Before I got pregnant, I thought I understood how DNA works: parents pass on some combination of their DNA, which codes for various heritable traits, to their children, who pass on some combination to their children, and so on down the neat branching lines of the genealogical tree. What I didn’t know was that women can also receive DNA from their children. During pregnancy, foetal cells get into the mother’s bloodstream, mixing freely with her own cells and resulting in what scientists call a ‘microchimera, a single organism harbouring a small number of cells from another individual. Microchimerism is the reason doctors can use my blood to do genetic testing that looks for markers of disease in the DNA of the growing foetus. And while the number of foetal cells in my bloodstream will drop after birth, some could stay there for decades, even for the rest of my life. These foetal cells may even sense the tissues around them and develop into the same types of cell, becoming an integral part of my body, which may have both positive and negative effects on my health – a sort of backwards inheritance. Foetal cells have been shown to regenerate a mother’s diseased thyroid gland and to help her body fight breast cancer. If a virus enters her body, even years after pregnancy, cells from the foetus may be among the first to attack it. But they may also make her more vulnerable to autoimmune diseases such as arthritis and scleroderma. And this DNA transfer works both ways: a pregnant woman’s cells – with her complete set of DNA – can enter the foetus, eventually becoming part of her child’s body and living on long after her own death. With a second pregnancy, foetal cells from the first could colonise the new foetus, turning the second infant who emerges blinking into the sharp light of a new day into a microchimera of mother, father and sibling. So much for the neat branching lines of vertical heredity.
We tend to think of heredity as having something to do with traits that are passed from generation to generation, but in many ancient societies, the words for ‘kin’ and ‘kinship’ often denoted connections of mutual responsibility. In Hawaii, the same word could be used for sisters and female cousins. In many South American societies, any man who had sex with a pregnant woman would be a father to her child. The concept of heredity also has a long history linked to the consolidation of wealth and power. In ancient Rome hereditas was a legal term that pointed to the state of being an heir – one to whom assets could be passed. In medieval Europe, powerful families began to put genealogies in writing to prove noble descent as well as their entitlement to ever greater accumulations of wealth. In France, the forked branches of genealogical trees looked to some like a pé de grue, or ‘crane’s foot’, which became the English ‘pedigree’, a biologically fuzzy idea related to shared blood that jumped from human families to valuable animals like dogs and horses, groups of related animals which were then defined, for the first time, as a ‘race’, another idea that leaped back across species in the 1400s, when the relatively new concept was used in Spain to separate Christians from Jews, who were considered inferior and immoral, sharing a lesser and somehow tainted sort of blood. Over the next few centuries, as Europeans embarked on brutal campaigns of colonisation and empire-building, the idea of separate human races that designated some fit to be rulers and others fit to be ruled spread perniciously around the globe, carried by trading ships and warships and scientific expeditions. While the biological mechanisms of bloodline lineages remained murky, by the 1800s it was widely accepted that physical and moral traits could be passed from generation to generation. Heredity became destiny. And then, a modern-day mutation: the genetic revolution. ‘At the dawn of the 20th century,’ Carl Zimmer writes, ‘scientists came to limit the word heredity to genes. Before long, this narrow definition spread in influence far beyond genetic laboratories. It hangs like a cloud over our most personal experiences of heredity, even if we can’t stop trying to smuggle the old traditions of heredity into the new language of genes.’
So what do we mean when we say ‘heredity’ today? Zimmer, who writes a column for the New York Times and whose previous books include Soul Made Flesh and Parasite Rex, as well as a co-authored textbook on evolutionary biology, is a trustworthy guide in this inquiry. Flummoxed by the questions a genetic counsellor asks when his daughter is about to be born, he has his own genome fully sequenced (it helps to know a few world-renowned geneticists) and rides the wave of his own curiosity and ignorance, moving from a consideration of now defunct homes for children once dubbed ‘morons’ to a lab buzzing with red-eyed flies that could hold the key to genetically engineered species of the future. She Has Her Mother’s Laugh is an unlikely page-turner spanning the primordial origins of life, Nazi eugenics, and the promise and perils of gene editing. In just one short section, he considers Charlie Chaplin’s paternity trial and the partial myth of Kunta Kinte and Roots, alongside the discovery of Nicholas and Alexandra’s murdered children and what this reveals about the matrilineal inheritance of mitochondria – ‘the mother’s mitochondria, and only the mother’s mitochondria, becomes the mitochondria of her child’.
