Louise Brown, The World's First Test-Tube Baby: Revisit Our Cover Story 40 Years Later

40 years ago, on July 25, 1978, Louise Brown became the world's first "test-tube baby." Newsweek featured the remarkable infant on its cover the following week and published a long piece about the rise of in vitro fertilization by longtime science editor Peter Gwynne. Brown is now happily celebrating her 40th birthday. Here is our cover story from 1978 in its entirety.

She was born at 11:47 p.m. with a lusty yell, and it was a cry heard round the brave new world. Louise Brown, blond, blue-eyed and just under six pounds, was the first child in history to be conceived outside her mother's body. Her birth last week in a dowdy British mill town was in its way a first—variously hailed as a medical miracle, an ethical mistake and the beginning of a new age of genetic manipulation. But perhaps more important, as Dr. Patrick Steptoe proudly reported, "The anxieties are over. We've got a nice, healthy, normal baby."

Steptoe and his medical collaborator, physiologist Robert Edwards, had achieved their breakthrough with just a minor variation on the technique they had been developing for 12 years, and the crucial element was apparently timing: the fertilized egg, reimplanted in Louise's mother's womb slightly ahead of earlier schedules, survived for almost the normal nine months to a Caesarean birth. But that was enough to promise fresh hope for millions of childless women, hundreds of whom immediately besieged Steptoe with requests to help them conceive children.

The birth announcement prompted at least one new attempt to implant another test-tube baby, and possibly more: according to the London Daily Express, three more women are already pregnant—including a countess. It also touched off fevered speculation and ethical debate over wonders to come: the possibilities of surrogate mothers, the creation of superbeings and an Aldous Huxley vision of embryos nurtured to birth in artificial wombs.

For the moment, Louise herself was wonder enough. Chubby and tousled, wrapped in a white muslin sheet in the plastic cot next to her mother's bed, she was the center ring of a classic Fleet Street circus. London's Daily Mail had long since bought the rights to the story and pictures, for a sum reported to be $570,000, and had printed first-person accounts by Gilbert John Brown, a 38-year-old truck driver for British Rail in Bristol, and his wife, Lesley, 31. In the competitive scramble, reporters for other newspapers and TV besieged the hospital, teasing out details to bolster their banner headlines. LITTLE MISS PERFECT, gushed the Evening News; THE WHOLE WORLD IN HER HANDS, said the Daily Express.

There was little enough to add about the Browns, who seemed extraordinary only in their determination to have a child; neighbors pictured them as quiet, working-class folk who kept to themselves. But there was no doubt about their joy over Louise. "She's so small, so beautiful, so perfect," Lesley Brown told the Mail. And John Brown exulted: "It was like a dream. I couldn't believe it."

For some, it had the ring of a scifi nightmare. Roman Catholic theologians, who consider even artificial insemination an unlawful tampering with God's will, expressed grave reservations. Jewish and Protestant authorities generally approved of the process, as long as the sperm used came from the husband of the woman who would bear the baby.

Odds on a miracle:

But there were widespread misgivings over the next possible steps: surrogate mothers who might rent out their wombs, or tailor-made babies whose genes might be altered in the test tube. "I fear that we may be slipping away from doctoring the patient to doctoring the race," said Father William Smith of New York's Catholic archdiocese.

Few doubted, however, that Louise's birth represented a major advance in medical research, with the promise of more breakthroughs in embryo research, the understanding of birth defects and their prevention, treatment of infertility and—paradoxically—the development of new contraceptives. For Steptoe, that irony would be familiar enough; lacking funding for his controversial work, he financed his research in part with the proceeds of legal abortions.

And miracle or not, the odds against Louise were long from the start. Her parents were able to pursue their quest only because they had won $1,500 in the football pools. Her conception, when her father's sperm penetrated her mother's egg in a vial an inch in diameter and two inches high, took place in a drowsy clinic called Dr. Kershaw's Cottage Hospital in Oldham, near Manchester in northwest England. And her birth, with all its science-fiction overtowns, occurred in the Oldham and District General Hospital, a cluster of Victorian buildings that were originally a Dickensian workhouse.

When they married in 1969, John and Lesley Brown hoped for a stepbrother or sister for Sharon, John's daughter by a previous marriage. But Lesley was unable to conceive even after an operation to open her blocked Fallopian tubes. The couple tried to adopt a child, but gave up after two years on a waiting list. Finally, a sympathetic nurse sent them to Steptoe and Edwards.

