Tracing genealogies has become immensely popular of late, and numerous companies offer to help you search through historical records or analyze your DNA. The pastime is no doubt enlivened by the scintillating possibility that you might discover noble blood, or even a notorious rogue, hiding in your family tree. But such discoveries generally don’t tell the searcher much; most of us have little idea of how our genes are bequeathed to us at all.
Carl Zimmer’s interest in genetic inheritance began when his wife, Grace, was pregnant with their first child, and the couple met with a genetics counselor. Zimmer, who has written books on evolution, neuroscience, and bacteriology, didn’t see the point of the meeting, for they had already decided to have the child regardless of any genetic flaws that might be found. It was only when the counselor asked the couple about their family histories that Zimmer realized how little he knew about his own, and began to be curious about his ancestry.
The result, many years later, is both two delightful, healthy daughters and She Has Her Mother’s Laugh, a grand and sprawling book that investigates all aspects of inheritance, from ancient Roman law to childhood learning, and on to the bacteria that inhabit our belly buttons (which are surprisingly varied among individuals). Along the way, the book provides many amusing historical anecdotes and important scientific insights.
Inheritance, as a means of endowing privilege, has been of vital importance to people ever since the Neolithic period some ten thousand years ago. Pedigrees (from pé de grue, the foot of a crane, which resembles the connecting lines on ancestral trees) have long been used to justify social hierarchies. In times past, the European nobility would spend lavishly to draw up impressive (and often invented) pedigrees for themselves.
In 1715 the Irish noble Viscount Mountcashel published a pedigree in which he claimed to be able to trace his ancestry all the way back to Adam and Eve. In Mountcashel’s time, the popular understanding of heredity didn’t extend much beyond the theory that men planted seeds in the wombs of women, where they were nurtured. Yet it does seem odd for Mountcashel to have averred that, in all the ages since Adam, not one of his female ancestors had ever become pregnant by anyone but her wedded partner. “Son of a bitch” is such a powerful insult not just because it slanders one’s mother, but because it questions one’s pedigree, and therefore the legitimacy of one’s position and inheritance.
If you are searching for your own noble blood, genetic research has both good and bad news for you. If you follow a pedigree, with all its forkings, back to the eighth century, you will trace over a trillion forks—an impossibility, because that is more than the number of people that have ever existed. When Joseph Chang developed the first statistical model of heredity in 1999 to explain the paradox, he established that many forks disappeared if our ancestors were closely related to one another, and that if you go back seven thousand years, “you reach a point in time when all the individuals who have any descendants among living people are ancestors of all living people.” So you might have pharaohs in your ancestry, and possibly caesars and Holy Roman emperors as well. Yet because of the swapping of DNA fragments during sexual reproduction, the DNA of our ancestors becomes diluted very quickly. Only 1 percent or less of an ancestor who lived four centuries ago is present in your DNA.
None of this, of course, was understood before the discovery of DNA in the 1950s. Early misconceptions about ancestry, along with a belief in superior breeds, were expressed in the eugenics movement in the late nineteenth century. In 1910 Henry Goddard, an American high school teacher turned psychologist, invented the word “moron” to describe people with mental deficiencies. He was director of research at the Vineland Training School in New Jersey, which had been established to care for “feeble-minded” boys and girls. He believed that “degeneracy,” in the form of children with special needs, was increasing. The deputy principal of the school argued that “we must stop the increase. And that means to find out where they come from, why they come and what to do to check the stream.”
Goddard soon convinced himself that moronism was an inherited condition, and he wrote a book about the delinquent ancestry of Emma Wolverton, one of the wards at the Vineland School, giving her the pseudonym Deborah Kallikak (from the Greek for “good” and “bad”). His best-selling book The Kallikak Family, published in 1912, propelled him to fame and remained influential well into the 1950s. It had made an impression on Hitler in the 1920s and informed the Reich’s racial hygiene laws, under which feeble-minded children and other “undesirable types” were sterilized or euthanized.
Goddard’s argument that feeble-mindedness was passed down from generation to generation turned out to be entirely spurious. In the 1980s two genealogists reexamined the Wolverton (Kallikak) family tree as given by Goddard and discovered that Emma Wolverton’s supposed pedigree was as false as Mountcashel’s claim of descent from Adam.
Fraud and error have been an ongoing theme among those interested in establishing the genetic basis of intelligence. When the British psychologist Cyril Burt published a series of studies of identical twins, he convinced many that intelligence was determined by inheritance. But in 1966 the Princeton psychologist Leon Kamin read Burt’s work and “within ten minutes…knew…that it just had to be fake.” The test scores given for identical twins were correlated to within a tenth of a percent: one such instance would be unlikely, but the twenty instances in Burt’s study were “astronomically improbable.” Not only had Burt invented his research findings, he’d published scientific papers under false names to give the impression that other researchers supported his work.
