Her brother’s disease leads a writer to challenge how we conceive of human abnormality in the emerging era of gene editing

Steve was a nationally ranked amateur pool player, for whom the game took “ungainliness and made it liquid, turned it into something elegant, beautiful, and normal.” (Photograph courtesy of the author)
Steve was a nationally ranked amateur pool player, for whom the game took “ungainliness and made it liquid, turned it into something elegant, beautiful, and normal.” (Photograph courtesy of the author)

My older brother Stephen was always tall. Extremely tall. He was that kid who occupied precisely the middle position in the last row of every class picture in elementary school. His arms hung awkwardly out of the sleeves of his shirts, which could never keep pace with his weedy growth. “Dear Friends,” our dad wrote in his annual Christmas letter in 1961, “Stephen is a 1st grader at Overlook school … He is a TALL 1st grader, standing just 4 inches below his daddy’s chin. We hope that this growth-pace declines.” It didn’t.

When I encounter Steve in family photos from the years before I was born, there’s still an unguarded lightness to him, a receptivity to the world. He was tall, yes, but he hadn’t been diagnosed with anything. He was seen—and, I believe, saw himself—as a child who simply happened to be unusually lanky and tall. He fit in among the other kids in our suburban Baltimore neighborhood, where children observed difference but did so ingenuously. They hadn’t yet acquired the malevolent acumen to sort, rank, and harass other kids based on physical characteristics. As I look at these photos, decades later, my heart aches for Steve. It’s as if he didn’t suspect anything was wrong. Whatever he imagined for his life in those days had nothing to do with what followed. He was enjoying a particular kind of innocence: it was the last time when his inner battle with the idea of normal wasn’t an elemental part of his existence.

What is normal? Is genetic variation something to be corrected? Or is variation simply variation, a natural (and crucial) link in the evolutionary chain?

The question of how to think about human difference is nothing new. In the late 19th century, at the dawn of what one British biologist declared to be the “century of the gene,” scientists were already debating the answer. English polymath Francis Galton coined the term eugenics in 1883, and his journal, The Eugenics Review, endorsed selective breeding and the sterilization of the atypical as a means of eliminating deviation from genetic norms. But Galton’s cousin Charles Darwin put forward a different view. Darwin called mutations “sports,” a more benign, even playful term. The opposite of the sport was not a normal gene but a wild type, the one most often found in the natural world. Likewise, physician Archibald Garrod influentially wrote about chemical individuality.

The new world of gene editing has reinvigorated the debate. In 2003, scientists completed mapping the human genome, and last year, the FDA approved CRISPR/Cas9 gene-editing therapy to treat sickle cell anemia. These developments have the potential to change fundamentally our understanding of (and approach to) human abnormality. Medical ethicists sometimes distinguish between genetic “treatment” and “enhancement”—condoning the former, condemning the latter—but the distinction is arguably flimsy. As it becomes ever easier to manipulate genes to our liking, how will we feel about genetic characteristics that fall short of affliction, such as lack of athleticism, but nevertheless deny certain advantages to those who inherit them? What about atypicalities, such as neurodivergence, deafness, dwarfism, and scores of others? Those who have these conditions don’t necessarily see them as disabilities. Might such people become candidates for gene editing? Whereas patients with mild symptoms might once have been able to pass as genetically normal, the mapping of the genome has largely eliminated this possibility. It’s disquietingly simple to envision a world, already fast approaching, in which the lack of genetic perfection itself comes to feel like an affliction.

What is normal? Is genetic variation something to be corrected? Or is variation simply variation, a natural (and crucial) link in the evolutionary chain? Much depends on how we perceive the line between the normal and the abnormal, the typical and the atypical, whether we approach genetics solely from a scientific standpoint or broaden our understanding to take in social, cultural, and political factors.

When Steve was around 10, a doctor informed him and my parents that he most likely had a genetic disorder called Marfan syndrome. Suddenly, the idea of physical normalcy became deeply and personally relevant. My brother’s life story had converged with the story of genetic medicine.

