The First Test-Tube Baby

The Director … continued with some account of the technique for preserving the excised ovary alive and actively developing; passed on to a consideration of optimum temperature, salinity, viscosity … actually showed them … how the eggs … were inspected for abnormalities, counted and transferred to a porous receptacle; how … this receptacle was immersed in a warm bouillion containing free-swimming spermatozoa …

—Aldous Huxley, Brave New World (1932)

To millions of people in Britain and elsewhere around the world last week, it seemed as if Huxley’s prophetic vision had become reality. Banner headlines in Britain called it OUR MIRACLE and BABY OF THE CENTURY. On television newscasts in Europe and the U.S., stories about an obscure British couple and the abstruse subject of embryology shouldered aside items about the Middle East, international trade balances and inflation. Some commentators heralded the coming birth as a miracle of modern medicine, comparable to the first kidney and heart transplants. Theologians—and more than a few prominent scientists—sounded warnings about its disturbing moral, ethical and social implications. Others, made wary by the recent cloning hoax, remained unconvinced that the child about to be born was indeed the world’s first baby conceived in a test tube.

The center of all the furor was a four-story red brick building in the old textile mill town of Oldham in the northwest region of England. There, in a guarded room of the maternity section of Oldham and District General Hospital, Lesley Brown, 30, a resident of Bristol, was being tended in her final month of pregnancy. For nine years she and her husband Gilbert John, 38, a van driver for British Rail, had futilely tried to have a child. Now, finally, the Browns were on the verge of achieving their hearts’ desire—in a most spectacular manner. Early in August, she is due to give birth by natural means to a child that her doctors say was conceived not in her body but in vitro (in glass) in a medical laboratory.

In anticipation of that scientifically assisted blessed event, normally quiet Oldham (pop. 227,000) last week was in a state of siege. From as far off as Japan, scores of reporters and cameramen had converged on the town to be on hand for the birth of Baby Brown. Despite pleas from the doctors that the hullabaloo was endangering both mother and child, journalists steadfastly prowled the hospital’s precincts. They were seeking any morsel of news. Perhaps a brief word with one of the doctors responsible for the Brown experiment: Patrick Steptoe, who came and went daily in his white Mercedes, dodging in and out of the hospital’s side doors to avoid the press. Or a chat with the equally elusive father. Or, scoop of scoops, a photograph of Lesley Brown peeking from behind her carefully curtained window.

But pickings were slim; the Browns had made a deal, estimated at $565,000, that allowed only reporters from the London Daily Mail to have access to the Brown family. Doctors and hospital personnel were also exasperatingly inaccessible. Frustration ran high, and after a bomb threat was called in to the hospital, there were rumors that it had been made by a reporter or photographer who, as a last resort, planned to intercept Lesley Brown as she was being evacuated from the building. (She was indeed moved, but only to a different part of the hospital.) Snarled a hospital guard at a cluster of reporters who had stationed themselves just under Lesley Brown’s room: “You bastards, don’t you care about the baby?”

In fact, journalists as well as the public cared all too much. As the Oldham Evening Chronicle commented: “It was not unnatural that the world’s press should scramble for information.

People want to know, and have a right to be curious about such things.” Indeed, long before anyone heard of Huxley or even Mary Shelley’s Frankenstein monster, people were fascinated and frightened by the prospects of creating life outside the womb.

A 16th century rabbi in Prague was thought by later generations to have been endowed with mystical powers that enabled him to create a golem, or artificial man, at will. Perhaps the most famous of these legends is that of Faust and Homunculus, the little manlike creature that was created in a vial.

Yet for all the breathlessness and hyperbole in the British press — “We could get baby farms, mass-produced kids, 1984 six years early!” exclaimed London Daily Express Editor Derek Jameson— the Brown venture fell far short of ushering in a Brave New World. Like countless other women with fertility problems, Lesley Brown suffered from a fallopian tube disorder. In their al most fanatic insistence on secrecy, her doctors declined to say whether the tubes were missing or merely blocked. Whatever the trouble, it was apparently serious enough to prevent her from becoming pregnant.

Under normal circumstances, pregnancy occurs when an ovum, or egg cell, released by a woman’s ovary during ovulation is fertilized as it passes through the fallopian tube, successfully penetrated by just a single sperm that has traveled through the uterus. After the fertilized egg undergoes a number of cell divisions, the tiny clump of cells enters the uterus, where it burrows into the wall and develops for nine months or so until birth.

