The Gene

by Siddhartha Mukherjee

  While Spider-Man and Fantastic Four introduced the mutant superhero to the American public, the X-Men, launched in September 1963, brought the mutant story to its psychological crescendo. Unlike its predecessors, X-Men’s central plot concerned a conflict between mutants and normal humans. The “normals” had grown suspicious of the mutants, and the mutants, under fear of surveillance and the threat of mob violence, had retreated to a cloistered School for Gifted Youngsters designed to protect and rehabilitate them—a Moore Clinic for comic-book mutants. The most remarkable feature of X-Men was not its growing, multifarious menagerie of mutant characters—a wolf man with steel claws or a woman able to summon English weather on command—but the reversed roles of the victim and the victimizer. In the typical comic book of the fifties, humans ran and hid from the terrifying tyranny of monsters. In X-Men, the mutants were forced to run and hide from the terrifying tyranny of normalcy.

  These concerns—about imperfection, mutation, and normalcy—leaped out of the pages of comic books into a two-foot-by-two-foot incubator in the spring of 1966. In Connecticut, two scientists working on the genetics of mental retardation, Mark Steele and Roy Breg, aspirated a few milliliters of fluid containing fetal cells from the amniotic sac of a pregnant woman. They grew the fetal cells in a petri dish, stained the chromosomes, and then analyzed them under a microscope.

  None of these individual techniques was novel. Fetal cells from the amnion had first been examined to predict gender (XX versus XY chromosomes) in 1956. Amniotic fluid had safely been aspirated in the early 1890s, and the staining of chromosomes dated from Boveri’s original work on sea urchins. But the advancing front of human genetics changed the stakes of these procedures. Breg and Steele realized that well-established genetic syndromes with evident chromosomal abnormalities—Down, Klinefelter, Turner—could be diagnosed in utero, and that pregnancy could voluntarily be terminated if fetal chromosomal abnormalities were detected. Two rather trivial and relatively safe medical procedures—amniocentesis and abortion—could thus be combined into a technology that would vastly exceed the sum of the individual parts.

  We know little of the first women to pass through the crucible of this procedure. What remains—in the barest sketches of case reports—are stories of young mothers faced with terrifying choices, and their grief, bewilderment, and its reprieve. In April 1968, a twenty-nine-year-old woman, J.G., was seen at the New York Downstate Medical Center in Brooklyn. Her family had been crisscrossed with a hereditary variant of Down syndrome. Her grandfather and her mother were both carriers. Six years earlier, late in pregnancy, she had miscarried one child—a girl—with Down syndrome. In the summer of 1963, a second girl was born, a healthy child. Two years later, in the spring of 1965, she gave birth to another child—a boy. He was diagnosed with Down syndrome, mental retardation, and severe congenital abnormalities, including two open holes in his heart. The boy had lived for five and a half months. Much of that brief life had been miserable. After a series of heroic surgical attempts to correct his congenital defects, he had died of heart failure in the intensive care unit.

  Five months into her fourth pregnancy, with this haunted history in the backdrop, J.G. came to her obstetrician and requested prenatal testing. An unsuccessful amniocentesis was performed in early April. On April 29, with the third trimester rapidly approaching, a second amniocentesis was attempted. This time, sheets of fetal cells grew out in the incubator. Chromosomal analysis revealed a male fetus with Down syndrome.

  On May 31, 1968, on the very last week that abortion was still medically permissible, J.G. decided to terminate the pregnancy. The remains of the fetus were delivered on June 2. It bore the cardinal characteristics of Down syndrome. The mother “withstood the procedure without complications,” the case report states, and she was discharged home two days after. Nothing more is known about the mother or her family. The first “therapeutic abortion,” performed entirely on the basis of a genetic test, entered human history shrouded in secrecy, anguish, and grief.

