She Has Her Mother's Laugh: The Powers, Perversions, and Potential of Heredity (22 page)

This ancient shuffling is the answer to some of the most common questions about heredity. When Grace gave birth to our second daughter, Veronica, we watched her grow and wondered how much she would turn out like her older sister, Charlotte. After all, they had the same parents, meaning that they had inherited DNA from the same two genomes. They were raised in the same house, eating the same food. But Charlotte and Veronica turned out to be far from clones. Charlotte is luminously pale, with freckles, greenish eyes, and strawberry-blond hair. Veronica has a deeper tone to her skin and mahogany-colored irises. Charlotte grew to five foot six, a fairly average height. Veronica has always been off the charts, making people assume she's a couple of years older than she really is. As a child, Charlotte would hold back when we introduced her to new people, sizing them up. Veronica, standing next to her, would launch herself into the air and shout her name. At age twelve, Charlotte became obsessed with
galaxies and dark matter. Veronica didn't care much what the universe is made of. She'd rather sing, or read Jane Austen.

The experiences our daughters have had probably account for some of their differences. But so does meiosis. Grace and I gave each of our children different combinations of the DNA we inherited from our own parents. The unique combination of alleles that each of our children ended up with had a unique influence on how she grew up.

Yet meiosis also works in strange ways that defy our intuitions. Parents pass down one copy of each chromosome to each child; which chromosome is inherited is a fifty-fifty matter of chance. The DNA in any pair of siblings, statistics would suggest, should be 50 percent genetically identical. Identical twins, by contrast, are 100 percent identical, because they are the product of a single fertilized egg. First cousins, who have only one set of grandparents in common, are on average 12.5 percent genetically identical.

All this is true—but only on average. It's just as true to say that if you roll a pair of dice, they'll turn up close to a seven. Yet of any particular roll may still turn up snake eyes. After meiosis shuffles DNA between chromosomes, it's possible for a woman's eggs to end up with more DNA from her father than her mother, or vice versa. Two siblings might arise from eggs that happen to have more DNA from their maternal grandmother than their maternal grandfather. The reverse may be true for other siblings. Meiosis can thus make two siblings more genetically similar to each other than to the rest of their siblings.

The ability to read DNA allowed scientists to measure this genetic similarity in real people. In 2006,
Peter Visscher, a geneticist at the Queensland Institute of Medical Research in Australia, and his colleagues studied 4,401 pairs of siblings, examining several hundred genetic markers in each volunteer. The siblings often had a series of identical genetic markers along a chromosome—segments they inherited from one of their parents. On average, they found about half of the DNA in the siblings was made up of these identical stretches. But many of the siblings deviated from a perfect 50 percent. At the high end, the researchers found a pair of siblings who shared 61.7 percent of their DNA. At the low end was a pair of siblings who shared only 37.4 percent. Along the spectrum of inheritance, in other
words, some of our siblings are more like our identical twins, others more like cousins.

Once Mendel's so-called laws evolved in the first eukaryotes, they passed them down to their descendants. It has endured in most of the lineages even till today. Nearly two billion years later, tarantulas use meiosis to mix chromosomes and shuffle genes. So do hummingbirds, roses, and death cap mushrooms. But for all the enduring advantages that meiosis may offer, under the right circumstances it can fade and vanish.

In thousands of species of plants, for example,
meiosis has crumbled away. Their ovules do not develop from precursor cells shuffling the DNA and then pulling apart pairs of chromosomes. Instead, these plants can produce ovules through a fairly ordinary division of cells. Mother cells with pairs of chromosomes produce daughter cells with precisely the same pairs.

Although these plants evolved a way to give up meiosis, they still cling to some vestiges of their history as sexual species. They can develop their ovules only if pollen grains settle on their flowers and deliver the right molecular signals. But all they need from the pollen are these signals. They make no use of the male DNA.

One of these odd plants happens to be
hawkweed, the plant Mendel chose to study as a follow-up to peas. His peas reliably carried out meiosis, producing a three-to-one ratio of dominant and recessive traits. It was his bad luck to then pick hawkweed—a plant that had evolved away from that sort of heredity—to search for those same ratios. When Mendel painted pollen onto hawkweed flowers, he usually triggered them to make seeds containing an identical copy of their own DNA, and taking in none of the DNA from the pollen. Only after geneticists learned to trace the path of genes from one generation of hawkweed to the next did they realize Mendel's great misfortune.

