Prologue
Monster in a Test Tube

Frightful must it be, for supremely frightful
would be the effect of any human endeavor
to mock the stupendous mechanism of the
Creator of the world.
-- Mary Shelley
Frankenstein, or The Modern Prometheus, 1818

On a cool fall morning in 1973, Doris and John Del-Zio arrived with her luggage at New York Hospital. It was a familiar routine for the Florida couple; Doris had been a patient there before. Her Manhattan infertility specialist, William Sweeney, had tried on three earlier occasions surgically to remove obstructions in Doris’ blocked fallopian tubes. The first time the surgery worked and Doris got pregnant, but three months along she had a miscarriage. The second time, and the third, the surgery made no difference at all. Neither did attempts at artificial insemination using her husband’s sperm, not after the first insemination, nor the second, nor the thir. Month after month after disappointing month, Doris Del-Zio, by then approaching thirty, got her menstrual period, and each one was a stinging rebuke. Every period taunted her – no baby, no baby, no baby – forcing her to acknowledge that she still wasn’t pregnant, and probably never would be.

Maybe she and John should have just left well enough alone. Maybe God, or fate, or whatever you call the keeper of her destiny, meant for Doris to be content with her ten-year-old daughter, Tammy, the child of her first marriage, and with her two college-aged stepdaughters, Denise and Debbie, who lived with John’s ex-wife. Maybe it should have been enough to have a beautiful home in Fort Lauderdale and an adoring husband, a professional man – a dentist – who had adopted Tammy and loved her as though she were his own. But Doris wanted to have John’s baby. And she was ready to do almost anything to make that happen.

“Isn’t there something else you can do?” Doris asked Sweeney after her third failed surgery. She was a pretty woman with brunette hair swept into a lacquered flip, and her dark eyes were sad. “They can put a man on the moon; isn’t there some way scientists can figure out how to help me have a child?” Well, yes, Sweeney conceded, a little reluctantly because of Doris’ long history of infertility surgery; yes, there was one more thing they could try. It had never been done in humans before, only in lab mice and rabbits. But if Doris was willing, he could try a new method that would bypass her clogged tubes altogether. Scientists were calling the method, which had never been done before in humans, in vitro fertilization, or IVF. The few journalists who wrote about it were calling it the creation of test tube babies.

If the Del-Zios consented – and Doris took barely ten minutes to decide that this was her last, best hope – Sweeney said he would surgically remove a few of Doris’ eggs and, with a collaborator who had done such things before, fertilize them with John’s sperm in a glass test tube; “in vitro” is Latin for “in glass.” If one of the sperm fertilized one of the eggs, the resulting zygote – the scientific term for a fertilized egg – would be placed in an incubator for three or four days and allowed to grow. In the incubator, kept at the body temperature it needed to survive, the single cell would become two, the two would become four, the four eight, the eight sixteen, and the sixteen thirty-two. It would take about three days for the zygote to grow into a thirty-two-celled ball known as a morula, and another day or so to grow into a blastocyst, made up of a few hundred cells arranged into a fluid-filled sphere. Even though it would still be smaller across than the width of an eyel, the blastocyst would now be ready to implant itself in the uterine wall. According to the plan, then, Sweeney would bring Doris back to the operating room four days after her eggs had been harvested, to introduce the minuscule blastocyst into her uterus at about the same time nature would have done so had it been given the chance. Her body, he hoped, could take it from there.

The logistics of such an undertaking were tricky, made even trickier by the geography of Sweeney’s collaboration. Sweeney worked at New York Hospital, an affiliate of the Cornell Medical School located on East 68th Street on Manhattan’s Upper East Side. That was where Doris’ eggs would be removed. But Sweeney believed that the only man in New York with the experience, the interest, and the nerve to try to fertilize those eggs in vitro was a scientist named Landrum B. Shettles – and Shettles worked clear across town, at Presbyterian Hospital on West 168th Street and Broadway. It was there, in a polyglot neighborhood two miles north of Harlem known as Washington Heights, that the fertilization would have to take place.

