The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code (44 page)

This history—fairly typical on the frontier—would probably have gone unremarked except for a few modern Swedish scientists. They got interested in Överkalix because they wanted to sort out whether environmental factors, like a dearth of food, can predispose a pregnant woman’s child to long-term health problems. The scientists had reason to think so, based on a separate study of 1,800 children born during and just after a famine in German-occupied Holland—the
Hongerwinter
of 1944–45. Harsh winter weather froze the canals for cargo ships that season, and as the last of many favors to Holland, the Nazis destroyed bridges and roads that could have brought relief via land. The daily ration for Dutch adults fell to five hundred calories by early spring 1945. Some farmers and refugees (including Audrey Hepburn and her family, trapped in Holland during the war) took to gnawing tulip bulbs.

After liberation in May 1945, the ration jumped to two thousand calories, and this jump set up a natural experiment: scientists could compare fetuses who gestated during the famine to fetuses who gestated afterward, and see who was healthier. Predictably, the starved fetuses were generally smaller and frailer babies at birth, but in later years they also had higher rates of schizophrenia, obesity, and diabetes. Because the babies came from the same basic gene pool, the differences probably arose from epigenetic programming: a lack of food altered the chemistry of the womb (the baby’s environment) and thereby altered the expression of certain genes. Even sixty years later, the epigenomes of those who’d starved prenatally looked markedly different, and victims of other modern famines—the siege of Leningrad, the Biafra crisis in Nigeria, the Great Leap Forward in Mao’s China—showed similar long-term effects.

But because famines had happened so often in Överkalix, the Swedish scientists realized they had an opportunity to study something even more intriguing: whether epigenetic effects could persist through multiple generations. Kings of Sweden had long demanded crop records from every parish (to prevent anyone from cheating on fealties), so agricultural data existed for Överkalix from well before 1800. Scientists could then match the data with the meticulous birth, death, and health records the local Lutheran church kept. As a bonus, Överkalix had very little genetic influx or outflow. The risk of frostbite and a garish local accent kept most Swedes and Lapps from moving there, and of the 320 people the scientists traced, just nine abandoned Överkalix for greener pastures, so scientists could follow families for years and years.

Some of what the Swedish team uncovered—like a link between maternal nutrition and a child’s future health—made sense. Much of it didn’t. Most notably, they discovered a robust link between a child’s future health and a
father’s
diet. A father
obviously doesn’t carry babies to term, so any effect must have slipped in through his sperm. Even more strangely, the child got a health boost only if the father faced starvation. If the father gorged himself, his children lived shorter lives with more diseases.

The influence of the fathers turned out to be so strong that scientists could trace it back to the father’s father, too—if grandpa Harald starved, baby grandson Olaf would benefit. These weren’t subtle effects, either. If Harald binged, Olaf’s risk of diabetes increased fourfold. If Harald tightened his belt, Olaf lived (after adjusting for social disparities) an average of thirty years longer. Remarkably, this was a far greater effect than starvation or gluttony had on Grandpa himself: grandpas who starved, grandpas who gorged, and grandpas who ate just right all lived to the same age, seventy years.

This father/grandfather influence didn’t make any genetic sense; famine couldn’t have changed the parent’s or child’s DNA sequence, since that was set at birth. The environment wasn’t the culprit, either. The men who starved ended up marrying and reproducing in all different years, so their children and grandchildren grew up in different decades in Överkalix, some good, some bad—yet all benefited, as long as Dad or his dad had done without.

But the influence might make epigenetic sense. Again, food is rich in acetyls and methyls that can flick genes on and off, so bingeing or starving can mask or unmask DNA that regulates metabolism. As for how these epigenetic switches got smuggled between generations, scientists found a clue in the timing of the starvation. Starving during puberty, during infancy, during peak fertility years—none of that mattered for the health of a man’s child or grandchild. All that mattered was whether he binged or starved during his “slow growth period,” a window from about nine to twelve years old, right before puberty.
During this phase, males begin setting aside a stock of cells that will become sperm. So if the slow growth period coincided with a feast or famine, the pre-sperm might be imprinted with unusual methyl or acetyl patterns, patterns that would get imprinted on actual sperm in time.

Scientists are still working out the molecular details of what must have happened at Överkalix. But a handful of other studies about soft paternal inheritance in humans supports the idea that sperm epigenetics has profound and inheritable effects. Men who take up smoking before eleven years old will have tubbier children, especially tubbier boys, than men who start smoking later, even if the grade-school smokers snuff the habit sooner. Similarly, the hundreds of millions of men in Asia and Africa who chew the pulp of betel nuts—a cappuccino-strength stimulant—have children with twice the risk of heart disease and metabolic ailments. And while neuroscientists cannot always find anatomical differences between healthy brains and brains addled with psychoses, they have detected different methyl patterns in the brains of schizophrenics and manic-depressives, as well as in their sperm. These results have forced scientists to revise their assumption that a zygote wipes clean all the environmental tarnish of sperm (and egg) cells. It seems that, Yahweh-like, the biological flaws of the fathers can be visited unto their children, and their children’s children.