Victor McKusick was one of the founders of medical genetics, and for many years, he was my brother’s doctor. At Baltimore’s Johns Hopkins Hospital in the 1950s, he encountered cases of Marfan, including one involving a patient with a serious heart anomaly. The patient was tall and gangly, with disproportionately long fingers and limbs, and had dislocated eye lenses. He looked malnourished, but he wasn’t. At the time, little was known about Marfan, named in 1896 after the French pediatrician who first documented its distinctive features. By the late 1930s, it had been determined that Marfan was an autosomal dominant hereditary trait, meaning that it’s expressed with only one copy of the gene from a parent. McKusick would later trace his professional legacy, in part, to this patient’s bedside. He was awed by the “intricate jigsaw puzzle” of connective tissue, in general, as well as the syndrome’s flamboyantly diverse manifestations and the questions that it raised. Genetically, how could being tall relate to catastrophic heart failure? Why would someone with an eye problem have long fingers?

McKusick had no platform on which to study Marfan or, as he called it, “the Marfan.” The term medical genetics had been knocking around for decades, but it wasn’t a discrete discipline. Hopkins was a good incubator for the emerging field because different specialists mingled in its cafeterias and corridors, and as McKusick saw it, genetics gave a doctor “license to swashbuckle through all of medicine.” Throughout his career, he described his work like this, as an invitation to “go on safari” intellectually, to delve into the invisible, uncharted world of the chromosome as if he were a global adventurer. After he arrived in Baltimore in 1943, he never left. Hopkins was “on the trade routes,” he said. “Thus I could pitch my tent beside the road and keep in touch with what was going on in far off Cathay without ever traveling there myself.”

Doctors usually saw people with Marfan as eye or orthopedic patients, but McKusick, ingeniously, redefined them as genetics patients with a genetic affliction. McKusick hypothesized that the gene in question must control the production of connective tissue. Problems arising from abnormalities in this gene can range from the innocuous (stretch marks after pregnancy) to the lethal. A human heart beats around three billion times in an average life, and over time, the force of a Marfan patient’s own pulse can catastrophically tear the aorta. It’s a paradox that Marfan is one of the most common single-gene disorders and yet one of the stealthiest, even to a physician. You’ve probably met people with this condition and haven’t known it; they may not know they have it themselves. Early studies of Marfan patients record deaths out of the blue. One dropped dead in the middle of a job interview, another after completing a high dive at a pool. Sportswriter Grant Wahl had undiagnosed Marfan and died suddenly while covering the 2022 World Cup.

At Hopkins, McKusick “collected a large number of Marfan patients.” He pored over medical files and amassed cases from every department. He also mined records at the Baltimore morgue for instances of coronary dissection, a condition that results from a tear in the wall of one of the heart’s arteries. In 1955, he described 74 Marfan cases and related disorders in what remains a flagship work in the field of medical genetics, Heritable Disorders of Connective Tissue. Two years later, he gave the emerging field an institutional home: the Moore Clinic at Hopkins, now the McKusick-Nathans Institute. The clinic had previously focused on chronic diseases like syphilis, but McKusick reasoned that genetic defects were the “ultimate chronic disease” and nudged syphilis aside to make room for medical genetics.

To move his work forward, McKusick needed access to contained, insular communities, characterized by intermarriage, where rare recessive genes were likelier to get expressed. In correspondence, this generation of geneticists would make comments such as, “On the wildcat road of the stony fork this afternoon, I found a nice trait of deaf-mutism,” and “Did you happen to see the Newsweek … in which there was a picture of a dwarf?” Well into the 1980s, McKusick made research trips into the Amish communities of Lancaster, Pennsylvania. He got a fundamentally “different concept of people,” he said, when he saw them “in situ”—nested in their lives, observing genetic anomaly in its habitat, where any number of stories about atypical bodies could be told. In her 2005 book, Moments of Truth in Genetic Medicine, science historian M. Susan Lindee describes the gossipy intimacy that McKusick enjoyed with many families, allowing him to collect blood and urine samples, family genealogies recorded in Bibles, and intimate secrets. His field notes are interspersed with various personal details: how he bought brooms from one family, purchased jams on his way home from another, and was “bitten by a small dog” during an interview.