Although Burt gave twin studies a bad name, other more honest researchers persisted in the field. They have established that about half of the variation in intelligence test scores can be attributed to inheritance, though just which genes are responsible remains a puzzle. As Zimmer says:
While identical twins often end up with similar test scores, sometimes they don’t. If you get average scores on intelligence tests, it’s entirely possible your children may turn out to be geniuses. And if you’re a genius, you should be smart enough to recognize your children may not follow suit.
The nongenetic factors that bear upon intelligence are important because they can be influenced by technology and social policies. The introduction of iodine into salt in the US, for example, raised the average IQ by 3.5 points (because iodine is vital for the production of some growth hormones, even a mild deficiency during pregnancy can impede fetal brain development). Poverty, meanwhile, can dumb us down: studies show that although living in poverty does not reduce the heritability of intelligence in Europe, in the US it does. Could it be that the existence in Europe of universal health care and more generous social programs is protecting the intelligence of its most vulnerable citizens?
Some of the most fascinating material Zimmer covers concerns the phenomena of mosaicism and chimerism, in which individuals are made up of cells with differing genetic inheritances. Mosaicism can occur in a number of ways. For example, if a genetic mutation arises in a cell early in development, the descendants of that cell will make up a large proportion of the cells present in the adult. One outcome is a skin disorder known as CHILD, in which half of a person’s body is darkly pigmented, while the remainder is pale. Cancer is a kind of mosaicism that often arises later in life, when some genetic mutation allows a cell and its descendants to grow in an uncontrolled manner.
Chimerism (from the Greek word for a mythological monster whose body is composed of parts from different animals) is an even more intriguing condition. Chimeric individuals are composed of cells originating from two or more separate origins. The term “genetical chimera” was first coined by Sir Peter Medawar, who used it to describe freemartins, female cattle that shared cells in the uterus with a male twin, and whose cellular makeup therefore includes both male (from the bull calf) and female cells.
Medawar’s pioneering studies of chimeras and immune tolerance led to breakthroughs in organ transplantation. He was also involved in the discovery of the first human to be recognized as a chimera. Known today only as “Mrs. McK,” she was twenty-five years old in 1953, when she decided to donate blood. When her blood sample was analyzed, it was discovered to consist of both A and O types. A baffled doctor wondered if she had recently had a blood transfusion. But Mrs. McK had not had one, so the doctor sent a blood sample to an expert in London, who thought to ask her if she had a twin. Mrs. McK replied that she had a twin brother, but that he had died when he was three months old. Her type A blood cells were all that remained of him. Medawar, in describing the case, wrote:
There is no telling how long Mrs McK will remain a chimera, but she has now been so for twenty-eight years; probably, in the long run, her twin brother’s red blood cells will slowly disappear, and so pay back the still outstanding balance of his mortality.
Other kinds of chimeras are even more astonishing than those only detectable by blood tests. A baby born in a Seattle hospital in 1960 had a clitoris so large that it resembled a penis. When she was two years old she was operated upon to reduce the size of the organ. But after the removed tissue was examined, some cells were found to be genetically male. Further tests revealed that her entire body was a mixture of male and female cells. The child was the result of two eggs that had been fertilized by different sperm—one with male chromosomes, the other with female. Normally the result would have been twins, a boy and a girl. But the fertilized eggs had fused, creating a single chimeric individual.
Such phenomena illustrate the multifariousness of inheritance: we can be stitched together, from a genetic perspective, in ways that complicate our understanding of what an individual is. Unsurprisingly, the law is poorly equipped to deal with such nuances. In 2003 Lydia Fairchild, a pregnant, single mother of three living in Washington State, sought welfare benefits. In order to qualify she had to take a DNA test to prove that she and her former partner were indeed the parents of their children. The tests proved paternity but, according to the Department of Social Services, showed that Fairchild could not possibly be the mother of her children.
Suspecting abduction or a child surrogacy scam, the court put Fairchild’s children in foster care and charged her with fraud. A court officer was present to witness the birth of her fourth child, but even that was not persuasive; only DNA would be accepted as evidence of the child’s maternity. Even Fairchild’s father, dazzled by science, began to have doubts about his daughter’s honesty. Thankfully, her lawyer recalled an earlier, similar case that had resulted from chimerism. Through sheer good fortune a hospital had kept a cervical smear taken years earlier, and analysis of the sample revealed that the cells of Fairchild’s body were derived from two genetically distinct female eggs that had fused to form one individual. Her sex cells came from one egg, while the parts of her body used in the DNA test came from the other. The court was finally convinced, and Fairchild’s children were returned to her, but not before severely traumatizing the family. As we contemplate the potentially dire consequences of the case, the fact that supposed scientific evidence is so persuasive that eyewitness testimony, and even the love of a parent, could be negated by it should act as a caution.
Chimeras can also result from pregnancy. Cells from embryos regularly cross via the placenta into the mother during gestation, while her cells can end up in the embryo. It is astonishing how long such cells can survive. One woman who had given birth to a son still had cells with Y-chromosomes in her body twenty-seven years later. In another case, an entire lobe of a woman’s liver that had been damaged by disease was repaired by fetal cells that remained in her body after an abortion. A mother’s brain cells, too, can be derived from offspring.
