and with care during the first week of life, produced nice calm pups. Standoffish mother rats who didn’t lick their pups much or neglected them entirely produced noticeably anxious pups. And as adults, the next generation of female rats mirrored their mothers’ behavior.
“For us, the Holy Grail was to identify the path that was being altered by this licking behavior,” Meaney says. “We identified one small region on the gene that responds to maternal care and directs changes in the brain cells.”
Meaney’s work is now looking at human child development. A highly stressed pregnant mother floods her fetus with glucocorticoids, which can reduce birth weight, shrink the size of the hippocampus (memory’s estate), and cripple the ability to deal with stress. Yet, as Meaney is the first to point out, many underweight babies turn out fine, which suggests that postnatal care must be able to reverse the ill effects. Environment and nurture do matter, and it doesn’t take long for their influence to show. In colonies of the desert locust, individuals are naturally shy and nocturnal. But if the population swells and overcrowding occurs, the densely packed grasshoppers give birth to gregarious, diurnal young. Or, in bird studies, if the mother lives in “socially demanding conditions,” holding high social rank, for example, her androgen level climbs. That leads to increased androgen in her eggs and produces more competitive chicks.
Is our moviegoer among the poor? As the health consequences of poverty drift into social medicine’s sights, ongoing human and animal studies link either enriched environments or impoverished ones to the health of children and grandchildren. Studies of the Dutch Hunger Winter in 1944–45 reveal that prenatal hunger can lead to schizophrenia and depression. In a U.K. study, poor prenatal nutrition is tied to a trio of risks for heart disease in older adults.
In other research, mothers who lived through the stresses of hurricanes and tropical storms while they were pregnant were more likely to have autistic children. Even if as an adult the redhead makes all the healthy choices, is happy during her own pregnancy, and becomes a doting mom, her child can still suffer from the stresses its neglected grandmother endured during the Great Depression. Or its grandfather suffered in Vietnam as a young recruit before she was even conceived. What her grandparents ate for breakfast matters.
Did our redhead’s father take Viagra? Thanks to such drugs, much-older men are siring offspring. What effect could so many older fathers, and aging genes, have on us and future generations? One unexpected finding is that, for some reason, older fathers endow their offspring with longer telomeres (which cap the ends of chromosomes like the tabs at the end of shoelaces do to keep them from fraying), a part of the gene that controls life span. So the children may live longer. On the other hand, older fathers are blamed for passing on mutations that can lead to such dreaded disorders as autism or schizophrenia. Dad’s diet was also important; if he was gluttonous, she may be more likely to develop diabetes. Fortunately, our moviegoer inherited telomeres long as a summer night.
None of this happens by unzipping and altering the codebook of DNA, yet it’s inherited by offspring. Epigenetics is the second pair of pants in the genetic suit, another weave of heredity, and although revising someone’s genome is hard, it’s relatively easy to change an epigenome. The marks are profound but not permanent. As a result, the field holds limitless promise.
“Genes can’t function independently of their environment,” Meaney says. “So every aspect of our lives is a constant function of the dialogue between environmental signals and the genome. The bottom line seems to be that parental care can have an even bigger impact than we ever dreamed on our children’s lives. We’re just starting to learn what that means.”
Yes, a trauma in your mother’s childhood could affect your health, and the health of your child—but it’s also reversible, even as an adult. In the McGill study, researchers were able to undo the chilly behavior of the second generation of mother rats by using epigenetic drugs to turn genes on or off.
The great promise of epigenetics is the possibility of curing cancer, bipolar disorder, schizophrenia, Alzheimer’s, diabetes, and autism by simply flipping the switches that tell some genes to wake up or work overtime, and others to lighten up or nap. Can we really hypnotize our genes like that, canceling out bad behavior and sparing innocent offspring before we plan to have any? The consensus is yes. Scientists have begun developing drugs such as azacitidine (given to patients with certain blood disorders) capable of silencing bum genes and spurring on healing ones. Many illnesses, such as ALS and autism, appear to be epigenetic, which puts them within reach. Three different types of epigenetic drug therapy are being actively investigated for schizophrenia, bipolar disorder, and other major psychoses. The FDA has already approved several epigenetic drugs, and in 2008 the National Institutes of Health (NIH) declared epigenetics “central” to biology and committed $190 million to understanding “how and when epigenetic processes control genes.” The Human Genome Project, completed in 2003, rightly celebrated as a wonder of human ingenuity, had only twenty-five thousand genes to map. The epigenome is much more complicated, with millions of telltale marks. So a full epigenome will take a while, but an international Human Epigenome Project is under way.
The good news is that these are problems with possible, if not simple, solutions: ban more environmental toxins known to trigger epigenetic havoc; work harder to ease famine, reduce poverty, and repair the ravages of war; and help people understand the long-term impact of their actions and the vital role that nurture plays in their families, societies, and environment. Genes may remember how they once behaved in parent and grandparent cells, but, fortunately, they can also learn healthy behaviors, based on use, just as muscles do. What you experience in your lifetime will become a vital part of your child’s legacy. Your adult experiences can rewire your genes in positive ways, and just as startlingly, the nurturing you do for friends, sweethearts, and other people’s children can have lasting epigenetic effects. Once that idea registers, it changes the relationship between generations, which suddenly have everything in common, and the tapestry of the human condition grows a little more visible, thread by thread. At the level of DNA’s phantom doormen, we can be connected to anyone and everyone.
There’s also a moral, social, and political lesson: while humanitarian programs may seem nonessential, an extravagance of resources and spirit we can’t afford, epigenetics teaches us that, on the contrary, poor education, violence, hunger, and poverty leave scars on one generation after another in a way that ultimately affects the future health and well-being of whole societies. What happens to war-torn soldiers and civilians during and after battle leaves epigenetic traces to wound future generations, adding to a country’s problems, even in peacetime. The same is true of natural disasters, and we’ve seen plenty of both of late. Who knows what epigenetic aftermath will result? Genetic engineering may seem like a diabolical threat to us as a species, and we do need scrupulous oversight and control of such life forms. But the political and environmental choices we make—those with epigenetic repercussions—are equally powerful engines of change, ones we can often identify and fine-tune.
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