Yet McKusick also needed access to urban populations. Medical geneticists could familiarize themselves with rare genetic disorders only in places densely populated enough to yield more than one or two cases. In August 1957, he offered a certain Miss Hawkins a job as a “pedigree-tracer” in the newly formed Division of Medical Genetics at the Hopkins medical school. Hawkins would gather “extensive information on members of families of persons with various hereditary diseases” by driving around Baltimore, collecting biographical and medical information, drawing blood, taking urine samples, and abstracting families’ physician reports and medical records. To do this work, as McKusick described it, Hawkins would have to obtain “the rapport and cooperation of the family.” Some cases required extraordinary finesse, since mutations might expose through the back door the open secret of infidelity. “Illegitimacy is so much more frequent than mutation,” McKusick wrote. Data collection in these cases required the “utmost tact and resourcefulness.” Indeed.

In the years that followed, McKusick’s growing number of colleagues generated data on Marfan and other genetic conditions in a variety of ways. For one study, they took measurements of 2,100 children in Baltimore’s public schools. In a festschrift published in 2012, British geneticist Malcolm A. Ferguson-Smith described how McKusick designed a study of chromosomal abnormalities that involved surveying “delinquent boys, county schools, and pediatric clinic populations” in Baltimore. By the early 1960s, “state institutions for the mentally retarded [had become] intellectually exciting places,” McKusick wrote in a 1975 survey of his field published in the American Journal of Human Genetics. His colleagues had discovered two new genetic syndromes through research at Rosewood, Maryland’s home for the “mentally retarded.” The patients’ specific treatment was not thereby “altered one whit,” but the institutions received attention and became something “other than the equivalent of pesthouses.” Conditions there may not have changed, but as McKusick saw it, genetic research reintegrated these exiled patients into the human population.

That language is jarring to 21st-century ears and ethics, as are the methodologies: trawling at public schools, reform schools, and state institutions for research subjects, or traveling the streets of Baltimore to collect samples. Keep in mind, this was before standardized HIPAA, or codified informed consent and institutional review boards. But for atypical humans like my brother, McKusick’s approach was turning perceptions away from spectacle. He repudiated older moral judgments that hereditary afflictions among children were the result of parental vices or failings. McKusick and his colleagues replaced this 19th-century narrative of parental sin and genetic retribution with an equally powerful yet morally disinterested clinical gaze.

Eventually my brother was among those collected. When he was diagnosed, Steve’s narrative about himself began to change. Having a genetic condition transliterated physical eccentricity into affliction, a rare genetic case. This wasn’t an inconsequential semantic matter, either for Steve, who had a life to navigate, or for McKusick, who had an ambitious new field of knowledge to advance against the indifferent and skeptical. Being physically atypical means you’re going to be looked at—it’s only a question of how (imagine never being able to blend into a crowd or be physically anonymous when you want to). McKusick tried to ensure that his patients were looked at in a particular way. For him, humans were not normal or abnormal; they existed on a continuum. He deliberately spoke of “instructive” cases, not “interesting” cases—the former emphasized a clinical sensibility; the latter, something closer to carnival freak shows.

I looked up to Steve, in both senses. He was my big brother in height and age. To me, he was normal—or as normal as anything else, since the term had no valence.

But doctors, and medicine, enjoyed a great deal of power and latitude all the same. In the 1950s, doctors were at the height of their cultural mystique and authority, and my mother delivered Steve into their arms on the expectation of merciful omnipotence. McKusick’s medical genetics course at Hopkins included the study of Baltimore families with hereditary disorders. For one assignment, he instructed, “students may wish to call in children who are affected with the Marfan syndrome. … The primary purpose would be to compare the growth characteristics of this group with normal data and with their normal sibs.” Steve was among the children summoned, and one day, he and our mother stood center stage in an amphitheater, where doctors pointed out to other doctors the physical traits of Marfan. “I didn’t realize there would be so many people,” my mother recalled, and she was intimidated—but compliant. It didn’t occur to anyone involved to question the psychological wisdom of this exhibition. My mother remembered only that “they kept talking about how long Steve’s arms were, and pointing.” My brother wasn’t presented as a carnival freak or the incarnation of parental sin but as a medical genetics subject, and that difference must have mattered—being gawked at and being studied can’t possibly feel the same. But neither can they feel entirely different.