To bypass Lesley Brown’s fallopian tubes, Oldham Hospital’s Steptoe, 65, a highly respected gynecologist, and his colleague, Cambridge University Physiologist Robert Edwards, 52, undertook a remarkable procedure they have been experimenting with for a decade. They removed a ripe egg from Mrs. Brown’s ovary, placed it in a laboratory dish and added sperm from her husband. After incubating the ovum as it began to divide, they finally placed the developing embryo in the uterus, where it became implanted and continued to grow into a fetus in what seemed to be an entirely normal way.

For Steptoe and Edwards, the Browns’ baby, apparently normal and so near birth, was a long-sought goal: in scores of previous transfers of externally fertilized eggs, a successful, full-term pregnancy had never been achieved. To many other doctors, including rival researchers, the feat was a stunning achievement.

If the baby is born normal and healthy, they pointed out, it will give new hope to women who have been unable to conceive be cause of tubal difficulties. In the U.S. alone, as many as 10% of all married women who want to bear children cannot. Possibly a third of these are infertile because of blocked tubes that cannot be surgically repaired.

For many scientists, there were even more sweeping ramifications. They noted that in-vitro fertilization techniques may give researchers an important new laboratory tool for devising ways of coping with genetic diseases, testing new methods of contraception and, perhaps most important of all, studying close up one of nature’s most awesome and still baffling processes: the first stirrings of life. Said one leading specialist on reproductive physiology, Dr. Carl Pauerstein of the University of Texas, of the British work: “It has the potential for adding greatly to the knowledge of the reproductive biology of our species.”

Other researchers were far more skeptical of going beyond in-vitro fertilization to the actual implantation of the developing embryo in the uterus. “The potential for misadventure is unlimited,” said Dr. John Marshall, head of obstetrics and gynecology at Los Angeles County’s Harbor General Hospital. How sure could anyone be that the Browns’ baby will not be deformed, he asked. “What if we got an otherwise perfectly formed individual that was a cyclops? Who is responsible? The parents? The doctor? Is the government obligated to take care of it?”

There was also widespread criticism of the secrecy in which the work of Steptoe and Edwards was conducted. The Uni versity of Pennsylvania’s Dr. Luigi Mastroianni, who has him self fertilized eggs in vitro but never attempted to implant them, points out that the British researchers had not provided any details about the condition of Mrs. Brown’s fallopian tubes. “If they are completely absent,” said Mastroianni, “you must accept the fact that the egg was fertilized in vitro. But if they are just damaged, there’s always the possibility that the egg may actually have been fertilized in vivo [in the body] — that the tubes may have functioned again.” Sir John Stallworthy, president of the British Medical Association’s board of science, agreed that the sensational claim “requires irrefutable proof.”

Some thoughtful observers saw the work as still another ominous step toward further control and manipulation of basic life processes — comparable perhaps to the recently acquired ability of molecular biologists to rearrange and recombine genes of different creatures and even to create new life forms. These critics are not really worried about the imminence of Huxley-style baby hatcheries that produce everything from superbrainy “Alphas” to dronelike “Epsilons.” After all, says one researcher, “test-tube babies are not going to be popping out like peanuts.” Rather the concern centers on the far-ranging social, ethical and legal repercussions. In the words of Nobel Laureate James Watson, there is the potential for “all sorts of bad scenarios.” What, for instance, could prevent a scientist from taking a fertilized egg from one woman, who perhaps did not want to carry her own baby, and implanting it in the womb of a surrogate. Who then would be the child’s legal mother? Or, in the words of an old joke, “Which one gets the Mother’s Day card?”

By a striking coincidence, the first legal reverberations from test-tube fertilization were being felt last week. In U.S. district court in New York, a jury of four women and two men was hearing testimony in an unusual $1.5 million damage suit against Manhattan’s Columbia-Presbyterian Medical Center and its chief of obstetrics and gynecology, Dr. Raymond Vande Wiele. The action was brought by a Fort Lauderdale, Fla., dentist, Dr. John Del Zio, 59, and his wife Doris, 34.Despite several operations, Mrs. Del Zio had apparently been unable to become pregnant because of tubal problems. In 1972, she agreed to let Dr. Landrum Shettles place in her womb an egg said to have been fertilized externally by her husband’s sperm. But upon learning of the experiment in his department, Vande Wiele destroyed the specimen, contending that the procedure was risky, that Shettles lacked the skills to undertake it and that it had not been approved by the hospital’s committee on human experimentation.