  The floodgates of prenatal testing and abortion were thrown open in the summer of 1973 by an unexpected maelstrom of forces. In September 1969, Norma McCorvey, a twenty-one-year-old carnival barker living in Texas, became pregnant with her third child. Penniless, often homeless, and out of work, she sought an abortion to terminate the unwanted pregnancy, but was unable to find a clinic to perform the procedure legally or, for that matter, sanitarily. The one place she found, she later revealed, was a closed clinic in an abandoned building, “with dirty instruments scattered around the room, and . . . dried blood on the floor.”

  In 1970, two attorneys brought her case against the state to a Texas court, arguing that McCorvey had a legal right to her abortion. The nominal defendant was Henry Wade, the Dallas district attorney. McCorvey had switched her name for the legal proceedings to a bland pseudonym—Jane Roe. The case—Roe v. Wade—moved through the Texas courts and climbed to the US Supreme Court in 1970.

  The Supreme Court heard oral arguments for Roe v. Wade between 1971 and 1972. In January 1973, in a historic decision, the court ruled for McCorvey. Writing the majority opinion, Henry Blackmun, associate justice of the Supreme Court, decreed that states could no longer outlaw abortions. A woman’s right to privacy, Blackmun wrote, was “broad enough to encompass [her] decision whether or not to terminate her pregnancy.”

  Yet a “woman’s right to privacy” was not absolute. In an acrobatic attempt to counterbalance a pregnant woman’s rights against the growing “personhood” of the fetus, the Court found that the state could not limit abortions during the first trimester of pregnancy but that as the fetus matured, its personhood became progressively protected by the state, and abortions could be restricted. The division of pregnancy into trimesters was a biologically arbitrary, but legally necessary, invention. As the legal scholar Alexander Bickel described it, “The individual’s [i.e., mother’s] interest, here, overrides society’s interest in the first three months and, subject only to health regulations, also in the second; in the third trimester, society is preeminent.”

  The power unleashed by Roe reverberated swiftly through medicine. Roe may have handed reproductive control to women, but it had largely handed the control of the fetal genome to medicine. Before Roe, prenatal genetic testing had inhabited an uncertain limbo: amniocentesis was permitted, but the precise legal stature of abortion was unknown. But with first- and second-trimester abortion legalized, and the primacy of medical judgment acknowledged, genetic testing was poised to diffuse widely through clinics and hospitals around the nation. Human genes had become “actionable.”

  The effects of widespread testing and abortion were soon evident. In some states, the incidence of Down syndrome fell between 20 and 40 percent between 1971 and 1977. Among high-risk women in New York City, more pregnancies were terminated than carried to full term in 1978.II By the mid-1970s, nearly a hundred chromosomal disorders, and twenty-three metabolic diseases, were detectable by genetic testing in utero, including Turner and Klinefelter syndromes and Tay-Sachs and Gaucher’s disease. “Tiny fault after tiny fault,” medicine was sifting its way “through the risk of several hundred known genetic diseases,” one geneticist wrote. “Genetic diagnosis,” as one historian described it, “became a medical industry.” “The selective abortion of affected fetuses” had transformed into “the primary intervention of genomic medicine.”

  Invigorated by its capacity to intervene on human genes, genetic medicine entered a period of such headiness that it could even begin to rewrite its own past. In 1973, a few months after Roe v. Wade, McKusick published a new edition of his textbook on medical genetics. In a chapter on the “prenatal detection of hereditary diseases,” Joseph Dancis, the pediatrician, wrote:

  In recent years the feeling has grown among both physicians and the general public that we must be concerned not simply with ensuring the birth of a baby, but one who will not be a liability to society, to its parents, or to itself. The “right to be born” is be
ing qualified by another right: to have a reasonable chance of a happy and useful life. This shift in attitude is shown by, among other things, the widespread movement for the reform or even the abolition of abortion law.

  Dancis had gently, but deftly, inverted history. 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.