It was the gene that had caused things to happen, not context, social attitudes, or people’s behavior. Steve embraced this idea, believing that his identity was both fixed and unfixable. The thought grew in his mind that he was a sort of transcriptional error—a fateful typo, if not a full-blown mistake. Steve used the term mutation a lot. By the time he reached high school, he seemed to have decided that he didn’t have a mutation; he was a mutation. Being almost 12 years younger than Steve and still in a somewhat feral stage, I provided a refuge for him—I had no demeaning agenda of pity or largesse. I looked up to Steve, in both senses. He was my big brother in height and age. To me, he was normal—or as normal as anything else, since the term had no valence. He used to play a terrifying zombie game with me: he’d go outside, knock on our door, stand there mutely with dead, unblinking eyes, arms extended straight out, and then he’d lurch at me like Frankenstein’s monster, never saying a word. I’d scream every time he did this, in turn terrifying my older sister, who would scold me for saying “there’s a monster in the house” when it was only Steve.

I understand the zombie game better, or at least differently, today. A fledgling genetics journal, founded in 1968, called itself Teratology, from the Greek for “the study of monsters.” The title, in turn, echoed prodigy books of early-modern Europe that interpreted unusual or extraordinary natural events and attributed imperfecta—abnormal human bodies—to supernatural causes. The atypical was monstrous, yes, but also powerful, imbued with a darkly divine provenance. Maybe this was the kind of power that Steve wanted to possess, play with, and inhabit; maybe it was the story of mutation that he preferred.

In high school, Steve was neither physically abnormal enough to be swaddled in pity nor normal enough to be ignored. This made him a prime target for bullying. Every day, he ran a gauntlet of jeers and taunts, a crucible imagined and reenacted long into adulthood. The bullying he suffered, like all bullying, was about the enforcement of normalcy and its authority—and some of the early figures in genetic medicine would pretty much have agreed with the self-loathing and genetic judgment that my brother applied to himself. They saw genetic medicine as aspiring toward the same goal: the dominance of the normal. In a 1950 paper, “Our Load of Mutations,” for example, American geneticist (and eugenicist) Hermann Joseph Muller outlined his vision of an ideal “all-normal man.”

But McKusick thought differently. He was a clinician, not a genetic idealist like Muller, and he envisioned a zone of normalcy, running from “normal or unaffected individuals” on one side to “affected individuals” on the other. In the middle are mildly affected individuals in a “zone of overlap,” where they can’t even be “recognized as abnormal.” Indeed, before the mapping of the human genome, genetic passing was possible. Doctors might know that a gene was involved in some disorder, but not its location. Besides, no genetic testing was yet available. This ambiguity was especially true with Marfan, which has a vast range of expressivity—the degree to which a genotype, the genetic code, is evident in the phenotype, the individual’s body. McKusick always suspected that Abraham Lincoln had Marfan and wanted to get a biological sample to confirm his hunch. (He never succeeded.) But other cases of the disease are more self-evident, such as that of a baby with Marfan who, McKusick wrote, died at eight months, the child’s heart so overactive that it caused the bed to shake. The atypical body can be lethally crippling or profitably exotic—a deadly genetic trait passing as a lucrative asset. Sometimes, it can be both. Genetically “perfect” bodies can be impeccably normal or spectacularly atypical—athletic and tall enough for someone to play in the NBA or become a supermodel.

