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August 15, 2018 - February 16, 2019
When I met Sarah, now my wife, for the fourth or fifth time, I told her about the splintered minds of my cousin and two uncles. It was only fair to a future partner that I should come with a letter of warning.
By then, heredity, illness, normalcy, family, and identity had become recurrent themes of conversation in my family. Like most Bengalis, my parents had elevated repression and denial to a high art form, but even so, questions about this particular history were unavoidable. Moni; Rajesh; Jagu: three lives consumed by variants of mental illness. It was hard not to imagine that a hereditary component lurked behind this family history.
In 2009, Swedish researchers published an enormous international study, involving thousands of families and tens of thousands of men and women. By analyzing families that possessed intergenerational histories of mental illness, the study found striking evidence that bipolar disorder and schizophrenia shared a strong genetic link.
In 2012, several further studies corroborated these initial findings, strengthening the links between these variants of mental illness and family histories and deepening questions about their etiology, epidemiology, triggers, and instigators.
This book is the story of the birth, growth, and future of one of the most powerful and dangerous ideas in the history of science: the “gene,” the fundamental unit of heredity, and the basic unit of all biological information. I use that last adjective—dangerous—with full cognizance. Three profoundly destabilizing scientific ideas ricochet through the twentieth century, trisecting it into three unequal parts: the atom, the byte, the gene.
the most crucial parallel between the three ideas, by far, is conceptual: each represents the irreducible unit—the building block, the basic organizational unit—of a larger whole: the atom, of matter; the byte (or “bit”), of digitized information; the gene, of heredity and biological information.
matter, information, and biology are inherently hierarchically organized: understanding that smallest part is crucial to understanding the whole.
When the poet Wallace Stevens writes, “In the sum of the parts, there are only the parts,” he is referring to the deep structural mystery that runs through language: you can only decipher the meaning of a sentence by deciphering every individual word—yet a sentence carries more meaning than any of the individual words. And so it is with genes.
“The whole organic world is the result of innumerable different combinations and permutations of relatively few factors. . . .
Genes reside on chromosomes—long, filamentous structures buried within cells that contain tens of thousands of genes linked together in chains.II Humans have forty-six such chromosomes in total—twenty-three from one parent and twenty-three from another.
The human genome contains about between twenty-one and twenty-three thousand genes that provide the master instructions to build, repair, and maintain humans.
Over the last two decades, genetic technologies have advanced so rapidly that we can decipher how several of these genes operate in time and space to enable these complex functions.
in just the last four years—between 2012 and 2016—we have invented technologies that allow us to change human genomes intentionally and permanently
evaluated). At the same time, the capacity to predict the future fate of an individual from his or her genome has advanced dramatically (although the true predictive capacities of these technologies still remain unknown).
The “action” of a gene is described in mechanistic terms: genes encode chemical messages to build proteins that ultimately enable form and function.
These efforts reach their peak in the Human Genome Project, an international project to map and sequence the entire human genome. The draft sequence of the human genome is published in 2001. The genome project, in turn, inspires attempts to understand human variation and “normal” behavior in terms of genes. The gene, meanwhile, invades discourses concerning race, racial discrimination, and “racial intelligence,” and provides startling answers to some of the most potent questions coursing through our political and cultural realms. It reorganizes our understanding of sexuality, identity, and
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In Vienna, science was crackling, electric—alive. At the university, just a few miles from his back-alley boardinghouse on Invalidenstrasse, Mendel began to experience the intellectual baptism that he had so ardently sought in Brno. Physics was taught by Christian Doppler, the redoubtable Austrian scientist who would become Mendel’s mentor, teacher, and idol.
The question of “likeness” had preoccupied scientists and philosophers for centuries. Pythagoras, the Greek scholar—half scientist, half mystic—who lived in Croton around 530 BC, proposed one of the earliest and most widely accepted theories to explain the similarity between parents and their children. The core of Pythagoras’s theory was that hereditary information (“likeness”) was principally carried in male semen.
The theory was eventually called spermism, highlighting the central role of the sperm in determining all the features of a fetus.
The central theme of Aeschylus’s Eumenides is the trial of Orestes, the prince of Argos, for the murder of his mother, Clytemnestra. In most cultures, matricide was perceived as an ultimate act of moral perversion. In Eumenides, Apollo, chosen to represent Orestes in his murder trial, mounts a strikingly original argument: he reasons that Orestes’s mother is no more than a stranger to him.
In one of the most intriguing passages in The Republic—borrowed,
argued that if children were the arithmetic derivatives of their parents, then, at least in principle, the formula could be hacked: perfect children could be derived from perfect combinations of parents breeding at perfectly calibrated times.
A political utopia would develop as a consequence of genetic utopia.
It took a mind as precise and analytical as Aristotle’s to systematically dismantle Pythagoras’s theory of heredity.
He set about dissecting the merits and problems of “spermism” using experimental data from the biological world. The result, a compact treatise titled Generation of Animals, would serve as a foundational text for human genetics just as Plato’s Republic was a founding text for political philosophy.
Aristotle rejected the notion that heredity was carried exclusively in male semen or sperm. He noted, astutely, that children can inherit features from their mothers and grandmothers (just as they inherit features from their fathers and grandfathers), and that these features can even skip generations, disappearing for one generation and reappearing in the next.
How could a father’s sperm “absorb” the instructions to produce his daughter’s “generative parts,” Aristotle asked, when none of these parts was to be found anywhere in the father’s body? Pythagoras’s theory could explain every aspect of genesis except the most crucial one: genitals.
perhaps females, like males, contribute actual material to the fetus—a form of female semen. And perhaps the fetus is formed by the mutual contributions of male and female parts.