‘We use words like sister and aunt as if they describe rigid laws of biology,’ Zimmer writes, ‘but these laws are really only rules of thumb. Under the right conditions, they can be readily broken.’ This is clear if you widen the lens, as Zimmer so artfully does, to explore multiple channels of heredity, including the microbiome, epigenetics and culture. Along the way, he reveals that the way we talk about heredity – he got his height from his uncle; she has her mother’s laugh – isn’t linked to science at all.
At every turn, Zimmer tries to complicate the concept of heredity and challenge received wisdom about why we are the way we are. You get half of your DNA from your mother and half from your father, but thanks to the specialised and ‘laughably baroque’ process of cell division known as meiosis, you and your sibling might get very different assortments of DNA from each parent. This explains why you may have more DNA from your maternal grandmother, say, than your paternal grandmother. Or why, if you have two siblings, you may be genetically more similar to one of them. Remarkably, researchers have found that a pair of siblings may share as much as 61.7 per cent of their DNA, or as little as 37.4 per cent. ‘Along the spectrum of inheritance, in other words,’ Zimmer writes, ‘some of our siblings are more like our identical twins, others more like cousins.’ She Has Her Mother’s Laugh is brimming with similarly surprising discoveries; and the cumulative effect is a radical destabilisation of the boundaries conventionally drawn around the individual, families, and even the human species.
Consider microbes, those single-celled organisms that so vastly outnumber us on planet Earth and which live so plentifully inside our gut. When a typical microbial cell replicates, it copies its chromosomes – the DNA molecules that carry genetic information – then cuts itself in half to form two new cells, giving each a nearly identical copy of its original DNA, a form of vertical inheritance close to cloning. But microbes can also gain copies of genes from totally unrelated microbes through recently discovered and utterly unintuitive processes known as horizontal inheritance. Some microbes will scoop up loose DNA and incorporate it into their own; some will insert their own DNA into nearby microbes by building a tube and passing plasmids into the neighbouring cell; some gain DNA from viruses that act like ferries between microbes, even transporting microbial DNA between organisms of different species. This viral transfer of microbial DNA between species helps to explain the emergence of new strains of antibiotic-resistant bacteria. Horizonal inheritance accounts for 8 per cent of the human genome: part of your DNA is actually viral DNA from retroviruses that once upon a time inserted their DNA into human reproductive cells (sperm, eggs), thus becoming heritable. So whenever humans have a child, we’re passing down, via vertical heredity, viral genes inserted sideways into our genomes via horizontal heredity. In fact, we wouldn’t be able to reproduce at all without horizontal heredity. A crucial membrane between foetus and placenta exists thanks to a viral gene from one of those retroviral horizontal transfers. That viral gene makes all mammalian pregnancy possible. So at the level of DNA, humans are actually a mash-up of different species.
Because cells in the human body divide throughout development, sprouting into an internal family tree of multitudinous lineages, Zimmer suggests that each of a person’s cells has a heredity of its own. To illustrate this, he tells the story of the geneticist Mary Lyon. In the 1950s, Lyon became curious about the pattern of fur on mottled mice – whose coats are a patchwork of colours similar to calico or tortoiseshell cats – which led her to uncover a fundamental secret of cellular heredity. As a female embryo develops, its cells begin to have more X chromosomes than they need, so they shut down one of their two X chromosomes at random; and when the mother cell divides into daughter cells, it passes along this selection, which is passed along in turn, resulting in an adult female animal whose ‘body is made up of lineages of cells, half of which have silenced one X chromosome, and half the other’. Hence the random patchy pattern on Lyon’s mottled mice. Lyonisation, as it is now known, may also make women’s brains inherently more diverse – with more diverse types of neurons connected in more diverse patterns – than the brains of men. In fact, any time mother cells divide into daughter cells, they can pass along random genetic mutations. So at the cellular level we are all what scientists call mosaics, ‘a rainbow of different genetic profiles’. Seen in this light, our intuitive tendency to equate genetic similarity with kinship looks a bit bizarre.