McKusick respected this ambiguity. In a 1969 textbook, he warned that “the dividing line between normal and abnormal variation is not fixed; indeed no dividing line exists. ‘Disease’ or ‘dis-order’ are not easily defined terms. Variation in one environment or social setting may be considered pathologic, where in another it may be advantageous. Keep in mind a variation constitutes a continuum.” Even so, harsher and more rigid attitudes toward those who lived outside the zone of normalcy kept insinuating their way back into the field of genetic medicine, past checkpoints of delicacy, tact, and sophisticated reasoning. In his 2012 book, The Science of Human Perfection, historian Nathaniel Comfort asserts that the boundary between eugenics and medical genetics was ideologically membranous. The medical geneticist’s goal of alleviating individual human suffering and the eugenicist’s goal of populational betterment were subtly interleaved throughout the 20th century, and the origin story of McKusick as the “father of medical genetics” created a useful but misleadingly clean break between the two. Comfort isn’t alleging that medical geneticists were eugenics advocates; indeed, McKusick couldn’t have condemned eugenics any more passionately than he did, discrediting the idea as “abominable” and “outrageous.” And in the clinic, when he encountered Steve, McKusick was concerned about his well-being rather than atypicality. He wasn’t striving for Steve to be normal but to have a full and long life.

So, the border drawn by medical geneticists against eugenicists was an adamantly sincere one—yet difficult to patrol. McKusick wrote expansively about the “mutational repertoire of man,” but even he championed the study of the “morbid map” of abnormal genes by noting how much that map could elucidate the normal. However sincere the intention to speak of variation and not aberration, genetic language was getting powerfully magnetized toward the poles of normal and abnormal. And in a 1973 volume edited by McKusick, contributor F. Clarke Fraser wrote, “If we are to aim at reducing the amount of ill health caused by deleterious genes we must aim at avoiding their transmission … by reducing the likelihood that [the ‘abnormal infant’] will be born or even conceived.” Fraser thought it “perfectly proper,” when counseling couples, “to say the equivalent of, ‘Now be quite sure that you have really thought about what another defective child would mean.’ ” He wrote also of the “deformed or diseased child.” However benevolent the intention, it’s hard to discern in this comment where the alleviation of human suffering ends and human improvement begins. As Comfort writes, “What they called preventive eugenics we today would call prenatal diagnosis with therapeutic abortion.”

As an adult, Steve was no longer an object of ridicule; he became merely “the tall guy.” For Steve, the world was a Procrustean exercise and puzzle. How could he better conform himself to its circumscriptions, spaces, boundaries, and limits? “I wish I could hack off the middle part of my legs,” he’d say—this wasn’t the ecumenical view of genetic variation that McKusick tried to champion. Barring a leg hack, how would he make himself fit? This was a literal question he had to answer every day, as he ducked to fit through doors, slumped into sofas to shrink himself down, stooped to look in a mirror or read a sign, tucked in his legs and arms on crowded trains. He custom-designed his bicycles; he shifted car seats as far back as they would go; he moved quickly, masking conspicuousness with speed, making himself a blur—bounding headlong through crowds, long limbs flying and head ducked. He shopped for groceries late at night to avoid people. And he leaned over hundreds of pool tables, many thousands of times.

The struggle to fit provoked an ambient envy in his life, and the idea of a deranged genetic code—“all the luck of the dice,” he’d say—deepened the existential injustice.

In his 20s, Steve was already an indefatigable pool player, on his way to becoming a nationally ranked amateur. I would hear him practicing in the basement, billiard balls making contact and plopping into a pocket, one after another after another. He was so good, even at the start—long fingers, able to make a beautiful bridge, such fluidity in his stroke. He could lean into shots and over tables better than anyone. This suited him. A billiards stance while shooting takes a good several inches off your height. You’re leaning, with cue in hand, and no one is likely to notice how long your legs are in that position. But if they notice how long your arms are, all the better. It’s an advantage. For Steve, pool took physical ungainliness and made it liquid, turned it into something elegant, beautiful, and normal. He was momentarily in conformity with a material world that otherwise almost cropped him. The sport sparked a psychological and a physical transformation in Steve. As he got better, he would talk about “mental toughness.” What it meant to him, specifically, was the capacity to be in control of which balls went where, in what order, and how the game unfolded and ended, entirely under his code and design.