By the time Doris checked into New York Hospital to attempt IVF, she had been taking fertility drugs for more than six months to pump up the activity in her ovaries. Sweeney met with her and John to discuss the procedure, and to have them read and sign all the consent forms. In addition to the ordinary forms, Sweeney handed the couple a one-page document that seemed almost improvised, so casual was its tone, so lacking in standard legalese: “Of our own free will and volition and with full knowledge of in vitro fertilization, . . . [we] hereby authorize Dr. William J. Sweeney to perform a laparotomy with embryo transplant and any other operation upon Mrs. Doris Del-Zio, and to employ any assistance as he may desire to assist him. We understand that there is no guarantee or assurance that a pregnancy could result. We understand that there is the possibility of complications of pregnancy and of childbirth and delivery, or the birth of an abnormal infant or infants, or undesirable tendencies or other adverse consequences.”

The IVF consent form, the first of its kind used in New York – indeed, possibly the first of its kind used anywhere in the world – was dated September 11, 1973. It was typed on a manual typewriter with a smudgy black ribbon, signed by Doris in a back-sloping handwriting with a black fine-point pen, and signed by John in bigger, bolder script, in blue.

On September 12, a Wednesday, Sweeney came in to the eighth-floor operating room where he’d encountered Doris so many times before, made a new incision in Doris’ abdomen, and used a syringe to draw out what is known as follicular fluid. In a woman who has been taking fertility drugs, these secretions from the ovaries usually contain at least a few eggs.

Sweeney collected about one cubic centimeter of fluid from Doris’ ovaries. He divided it between two test tubes, added some tissue scraped from the fallopian tubes for nourishment, and phoned Landrum Shettles at Presbyterian Hospital to tell him the eggs were on their way.

It was John Del-Zio’s job to get them there. Nestling his wife’s eggs inside his jacket pocket, safe in two corked test tubes swaddled in bubble wrap, he took the elevator down to the York Avenue exit of the hospital. Then Del-Zio, a good-natured man with a reedy voice, thinning black hair, and the looks of Phil Silvers on the Sergeant Bilko television show, began the journey that he and his wife hoped would lead to the world’s first test tube baby.

The Del-Zios might have thought they were just trying to make a baby, but in truth they were also making history. And, by finding themselves in the swirl of an epoch-defining vortex, they were about to come face to face with their own true selves: part courage, part vanity; part selflessness, part greed.

But John Del-Zio did not know that yet. All he knew was that he had to get over to the West Side. So he stood in the morning chill, peered at the traffic going north on York Avenue and, bearing his precious cargo, hailed a cab.

[ ]

The enterprise the Del-Zios were embarked upon, in vitro fertilization, carried a slightly sinister overtone in September 1973, sort of like back alley abortions before the Supreme Court issued the Roe v. Wade decision just eight months earlier. Within a few short years, spurred mostly by scientists’ ability to bring into the world test tube babies who were perfectly beautiful and normal-looking in every way, society’s view would begin to change. The change was subtle, a cultural and intellectual shift so gradual as to be almost imperceptible to those living through it. But it added up to something radical indeed. Graphic demonstration of this evolution can be seen in the story of the Del-Zios, their physicians Sweeney and Shettles, and Raymond Vande Wiele, the chairman of Shettles’ department who underwent a dramatic reversal in his attitude toward IVF during a single, crucial decade. This book is about that transformation, the people who struggled through it, and the regulatory mechanisms that society put in place during that tumultuous time – mechanisms that are still in place today to guide us through our next adventures in reproductive technology.

It’s an American story, even though early IVF is often associated with England, because that was where the world’s first test tube baby – Louise Brown, billed as “The Baby of the Century,” her doctors hailed as heroes – was born. But the American IVF attempt, the one involving the Del-Zios, Shettles, and Vande Wiele, began five years before Louise came on the scene in 1978. The American story reveals, perhaps even better than the more familiar British one, what can happen when society faces a new and frightening technology: how it is greeted first with resistance and expectations of the worst, then with grudging permission, then with acceptance, and finally by incorporating it so seamlessly into the rest of life that no one even notices it anymore. Because the two stories, the American and the British, took place concurrently, both will make appearances here. And alongside the stories of the research itself will be some larger, more perennial issues: the struggle between the drive to know and the drive to not-know; the growth of the field of bioethics; mechanisms by which new technologies are introduced and regulated; and the factors that motivate scientists, including altruism, ego, personal bravura, economics, and a lust for power.