Plants and other eukaryotes lose meiosis when the evolutionary benefits no longer outweigh the costs. In certain situations, organisms can reproduce more successfully if they simply duplicate their own DNA rather than
combine them with the opposite sex and break apart the links between their genes.

But there are other ways for them to break Mendel's Law as well. Sometimes individual genes take over heredity for their own evolutionary benefit.

These molecular hackers first came to light in the 1920s with the discovery of flies with too many daughters. A Russian biologist named
Sergey Gershenson went into a forest to trap a species of fly called
Drosophila obscura
. When he brought the flies back to the Institute of Experimental Biology in Moscow, he figured out how to keep them alive on a diet of fermented raisins, potatoes, and water. Some of the female flies he trapped were carrying fertilized eggs, which they then laid by the thousands. Gershenson picked some of their offspring to breed new lines he could study for inherited traits.

There was something peculiar about two of the lines, Gershenson noticed. Typically, a batch of eggs produced by
Drosophila obscura
contains an even balance of males and females. But in two of Gershenson's lines, the mothers tended to produce far more daughters than sons. Sometimes they had no sons at all. The ratios were so extreme, Gershenson said, “that
it seemed impossible to explain them by accidental causes.”

To find the true cause, Gershenson carried out a series of breeding experiments. The penchant for daughters could be passed down like a simple genetically encoded trait. Eventually, Gershenson figured out that it was determined by a gene on the X chromosome. But he couldn't understand how the gene tilted the balance away from sons and toward daughters. Whatever its particular trick might be, Gershenson realized it had slipped through a loophole in Mendel's Law.

Flies normally have a 50 percent chance of becoming male or female, because sperm have a 50 percent chance of acquiring an X or a Y chromosome. As a result, a normal gene on the X chromosome will end up in about half of a male fly's offspring. In Gershenson's flies, on the other hand, the math is different. If a male fly carried the mysterious mutation he discovered, most—or even all—of his offspring inherited his X chromosome. Few if any inherited his Y. Those flies could then pass the daughter-producing
gene down to their own offspring. Overall, the odds of flies inheriting the daughter-favoring mutation would be much higher than 50 percent. As a result, it would become more common in a population.

“This,” Gershenson concluded, “favors its extension.”

At first, Gershenson's discovery might have seemed like an oddball exception to the rules of heredity. But it didn't take long for scientists to find other cases where genes were
fixing Mendel's dice in their own favor. Collectively, these violations came to be known as gene drive. Gene drive is so powerful that it can spread a gene like an intergenerational epidemic, until it dominates an entire population. Today, the gene drive catalog has many entries, not just in flies, but in plants, fungi, mammals, and—perhaps—even humans.

In some cases, a gene drive spreads itself by encoding a toxin. Sperm cells carrying it make the toxin, which then spreads to other sperm. The other sperm die—unless they have the gene drive element, which also contains an antidote to the toxin. In other cases, the gene drive waits until male embryos start developing before switching on and killing them.

Gene drive can break Mendel's Law in females, too. When a precursor egg cell develops, it divides into four cells. One becomes the egg, while the other three become polar bodies—in other words, three reproductive dead ends. A given copy of a gene normally has a fifty-fifty chance of ending up in the egg rather than in a polar body. Some genes have evolved the ability to manipulate those odds. They're more likely to end up in the egg—and thus to get passed down to future generations of daughters.

With so much evidence for the power of gene drive among other eukaryotes, it stands to reason that we might be subject to it as well. But the evidence for cheating on Mendel is
still unclear in humans. It's not surprising that it would be hard to study gene drive in our own species. Scientists can breed flies and fungi, inspecting every step of reproduction to catch gene drive in the act. When it comes to humans, geneticists must make the best of uncontrolled history.

The most obvious sign of a human gene drive would be a human version of what Gershenson observed: families full of daughters. But the relatively small size of human families makes it hard to know if such families are the result of gene drive. Just because I have two daughters doesn't mean Grace and I might not have had sons if we had ten children.

One way to search for it in humans is to step back from individual families and combine thousands of them into one big analysis. Even if each family is relatively small, they can add up to a horde of people big enough to let scientists distinguish between chance and drive.
Some of those databases include genetic markers. It should be possible to find some genetic markers that are passed down from parents to children more often than you'd expect based on Mendel alone.

While the concept is sound, scientists are struggling to get a clear picture of gene drive in our species.
A few promising genes have turned up in recent studies. But when scientists have tried to replicate those studies in other groups of people, they have not found an effect. It's possible that we need to wait for more accurate and detailed DNA sequences before scientists can find a clear sign of gene drive rampaging through our species.