The struggle to fit provoked an ambient envy in his life, and the idea of a deranged genetic code—“all the luck of the dice,” he’d say—deepened the existential injustice. Those who covet the normal, by definition, are unrelievedly confronted by the thing they covet every single day. For Steve, the subtractive simplicity and modesty of his longing only made it worse. Unlike the person who envies extraordinary physical traits, athleticism, or beauty and must seek them out—at stadiums, on movie screens, in magazines—Steve found hundreds of objects of ordinary desire in each moment. How many of us come to feel, as Steve did, that we’re waging the same struggle with normalcy to some lesser degree or another; that having a typical body, be it typical in weight, height, the construction of limbs, the proportion of limbs to torso, the angle of facial features and cheekbones, the straightness of the spine, the clearness of the skin, the size of the breasts, the daintiness of the nose, or the bulk of the muscles, would resolve our lives and set things straight? I learned from him that normal is the most profoundly craved thing when we don’t have it and the most effortlessly ignored thing when we do.

Steve and McKusick were obsessed with mutations, albeit in different ways. One Christmas, McKusick sent us a beautiful card featuring an image of Madonna and child, but the Madonna was an Amish mother with Ellis-van Creveld syndrome, a rare dwarfism, who had an extra digit on both hands.

The early phases of his work were about observing and cataloging. McKusick always had a camera with him. Every person he met was part of his fieldwork. He took photographs of my parents once, when their paths crossed at a party. McKusick engaged in more systematic cataloging on the first Wednesday of each month, when his colleagues gathered at his home in the verdant, affluent Baltimore neighborhood of Guilford. As they drank coffee and enjoyed homemade sticky buns, they prepared index cards summarizing articles in medical journals pertinent to genetic conditions. These index cards became the first entries in the groundbreaking Mendelian Inheritance in Man, known today as the OMIM (the O standing for “online”). It’s the definitive database of human genetic identity—hailed as “the bible of clinical genetics”—with entries on 16,000 genes. Steve is #154700.

McKusick considered this work one of his most important achievements, yet it was still what he called an “encyclopedia of phenotypes”—and looks deceive. McKusick tellingly compared the distinction between genotype and phenotype to that of a person’s “character and reputation. Genotype and character are what one really is. Phenotype and reputation are what one appears to be.” A reputation can lie, but character cannot. Our authentic identity resides in DNA. It’s almost as if in cases of genetic passing, the phenotype has pulled one over on the genotype: appearance is a trick of the eye, or an act of diagnostic treachery.

At a conference on birth defects, McKusick famously elaborated this point with reference to “lumpers and splitters.” He argued that doctors were often guilty of “lumping” patients into one syndrome because of physical similarities, or “excessive and improper splitting” of patients with the same genetic disorder into separate identities because of physical variations. We are what our genes say we are. Those working on genes had become impatient with gray zones: “Disease A and Disease B are either the same disease, if they are based on the same mutation, or different diseases.” And if this was so, McKusick concluded, then what he really needed wasn’t an encyclopedia.

He needed a map.

Some of McKusick’s colleagues viewed his aspiration to locate and map every disease-causing gene as dilettantism akin to stamp collecting and about as edifying as bricklaying. In August 1968, a Newark Evening News reporter likened McKusick’s annual Bar Harbor “short course” on medical genetics to the engrossing pointlessness of counting angels on the head of a pin. What did the discovery of a defective gene for “the circus-rubber-man syndrome” gain humanity in comparison with other research? A doctor who played agent provocateur at the course lectured that most of the information harvested by medical genetics had no practical application, was “not very interesting,” and was largely “a waste of time.” But none of this extinguished McKusick’s “burning interest in mapping.” So often a momentous, paradigm-shifting idea gets smuggled inside a cozy metaphor, and this was true for genetic medicine. In 1975, New York Times science reporter Harold Schmeck Jr. did much to popularize a gene-centric worldview by drawing heavily on McKusick’s adventurous notion of himself as a voyager to “chromosomal continents,” the expeditionary mapmaker of “uncharted terrain.”

Steve continued to visit McKusick at Hopkins mostly to determine whether his aorta was dilating. Steve admired and spoke highly of McKusick. He found him gracious and well mannered, calm and tolerant. At a checkup in the 1980s, McKusick asked Steve what he was up to. My brother was early into his 33-year career as a cartographer with the federal government. “The two of us are not so different,” McKusick said. “I’m a cartographer, too. I map genes.” This made him the cartographer of my cartographer brother’s affliction. I used to think that Steve liked maps because their point of view normalized his own. In cartography, the view from high up is the privileged one. As for McKusick, he later wrote, “I am not certain why … I became enthralled with mapping genes on human chromosomes.” It would be useful for “understanding the basic derangements in birth defects,” but his inspirations were also visceral. There “are people, and I am one, for whom mapping has an intrinsic attraction.”