Shine that light a little brighter, zoom out the lens as Zimmer does, and the view gets more weird. If you have a biological sibling, you share at least one parent, which means you are both likely to have large chunks of DNA from that parent in your own genome. With a more distant relative, like a fourth cousin, you have to go further back in the family tree to find a common ancestor – a great-great-great-grandparent. Over the generations, the DNA from that ancestor got cut up – essentially diluted – into smaller and smaller pieces as it made its way down the family tree, mixing with more and more DNA from ancestors that you and your fourth cousin don’t share. Zimmer cites research showing that out of any hundred pairs of third cousins, one pair wouldn’t share any identical segments of DNA. Out of any hundred pairs of fourth cousins, 25 pairs wouldn’t share any identical segments. And yet, we would never say these cousins are not kin. When you look at heredity in terms of genes, using genes alone to define kinship (or even to draw strict boundaries round what it means to be human) starts to seem a little dubious.
The question of who we are related to also bucks intuition on much broader levels of human ancestry. Leaving DNA aside, if we think of our ancestors simply as people who procreated with each other, we soon run up against an inescapable paradox:
We think of genealogy as a simple forking tree, our two parents the product of four grandparents, who are descended from eight great-grandparents, and so on. But such a tree eventually explodes into impossibility. By the time you get back to the time of, say, Charlemagne, you have to draw over a trillion forks. In other words, your ancestors from that generation alone far outnumber all the humans who ever lived. The only way out of that paradox is to join some of those forks back together. In other words, your ancestors must have all been related to each other, either closely or distantly … If you go back far enough in the history of a human population, you reach a point in time when all the individuals who have any descendants among living people are ancestors of all living people.
This is why, as has been repeatedly pointed out in recent years, every European alive today is a descendant of Charlemagne. Such ancestral tree-twisting is hard to keep up with, but it reveals that the obsession with being a ‘direct descendant’ of a celebrated historical figure has more to do with the way certain relationships are culturally valued – for example ‘legitimate’ v. ‘illegitimate’ children – than with science. In a sense, we are all royals, even if we don’t all have royal DNA in our genomes. And yet, we are obsessed with genealogies. ‘By one estimate,’ Zimmer writes, ‘genealogy has now become the second most popular search topic on the internet. It is outranked only by porn.’
In 2002, a geneticist called Jonathan Pritchard and his team at Oxford, collaborating with Noah Rosenberg at Stanford, found they could use a program they’d designed called Structure to identify clusters of people based only on their DNA. The program scanned genetic variation and assigned each individual’s DNA to one or more groups of ancestors who shared similar variations. When the researchers set the parameters of the program to sort people into five groups, they found clusters that matched the continents the people lived on, which meant the program roughly grouped Africans, Eurasians, East Asians, Pacific Islanders and people in the Americas. Crucially, these ancestral groups didn’t have sharp boundaries. ‘Where two clusters met on a map of the world,’ Zimmer writes, ‘the researchers found people who had some DNA that linked them to one group, and some that linked them to the other.’ And if you set the parameters differently, you got different results. When the researchers asked the program to sort people’s genomes into six groups, a single population emerged from the Eurasian cluster to form a new cluster. This turned out to be a tiny population of a few thousand people who live in the Hindu Kush mountains of Pakistan, known as the Kalash. ‘Their separation in Pritchard’s study may tell us something important about the history of the Kalash,’ Zimmer writes, ‘perhaps a long isolation from other tribes in Pakistan, allowing them to accumulate a small number of genetic variations that set them off from much larger clusters of people. But it doesn’t mean the Kalash are a race of their own.’ In fact, he and his collaborators found that ‘the overwhelming amount of genetic diversity was between individuals. The genetic differences between major groups accounted for only 3-5 per cent.’ Rather than defining biological boundaries between racial groups, cutting-edge genetic studies like Pritchard’s suggest a dissolution of these boundaries.
