The Gene - Vignesh Prasad

## Highlights The Nazis—believing in absolute genetic immutability (“a Jew is a Jew”)—had resorted to eugenics to change the structure of their population. The Soviets—believing in absolute genetic reprogrammability (“anyone is everyone”)—could eradicate all distinctions and thus achieve a radical collective good. — location: 2423 ^ref-59926 --- By the mid-twentieth century, the gene—or the denial of its existence—had already emerged as a potent political and cultural tool. It had become one of the most dangerous ideas in history. — location: 2442 ^ref-59485 --- The abortion movement, in Dancis’s formulation, had not pushed the frontiers of human genetics forward by enabling doctors to terminate fetuses with genetic disorders. Rather, human genetics had pulled the reluctant cart of the abortion movement behind it—by shifting the “attitude” toward the treatment of devastating congenital diseases and thus softening the stance against abortion. In principle, Dancis continued, any illness with a sufficiently powerful genetic link could be intervened upon by prenatal testing and selective abortion. The “right to be born” could be rephrased as a right to be born with the right kind of genes. — location: 5084 ^ref-47737 --- “Where the traditional view had been that ‘nature’ spelt destiny, and ‘nurture’ freedom, now the roles appeared to be reversed. . . . We could more readily control the former i.e., genes, than the latter i.e., the environment—not simply as a long-term goal but as an immediate prospect.” — location: 5518 ^ref-37079 --- Medicine, the sociologist Everett Hughes once observed wryly, perceives the world through “mirror writing.” Illness is used to define wellness. Abnormalcy marks the boundaries of normalcy. Deviance demarcates the limits of conformity. This mirror writing can result in an epically perverse vision of the human body. An orthopedist thus begins to think of bones as sites of fractures; a brain, in a neurologist’s imagination, is a place where memories are lost. — location: 6198 ^ref-62992 --- Once genes had been implicated in the development of sexual preference, the gay child was instantly transformed to normal. His hateful enemies were the abnormal monsters. — location: 7018 ^ref-23384 --- Descent of Man is to biologists what War and Peace is to graduate students of literature: nearly every biologist claims to have read the book, or appears to know its essential thesis, but few have actually even opened its pages. — location: 7036 ^ref-51949 --- When Bailey looked for concordance of gayness among twins, the results were striking. Among the fifty-six pairs of identical twins, both twins were gay in 52 percent. Of the fifty-four pairs of nonidentical twins, 22 percent were both gay—lower than the fraction for identical twins, but still significantly higher than the estimate of 10 percent gay in the overall population. — location: 7060 ^ref-62075 --- If we did not think of variations in height or the development of dyslexia or type 1 diabetes as choices, then we could not think of sexual identity as a choice. — location: 7074 ^ref-54602 --- Hamer was attacked left and right—literally. Antigay conservatives argued that by reducing homosexuality to genetics, Hamer had justified it biologically. Advocates of gay rights accused Hamer of furthering the fantasy of a “gay test” and thereby propelling new mechanisms of detection and discrimination. — location: 7138 ^ref-63868 --- Social and political attitudes between twins reared apart were just as concordant as those between twins reared together: liberals clustered with liberals, and orthodoxy was twinned with orthodoxy. Religiosity and faith were also strikingly concordant: twins were either both faithful or both nonreligious. Traditionalism, or “willingness to yield to authority,” was significantly correlated. So were characteristics such as “assertiveness, drive for leadership, and a taste for attention.” — location: 7226 ^ref-64456 --- “Empathy, altruism, sense of equity, love, trust, music, economic behavior, and even politics are partially hardwired.” As one startled observer wrote, “A surprisingly high genetic component was found in the ability to be enthralled by an esthetic experience such as listening to a symphonic concert.” — location: 7232 ^ref-46128 --- The picture that emerged from the Minnesota study was not that reared-apart twins were identical, but that they shared a powerful tendency toward similar or convergent behaviors. What was common to them was not identity, but its first derivative. — location: 7267 ^ref-34302 --- Is that an infuriating answer? After decades of musing, have we reached the conclusion that fate is, well . . . fate? That being happens through . . . be-ing? I find that formulation illuminatingly beautiful. — location: 7371 ^ref-21156 --- Epigenetics, Waddington wrote, concerns “the interaction of genes with their environment . . . that brings their phenotype into being.” — location: 7447 ^ref-33233 --- The Hongerwinter had etched itself into national memory, but it had penetrated genetic memory as well. — location: 7474 ^ref-53512 --- An embryonic cell might be able to write a thousand novels from the same script. But Young Adult Fiction, once scripted, cannot easily be reformatted into Victorian Romance. — location: 7616 ^ref-27644 --- Environmental information can certainly be etched on the genome. But most of these imprints are recorded as “genetic memories” in the cells and genomes of individual organisms—not carried forward across generations. — location: 7693 ^ref-8387 --- Technologists seek to liberate us from the constraints of our current realities through those transitions. Science defines those constraints, drawing the outer limits of the boundaries of possibility. Our greatest technological innovations thus carry names that claim our prowess over the world: the engine (from ingenium, or “ingenuity”) or the computer (from computare, or “reckoning together”). Our deepest scientific laws, in contrast, are often named after the limits of human knowledge: uncertainty, relativity, incompleteness, impossibility. — location: 7739 ^ref-64952 --- Gurdon’s technique—of evacuating the egg and inserting a fully fertilized nucleus—has already found a novel clinical application. Some women carry mutations in mitochondrial genes—i.e., genes that are carried within mitochondria, the energy-producing organelles that live inside cells. All human embryos, recall, inherit their mitochondria exclusively from the female egg—i.e., from their mothers (the sperm does not contribute any mitochondria). If the mother carries a mutation in a mitochondrial gene, then all her children might be affected by that mutation; mutations in these genes, which often affect energy