The Gene: An Intimate History - Siddhartha Mukherjee Page 0,123

correct specific deformities as they arose. The goal was not to restore “normalcy”—but vitality, joy, and function.

McKusick had rediscovered the founding principles of modern genetics in the realm of human pathology. In humans, as in wild flies, genetic variations abounded. Here too genetic variants, environments, and gene-environment interactions ultimately collaborated to cause phenotypes—except in this case, the “phenotype” in question was disease. Here too some genes had partial penetrance and widely variable expressivity. One gene could cause many diseases, and one disease could be caused by many genes. And here too “fitness” could not be judged in absolutes. Rather, the lack of fitness—illness, in colloquial terms—was defined by the relative mismatch between an organism and environment.

“The imperfect is our paradise,” Wallace Stevens wrote. If the entry of genetics into the human world carried one immediate lesson, it was this: the imperfect was not just our paradise; it was also, inextricably, our mortal world. The degree of human genetic variation—and the depth of its influence on human pathology—was unexpected and surprising. The world was vast and various. Genetic diversity was our natural state—not just in isolated pockets in faraway places, but everywhere around us. Seemingly homogeneous populations were, in fact, strikingly heterogeneous. We had seen the mutants—and they were us.

Nowhere, perhaps, was the increased visibility of “mutants” more evident than in that reliable barometer of American anxieties and fantasies—comic strips. In the early 1960s, human mutants burst ferociously into the world of comic characters. In November 1961, Marvel Comics introduced the Fantastic Four, a series about four astronauts who, trapped inside a rocket ship—like Hermann Muller’s fruit flies in bottles—are exposed to a shower of radiation and acquire mutations that bestow supernatural powers on them. The success of the Fantastic Four prompted the even more successful Spider-Man, the saga of young science whiz Peter Parker, who is bitten by a spider that has swallowed “a fantastic amount of radioactivity.” The spider’s mutant genes are transmitted to Parker’s body presumably by horizontal transfer—a human version of Avery’s transformation experiment—thus endowing Parker with the “agility and proportionate strength of an arachnid.”

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