It seems hard to believe today, when the procedure is so routine that it’s covered by most medical insurance, that IVF in 1973 was thought by some to threaten the very fabric of civilization. Marriage, fidelity, the essence of family; our sense of who we are and where we’re headed; what it means to be human, connected, normal, acceptable; ideas about love, sex, and nurturance; the willingness to yield to the inscrutable, marvelous mystery of it all – if in vitro fertilization were allowed, some said, all these stabilizing threads would unravel.

The threads were unraveling already, of course, which is probably why IVF seemed so threatening, just one more tug at the ever-loosening weave. Feminism was a major source of the fraying. In the early seventies women were rewriting their social roles, moving out of housewifery, delaying childbearing or choosing to be childless altogether, demanding access to traditionally male domains. With the feminist movement turning motherhood into an option instead of an obligation, any proposed change in the relationship between a woman and her reproductive capability was particularly fraught. The birth control pill had already separated sex from procreation; the Roe v. Wade decision had already separated pregnancy from birth; no-fault divorce laws had already separated marriage vows from forever. With all these coincident changes, what would reproductive technology do to our perception of children as the fruit of a loving, lifelong union?

“Marriage and the family must be abolished as institutions,” wrote Ti-Grace Atkinson, one of the most radical feminists of the day and author of Amazon Odyssey. “And `love’ as an ideology to justify them must also go.”

Even more than the institutions that supported it, the act of procreation itself was reassessed and found to be politically suspect. This was the era of Zero Population Growth (ZPG), when couples who had more than two children were viewed askance, as though they were wantonly gobbling up the planet’s precious gifts. To true believers, nothing less than the fate of the earth was at stake, its environment imperiled by too many people and too much technology.

Just as ZPG was making people think twice about having babies, a growing environmental movement was making them think twice about scientific advancement for its own sake. The notion that progress almost always comes at a cost underlay one of the movement’s earliest achievements, the Environmental Impact Assessment, introduced in the National Environmental Protection Act of 1970. Good social policy, the Environmental Impact Assessment implied, denied neither the progress nor the cost, but sought to balance the two in a socially responsible way.

Comfortable conventions were suddenly open to re-evaluation, too. The anti-war movement, which led to America’s humiliating withdrawal from Vietnam in 1973, provided a new matrix for social cynicism and the belief that the government sometimes makes grave mistakes. The government’s fallibility was reinforced when Watergate erupted on national television. The daily dose of Congressional hearings turned the summer of 1973 into an object lesson in how long, and how destructive, can be the shadow cast by a single too-powerful man.

That year, 1973, was the same year in which a Vice-President resigned in ignominy over charges of graft and tax evasion; when a group of enraged Native Americans laid siege for three months to a tiny South Dakota town; when an Arab oil embargo quadrupled gas prices and made Americans question their dependence on foreign oil. Into this bubbling mess of social change came scientists who wanted to create life in the laboratory. No wonder it looked like such a dangerous idea.

[ ]

No one but the gods should tamper with the natural order of things. That, at least, is the moral of the parables handed down for generations, designed to quell mankind’s unpredictable, irrepressible, sometimes foolhardy impulse to twist nature according to his own whims. The folly of such action has been the point of myths and folk tales dating back to the ancient Greeks. They told the story of Prometheus to show that any attempt by a mere mortal to create life – or, more blasphemous still, to conjure a thinking, feeling, independent organism – could lead only to ruin.

Prometheus was a Titan, not a god, but the gods adored him. During the time when all the earth’s creatures were being made, Zeus gave Prometheus a special task: to create Man. Prometheus took great pride in Man – some might say too much pride, the kind the Greeks called hubris. He wanted to endow his creation with a special gift, something unique to Man, something more valuable than the gifts of flight, or strength, or speed, or camouflage that had already been bestowed upon earth’s other creatures. Prometheus decided to give Man a tool that the gods alone possessed, which would enable him to fashion other tools, to provide himself with clothing, shelter, and food. He decided to give Man the gift of fire.

Prometheus stole the fire from Mt. Olympus in the dead of night, and carried it to earth, nestled carefully in the crook of his arm. When Zeus saw the flickering light of the flames that Man had built, he knew what Prometheus had done. He concocted a brutal punishment: he grabbed Prometheus, lashed him to a rock at the top of the Caucasian Mountains, and brought a vulture to tear ceaselessly at his liver. The agony never ended. The vulture was forever hungry, and every night the liver in Prometheus’ ravaged body regenerated, ready to become a new morning’s meal.