Unfortunately, some people got stuck on the idea that people could be separated into ancestral groups from five continents. ‘Much to the chagrin of Pritchard and his colleagues, some people mistakenly took these results as evidence for a biological concept of race. But any resemblance between genetic clusters of people and racial categories concocted before genetics existed can have no deep meaning.’ Just because your genome has variants statistically more similar to variants in the genomes of other people on the same continent, that doesn’t mean you are all members of some shared biological ‘race’, or that you share a similar skin colour, that ubiquitous cultural marker for race. But misconceptions like these have contributed to some astonishingly wrong-headed conclusions about race and human cultures in recent years. Perhaps one of the most egregious was a book from 2014 written by one of Zimmer’s former colleagues on the New York Times science desk, Nicholas Wade. In his dangerous and deeply unscientific book on genetics and race, A Troublesome Inheritance, Wade speculates that as humans evolved over tens of thousands of years, the genetic basis for human behaviour and social institutions changed, just as the genetic basis for skin colour changed. This thesis leads to further unscientific speculation about the differences between societies on different continents, including the relative ‘success’ of some over others. In response, more than a hundred geneticists and biologists dismissed Wade’s conclusions in a letter published in the New York Times: ‘Wade juxtaposes an incomplete and inaccurate account of our research on human genetic differences with speculation that recent natural selection has led to worldwide differences in IQ test results, political institutions and economic development. We reject Wade’s implication that our findings substantiate his guesswork. They do not.’ More recently, David Reich’s Who We Are and How We Got Here, as well as his March op-ed in the New York Times, ‘How Genetics Is Changing Our Understanding of “Race”’, prompted an impassioned response.In an open letter published on Buzzfeed 67 scientists flatly stated that Reich ‘misrepresents the many scientists and scholars who have demonstrated the scientific flaws of considering “race” a biological category’.
Zimmer does not attempt to erase the concept of race as a meaningful category, and his skilful handling of the subject is a welcome contribution to current contentious discussions of race and genetics. ‘Race may not be a meaningful biological concept,’ he writes, ‘but it does exist: it has a powerful existence as a tradition of putting people in social categories. Those categories, then, had profound influences on people’s lives … Because race is a shared experience, it can join people together who aren’t closely related.’ The experience of political oppression based on race remains a crucial tool for liberation struggles around the world, a powerful locus around which marginalised groups can organise and mobilise. And race can have serious implications for medicine. As Zimmer acknowledges, ‘some people who identify themselves with certain labels – black, Hispanic, Irish, Jewish – have relatively high rates of certain diseases,’ but to understand why this might be and to identify more successful treatments, the medical establishment needs to look beyond biology:
doctors need to examine the experiences of blacks and whites in the United States – the stress of life in high-crime neighbourhoods and the difficulty of getting good healthcare, for example. These are powerful inheritances too, but they’re not inscribed in DNA. For scientists carrying out the hard work of disentangling these influences, an outmoded biological concept of race offers no help.
To drive this point home, Zimmer shows how the emerging field of paleogenetics uses the DNA extracted from ancient skeletons to offer an even longer view of human history, revealing that we are all genetic mongrels and any notion of biological racial purity is just a fantasy. Among the outmoded biological concepts that science suggests we need to abandon is that of a ‘white’ race.
We tend to think of white people as the pale-skinned people of Europe and their descendants, a group of humans joined together on one continent, sharing the same uniform heredity that reaches back for tens of thousands of years. The people who lived in Europe twenty thousand years ago might be different in the ways they lived, hunting woolly rhinos instead of posting pictures on Instagram. But we still think of them as white. As scientists have examined the DNA of Europeans – both people who live on the continent today and those who lived there tens of thousands of years ago – they’ve demonstrated just how wrong-headed those notions are.
As Zimmer notes, ‘ancient DNA doesn’t simply debunk the notion of white purity. It debunks the very name white.’ Specious biological categories have long been used to bolster racist or xenophobic speculation about inherent differences between people and cultures, but modern genetics makes notions of racial ‘purity’ laughable, and shows them to be rooted in cultural and political desires that have nothing to do with biology.
When scientists mapped the human genome just 15 years ago, their work promised to change the world. Starry-eyed optimists predicted an end to human disease. The more circumspect among us worried about genetic discrimination. When CRISPR/Cas9 technology appeared, allowing researchers to edit the genome of any living organism, some predicted transgenic crops would end world hunger while others expressed grave concerns about ‘designer babies’ that would allow the rich to buy themselves even greater social advantage. Predictions about the future, of course, are nearly always wrong. And yet. Genies do not go back into bottles. Just a few weeks ago, researchers in China reported using CRISPR gene editing technology to repair Marfan syndrome in a viable human embryo, causing a flurry of anxious attention. Even if these researchers have successfully edited one gene known to be involved in Marfan, no small task given the complications of this still nascent technology, we don’t know what would happen if the embryo were to grow into an adult. Would the disease be corrected? Would unintended side-effects appear? If we could get this technology to work in humans, should we use it?