The completion of the genome map gave a powerful boost to the authority of the genetic code as a set of instructions for our identities. In McKusick’s term, a map “confers a concreteness” to genetics. Before the map existed, a patient with mild symptoms could still pass as genetically normal and the concept of physical normalcy itself maintained a tensile ambiguity owing to incomplete genetic knowledge. But as it became apparent that the human genome would be decoded in his lifetime, McKusick, an instinctive humanist, anticipated that the future of genetic medicine would seek to accommodate, not edit, human variation (although he did predict “gene surgery” as early as 1981). It would involve “gene screens” and “interpreting the results to individuals, and designing programs to make the most of the strong points … and to avoid troubles from some of the weak points.” McKusick believed that maps drew and bound people together—not genotypical subgroups, but all of us.

Inevitably, though, maps define boundaries that group people within and exclude them without. People create maps, and then maps create them. In the 1990s, epidemiologist Abby Lippman criticized the genome map for defining normal and abnormal as a genetic construct, not a social one. Yet mapping is, as much as anything else, a political and cultural project. The genetic normal began as a gray zone. Then it became a binary, and then, over time, with the genome mapped, it became slyly normative. James Watson, the co-discoverer of DNA structure, wrote in 1995 that “the genetic dice will continue to inflict cruel fates on all too many individuals. … Decency demands that someone must rescue them from genetic hells.” In milder terms, the United States Office of Technology predicted, also in 1995, that the Human Genome Project eventually would mean that each of us has “a paramount right to be born with a normal, adequate, hereditary endowment.” In a 1993 New York Times advertising supplement, the March of Dimes described its quest for “perfectly beautiful” and “beautifully perfect” babies—the two standards transposed—“born free of sickness and disability.” Underlying this ideal, wrote feminist scholar Joan Rothschild, is the “imperfect child … who cannot be allowed to happen.”

At one time, these statements were hypotheticals, albeit disturbing ones, but now the innovation to support them is here. Science gallops ahead of ethics. It’s tempting to analogize the relationship between the two to an exquisite, impeccably designed sportscar—a McLaren or a Bugatti—that’s put in the hands of a 16-year-old, who then totals it. After the discovery of a gene responsible for a common form of dwarfism, a scientist went to the annual Little People of America convention and saw a dwarf wearing a T-shirt that said, “Endangered Species.”

Toward the end of his life, McKusick seemed to be grappling with problems of human empathy and solidarity that his own work as a founder of genetic medicine had provoked. Did the “mere existence” of the map pose a danger per se, if it risks “distort[ing] the way we think about ourselves and our fellow human beings?” McKusick warned of the “absurdity of determinism, that what we are is a direct and inevitable consequence of what our genome is.” He also worried about “the absurdity of reductionism,” a “misconception that we … know everything it means to be human.” We may lose “profound respect” for the genetic variability that benefits both the species and the individual. The “genetical-commercial complex,” he said, might lead to “the Madison Avenue type of pressure” for couples to make “value judgments” on gametes that would corrode meaningful freedom of choice. “In this era of growing scientific sophistication,” McKusick said in a 1997 interview, “people need to learn to look through a variety of lenses to understand what’s happening.”

How did a gene-centric worldview change perceptions for the physically atypical? For Steve, did it matter to know the mapped location of his mutated gene? Did DNA tell him who he was and write his biography? Did that knowledge afford him absolution, fortitude, insight, solace, or self-knowledge? I think that it did, and it didn’t. Genetic medicine was a double helix that translated everything into nothing and nothing into everything. One story about Steve, and a plausible one, is that the nothing of a minuscule genetic typo became the everything of his fate. His genetic code became the scrivener of his life—and of his sudden death. He died in 2015, just two days shy of his 60th birthday. The cause was a birth defect, inscribed by a gene: his aorta dissected while he was on his daily 30-mile bike ride. He had lived his life with a genetic condition that someday could kill him. Then that someday arrived. Even in death, his genetics dictated things: cremation was delayed because Steve’s body was too long for the standard crematory.

