In 1555, Holy Roman Emperor Charles V announced his plans to abdicate, and his 28-year-old son, Philip II, became the king of Spain the following year. The throne was Philip’s natural—hereditary—right. The Habsburg dynasty, to which Charles and Philip belonged, had raised strategic matrimony to an art form, using marriage bonds among relations distant and close to seize control over much of Europe. Power came with a price, however: severe, recurring mental and physical problems. Charles’s mother was Joan the Mad; his son Philip was said to be “of weakly frame and of a gloomy, severe, obstinate, and superstitious character.” Philip’s descendant Charles II was 4 before he could talk and 8 before he could walk. He died in 1700, not yet 40, childless and sterile. Geneticists have calculated that he was more inbred than he would have been had his parents been siblings. After his death, the Spanish Habsburg dynasty collapsed, crushed under the weight of a heredity that as yet had no name.
Though Renaissance nobles could not have missed the unfortunate traits that ran like fractures through the House of Habsburg, not until the 1830s did the term heredity acquire its modern connotation as a biological legacy. Because the term first specified material inheritance, often from eldest son to eldest son, we tend to think about heredity in terms of straight lines: bloodlines, patrilines, and eventually germ lines. Our word for a diagram of the lines of descent—pedigree—is probably derived from the French pé de grue, or “crane’s foot,” evoking an image of a pencil-like leg ending in straight, splayed toes.
Yet linear thinking doesn’t begin to do heredity justice, and in his sprawling, magisterial new book, the science writer Carl Zimmer shows why. She Has Her Mother’s Laugh brims with rich stories and colorful actors—some sinister, some brilliant, some both—and delves into scientific research, history, and ideas made intimate through the author’s personal experiences. The result explodes any unitary idea of heredity. Zimmer limns portraits of multiple intersecting heredities, more like the web of a spider than the foot of a bird.
Despite this proliferation, dreams of human control over the process continue to soar.
The biological concept of heredity came too late for the Habsburgs, but not for Francis Galton, a half-cousin of Charles Darwin. When Galton looked at distinguished pedigrees in the 1860s, he saw concentrations of virtues: intelligence, good looks, strength of character. This Victorian gentleman, who gave us the phrase nature versus nurture, convinced himself that talent and character were hereditary, because they ran in families. After abandoning the awkward word viriculture, he christened the science of hereditary improvement “eugenics,” from the Greek for “wellborn.”
Galton’s eugenic scheme relied on persuasion and social incentives to discourage those he considered unfit from reproducing, while encouraging procreation among the posh and brilliant. The result, he earnestly believed, would be a “galaxy of genius.” Later editions of eugenics were less optimistic. If you take Galton’s recipe, add Mendel’s peas and Morgan’s fruit flies, simmer in the politics and culture of the Progressive era, and stir vigorously, you get the American eugenics movement—dogmatic, ideological, and coercive. (Sadly, some choice examples of its rhetoric may be found in the archives of this magazine.) Serve warm to German fascists, and you get the Final Solution.
It is all too easy to shake our heads at the cruelty and naïveté of the eugenic creed, which held that society could be “cured” of crime, disease, and poverty by eliminating the “unfit” from the gene pool, or to tsk-tsk at the monstrous confidence that led eugenicists to believe they understood heredity well enough to engineer it. Much more difficult is to bear in mind that in 20 years, many of today’s received truths will also be thought wrong. Playing God is always harder than it looks.
Step by measured step, Zimmer walks us deep into the thickets of genetics and genomics, revealing complications and exceptions that challenge what we think we know about heredity. Following his own family tree, Zimmer shows us that counterintuitive facts lie even in the humble pedigree. If you pursue your lineage far enough, the branching forks of a family tree begin to rejoin, such that if your ancestry is European back to the time of Charlemagne, you are related to Charlemagne himself!
To focus in is to find chromosomes playing all sorts of tricks. Take, for example, chimeras. To the ancient Greeks, the Chimera was a fire-breathing hybrid monster; to a biologist, chimeras are organisms that comprise cells from two different individuals. Ranchers are familiar with one type of chimera, the freemartin, which results when a cow carries opposite-sex twins. Connected by a shared placenta, the fetal calves exchange stem cells. The bull calf grows up into a more or less normal bull, while the heifer—the freemartin—has undeveloped ovaries and exhibits masculinized behavior (and is particularly tasty on the grill). Where does one calf end and the other begin?
Zimmer describes a bizarre twist on the free-martin: a girl with different-colored eyes and ambiguous genitals who appeared at a Seattle genetics clinic. Her ovaries proved to have only XX chromosomes—typical female—but her other tissues were mixtures of XX and XY. Further analysis showed that she had started out as opposite-sex twins. But early in development, the two embryos had fused, becoming a single, highly unusual child. Like a verse from the old Ray Stevens novelty song “I’m My Own Grandpa,” this girl was her own twin brother.
But chimeras are not just oddities. You surely know one. In pregnant women, fetal stem cells can cross the placenta to enter the mother’s bloodstream, where they may persist for years. If Mom gets pregnant again, the stem cells of her firstborn, still circulating in her blood, can cross the placenta in the other direction, commingling with those of the younger sibling. Heredity can thus flow “upstream,” from child to parent—and then over and down to future siblings.
The genome, Zimmer goes on to reveal, eludes tidy boundaries too. Forget the notion that your genome is just the DNA in your chromosomes. We have another genome, small but vital, in our cells’ mitochondria—the tiny powerhouses that supply energy to the cell. Though the mitochondrial genes are few, damage to them can lead to disorders of the brain, muscles, internal organs, sensory systems, and more. At fertilization, an embryo receives both chromosomes and mitochondria from the egg, and only chromosomes from the sperm. Mitochondrial heredity thus flows strictly through the maternal line; every boy is an evolutionary dead end, as far as mitochondria are concerned.