In emotional, sobbing testimony, Mrs. Del Zio charged that Vande Wiele’s action robbed her of a chance to have a child by her current husband (she had one child in a previous marriage before the tubal problems), damaged her both physically and psychologically, upset her sex life and jeopardized her marriage. The defense, for its part, questions whether the flamboyant Shettles, who has since left the hospital, ever managed to fertilize Mrs. Del Zio’s egg and whether his other claims of in-vitro fertilization were valid. Scornfully, a defense lawyer said Shettles’ work was as different from the achievement of Steptoe and Edwards as “a Model T Ford is from a Porsche.”

The courtroom histrionics tended to obscure the real question in the case: Was Vande Wiele’s action, which he freely admits, medically and legally justifiable, and did Mrs. Del Zio’s emotional and physical problems stem from any trauma she might have suffered from learning of the destruction of her ovum? Should the jury find for Mrs. Del Zio, doctors involved in such experiments will have to weigh carefully their legal liabilities before considering these new procedures.

Perhaps because of past difficulties with their own research, as well as the controversies it has stirred, Steptoe and Edwards remained quiet about their successful implanting through most of Lesley Brown’s pregnancy. Even though fertility experts round the globe were generally aware of their research, no announcement was forthcoming from the British doctors until April, when a reporter closing in on the story got them to admit that the birth of a test-tube baby was at hand. Even so, Steptoe and Edwards were reluctant to give any details; they even withheld the patient’s name for fear that the mother might not be able to withstand the pressure of all the public prying.

Yet, as journalists pursued the story, information slowly dribbled out. Some of it came directly from the family through the Daily Mail under the syndication deal, but other facts were unearthed by reporters in Oldham, some of whom were not above using £20 notes to loosen the lips of anyone even vaguely in the know.

Thus the world learned, in prose and tone that often seemed straight from a Monty Python satiric sketch, that Les ley Brown is a pretty woman of 5 ft. 5 in., who wears her brownish hair in a pageboy cut. In her turquoise-blue hospital room, she often lounges in an easy chair, wearing a brown-and-white bell-sleeved housecoat. She spends much of her time making telephone calls, doing puzzles, knitting, nibbling on mints and eating ordinary hospital food (a typical lunch: steak and kidney pie with mashed potatoes, followed by fruit tart). Occasionally, added the Evening Chronicle, she has become weepy and depressed, and was briefly worried, until reassured by other expectant mothers, about the seemingly small size of the baby in relation to the weeks of pregnancy. Steptoe apparently tried to get her to stop smoking, but she still sneaks an occasional cigarette. Presumably, she knows of all the concern about her and her baby because she has a television and a radio in her room. From her window, she can see the hospital’s children’s unit with its gaily colored swings, whirling merry-go-rounds and playful youngsters. Reported a nurse: “She just feels like any other mother-to-be: tired, fed up and fat.”

Before the “Browns became international celebrities, they lived quietly in a white row house in Easton, a neighborhood in Bristol, about 150 miles from Oldham. “Ever such a nice couple,” say neighbors. John Brown apparently likes few things better than to tinker with his automobile and, even before the current furor, kept largely to himself. Says a friend: “He is a very polite bloke. I don’t think he socializes with a lot of people.” Still, the Browns, who live with John’s 17-year-old daughter by a previous marriage, are hardly recluses. Before Lesley Brown was sequestered in the hospital for round-the-clock monitoring, she talked about babies with neighbors, but gave no hint of her own extraordinary pregnancy. Recalls one surprised neighbor, “I never knew there was anything unusual.”

Many scientists shared that surprise. For years they have talked about fertilizing the human egg in a test tube. But with every claim of success has come the inevitable countercurrent of doubt. Indeed as early as the 1940s, the eminent Boston gynecologist Dr. John Rock, a pioneer in development of the birth control pill, reported that he and colleagues had managed to fertilize an egg in vitro. But other scientists believe that the few cell divisions observed by Rock were nothing more than “parthenogenic cleavage” (division of the egg without the involvement of a sperm), probably induced by incidental stimulation of the ovum. Scientists were similarly skeptical of claims by Shettles in the 1950s that he had brought an externally fertilized human egg into the sixth day of cell division, and by an Italian scientist, Daniele Petrucci, who a few years later announced that he had kept alive an embryo in a test tube for 29 days. The embryo was destroyed, Petrucci said, because it was growing “monstrous.” He dropped the work entirely after it was condemned by the Vatican.