The mythic hero’s suffering inspired much poetry. Lord Byron wrote one such poem in 1816. This was, providentially, the same year in which Byron took an excursion to the French Alps with fellow poet Percy Bysshe Shelley and Shelley’s teenaged mistress. Shelley at the time was a married man, but a few months later he was widowed – his jilted wife drowned herself in the Serpentine River – and he was able to marry his young lover, Mary Godwin, who became known as Mary Shelley.

During that trip to the Alps, the weather was bad, and Byron proposed that he, Shelley, and Mary pass the time writing ghost stories. Mary, much less accomplished than the two men, was at first struck nearly dumb by the idea. But the story she put together, about a scientist she called “the modern Prometheus,” eventually became the novel Frankenstein, a book whose impact far outlasted the ghost stories that either Byron or Shelley contributed.

Byron’s own ode to Prometheus was more traditional than Mary’s. He addressed Prometheus directly, extolling his bravery in the face of injustice.

Thy godlike crime was to be kind;
To render with thy precepts less
The sum of human wretchedness,
And strengthen man with his own mind.

Prometheus’ transgression was in bringing mankind such a powerful tool, one that would enable him to “strengthen man with his own mind.” Fire was like knowledge; it was a double-edged gift, with the capacity for both creation and destruction. So it is with our most potent scientific discoveries. The more wonderful are the things made possible through science, the more they can potentially do things that are quite terrible, too.

When the gods looked at Prometheus and Man, they saw what they themselves had wrought: the fierce attachment that inevitably grows between creator and creation. What if Man, with the tools and capability of fire at his disposal, developed a stronger allegiance to Prometheus than to the gods? Once the ability to create life was bestowed on a mere mortal, how could anyone maintain order or decency or restraint?

[ ]

The Promethean trick of creating life was the essence of in vitro fertilization. But it entwined two opposing sides of life: on the one hand, life at its most fragile and natural, involving acts of love and touch and sex and generation; and on the other hand life at its most contrived, with surgical interventions, microscopic examinations, and lab cultures turning it all into a matter of technology rather than creation. In the early days of IVF, before it became a focus of widespread public attention, the debate was mostly about science: whether human sex cells and embryos could be grown successfully in a petri dish; whether fertilizing them there would lead to gross abnormalities; whether more animal research should be done before starting work on humans. But the debate soon took on a more philosophical tone. Some people argued that a human embryo, even a one-celled zygote, deserved the same respect due any human being – not because the zygote was a person, really, but because it was a potential person, containing all the DNA necessary to make a new and unique individual. “A blastocyst . . . is not humanly nothing,” wrote biologist Leon Kass, one of the loudest opponents of IVF in the seventies – and today as forceful a critic of cloning. “[I]t possesses a power to become what everyone will agree is a human being.”

The very notion of artificial fertilization went against the teachings of many religious groups, including the Catholic church. “Fecundation must be carried out according to nature and through reciprocal and responsible love between a man and a woman,” said the Rev. Pierfranco Pastore, a spokesman for the Vatican, shortly after Louise Brown was born. Added the Rev. Anthony Bevilacqua of the Catholic Diocese of Brooklyn, New York: “We would not like to see the point where science dehumanizes the act of marriage.”

If some of this sounds like a rehearsal for today’s debates about human cloning, that’s because there are some very real parallels. Cloning today evokes many of the same responses that IVF did thirty years ago. In fact, early opponents of IVF deliberately linked the two by predicting that human cloning is what lay at the bottom of a long and treacherous “slippery slope” down which we would inevitably stumble if IVF were allowed.

Throughout recent history, scientific and cultural changes have been subjected to the slippery slope argument. People talked about the slippery slope when the first artificial insemination was publicized in 1909, conjuring images of selective breeding and a race of illegitimate souls. They talked about it after the first heart transplant in 1967, after the first animal-to-human transplant in 1984 and, in the summer of 2001, after the first attempt to create human embryos explicitly for research. Early cases of assisted suicide stimulated talk about a slippery slope toward wholesale killing of the aged or infirm; early attempts at amniocentesis, about a slippery slope toward the elimination of fetuses that were imperfect in some inconsequential way – or that maybe were simply the “wrong” sex.