Beyond the genome are more surprises. Schoolchildren learn that Darwin’s predecessor, the great French naturalist Jean-Baptiste Lamarck, got
heredity wrong when he suggested that traits acquired through experience—like the giraffe’s neck, elongated by straining and stretching to reach higher, perhaps tenderer, leaves—could be passed down. The biologist August Weismann famously gave the lie to such theories, which collectively are known as “soft” heredity. If Lamarckism were true, he said, chopping the tail off mice and breeding them, generation after generation, should eventually produce tailless mice. It didn’t. Lamarck wasn’t lurking in the details.
Recent research, however, is giving Lamarck a measure of redemption. A subtle regulatory system has been shown to silence or mute the effects of genes without changing the DNA itself. Environmental stresses such as heat, salt, toxins, and infection can trigger so-called epigenetic responses, turning genes on and off to stimulate or restrict growth, initiate immune reactions, and much more. These alterations in gene activity, which are reversible, can be passed down to offspring. They are hitchhikers on the chromosomes, riding along for a while, but able to hop on and off. Harnessing epigenetics, some speculate, could enable us to create Lamarckian crops, which would adapt to a disease in one or two generations and then pass the acquired resistance down to their offspring. If the disease left the area, so would the resistance.
All of these heredities—chromosomal, mitochondrial, epigenetic—still don’t add up to your entire you. Not even close. Every one of us carries a unique flora of hundreds if not thousands of microbes, each with its own genome, without which we cannot feel healthy—cannot be “us.” These too can be passed down from parent to child—but may also move from child to adult, child to child, stranger to stranger. Always a willing volunteer, Zimmer allowed a researcher to sample the microbes living in his belly-button lint. Zimmer’s “navelome” included 53 species of bacteria. One microbe had been known, until then, only from the Mariana Trench. “You, my friend,” the scientist said, “are a wonderland.” Indeed, we all are.
With this in mind, reconsider the ongoing effort to engineer heredity. The motto of the Second International Eugenics Congress, in 1921, was “Eugenics is the self-direction of human evolution.” Since then, controlling heredity has become technically much easier and philosophically more complicated. When, in the 1970s, the first genetic engineering made medical gene therapy feasible, many of its pioneers urged caution, lest some government try to create a genetic Fourth Reich. In particular, two taboos seemed commonsense: no enhancement, only therapy (thou shalt not create a master race); and no alterations in germ-line tissues, only in somatic cells (thou shalt not make heritable modifications).
To today’s genetic engineers, those parameters seem quaint. Researchers can now convert mature somatic tissue taken from, say, a cheek swab into stem cells able to become any type of cell, even sperm and eggs. New technologies such as the gene-editing technique known as crispr have greatly expanded the repertoire of engineering. Ethical quandaries abound. Although injecting the hormone erythropoietin can be lifesaving for people with severe anemia, it is illegal for athletes. What about gene therapy to raise one’s “natural” erythropoietin production? Is it better to eliminate gene variants for sickle cell anemia and thalassemia, or to retain the malaria resistance those genes confer? What kinds of side effects would seem tolerable in order to raise your child’s IQ by a few points?
The ethics of some reproductive technologies become blurrier in light of the newly complex understanding of heredity’s cross-currents. A maternal surrogate, for example, will likely exchange stem cells with the fetus she carries, opening the door to claims that baby and surrogate are related. If the surrogate later carries her own baby, or that of a different woman, are the children related? Parenthood becomes even stranger with so-called mitochondrial-replacement therapy. If a woman with a mitochondrial disorder wants a biological child, it is now possible to inject the nucleus of one of her eggs into a healthy woman’s egg (after removing its nucleus), and then perform in vitro fertilization. The result is a “three-parent baby,” the first of which was born in 2016. Zimmer doesn’t presume to make ethical judgments about procedures such as this, but warns that “informed consent” in such cases can be unexpectedly thorny.
And why stop with people? A so-called gene drive could enable researchers to release into nature organisms that would genetically engineer one another, spreading a desirable trait throughout a population within a couple of generations. Scientists imagine using this process to create pest-proof crops, malaria-free mosquitoes, and limitless other innovations in agriculture and public health. Trials are in progress.
Engineering the global genome could save millions of lives—or produce a chimeric hybrid of Gattaca and Jurassic Park. We could alter the gene pool of the future in ways we cannot yet even imagine, let alone understand. Zimmer is excited about the possibilities, but in a world where headlong innovation always trumps careful contemplation, he urges scientists and the public to learn from history. “We would do well,” he writes, “to look back at how the tools we’ve already invented have altered our ecological inheritance over the past ten thousand years.”
An old saw of biology runs “Evolution is cleverer than you are.” And ecology, involving as it does the dovetailed evolution of countless organisms in a constantly changing world, is cleverer than evolution. In Zimmer’s pages, we discover a world minutely threaded with myriad streams of heredity flowing in all directions, in variegated patterns and different registers—from a newt’s truncated, regenerating tail; to the pond in which the newt paddles; to the meadow where the pond fills and dries, fills and dries, down the centuries. The computing power alone required to play puppet master for such a scene, tugging and twirling the strings of its DNA, is staggering. Whether we have the wisdom to nurture nature is a question that Zimmer leaves, held aloft like a dandelion puff, for us to contemplate.
This article appears in the July/August 2018 print edition with the headline “Your DNA Is Weirder Than You Think.”