Not until the mid-1960s did researchers learn how to fertilize mammalian eggs in vitro on a regular basis. The groundwork was laid by M.C. Chang of the Worcester Foundation for Experimental Biology in Shrewsbury, Mass., and C.R. Austin of Cambridge University, who had solved the problem of in-vitro capacitation of rabbit sperm, a process that enabled sperm to penetrate the egg in the laboratory. Until then, the sperm were notably ineffectual in that role. But these early successes ‘involved creatures no higher than rabbits, hamsters and mice.

Finally, in 1969, Steptoe and Edwards announced that they had done the same thing with human eggs. The report caused a worldwide sensation and drew considerable fire, particularly from conservative churchmen. Trying to allay fears that he was actually attempting to create babies outside the womb, Steptoe insisted that his true goal was quite different. Said he: “All that I am interested in is how to help women who are denied a baby because their tubes are incapable of doing their small part.”

In 1974, another English scientist, Dr. Douglas Bevis, casually dropped an even bigger bombshell. Not only had human eggs been fertilized in the test tube, said Bevis, but they had been successfully implanted in three women who subsequently gave birth. It was widely suspected that he was talking about his own work. When he proved unwilling or unable to document his claims, Bevis was so roundly denounced that he soon vowed to give up all such research. To this day, no one really knows whether Bevis was making phony claims or was a victim of the furious scientific competition between rival fertility researchers. In any case, the Bevis case sharply increased public concern and brought vociferous right-to-life advocates into the fray. They equated the fertilization experiments—and the frequent destruction of apparently live embryos in the lab—with outright abortions of far more developed embryos and fetuses in women.

The clamor had its effect. Researchers like ‘Steptoe and Edwards made fewer and fewer ‘public reports on their work. In the U.S., almost all research with human eggs came to an abrupt halt; under a 1975 federal order, the Department of Health, Education and Welfare was barred from funding any invitro fertilization experiments unless they were first approved by a national ethics advisory board appointed by the HEW Secretary. Perhaps because it involved such a touchy subject, the panel was not formed until January of this year. One of its first orders of business: to weigh the long-pending application from a Vanderbilt University fertility researcher, Dr. Pierre Soupart. His objective: to resume tests, suspended in 1975, that are designed to show if there is any increased risk of chromosomal abnormalities when human eggs are fertilized in the test tube rather than in the body. Commenting on the delays forced upon American researchers by what is, in effect, an unofficial federal moratorium, U.C.L.A. Obstetrician Jaroslav Marik bitterly notes that “if all the pulls and pressures had not been applied, there might be an American woman now about to deliver” a test-tube baby.

Perhaps so, but the skills and know-how of the Steptoe-Edwards team are almost universally acclaimed, even if its inclination toward secrecy is not. Silver-haired and elegant, Steptoe is a pioneer in the use of laparoscopy, a technique for exploring the abdomen and observing the reproductive tract by means of a long, thin telescope equipped with a fiber optics light. He is also an impeccable dresser, enjoys watching cricket and is a fine organist. In the words of a colleague, he is “a man of character and determination who if someone is speaking nonsense is perfectly willing to say so.” His partner Edwards, the father of five daughters, is no less accomplished in his own field, the physiology of fertilization, and just as dedicated. During early experiments at Cambridge, he often returned to the physiology department at night, scaled a wall, and slipped into his lab to see if fertilized eggs were still alive.

Those qualities are surely as essential in this difficult field as are flasks, hormones and microscopes. Though man has wondered about human reproduction since the dawn of history, it remains, in many respects, as mysterious—some would even say as mystical—as ever. At birth, the infant human female is endowed with as many as a million egg cells, many more than she will ever need during her 30 or so child-bearing years. Starting at puberty, eggs are released, usually one at a time, about midway in the menstrual cycle. The process is intricate and marvelous. Stimulated by hormones, part of the body’s chemical signaling system, a ripe egg is expelled from its grapelike encasement, or follicle, in the ovary; in any month, either of the female’s two ovaries may contribute an ovum. Then the egg enters the nearby fallopian tube. If coitus has taken place, the egg will shortly run into a swarm of tailed sperm that have managed, like salmon battling upstream, to fight their way into this passageway. In a dramatic headlong plunge, a single sperm will penetrate the waiting ovum’s outer layer, its 23 chromosomes joining the egg’s 23. That produces the full complement of 46 chromosomes, which contain all the genetic instructions necessary to produce a complete human being.