There’s power to the argument, because if we hadn’t allowed those first steps – the refinement of intrauterine diagnosis, the definition of brain death, the limbo created by the heart-lung machine – the more disturbing applications could not have come to pass.

The same can be said of IVF. Scientists first had to learn how to fertilize human eggs in the lab, and how to transfer them back into the womb, before they could even begin to think about the genetic interventions that are now causing so much angst: not only cloning but also pre-implantation genetic diagnosis, genetic engineering of sex cells, the creation of human/animal chimeras, the culturing of human embryos as a source of replacement parts. None of these interventions could have been accomplished without first perfecting the techniques of artificial fertilization and embryo transfer.

But for all that people railed against IVF because of where it might lead, their protests had an unintended and paradoxical effect: they led to less control over IVF rather than more. Early on, opponents thought the best way to stop troublesome science was to keep the government from financing it, and they fought against using taxpayer money for research involving fetuses or embryos – which, by extension, included IVF. One by one a succession of bioethics commissions were formed to review these bans; one by one the commissions recommended that the bans be lifted. But politicians, afraid of alienating a vocal anti-abortion lobby that took on IVF as its cause, generally did not want to hear that they should underwrite such controversial research. So they tended to ignore each report and form a new commission in the hopes that it would reach a different conclusion. This became the pattern for bioethicists’ role in the regulatory minuet: sit on a commission, hold meetings, attend public hearings, write a report that says the research is ethically acceptable, have the report ignored, watch the next President or Congress convene a new commission, and repeat.

Even after the fetal research ban was finally lifted, and then the embryo research ban, the government still refused to sponsor IVF research. But the lack of federal support for IVF didn’t stop scientists from working on it – it just forced them to carry on beneath the radar, out of the reach of the main mechanism for oversight, which was (and still is) the federal research grant and the standards it imposed on its recipients. If no one was getting government grants for in vitro fertilization, then no one was being forced to adhere to any standards. But entrepreneurial scientists were doing IVF anyway, bolstered by private money from infertile couples desperate for babies of their own. Many of these scientists were honorable men and women with solid reputations and the loftiest of goals. But some of them were motivated by the things that drive so many innovators, scientists included: ego, curiosity, ambition, even greed. They were free agents who essentially did whatever they wanted and whatever the market would bear. Their privately-funded efforts turned some of IVF into a cowboy science driven by supply and demand.

Cloning is in many respects the contemporary version of cowboy science; cloners are today’s daredevils and rogues, making claims on television and at Congressional hearings that they can rarely back up with genetic proof or even an actual baby. This is why so many politicians, in the United States and elsewhere, have been trying so hard to put cloning in its place – not by refusing to fund it, as happened to ill effect with IVF, but through legislation to outlaw cloning altogether – whether the cloning takes place for research or for the sake of creating a baby clone. They want to keep human cloning from going the way of IVF, developing at its own pace, and becoming part of the ordinary landscape, simply because it was easier to ignore a controversial new technology than to regulate it.

[ ]

Cloning resembles IVF not only in the halls of Congress, but in the laboratory as well. For both IVF and cloning, the first step is to create a dividing human zygote in culture. But as similar as they might be in terms of laboratory technique, and in terms of their intention to bring biological children to infertile couples, cloning and IVF have some crucial differences – and we misread the lessons of IVF for today’s cloning debates if we fail to see that.

The goal of in vitro fertilization is to mimic sexual reproduction in order to produce a genetically unique human being, a baby with one father and one mother. Only the locus of conception changes, after which events proceed much the way they normally do. Cloning, however, disregards sexual reproduction; it mimics not the process but the end result, the human being himself. What is being produced is not a new person with a unique combination of Mother’s and Father’s DNA, but the identical twin, a genetic replica in every way, of a person who already exists.

Perhaps the biggest difference between IVF and cloning is the focus of our anxieties about them. In the seventies the greatest fear about in vitro fertilization was that it might fail, leading to sorrow, disappointment and possibly the birth of grotesquely abnormal babies. Today, the greatest fear about cloning is that it might succeed.