Aristotle was wrong in his partitioning of male and female contributions into “material” and “message,” but abstractly, he had captured one of the essential truths about the nature of heredity. The transmission of heredity, as Aristotle perceived it, was essentially the transmission of information. Information was then used to build an organism from scratch: message became material. And when an organism matured, it generated male or female semen again—transforming material back to message.
Centuries later, the biologist Max Delbrück would joke that Aristotle should have been given the Nobel Prize posthumously—for the discovery of DNA.
theory was so seductive—so artfully vivid—that even the invention of the microscope was unable to deal the expected fatal blow to the homunculus. In 1694, Nicolaas Hartsoeker, the Dutch physicist and microscopist, conjured a picture of such a minibeing, its enlarged head twisted in fetal position and curled into the head of a sperm. In 1699, another Dutch microscopist claimed to have found homuncular creatures floating abundantly in human sperm.
While biologists, philosophers, Christian scholars, and embryologists fought their way through vicious debates between preformation and the “invisible hand” throughout much of the eighteenth century, a casual observer may have been forgiven for feeling rather unimpressed by it all. This was, after all, stale news. “The
In the winter of 1831, when Mendel was still a schoolboy in Silesia, a young clergyman-in-training, Charles Darwin, boarded a ten-gun brig-sloop, the HMS Beagle, at Plymouth Sound, on the southwestern shore of England.
But the second problem, Herschel thought, was more tractable: Once life had been created, what process generated the observed diversity of the natural world? How, for instance, did a new species of animal arise from another species? Anthropologists, studying language, had demonstrated that new languages arose from old languages through the transformation of words.
elements. “Battered relics of past ages,” Herschel wrote, “contain . . . indelible records capable of intelligible interpretation.”
A descriptive view of nature—i.e., the identification, naming, and classification of plants and animals—was perfectly acceptable: in describing nature’s wonders, you were, in effect, celebrating the immense diversity of living beings created by an omnipotent God. But a mechanistic view of nature threatened to cast doubt on the very basis of the doctrine of creation: to ask why and when animals were created—by what mechanism or force—was to challenge the myth of divine creation and edge dangerously close to heresy.
Perhaps unsurprisingly, by the late eighteenth century, the discipline of natural history was dominated by so-called parson-naturalists—vicars, parsons, abbots, deacons, and monks who cultivated their gardens and collected plant and animal specimens to service the wonders of divine Creation, but generally veered away from questioning its fundamental assumptions.
It was this static view of nature that Darwin found troubling. A natural historian should be able to describe the state of the natural world in terms of causes and effects, Darwin reasoned—just as a physicist might describe the motion of a ball in the air. The essence of Darwin’s disruptive genius was his ability to think about nature not as fact—but as process, as progression, as history.
The Beagle rounded the sharp jaw-bend of Tierra del Fuego and climbed the western coast of South America. In 1835, the ship left Lima, on the coast of Peru, and headed toward a lonely spray of charred volcanic islands west of Ecuador—the Galápagos. The archipelago was “black, dismal-looking heaps . . . of broken lava, forming a shore fit for pandemonium,” the captain wrote. It was a Garden of Eden of a hellish sort: isolated, untouched, parched, and rocky—turds of congealed lava overrun by “hideous iguanas,” tortoises, and birds. The ship wandered from island to island—there were about
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Over five weeks, Darwin collected carcasses of finches, mockingbirds, blackbirds, grosbeaks, wrens, albatrosses, iguanas, and an array of sea and land plants. The captain grimaced and shook his head.
When Darwin returned to England after five years at sea, he was already a minor celebrity among natural historians. His vast fossil loot from South America was being unpacked, preserved, cataloged, and organized; whole museums could be built around it.
as Owen and Lyell pored through the fossils, they found an underlying pattern in the specimens. They were typically skeletons of colossal, extinct versions of animals that were still in existence at the very same locations where the fossils had been discovered.
The second bizarre fact came from Gould. In the early spring of 1837, Gould told Darwin that the assorted varieties of wrens, warblers, blackbirds, and “Gross-beaks” that Darwin had sent him were not assorted or various at all. Darwin had misclassified them: they were all finches—an astonishing thirteen species.
What if all the finches had arisen from a common ancestral finch? What if the small armadillos of today had arisen from a giant ancestral armadillo?
rather than all species radiating out from the central hub of divine creation, perhaps they arose like branches of a “tree,” or like rivulets from a river, with an ancestral stem that divided and subdivided into smaller and smaller branches toward dozens of modern descendants.
In Malthus’s paper, Darwin immediately saw a solution to his quandary. This struggle for survival was the shaping hand.
Individuals within a species are constantly competing for scarce resources. When these resources form a critical bottleneck—during a famine, for instance—a variant better adapted for an environment is “naturally selected.”
As new Malthusian limits were imposed—diseases, famines, parasites—new breeds gained a stronghold, and the population shifted again. Freaks became norms, and norms became extinct. Monster by monster, evolution advanced.
Darwin had also fueled his critics. Perhaps wisely, he had been deliberately cagey about the implications of his theory for human evolution: the only line in Origin regarding human descent—“light will be thrown on the origin of man and his history”—might well have been the scientific understatement of the century.
It is a testament to Darwin’s scientific audacity that he was not particularly bothered by the prospect of human descent from apelike ancestors. It is also a testament to his scientific integrity that what did bother him, with far fiercer urgency, was the integrity of the internal logic of his own theory. One particularly “wide blank” had to be filled: heredity.