It's also possible that our ancestors were besieged by gene drives, but overcame them. Gene drives are shortsighted in their victory. They can sweep quickly through a population, but in the process they can put a species at grave risk. If a gene kills off sperm with Y chromosomes, males can become dangerously rare in a population. More and more females never encounter a male in their life, and die without offspring. The population shrinks and then collapses. In some cases, it may take just a few dozen generations for a gene drive to
push a population to extinction.

While gene drive extinctions can theoretically happen, no one has yet seen one unfold in the wild. Many gene drives may fall short of total oblivion because organisms evolve defenses against them. Animals and plants will sometimes evolve special RNA molecules that can interfere with gene drives, blocking the production of new proteins. Mutations may then disable gene drives, rendering the defenses no longer necessary. The genes for
these defenses may mutate as well. Yet even after millions of years, the vestiges of these defenses can still be recognized.

It turns out our own genome is littered with relics of this conflict. Even if gene drives are not exploiting us today, they have been an important part of our history. And today we inherit the genetic scars of ancient struggle. What Mendel discovered was not a law so much as a battleground.

I
DOUBT MANY CHILDREN
give much thought to meiosis. But there comes a point early in the life of all children when they realize that they weren't simply brought into existence by their parents. They get up on their toes and peer beyond their mother and father, back into their genealogical past. They realize that their parents have parents of their own, who have parents, too, and so on back along family branches that stretch over memory's horizon. They realize all those ancestors are part of the reason they are alive. They wonder what would have happened if one great-great-great-grandmother decided to turn down the marriage proposal of a great-great-great-grandfather. Somehow, through an improbable flow of heredity down merging streams, they all converged on one baffled child.

I can remember my own first bafflement. When I interrogated my parents about their ancestry, I was amazed at how quickly they ran out of answers. My father, who was born in 1944 in Newark, told me about his parents. William Zimmer had been a doctor, and Evelyn Rader a librarian. They were both Reform Jews and dedicated socialists who played Paul Robeson records around the house when my father was a boy. It took me years to notice those Robeson 78s tucked away on a shelf in my parents' house. Those licorice slabs are among the few points of contact I have ever had with my paternal grandparents. My grandfather died when my father was three, my grandmother the summer before he went to college. I never
got to see them get into a Passover argument about politics with their son, who turned Republican in college and later became a congressman. When I pushed my father to tell me about my older ancestors, his genealogical knowledge sputtered out quickly, leaving me with a blurry origin story that put his ancestors somewhere in the neighborhood of Germany, or Ukraine, or somewhere in between.

My mother came from shiksa stock: a German-Irish Catholic mother, Marilou Pohl, and an English Protestant father, Harrison LeGrande Goodspeed, Jr. Her parents met at a tennis match as teenagers growing up in Grand Rapids, Michigan. Things then moved fast, as they often did in the 1940s. My grandfather, whom everyone called Peter, converted to Catholicism, married Marilou, headed off to Germany to fight Nazis, and then returned a year later to his wife and daughter—my mother. They went on to have three more children, whom they raised in a world of optimistic little businesses, tidy bowling lanes, tipsy games of bridge, and endless rounds of golf. The first time my father stepped aboard a commercial airplane was to fly to Michigan to marry my mother at her parents' house in 1965. It must have felt like an alien planet to him. To the Goodspeeds, the twenty-one-year-old Jew from New Jersey may well have seemed like an extraterrestrial.

I was fortunate to know my mother's parents for several decades, but beyond them, the maternal line dims as well. On the Pohl side, my great-grandparents died in the fifties, leaving behind only vague tales of sadness and early death. Harrison Goodspeed's father, on the other hand, lived long enough to give me a purple toy car for an early birthday, and to puzzle me by disappearing from life. I never met my great-grandmother Dorothy Rankin. What little I know of her comes from two photographs. In one, she poses in a flapper dress and necklaces; on the back of the picture, she scribbled a note to someone back in Michigan, explaining how grand Paris is. In the other picture, she stands in a shady front yard next to my great-grandfather, cradling my grandfather. Dorothy Rankin died a few months after that picture was taken.

In her thirties, my mother began investigating our ancestors, leading us on trips to rub gravestones in old New England cemeteries. Seeing her
interest in the family history, my great-grandfather decided she should inherit a book of his about the family, published in 1907. One day the old leather volume appeared on a shelf in our living room:
History of the Goodspeed Family, Profusely Illustrated, Being a Genealogical and Narrative Record Extending from 1380 to 1906, and Embracing Material Concerning the Family Collected During Eighteen Years of Research, Together with Maps, Plates, Charts, Etc.