Celebrated team:

It was an unusual partnership. Steptoe, 65, is a flamboyant and somewhat mysterious figure: he declines to discuss his origins (reported to be in Eastern Europe) or his childhood, but he served in the British Royal Navy in World War II, spent time as a prisoner in Italy and later built an unquestioned reputation in gynecology as the developer of the technique for peering at a woman's ovary through a small abdominal incision and selecting and removing a ripe ovum. Edwards, 52, a part-time farmer and dabbler in politics, is an expert in the delicate and complex chemical changes needed to support the development of the human embryo.

Both men have been controversial—Steptoe largely for his celebrity in the popular press, Edwards because of the nature of his experiments. He has had research grants canceled, and once had to suspend his research until a panel of specialists could explore its ethical and social implications. Their 12 years of collaboration haven't been easy; Edwards estimates he's driven more than 50,000 miles between his home in Cambridge and the Oldham clinic, often in the company of a rabbit that was serving as traveling receptacle for an egg under study. But they had succeeded in removing and fertilizing more than 8 human eggs in vitro—literally, in glass laboratory vessels—and then implanting the fertilized eggs in the would-be mothers' wombs. Not one of the embryos had survived more than a few months inside the womb. But about the time when Lesley Brown was ready to conceive, the two men were to try a new wrinkle in their technique.

From rabbits to people:

Steptoe and Edwards had few precedents to guide them in their development of the test-tube-baby technique. The first report of an in-vitro fertilization came in 1936 from Dr. Gregory Pincus of Harvard University; he united a rabbit egg and sperm. Eight years later Dr. John Rock, also of Harvard and, like Pincus, a major figure in the development of the contraceptive pill, claimed to have fertilized a human egg outside the body and watched it divide into three cells. In 1961, Dr. Daniele Petrucci of the University of Bologna shocked the world with his claim—backed up by movie films—that he had fertilized 20 separate human eggs in vitro. There were even rumors that Petrucci had reimplanted some of them. But so bizarre did the idea of test-tube babies appear to most scientists and laymen that the research was either ignored or greeted with outraged disbelief.

The scientific community was hardly more receptive when Steptoe and Edwards started their historic collaboration, and in the early years the pair proceeded cautiously. Edwards took the lead in perfecting means of fertilizing human eggs and improving the chemical solutions necessary to keep them alive and healthy outside the body. Steptoe, in the meantime, worked on the mechanical technique of removing ova from would-be mothers and returning the dividing, fertilized eggs to the womb. His major contribution—and perhaps the most important event in the chain that led to last week's birth—was to pioneer use of the laparoscope. A foot-long tube equipped with its own eyepiece and internal lighting, it can be inserted through a small slit in a woman's abdomen and used to select a ripening egg that a suction needle can then remove from her ovaries.

Success came slowly. In 1970, the pair reported in the journal Nature that fertilized human ova had grown to the eight and sixteen-cell stage, and a few years later they started serious efforts to reimplant such test-tube ova, which are no larger than the period a the end of this sentence.

Conceived in a cottage:

In 1975, Steptoe and Edwards produced their first definitite pregnancy, but the embryo reimplanted itself in the patient's diseased Fallopian tube rather than in the uterus, and it miscarried after ten weeks. The researchers nonetheless remained confident they were on the right track, and continued to make small alterations in the procedure.

Lesley Brown was an excellent subject. "She was in an age grup that was highly suitable," explained Steptoe in a news conference last week, "not too old and highly fertile." Shortly after her visits started two years ago, Steptoe removed Mrs. Brown's diseased Fallopian tubes. That operation destroyed any faint chance that she might be able to conceive normally, but it gave the obstetrician an unobstructed internal view of his patient's ovaries when he took the first step in creating Louise last November. At that point, Mrs. Brown was given hormone treatment to stimulate egg production before she made the crucial visit to Oldham, for the actual conception of her child. It took place in Dr. Kershaw's Cottage Hospital, a little-used brick building originally donated to the town by an Edwardian eccentric.

Operation in the institution's tiny, white-tiled surgical theater, Steptoe extracted an egg from his patient. Edwards placed the egg in a small jar, where it was mixed with John Brown's sperm and sustained by special fluids. Once fertilized, the egg was transferred to another nutrient solution. The researchers monitored the egg as it divided into two, four, and finally—after more than 50 hours—eight cells.