  In June 1969, a woman named Hetty Park gave birth to a daughter with infantile polycystic kidney disease. Born with malformed kidneys, the child died five hours after birth. Devastated, Park and her husband sought the counsel of a Long Island obstetrician, Herbert Chessin. Assuming, incorrectly, that the child’s disease was not genetic (in fact, infantile PKD, like cystic fibrosis, results from two copies of mutated genes inherited from the child’s parents), Chessin reassured the parents and sent them home. In Chessin’s opinion, the chance that Park and her husband would have another child born with the same illness was negligible—possibly nil. In 1970, following Chessin’s counsel, the Parks conceived again and gave birth to another daughter. Unfortunately, Laura Park was also born with polycystic kidney disease. She suffered multiple hospitalizations and then died of complications of kidney failure at age two and a half.

  In 1979, as opinions such as Joseph Dancis’s began to appear regularly in the medical and popular literature, the Parks sued Herbert Chessin, arguing that he had given them incorrect medical advice. Had the Parks known the true genetic susceptibilities of their child, they argued, they would have chosen not to conceive Laura. Their daughter was the victim of a flawed estimation of normalcy. Perhaps the most extraordinary feature of the case was the description of the harm. In traditional legal battles concerning medical error, the defendant (usually the physician) stood accused of the wrongful causation of death. The Parks argued that Chessin, their obstetrician, was guilty of the equal and opposite sin: “the wrongful causation of life.” In a landmark judgment, the court agreed with the Parks. “Potential parents have a right to choose not to have a child when it can be reasonably established that the child would be deformed,” the judge opined. One commentator noted, “The court asserted that the right of a child to be born free of [genetic] anomalies is a fundamental right.”

  * * *

  I. The abnormal chromosomal number in Down syndrome was discovered by Jérôme Lejeune in 1958.

  II. Across the world too, the legalization of abortion opened the floodgates for prenatal testing. In 1967, a parliamentary act legalized abortion in Britain, and prenatal testing rates and pregnancy termination rates increased dramatically in the 1970s.

  “Interfere, Interfere, Interfere”

  After millennia in which most people have produced babies in happy ignorance of the risks they run, we may all have to start acting with the severe responsibility of genetic foresight. . . . We never had to think about medicine like this before.

  —Gerald Leach, “Breeding Better People,” 1970

  No newborn should be declared human until it has passed certain tests regarding its genetic endowment.

  —Francis Crick

  Joseph Dancis was not just rewriting the past; he was also announcing the future. Even a casual reader of the extraordinary claim—that every parent had to shoulder the duty to create babies “who will not be a liability to society,” or that the right to be born without “genetic anomalies” was a fundamental right—might have detected the cry of a rebirth within it. This was eugenics being reincarnated, if more politely, in the late half of the twentieth century. “Interfere, interfere, interfere,” Sidney Webb, the British eugenicist, had urged in 1910. A little more than six decades later, the legalization of abortion and the growing science of genetic analysis had provided the first formal framework for a novel kind of genetic “interference” on humans—a new form of eugenics.

  This—as its proponents were quick to point out—was not your Nazi grandfather’s eugenics. Unlike American eugenics of the 1920s, or the more virulent European strain of the 1930s, there were no enforced sterilizations, no compulsory confinements, and no exterminations in gas chambers. Women were not sent away to isolation camps in Virginia. Ad hoc judges were not called in to classify men and women as “imbeciles,” “morons,” and “idiots,” nor was chromosome number decided as a matter of personal taste. The genetic tests that formed the basis of fetal selection were, its proponents insisted, objective, standardized, and scientifically rigorous. The correlation between the test and the development of the subsequent medical syndrome was nearly absolute: all children born with an extra copy of chromosome twenty-one or a missing copy of the X chromosome, say, manifested at least some of the cardinal features of Down or Turner syndrome respectively. Most important, prenatal testing and selective abortion were performed with no state mandate, no centralized directive, and with full freedom of choice. A woman could choose to be tested or not, choose to know the results or not, and choose to terminate or continue her pregnancy even after testing positive for a fetal abnormality. This was eugenics in its benevolent avatar. Its champions called it neo-eugenics or newgenics.