It is a popular misconception about gene editing that changing one gene reliably produces a dramatically different outcome. ‘Sometimes,’ Zimmer writes, ‘heredity does act with a diamond-like simplicity.’ Two defective copies of a single gene – one from each parent – can cause certain diseases, which is the reason I had my microchimerical blood drawn for genetic testing. But most traits are not tied to a single gene. They appear as the result of an extremely complex interplay between multiple genes and the environment. To illustrate, Zimmer investigates height, a deceptively simple measurement:
There may be a core group of genes lurking in growth plates that take the lead in determining how tall we get. But some of those genes also have other jobs. They work with other genes in other kinds of cells … Thanks to the way these networks are organised, it may take only a few steps to go from any given gene to any other gene in the human genome. With all these connections, a mutation to a single gene can have wide-ranging effects.
The mutated gene might alter another gene that doesn’t directly influence height, but which interacts with those that do. This genetic interconnectivity is the reason a trait like syndactyly – webbed fingers and toes – can be associated with both Crouzon syndrome and Apert syndrome, genetic disorders that cause abnormal growth in the bones of the hands and feet, as well as some three hundred other less obviously related syndromes, including Down’s syndrome. Zimmer points out that genome-wide association studies, which can now identify genetic variants that have an effect on a particular trait, have uncovered nearly two million variants involved in height. ‘Each of the two million variants had, on average, an exquisitely tiny effect – adding or subtracting the width of a human hair.’
The picture gets even more complicated when you look at the heritability of something as complex as intelligence – researchers still can’t say what intelligence is, much less how it might be inherited. That IQ scores are rising around the world, a well-documented phenomenon known as the Flynn effect, may speak more to a homogenisation of human culture and what we value under global capitalism than to genetic variants influencing some monolithic human trait we can call intelligence. Beginning to appreciate the complexity of the way genes work can help to clarify why it’s so hard to cure complex diseases and calm (for now) rising fears about ‘designer babies’ with superlative intelligence.
There’s no danger of the super-rich fiddling with a few genes to program super-tall or super-smart progeny over the next year or two, because even if the technology existed, no one knows what the actual effects might be. (This presents a rather stunning Catch 22 – researchers need to edit the genomes of actual human babies and watch them grow to know if they’re doing it correctly.) One study by researchers at the Wellcome Sanger Institute published this year in the journal Nature Biotechnology found CRISPR/Cas9 caused more damage to DNA than previously thought. In the US, the National Academy of Sciences recently issued a report recommending widescale public debate on CRISPR and gene editing. In the UK in July, the Nuffield Council on Bioethics said that changing the DNA of a human baby could be ‘morally permissible’ if it was in the interest of the child and did not exacerbate existing social inequalities. But in a hundred years, we may have enough knowledge and technological knowhow for the rich to buy themselves designer babies, which is just one reason to consider the ethics of this technology, now.
If tweaking the genome of a single human embryo is ethically fraught, introducing heritable changes into the human germline is even more controversial. In the last section of the book, Zimmer spends time with researchers who may have found a way to alter for good the DNA of transgenic mosquitoes in an attempt to wipe out their ability to transmit disease. Building on the work of Jennifer Doudna, who pioneered CRISPR, as well as Valentino Gantz and others (the transmission of knowledge is a form of heredity), the biologist Anthony James found a way to cut a long piece of DNA out of the mosquito genome and replace it with genes engineered to make mosquitoes unable to transmit malaria, as well as CRISPR genes that can copy this DNA to other chromosomes. All the mosquitoes in this lineage then carry these genes, which could potentially spread through a population and overpower other genes. The implications are both promising and chilling – diseases could be wiped out, but using similar technology a few people could conceivably make choices that alter the genetic inheritance of the human species for ever. Zimmer ends his book in James’s lab full of red-eyed flies. Twenty-nine generations have inherited the trait, along with CRISPR genes from their ancestors. But this inheritance is not perfect – there are weak links. There is still work to be done and more, no doubt, to come.
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