metabolism, can cause muscle wasting, heart abnormalities, and death. In a provocative series of experiments in 2009, geneticists and embryologists proposed a daring new method to tackle these maternal mitochondrial mutations. After the egg had been fertilized by the father’s sperm, the nucleus was injected into an egg with intact (“normal”) mitochondria from a normal donor. Since the mitochondria were derived from the donor, the maternal mitochondrial genes were intact, and the babies born would no longer carry the maternal mutations. Humans born from this procedure thus have three parents. The fertilized nucleus, formed by the union of the “mother” and “father” (parents 1 and 2), contributes virtually all the genetic material. The third parent—i.e., the egg donor—contributes only mitochondria, and the mitochondrial genes. In 2015, after a protracted national debate, Britain legalized the procedure, and the first cohorts of “three-parent children” are now being born. These children represent an unexplored frontier of human genetics (and of the future). Obviously, no comparable animals exist in the natural world. — location: 7820 ^ref-44416 --- By the early 1990s, hundreds of strains of transgenic mice had been created in laboratories around the world to decipher the functions of genes. One mouse was made with a jellyfish gene inserted into its genome that allowed it to glow in the dark under blue lamps. Other mice, carrying variants of the growth hormone gene, grew twice the size of their normal counterparts. — location: 7949 ^ref-2824 --- Unlike the mouse ES cells, which had proved so amenable to experimental manipulations, human ES cells did not behave themselves in culture. “It may be the field’s dirty little secret: human ES cells do not have the same capabilities as mouse ES cells,” the biologist Rudolf Jaenisch said. “You can’t clone them. You can’t use them for gene targeting. . . . They are very different from mouse embryonic stem cells, which can do everything.” At least temporarily, the genie of transgenesis seemed contained. — location: 7961 ^ref-13154 --- Familial schizophrenia (like normal human features such as intelligence and temperament) is thus highly heritable but only moderately inheritable. In other words, genes—hereditary determinants—are crucially important to the future development of the disorder. — location: 8414 ^ref-14495 --- If the most pathological variants of a mental illness can be sifted out or discriminated from the high-functioning variants by genes or gene combinations alone, then we can hope for such a test. But it is much more likely that such a test will have inherent limits: most of the genes that cause disease in one circumstance might be the very genes that cause hyperfunctional creativity in another. As Edvard Munch put it, “My troubles are part of me and my art. They are indistinguishable from me, and treatment would destroy my art. I want to keep those sufferings.” — location: 8485 ^ref-38234 --- Should we consider allowing parents to fully sequence their children’s genomes and potentially terminate pregnancies with such known devastating genetic mutations? We would certainly eliminate Erika’s mutation from the human gene pool—but we would eliminate Erika as well. I will not minimize the enormity of Erika’s suffering, or that of her family—but there is, indubitably, a deep loss in that. To fail to acknowledge the depth of Erika’s anguish is to reveal a flaw in our empathy. But to refuse to acknowledge the price to be paid in this trade-off is to reveal, conversely, a flaw in our humanity. — location: 8534 ^ref-34466 --- Prenatal diagnosis and the termination of pregnancies still remained the simplest choice for such rare devastating diseases—but also ethically the most difficult to confront. “The more technology evolves, the more we enter unknown territory. There’s no doubt that we have to face incredibly tough choices,” Eric Topol, the conference organizer, told me. “In the new genomics, there are very few free lunches.” — location: 8541 ^ref-3282 --- Even so, this triangle of limits—high-penetrance genes, extraordinary suffering, and noncoerced, justifiable interventions—has proved to be a useful guideline for acceptable forms of genetic interventions. — location: 8661 ^ref-61140 --- The most brittle or fragile forms of psyche are the most likely to be distorted by trauma-inducing environments—but are also the most likely to be restored by targeted interventions. It is as if resilience itself has a genetic core: some humans are born resilient (but are less responsive to interventions), while others are born sensitive (but more likely to respond to changes in their environments). — location: 8688 ^ref-8931 --- The genetic code is universal. A gene from a blue whale can be inserted into a microscopic bacterium and it will be deciphered accurately and with nearly perfect fidelity. A corollary: there is nothing particularly special about human genes. — location: 9094 ^ref-38095 --- it is an old sin of biology to confuse the definition of a feature with the feature itself. If we define “beauty” as having blue eyes (and only blue eyes), then we will, indeed, find a “gene for beauty.” If we define “intelligence” as the performance on only one kind of problem in only one kind of test, then we will, indeed, find a “gene for intelligence.” The genome is only a mirror for the breadth or narrowness of human imagination. — location: 9108 ^ref-65311 --- Every generation of humans will produce variants and mutants; it is an inextricable part of our biology. — location: 9118 ^ref-59889 --- Every genetic “illness” is a mismatch between an organism’s genome and its environment. — location: 9128 ^ref-41121 --- It is a peculiar modern fallacy to imagine that the definitive solution to illness is to change nature—i.e., genes—when the environment is often more malleable. — location: 9132 ^ref-4198 --- A triangle of considerations—extraordinary suffering, highly penetrant genotypes, and justifiable interventions—has, thus far, constrained our attempts to intervene on humans. — location: 9142 ^ref-22654 --- History repeats itself, in part because the genome repeats itself. And the genome repeats itself, in part because history does. The impulses, ambitions, fantasies, and desires that drive human history are, at least in part, encoded in the human genome. — location: 9146 ^ref-9010 --- Scientists divide. We discriminate. It is the inevitable occupational hazard of our profession that we must break the world into its constituent parts—genes, atoms, bytes—before making it whole again. We know of no other mechanism to understand the world: to create the sum of the parts, we must begin by dividing it into the parts of the sum. — location: 9174 ^ref-18101 ---