Now came the crucial point of difference. In previous experiments, Steptoe and Edwards had tried to simulate the natural development of the egg, which is normally fertilized within the Fallopian tube and has multiplied into 64 or more cells by the time it reaches the womb. But new research with rhesus monkeys—though it involved only implantation of conventionlaly fertilized eggs—suggested that an embryo as small as two cells might survive in the uterus. So the researchers decided to reimplant Lesley Brown's ovum at the eight-cell stage, reducing the complexities of sustaining its development outside her body. She had already received a second batch of hormones to prepare her womb chemically to receive the embryo.

The Brown fetus, which was conceived last Nov. 10 and reimplanted two and one-half days later, survived and thrived. Seven weeks ago, Lesley Brown checked into the Oldham Hospital's maternity ward, where she assumed the name Rita Ferguson, to allow doctors to monitor her around the clock. Other mothers told reporters that she was quiet and subdued, spending her time knitting, watching television and doing crossword puzzles. She chewed gum, developed a craving for mints and couldn't resist disobeying Steptoe's orders by taking an occasional puff from a cigarette—and blowing the smoke out of a window to conceal it.

Premature but beautiful:

Steptoe had expected the birth to occur sometime this week, but when Lesley developed a mild case of high blood pressure, threatening complications in the delivery, he decided to deliver the baby immediately by Caesarean section. In a ten-minute conventional operation, he left the mother with a horizontal "bikini cut" and brought forth Louise, several days premature and weighing just five pounds 12 ounces. The baby's looks benefited from the operation: because they don't have to struggle through the birth canal, babies delivered by Caesarean section tend to look prettier than children who undergo normal births. "She has a marvelous complexion, not red and wrinkly at all," boasted her father to the Daily Mail. Edwards, a godfather of sorts, added a unique view: "The last time I saw the baby it was just eight cells in a test tube. It was beautiful then, and it's still beautiful now."

Any further uniqueness remained to be discerned. Louise was so obviously healthy that her doctors allowed her out of the hospital's premature-baby unit, just a few hours after she had been taken there as a precautionary measure. Nestled in her bassinet, she squalled like any baby for the bottle she was being given while her mother's breasts filled. "She has a set of lungs like a glass blower," said one staffer on the hospital's fourth floor. "That girl is going to grow up to be a politician or a pop singer."

John Brown himself almost missed the magic moment: he had left the hospital almost two hours before the operation, reported the Mail, concerned that his wife had been unnaturally quiet during his visit. Only when he called back later did he learn the reason for her silence. She had been sedated in readiness for the delivery, and in the fashion of hospitals everywhere, nobody had thought to tell him about it. Brown rushed back to the hospital and spent anxious minutes pacing around a waiting room. "Then a nursing sister came up to me full of smiles and said, 'Mr. Brown, you're the father of a wonderful little girl,'" he told the paper. "And almost before I knew it, there I was holding our daughter in my arms."

Brown then ran up and down the corridors of the gloomy Victorian hospital, hugging everyone he met and repeating: "It's a girl, I've got a baby daughter." Later, he went out and stood in the pouring rain in order, he explained, to calm down a little. "The man who deserves all the praise is Mr. Steptoe," he said to the Mail. "What a man to be able to do such a wonderful thing."

How great an achievement is the birth of the world's first test-tube baby? Medical researchers are certainly impressed, but some suggest that the media hoopla is a bit overwrought. "I doubt it will win a Nobel Prize," said Dr. Malcolm Potts, executive director of the International Fertility Program in North Carolina. "It's a human and useful thing, but it's a cookbook thing." Indeed, added Potts, fertilization outside the body, "is something frogs do in a dirty stream." Some of the scientific competitors of Steptoe and Edwards were also slightly dubious. "What we do not know at this stage," said a member of the team at London's St. Thomas' Hospital, which implanted a fertilized ovum within 12 hours of Louise Brown's birth, "is whether Dr. Steptoe has been able to overcome the problems we have found, or whether Mr. and Mrs. Brown's baby must be put down to good luck."