1380?
I was binge-reading
Lord of the Rings
at the time. Seeing my genealogy pushed into the Middle Ages felt like gaining citizenship in Gondor. When my mother explained to me that the name Goodspeed came from the early English exclamation
Godspeed,
I saw knights bidding each other well as they rode off to fight orcs.

When I got around to dipping into
History of the Goodspeed Family
, my medieval ancestors didn't live up to my hopes. The Goodspeeds first appear in the historical record in 1380, when one John Godsped was sued “touching a trespass.” In 1385, another Goodspeed failed to pay a debt. In 1396, Robert Godsped killed a man named John Archebaud, but was pardoned “out of regard for Good Friday.”

The author of
History of the Goodspeed Family
, a distant cousin named Weston Arthur Goodspeed, downplayed our family's criminal debut. “All of these offences, except the one causing the death of John Archebaud, were trivial and would have no standing in the courts of today, except in civil suits,” Weston sniffed. I could imagine him then giving a careless shrug, adding, “Besides, does anybody
really
miss John Archebaud?”

In his eighteen years of research, Weston Goodspeed looked hard for signs of nobility. He found nothing. “A thorough examination of the English books on peerage fails to reveal the name Goodspeed,” he admitted. “To those of our great family who will regard this as a serious social blow, the author of this volume extends his profound pity, sympathy and commiseration.”

But what did that really matter, Weston asked, since all of the coats of arms displayed by American families were fake? “Some were fictitious or fraudulent,” he declared. “Some were even ludicrous in their pretensions.”
The Goodspeeds should be proud of their humble origins, of the fact that the original Goodspeed who came to America, my great-great-great-great-great-great-great-great-great-grandfather Roger Goodspeed, was just a yeoman. “The undoubted respectability and sterling qualities of the English yeomanry may be considered in democratic America as far superior to a coat of arms thus bought and unearned,” Weston declared.

Roger Goodspeed was born in 1615 in Wingrave, England, and sailed to Massachusetts in his early twenties. There's no evidence that he took the journey as a Puritan fleeing persecution. He “merely wished like thousands of others to improve his surroundings and America seemed to offer the best opportunity,” Weston wrote. Roger Goodspeed's name first pops up in historical records in 1639 as one of the first farmers to settle in Barnstable, a town on Cape Cod. A decade later, he built a new farmhouse a few miles away on the bank of the Herring River, which came to be known as Goodspeed's River. There he lived till his death in 1685. Over the course of his entire life, Roger Goodspeed made only a few ripples in written history: accusing a neighbor of stealing a goat, signing his will with a single letter,
R
.

Roger Goodspeed had three daughters and four sons. They inherited his DNA and his name. Later, they also inherited his bridles and saddles, his trenchers and his spinning wheel. They bore him twenty-two grandchildren, and in later generations his descendants spread through the colonies and then across the United States. About 250 years after Roger Goodspeed's arrival in Massachusetts, Weston Goodspeed started gathering information about his descendants, writing letters to relatives and searching archives, and eventually amassed biographical details on 2,429 Goodspeeds.

History of the Goodspeed Family
ended up stretching to 561 pages. But Weston didn't treat it as the last word. It was supposed to be the opening salvo of a long campaign. Weston cataloged only American Goodspeeds through the male line; he promised to add the female branches in a future edition. He even dreamed the book would inspire yearly Goodspeed conventions. “It is the intention to call the first general assembly of the Goodspeeds,” he declared, “for the purpose of effecting an organization which thereafter, it is hoped, will be permanent, will hold annual meetings, will
continue the publication of these records in the future, and will take any other steps that shall be in the interest of the family and agreeable to all.”

The Goodspeed meetings never came to pass, nor did Weston ever expand the family tree. The scraps of information that survive about Weston suggest a life marinated in disappointment. He worked at a small publishing company run by his brothers until it shut down near the end of the 1800s. The 1900 census listed Weston Goodspeed as unmarried and unemployed at age forty-eight. Seven years later he published
History of the Goodspeed Family
, and by 1910 the census showed he had moved to a Chicago boardinghouse run by a widow. Weston died in 1926, at age seventy-four, without producing a new volume of his genealogy, not to mention any heir to the Goodspeed name.