As long as chimeras and mosaics were detected on the basis of physical manifestations or blood type, they were considered to be phenomenally rare—indeed freakish. By 1983, only seventy-five cases of human chimeras, as detected from blood type, were known, while mosaicism was mostly known from medical cases. Joseph Merrick, the “Elephant Man,” suffered from a form of mosaicism known as Proteus syndrome, which left parts of his body deformed by monstrous growths, while other parts remained completely normal. For decades, his sad example defined the condition for many.
Recent advances in genetic analysis have revealed that chimerism is common. In fact, chimeric individuals may be the rule, rather than the exception, among mammals. One Danish study of the blood of 154 girls aged ten to fifteen discovered that around 13 percent of them had blood cells with Y-chromosomes. These cells probably originated from an older brother and had crossed into the mother, where they survived before crossing into, and taking root in, the daughter. A Seattle study of fifty-nine women who died, on average, in their seventies found that 63 percent had cells with Y-chromosomes in their brains.
As bizarre as chimeras might seem, they represent only the surface waters of Zimmer’s deep dive into the nature of inheritance. Epigenetics, a fast-expanding area of science that explains how things experienced by individuals can influence the traits that are inherited by their offspring, seems to contradict our conventional understanding of genetics. The epigenome, “that collection of molecules that envelops our genes and controls what they do,” as Zimmer puts it, operates through methylation—the process whereby methyl-group molecules are added to the molecular envelope surrounding the DNA, and so inhibit certain genes from operating (and, in some cases, from operating in descendants as well).
We owe one of the most penetrating insights into epigenetics to a laboratory accident. Michael Skinner of Washington State University was examining the impact of the anti-fungal agent vinclozolin on laboratory rats. He discovered that the offspring of rats exposed to the chemical produced deformed sperm. When a laboratory assistant accidentally used these offspring to breed a new generation of lab rats, researchers discovered that the grandsons of the poisoned rats also produced deformed sperm.
Skinner’s rats sparked a flurry of new experiments that showed how methylation could lead to the inheritance of acquired traits. As some researchers commented, it was as if the work of Jean-Baptiste Lamarck (who famously posited that the necks of giraffes had lengthened over generations because they were stretched as the animals reached up to feed) had become reestablished. Science is rarely so simple—still, epigenetics has Zimmer wondering whether “poverty, abuse, and other assaults on parents also impress themselves epigenetically on their children.” The study of epigenetics is still in its infancy, so it may be years before we know the answer. With some recent studies showing that epigenetic effects fade over time, many researchers are unsure whether epigenetics is anything but an interesting codicil to the conventional genetic theory of inheritance.
The recent development of CRISPR-Cas9 technologies has elucidated yet another potential pathway of inheritance. Cas9 is an enzyme produced by the immune systems of bacteria that fights viruses by breaking up their DNA. As it turns out, it also offers a way to use RNA to guide precise editing of a genome by removing or adding genetic sequences to chromosomes. CRISPR-Cas9 could be used to edit out defective genes and even insert new ones. Reporting on CRISPR in 2014, Zimmer realized that he “was witnessing the beginning of something enormous.” One of the discoverers of the technique, Jennifer Doudna, was meanwhile having recurring nightmares about her discovery. In one nightmare she found herself on a beach staring directly at an oncoming tsunami. In another she met Hitler, who had the face of a pig. As Doudna spoke, the pig-Hitler jotted down notes.
In one of the first uses of CRISPR-Cas9 for biological control, attempts are being made to modify mosquitoes so that they cannot carry the malaria parasite. But because relatively few mosquitoes bear the inserted genes for malaria resistance, their genetic inheritance is quickly diluted when they are released into the wild. If the inserted genes are to spread, another technology known as a gene drive is required. A gene drive is an additional bit of genetic modification to propagate genes in a population by giving them a greater than 50 percent chance of being inherited.
As of 2015, results from the mosquito work were mixed, with some female descendants eliminating the gene that had been inserted into their ancestor’s genome using CRISPR. But in 2018, after the publication of Zimmer’s book, researchers announced that they had successfully propagated genes in mosquitoes using a gene drive. With both CRISPR and gene drive technologies becoming more powerful by the year, we must look to visionaries to comprehend its potential. George Church, a geneticist at Harvard and MIT, believes that CRISPR will inevitably be used to create genetically “superior” humans. Alterations to our genome will creep in the door through the treatment of diseases, he says. Imagine if gene editing can be used to treat wasting muscles, or Alzheimer’s, or to prevent HIV infection (as was allegedly done to a pair of unborn twins recently in China)—how long would it be before those same techniques are used to create super-muscles or super-cognition?
Church is rightly concerned about CRISPR’s potential to permanently alter human gene lines, as are other scientists. Marcy Darnovsky, the executive director of the Center for Genetics and Society, thinks it will lead to an “unregulated marketplace” in which gene editing, which can inflict harm on unborn children, will run rampant. Given the history of earlier misunderstandings of inheritance that Zimmer relates, it’s a warning we better take seriously.