  A crucial distinction between newgenics and old eugenics was the use of genes as units of selection. For Galton, for American eugenicists such as Priddy, and for Nazi eugenicists, the only mechanism to ensure genetic selection was through the selection of physical or mental attributes—i.e., through phenotypes. But these attributes are complex, and their link to genes cannot be simply captured. “Intelligence,” for instance, may have a genetic component, but it is much more evidently a consequence of genes, environments, gene-environment interactions, triggers, chance, and opportunities. Selecting “intelligence,” therefore, cannot guarantee that genes for intelligence will be selected any more than selecting “richness” guarantees that a propensity for accumulating wealth will be selected.

  In contrast to Galton’s and Priddy’s method, the major advance of newgenics, its proponents insisted, was that scientists were no longer selecting phenotypes as surrogates for the underlying genetic determinants. Now, geneticists had the opportunity to select genes directly—by examining the genetic composition of a fetus.

  To its many enthusiasts, neo-eugenics had shed the menacing guise of its past and emerged anew out of a scientific chrysalis. Its scope broadened even further in the mid-1970s. Prenatal testing and selective abortion had enabled a privatized form of “negative eugenics”—a means to select against certain genetic disorders. But coupled to this was the desire to instigate an equally expansive, laissez-faire form of “positive eugenics”—a means to select for favorable genetic attributes. As Robert Sinsheimer, a geneticist, described it, “The old eugenics was limited to the numerical enhancement of the best of our existing gene pool. The new eugenics would in principle allow the conversion of all the unfit to the highest genetic level.”

  In 1980, Robert Graham, a millionaire entrepreneur who had developed shatterproof sunglasses, endowed a sperm bank in California that would preserve sperm from men of the “highest intellectual caliber,” to be accessed only to inseminate healthy, intelligent women. Called the Repository for Germinal Choice, the bank sought sperm from Nobel laureates across the world. The physicist William Shockley, the inventor of the silicon transistor, was among the few scientists who agreed to donate. Perhaps predictably, Graham ensured that his own sperm was added to the bank on the pretext that—although the committee in Stockholm was yet to recognize it—he was a “future Nobel laureate,” a genius-in-waiting. However ardent its fantasies, Graham’s cryogenic utopia was not embrace
d by the public. Over the next decade, only fifteen children would be born from sperm banked at the Repository. The long-term achievements of most of these children remain unknown, although none, thus far, appears to have won another Nobel Prize.

  Although Graham’s “genius bank” was ridiculed and eventually disbanded, its early advocacy of “germinal choice”—that individuals should be free to pick and choose the genetic determinants of their offspring—was hailed by several scientists. A sperm bank of selected genetic geniuses was obviously a crude idea—but selecting “genius genes” in sperm, on the other hand, was considered a perfectly tenable prospect for the future.

  But how might sperm (or eggs, for that matter) be selected to carry specific enhanced genotypes? Could new genetic material be introduced into the human genome? Although the precise contours of the technology that would enable positive eugenics were yet unknown, several scientists considered this a mere technological hurdle that would be solved in the near future. The geneticist Hermann Muller, evolutionary biologists Ernst Mayr and Julian Huxley, and the population biologist James Crow were among the vociferous proponents of positive eugenics. Until the birth of eugenics, the only mechanism to select for beneficial human genotypes had been natural selection—governed by the brutal logic of Malthus and Darwin: the struggle for survival and the slow, tedious emergence of survivors. Natural selection, Crow wrote, was “cruel, blundering and inefficient.” In contrast, artificial genetic selection and manipulation could be based on “health, intelligence or happiness.” Support from scientists, intellectuals, writers, and philosophers poured into the movement. Francis Crick staunchly backed neo-eugenics, as did James Watson. James Shannon, director of the National Institutes of Health, told Congress that genetic screening was not just a “moral obligation of the medical profession, but a serious social responsibility as well.”