In terms of the evolution of the species, cloning could have serious unintended consequences – far more consequences than with “basic” IVF. As early as the nineteen-forties, the British author C. S. Lewis warned that the net result of reproductive technology might well be not advancement but, perversely, a bizarre kind of petrification, the freezing of the world at a particular moment in time – at whatever moment the world happened to be in when the new technology was introduced. It would be like walking into a home and finding an avocado-colored refrigerator and brown shag carpeting. It all might have been the latest fashion when the current owners first made their decorating decisions – but now, thirty years later, it all looks shabby and out-of-date. Something analogous could happen to the human species, too, said Lewis. Designing babies according to one era’s fashion could become, like pine-paneled rumpus rooms, something we regret having committed to when the fashions change. And an outdated genome can’t be ripped out the way an outdated carpet can.

“If any one age really attains, by eugenics and scientific education, the power to make its descendents what it pleases,” wrote Lewis in a 1943 essay called The Abolition of Man, “all men who live after it are patients of that power. They are weaker, not stronger; for though we may have put wonderful machines in their hands we have pre-ordained how they are to use them.”

Lewis’ warning carries an important reminder: that the doors we open automatically close off other doors, keeping us from traveling down the road not taken. But his emphasis is slightly askew. He makes it sound as though once we set off along a particular path of discovery, we keep making decisions that cannot be undone. More often, however, the doors we close and open along the way are like swinging saloon doors; the process does not only happen in one direction. Our choices have ramifications, to be sure, but the ramifications are not necessarily linear – nor are they necessarily permanent. If we seem to have chosen the wrong fashion to enshrine, we would probably have time to find different doors to close and open that would undo our mistake. The challenge is to achieve the right balance between making the wrong choices, and being so frightened of the wrong choices that we make no choices at all.

[ ]

The Prometheus story has a sequel. It involves the first woman, the ancient Greek equivalent of Eve, whom the gods sent to earth in direct retribution for Prometheus’ misdeed. Her name was Pandora, meaning “all gifted.” The gods fashioned her on Mt. Olympus by loading on all the most alluring traits they could think of. Aphrodite gave her beauty; Hermes, persuasion; Apollo, his magnificent music.

When Pandora arrived on earth, she was carrying a beautiful and mysterious box. The box (some myths describe it as a jar) was a gift from the gods, who handed it to her and told her never to open it. But among Pandora’s many gifts were some distinctly human qualities – curiosity, audacity, impetuousness, cheek – at play in a fatally flawed combination. She defied the gods’ injunction and opened the box. In doing so, she unleashed all the terrors that had until then been unknown to Man, living as he did in a blissful, innocent paradise, and that would now and forever after cause him endless anguish and pain. These grievous sorrows, as one account of the Pandora myth put it, rushed from the box “in a black stinking cloud like pestilent insects - sickness and suffering, hatred and jealousy and greed, and all the other cruel things that freeze the heart and bring on old age.”

The release of these miseries represented an end to the golden age of paradise, a coda to mankind’s idyllic childhood.

When scientists started talking, in the early seventies, about creating a kind of Pandora’s baby, a lab-fertilized child brought forth by man instead of by the gods, some observers thought again about the lessons the Greeks had tried to teach. It seemed to boil down to a struggle between two competing impulses: the creative drive to understand nature, versus the conservative drive to impose limits and maintain the status quo. This is the way frontier science has always been done, through the raucous to-ing and fro-ing of contradictory desires. The conflict between knowing and not-knowing has been with us since Eve tasted the apple, since Prometheus brought fire to mankind.

Would Pandora’s baby lead to something so close to what happened in the myth, people wondered, that the only responsible thing would be to make sure it was never born? Would it demand a re-assessment of qualities so central to our humanity – our sense of doom and destiny, our understanding of who we are and where we are headed, our definitions of parents, children, love, sex, generation – that its very existence would threaten our collective soul? These questions might seem overdramatic today, unless you replace “in vitro fertilization” with “human cloning.” And in the years before the first test tube baby, they applied just as convincingly to IVF. These were questions asked by reasonable men and women who were sincere in their belief that there was trouble ahead – that IVF might open up a scourge of woeful possibilities that, as with Pandora’s unleashing from her dreadful box, we would be better off never to have seen.