It’s incomprehensibly lopsided—a fate determined by one wrongly transcribed gene in the equivalent of 300 volumes of code. The gene is located at 15q21.1: it’s on the long arm (q) of chromosome 15, at band 21 and sub-band 1. The gene’s molecular location is from base pairs 48,408,306 to 48,645,788. These 237,482 base pairs, like all others, are built of four nucleotides that must be arranged in a precise sequence for the gene to work. In this case, the amino acids are strung together to create fibrillin-1. At position 6169 on this gene, a C (cytosine) is replaced by a T (thymine). Geneticists note the change as “FBN1 Exon 50/c.6169C>T; Arg2057Term.” Because of this genetic typo, an amino acid down the line gets a STOP instead of a GO message. As with Christmas tree lights, one faulty bulb causes the entire string to short out.

One story about Steve is that the nothing of a minuscule genetic typo became the everything of his fate. His genetic code became the scrivener of his life—and of his sudden death.

In December 2013, more than 50 years after he was diagnosed with Marfan and just 20 months before it killed him, Steve got confirmation from the Connective Tissue Gene Tests laboratory in Allentown, Pennsylvania, that he did, indeed, have Marfan syndrome. Then again, McKusick had known it decades ago—just by looking at Steve. The record from my brother’s last visit at Hopkins noted that he was “diagnosed long ago based on clinical features by Dr. Victor McKusick.” Steve’s genetic code might have been a nothing that became everything, but it was also an everything that became nothing. Genes don’t tell us who we are; how we tell about genes tells us who we are. This was McKusick’s insight, now in ethical remission—that much depends on how we create habitats and tell stories, on how much we embrace atypicality as part of a shared human experience rather than a deviation to be palliatively edited. It’s the difference between seeing a little person as locked in a “genetic hell” or as an example of natural variation.

When Jennifer Doudna, the co-inventor of CRISPR, won the Nobel Prize for chemistry in 2020, along with Emmanuelle Charpentier, the committee enthused that their work was about “rewriting the code of life.” McKusick was a first step in that process; one of his patients, my brother, rewrote the code of a life—his own. In Sapiens, historian Yuval Noah Harari describes the revolution of more than 70,000 years ago, when humans developed the capacity to tell fictional stories and communicate about things that don’t exist. Ever afterward, we have lived in a “dual reality,” of things real and imagined. This sounds like an evolutionary liability. Someone who imagines unicorns squanders time away from prime directives of reproduction and survival. But the opposite is true, Harari asserts, because stories allow humans to bypass the genome. Through storytelling, we can alter behavior quickly and transmit new behaviors to the next generation. We create solidarities and communities around a god, a flag, an idea, or a logo. Other social animals can change only when their DNA changes through a protracted, uncertain evolutionary process in which their behavior is “determined to a large extent by their genes,” Harari writes.

The stories Steve told to himself about himself as an adult bypassed DNA and moved more quickly than mutation, and this made him an early resister to genetic determinism. Although he never stopped jumping at the shadow of the person he was at 15, he embraced ideas and places that freed him from the genome’s conceits. His pool game, where his body fit with the table and motions; libertarianism, with its ferocious individualism that removed genetic determinism, or any kind of determinism, from the equation; and a virtual life that removed physical normalcy, or any kind of physicality, from the picture. Also, he loved sports. He looked always for moments of belonging and found them in the tribe of fans. Steve sent me an email after a memorable Baltimore Ravens victory in 2000 and described how all the fans had felt the energy—“70,000, as one.” As cartographers, my brother and his doctor preferred the painstaking labor of observing and charting variations and then drawing them together into a whole. Sports, not mutations. I learned only at Steve’s memorial service from his acquaintances and colleagues that he had never once mentioned Marfan, the genetic story of his life, to any of them.

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Pamela Haag is the author of Marriage Confidential, The Gunning of America, and most recently, Revise.


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