I still sometimes take the
History of the Goodspeed Family
down from the shelf on visits back home. Scanning its parade of wills, court records, and inventories of children
,
I puzzle about the genealogical drive that propelled its creation, the force that made Weston spend a large fraction of his time on Earth building a catalog of 2,429 people—people who were mostly unaware of one another.

Weston left a clue at the beginning of his book. He dedicated it “to the rapid, symmetrical and beautiful growth of the family tree; to the avoidance of all wind-storms likely to damage the orchard; to the eradication of the insects of ignorance and immorality certain to contaminate the fruit; to the transplantation of buds and scions in all agreeable soils; to the awakening of the sleeping branches to bright foliage and sweet blossoms; and to plenteous harvests of golden children grown in the sunshine of love, liberty and law.”

Weston saw himself as a naturalist, in other words. He was describing an organism that extended itself seamlessly through the United States—a tree of heredity that sprouted from Roger Goodspeed, the Adam to all American Goodspeeds.

Yet Weston didn't do a very good job of showing what, if anything, binds the branches of the Goodspeed tree together, what made that tree a thing worth documenting in such painstaking detail. The Goodspeeds had
no crown to pass down from king to prince, realigning the world along the way. We're not Rockefellers, with a vast fortune carried down through generations. In all honesty, American history would not have been any different if Roger Goodspeed's ship sank halfway across the Atlantic.

As far as I can tell, Weston believed what bound the Goodspeed family together, what he believed was inherited by every new generation, was goodness. A number of Goodspeed men fought in the Civil War—not as generals or colonels, granted, but as valiant Union Army soldiers nonetheless. “The splendid military record of these men will ever be a heritage of pride and glory for all who bear the family name,” Weston declared. Of course, it would be hard to find a family in the United States in the 1860s that didn't send some sons to war. Having never served in the military myself, I don't see how I'm entitled to bask in that heritage of Civil War bravery.

Most Goodspeeds didn't fight in wars, but Weston still found some goodness in them as well. Francis Goodspeed, Weston wrote, “even as a boy was broad-minded and loved his books.” John F. Goodspeed “was engaged in the furniture business; he devised ‘Goodspeed's Superior Polish.'” Seymour Goodspeed “has accumulated a comfortable competence, reared a large family to correct and useful lives, is passing a clean and honorable career, and has the respect of all who know him.” Thomas Goodspeed “has never failed to vote at State and National elections.” Of one family of Goodspeeds, Weston simply noted, “All became good citizens.”

Not long ago I discovered that Google put
History of the Goodspeed Family
online. I decided to play a game, seeing if I could find any keywords of a scandal. I tried
murder
,
bribery
,
illegitimate
,
alcohol
. I have yet to win. At best, I can only find faint shadows cast across the inherent goodness of Goodspeeds. Riland Goodspeed, born in 1841, became the manager of a California ranch—an “immense and beautiful ranch,” of course. Eventually he fell in love with the owner's daughter—“a gifted and most fascinating woman,” of course. Then Cousin Weston gets cryptic. Riland and his wife got married “under romantic circumstances and after several notable escapades.” As for the rest of the marriage, Weston simply noted that “after many years they were divorced, largely upon whimsical grounds.”

Compare the unblemished saga of the Goodspeeds with
The Kallikak Family
, which Henry Goddard published only five years later. They're both quintessentially American expressions of our beliefs about heredity
.
Goddard envisioned a pure line of crime and feeblemindedness. Weston presented a pedigree of middling Protestant prosperity. While Goddard envisioned some Mendelian factor poisoning the Wolvertons, Weston Goodspeed seems to have believed that the Goodspeeds inherited a moral factor, perhaps acquiring it from their parents among the lessons they got about democracy and furniture polish.

The American obsession with genealogy was caused by a case of transoceanic amnesia. Roger Goodspeed, born and raised in seventeenth-century England, was
steeped in traditional European customs for remembering ancestors. The Bible's genealogies linked Jesus by blood back to the Old Testament patriarchs. Kings and noblemen justified their power with hereditary chains linking them back to the mythic past. William the Conqueror's genealogy reached all the way back to the warriors of ancient Troy.

By the Renaissance, rich merchants were hiring genealogists, too, in order to track their investments and determine how to wed their children so as to keep the wealth within the family. A yeoman like Roger Goodspeed couldn't afford to hire a professional London genealogist. Judging from the
R
he wrote for his signature, he probably couldn't have read a genealogist's report anyway. Nevertheless, Roger probably carried family stories in his mind from England to America, where he transmitted them to his children; they told his grandchildren in turn.