Short cut to success:

Lucky or not, Steptoe and Edwards did overcome at least one formidable barrier: the lack of substantial animal studies to guide them. Normally, researchers start testing new medical procedures near the bottom of the evolutionary tree, using rats and mice. They then work gradually up to monkeys and apes, man's closest relatives, before experimenting with humans. But before Lesley Brown's case, only rats, mice and rabbits had undergone successful test-tube fertilization followed by reimplantation and birth. The British scientists were apparently so confident that they simply skipped the non-human primates. That prompted a wry comment from W. Richard Dukelow, a physiologist at Michigan State University: "The work by Steptoe and Edwards should do a lot to help those of us who experiment with monkeys."

Nonetheless, such animal research is still highly valuable. For one thing, it promises to complement and extend the achievement of Steptoe and Edwards. Dukelow, for example, hopes to reimplant fertilized squirrel-monkey eggs that have been exposed to various drugs and environmental toxins in order to detect the chemicals' influence on birth defects. Groups at the Universities of Pennsylvania and Wisconsin are starting experiments to monitor in-vitro fertilization of cows' eggs by bull sperm. The scientists have a twofold purpose: by identifying just what makes sperm effective, the studies might help to identify and treat causes of male infertility; and they could point the way to contraceptive chemicals that prevent fertilization.

Ethical nightmare:

Some animal experimentation, however, foreshadows future ethical dilemmas. One example is embryo transfer. After treatment with hormones, a genetically superior cow can be inseminated artificially. She produces as many as 16 embryos. They are flushed from the cow's womb and reimplanted in inferior cows, which brings the calves to term. The result is a far more rapid improvement of the breed than unaided nature permits—but a human parallel would be an ethical nightmare.

Animal researchers are also slowly moving toward a true test-tube baby. In the 1960s, U.S. and Canadian scientists managed to preserve lambs withdrawn prematurely from their mothers. Placed in plastic containers, the fetal lambs were bathed in a solution similar to amniotic fluid, and linked to a mechanical blood-circulation system similar to the heart-lung machines used in cardiac surgery. They survived in the artificial environment, and were then reborn—decadented, as Huxley termed it in Brave New World. At Johns Hopkins University, Dr. Yu-Chih Hsu has succeeded in keeping mice embryos alive in vitro for eight and one-half days after fertilization—almost half their typical 19-day gestation period. The chances that experts will be able to produce artificial wombs that will take test-tube humans from conception to birth are remote, but hardly impossible.

Brave new medicine:

The boundaries of biomedicine—and the manipulation of life's mysteries—are expanding at an astonishing rate. A group of scientists from Harvard, Yale and Turkey's Hacettepe University reported last week that they had identified, for the first time, a single gene among the millions in one human cell. Their technique derives from the controversial tinkering with heredity known as a recombinant DNA technology. Their finding promises the possibility of detecting genetic diseases in fetuses still in the womb. But the same recombinant technology might eventually be used to alter the genes of human fetuses just fertilized in the test tube. Farther ahead lies the prospect of cloning individuals with identical sets of genes—a process that would require such test-tube-baby technology as reimplantation. "The whole idea of designing our descendants, of fabricating the next generation, of making reproduction synonymous with manufacturing, is almost in the picture," warns Protestant theologian Paul Ramsey of Princeton.

What alarms many philosophers and theologians is the fact that so many steps in the brave new biomedicine have actually been taken—with the best of motives. "At least one good humanitarian reason can be found to justify each step," says Dr. Leon Kass, a biochemist at the University of Chicago. "The first step serves as a precedent for the second and the second for the third, not just technologically but also in moral arguments. Perhaps a wise society would say to infertile couples: 'We understand your sorrow, but it might be better not to go ahead and do this.'"

Technological control:

But can the genie be forced back into the test tube—and should it? Science writer Isaac Asimov thinks that new technology can be controlled. "Scientists develop a potentiality," he explains. "Governments and people decide how to use that potentiality." One problem with that rationalization, however, is that new techniques tend to ratify themselves. Daniel Callahan, director of the Hastings Institute of Society, Ethics and the Life Sciences, declared that the experiment on Lesley Brown was in fact unethical, since she stood to benefit if it worked but the unborn child bore the risk of failure. However, Callahan added, once the procedure had been safely done, "it appears to be justifiable."