The primacy of sperm in determining a child’s long-term health is probably the most curious aspect of the whole soft inheritance business. Folk wisdom held that maternal impressions, like exposure to one-armed men, was devastating; modern science says paternal impressions count as much or more. Still, these parent-specific effects weren’t wholly unexpected, since scientists already knew that maternal and paternal DNA don’t quite contribute equally to children. If male lions mount female tigers, they produce a liger—a twelve-foot cat twice as heavy as
your average king of the jungle. But if a male tiger knocks up a lion, the resulting tiglon isn’t nearly as hefty. (Other mammals show similar discrepancies. Which means that Ilya Ivanov’s attempts to impregnate female chimpanzees and female humans weren’t as symmetrical as he’d hoped.) Sometimes maternal and paternal DNA even engage in outright combat for control of the fetus. Take the
igf
gene (please).

For once, spelling out a gene’s name helps make sense of it:
igf
stands for “insulin-like growth factor,” and it makes children in the womb hit their size milestones way earlier than normal. But while fathers want both of a child’s
igf
genes blazing away, to produce a big, hale baby that will grow up fast and pass its genes on early and often, mothers want to temper the
igf
s so that baby number one doesn’t crush her insides or kill her in labor before she has other children. So, like an elderly couple fighting over the thermostat, sperm tend to snap their
igf
into the on position, while eggs snap theirs off.

Hundreds of other “imprinted” genes turn off or on inside us, too, based on which parent bestowed them. In Craig Venter’s genome, 40 percent of his genes displayed maternal/paternal differences. And deleting the exact same stretch of DNA can lead to different diseases, depending on whether Mom’s or Dad’s chromosome is deficient. Some imprinted genes even switch allegiance over time: in mice (and presumably in humans) maternal genes maintain control over brains as children, while paternal genes take over later in life. In fact, we probably can’t survive without proper “epigender” imprinting. Scientists can easily engineer mice embryos with two sets of male chromosomes or two sets of female chromosomes, and according to traditional genetics, this shouldn’t be a big deal. But these double-gendered embryos expire in the womb. When scientists mixed in a few cells from the opposite sex to help the embryos survive, the males
²
became huge Botero babies (thanks to
igf
) but had puny
brains. Females
²
had small bodies but oversized brains. Variations, then, between the brain sizes of Einstein and Cuvier might be nothing but a quirk of their parents’ bloodlines, like male pattern baldness.

So-called parent-of-origin effects have also revived interest in one of the most egregious scientific frauds ever perpetrated. Given the subtlety of epigenetics—scientists have barely gotten a handle in the past twenty years—you can imagine that a scientist stumbling across these patterns long ago would have struggled to interpret his results, much less convince his colleagues of them. And Austrian biologist Paul Kammerer did struggle, in science and love and politics and everything else. But a few epigeneticists today see his story as maybe, just maybe, a poignant reminder about the peril of making a discovery ahead of its time.

Paul Kammerer had an alchemist’s ambitions to remake nature, coupled with a teenage boy’s talent for harassing small animals. Kammerer claimed he could change the colors of salamanders—or give them polka dots or pinstripes—simply by foisting them into landscapes of unusual hues. He forced sun-loving praying mantises to dine in the dark, and amputated the proboscises of sea squirts just to see the effect on their future children. He even claimed he could grow certain amphibians with or without eyes, depending on how much sunlight they got as youngsters.

Kammerer’s triumph, and his undoing, were a series of experiments on the midwife toad, a most peculiar species. Most toads mate in water, then let their fertilized eggs float away freely. Midwife toads make love on land, but because tadpole eggs are more vulnerable on land, the male midwife toad ties the bundle of eggs to his back legs like a bunch of grapes and hops along with them until they hatch. Unmoved by this charming habit, Kammerer decided in 1903 to start forcing midwife toads
to breed in water, by cranking the heat way, way up in their aquariums. The tactic worked—the toads would have shriveled like dried apricots if they hadn’t spent all their time submerged—and those that survived became more waterlike each generation. They had longer gills, produced a slippery jelly coating to waterproof their eggs, and (remember this) developed “nuptial pads”—black, calluslike growths on their forelimbs, to help male toads grip their slippery mates during aqueous coitus. Most intriguing, when Kammerer returned these abused toads to cooler and moister tanks and let them reproduce, the toads’
descendants
(who never experienced the desert conditions) supposedly inherited the water-breeding preferences and passed them along to still more descendants.

Kammerer announced these results around 1910. Over the next decade, he used this and other experiments (and no experiment of his ever failed, it seemed) to argue that animals could be molded to do or be almost anything, given the proper environment. Saying such things at the time had deep Marxist implications, since Marxism held that the only thing keeping the wretched masses down was their terrible environment. But as a committed socialist, Kammerer readily extended his arguments to human society: to his thinking, nurture
was
nature, a unified concept.

Indeed, while biology itself was in serious confusion at the time—Darwinism remained controversial, Lamarckism was all but dead, Mendel’s laws hadn’t yet triumphed—Kammerer promised he could unite Darwin, Lamarck, and Mendel. For instance, Kammerer preached that the proper environment could actually cause advantageous genes to spring into existence. And far from scoffing, people lapped his theories up; his books became bestsellers, and he lectured to SRO audiences worldwide. (In these “big-show talks” Kammerer also suggested “curing” homosexuals with testicle transplants and enacting American-style Prohibition worldwide, since Prohibition would undoubtedly produce a generation of American Übermenschen, a race “born without any desire for liquor.”)