Louise Brown's arrival has sparked more practical concerns as well. For a start, there is the certainty that thousands of infertile women will now hope that they can actually bear children. But many are apt to be disappointed, since few teams apart from Steptoe and Edwards seem capable of quickly picking up the skills to carry out test-tube conceptions. "I don't think this ought to be performed at any crossroads hospital," says Dr. Griff Ross of the National Institutes of Health. The two British researchers went to great pains last week to emphasize that their work is still experimental. "We are in the early stages, and still have a lot to learn," declared Edwards.

Legal mine field:

What if the learning process leads to mistakes, in the form of test-tube babies born with mental or physical defects? Harvard lawyer William Curran envisions malpractice suits by such children against either their parents or the physicians who created them. Another potential legal mine field concerns the status of fertilized eggs before they are reimplanted. Should they be regarded as living human entities with a well-defined right to life, or as nonhuman material that can be capriciously pitched down the drain or even subjected to experiemnts? Certainly such external ova are different from fetuses inside the womb, because their existence does not affect the physical well-being of the mother. Thus, argues Leon Kass, abortion laws can't easily be applied to these "nascent lives."

Disposal of such eggs, of course, is paralleled in nature. In practice, about 67 percent of the fetuses that are conceived in the human body don't make it out of the womb alive. Each year in the U.S., about 6 million fetuses abort spontaneously or die in the uterus, most of them so early in gestation that the mother doesn't even realize she is pregnant. "When a husband and wife go to the bedroom and experiment, the experiment will fail two-thirds of the time," says Donald Chalkley of the National Institutes of Health.

But to many people, the deliberate destruction of a fertilized egg may seem a far different matter. In a New York Federal court, John and Doris Del Zio are suing Columbia University gynecologist Dr. Raymond Vande Wiele, New York City's Presbyterian Hospital and the university for $1.5 million. Their complaint: Vande Wiele caused them physical and emotional damage when, in 1973, he opened up the jar in a Presbyterian Hospital laboratory that contained a fertilized egg ready for reimplantation in Doris Del Zio. "I don't think it right that it was stopped without my consent," she said. Vande Wiele freely admits that he did it—for medical reasons. He has no objections to test-tube babies. Indeed, he greeted the birth of Louise Brown as a "crowning event." But the experiment hat he destroyed, he said, was scientifically unsound at the time, and Drs. William Sweeney and Landrum Shettles, who performed the operation, did so without hospital permission.

There is scant chance that such an experiment will be repeated in the U.S. in the near future. In 1975, Federal support for research on human in vitro fertilization was halted, and a resumption in the flow of funds awaits the next meeting of a new ethics advisory board. The board, which will assemble in mid-September, is charged with reviewing search proposals on a case-by-case basis. Only one proposal is now under consideration: Vanderbilt University's Piers Soupart wants to determine whether in vitro fertilization increases the risk of genetic abnormalities. That risk may be real: in normal fertilization, only strong sperm can win the long race through the vagina, the uterus and the Fallopian tube to meet the descending egg. In a laboratory dish, strong and weak sperm have an almost equal chance—and some experts fear the result may be hard-to-spot genetic irregularities.

Detective work:

The fear that such test-tube babies may be prone to such defects might act as a brake on researchers' plans to repeat the procedure pioneered by Steptoe and Edwards. Although Louise Brown appears quite normal now, there is no guarantee that minor genetic problems might not crop up in years to come. Furthermore, because genetic detective work is still in a fairly rudimentary stage, it will be impossible to link any defects—or special attributes—that might emerge in Louise Brown to the unusual circumstances surrounding her conception.

Perhaps the major worry that Louise faces stems from her uniqueness. "The child will be watched the rest of her life, and will be seen as extraordinarily unusual," says Daniel Callahan. "People will be taking pictures of her all her life, as they did of the Dionne quintuplets. I can't imagine that this will be a great help to her." It could even threaten the family bond. "Excessive publicity distorts normal relationships," says Dr. Nicholas Zill of New York's Foundation for Child Development. "The parents might end up resenting the child because she's a constant freak show."

Louise might avoid some measure of notoriety if she had company; as Steptoe said last week, "The best bet is to make sure that babies like this are commonplace." In the meantime, her young life seemed commonplace enough. She was scheduled to leave the hospital this week for a private holiday with her parents. She had started to breastfeed. And she had gained two ounces.

This story originally appeared in the August 7, 1978 issue of Newsweek with the headline "About That Baby." Reported by Peter Gwynne, with Tony Clifton in Oldham, Mary Hager in Washington, and Sharon Begley and Barbara Gastel in New York.