The fertilized egg continues its journey, dividing as it moves through the tube. Finally, after several days, it will have become a blastocyst, a hollow, ball-shaped cluster of fewer than 100 cells. By now, it will have reached the uterus. There the blastocyst embeds itself in the uterine wall, where it begins drawing nourishment from the mother and starts the miracle of differentiation: the rapid transformation of cells into tissue that soon becomes recognizable as heart, brain, muscle, kidneys and all the other components of a living, self-sufficient being.

Yet the egg’s journey is precarious. Unless the proper hor mones are present in appropriate concentrations, setting the stage for ovulation and fertilization, this intricate chain of events will not be initiated. The egg will not burst from the ovary, the cervical mucus will be too sticky for the entry of sufficient sperm into the uterus, and the lining of the uterus will not prepare to receive the fertilized egg. Indeed, hormonal disorders at any point in the sequence make it so fraught with peril for eggs and sperm that perhaps a third of all potential pregnancies end at the time of implantation. As Dr. Albert Decker of the New York Fertility Research Foundation puts it, “Pregnancy is not simple. Women do not get pregnant at the drop of a hat.”

In Lesley Brown’s case, the difficulties were not hormonal but tubal. In recent years surgeons have managed to repair many tubes with precise microsurgery. But for Mrs. Brown that did not appear possible. The door to pregnancy seemed to be tightly shut until she was referred to Steptoe, who with Edwards had probably made more attempts than any other researchers to get around such blockages by in-vitro fertilization and implanting techniques.

Yet despite the British team’s long experience, the procedure had never resulted in a live birth. To bring it off successfully requires scientific ingenuity, surgical dexterity and, some might say, a lot of plain luck. The doctor must remove the egg at the exact moment in the monthly cycle when it has reached maturity. To ensure the success of that crucial initial step, Steptoe and Edwards follow a standard procedure for treating infertility: they administer fertility hormones, like those that have been responsible for the rash of multiple births in recent years. That encourages the ripening of several eggs at one time. To get at the eggs, Steptoe turns to laparoscopy. While the woman is under anesthesia, an incision is made near the navel. Inert gases are pumped into the abdominal cavity to expand itand separate the organs, and the laparoscope is inserted to seek out appropriate eggs, which are then sucked into a small hollow needle.

Unless the extracted eggs and the husband’s sperm — usually obtained by masturbation — are kept at the right temperature and pressure, free of contamination and in an appropriate culture medium (salts, nutrients and sometimes blood serum), fertilization will not occur. Explains the University of Pennsylvania’s Benjamin G. Brackett: “You don’t want the eggs to suspect they are out of the body.”

Equally important, the sperm must be primed for fertilization or, in the technical term, capacitated. This means that the chemical inhibitors preventing the sperm from penetrating the egg must be removed from the surface of the sperm. How this trick is accomplished in the body remains a puzzle; some scientists think that the woman’s secretions do the job. But in the lab, experimenters usually are able to prime the sperm simply by gently bathing them in a salt solution. There is also the critical matter of timing: neither eggs nor sperm have unlimited lifetimes, nor does the uterus remain receptive for long. So egg and sperm should be quickly brought together.

Even after fertilization, doctors have no assurance that the egg will divide; again the culture medium must be carefully controlled. Some researchers think that the highest rate of success could be achieved if the content of the solution were continually altered as the cells go through stages of division. Finally, when the egg becomes a blastocyst or shortly before, it is ready for implanting. One way this can be done is by picking up the egg, which is still no bigger than the dot at the end of this sentence, with a tiny hollow tube, or pipette, then inserting it through the cervix and into the uterus. If all goes well, it will implant itself in the uterine wall. At least a week must pass before the doctors know if the patient is indeed pregnant.

Since the beginning of their partnership more than a decade ago, Steptoe and Edwards are believed to have attempted in-vitro fertilization and implantation in hundreds of women. In perhaps half of these cases, eggs were fertilized. But successful implantations have been rarer. Shortly before Mrs. Brown was treated last fall, a medical publication quoted Steptoe as saying that of 60 attempted implants, only three showed signs of lasting — one for nine weeks, the others for two. Why the difficulty?

Vanderbilt’s Soupart gives least three reasons for failure: 1) difficulties in the tiny egg the culture chamber into the uterus, 2) undetected chromosomal abnormalities that doom the egg before it has a chance to implant itself, and 3) interference in the acceptance of the egg by the very hormones that were used to encourage ovulation.

According to the British newspapers, all these critical steps in the Brown case — removal of the eggs, fertilization in the laboratory and implantation — took place in a small turn-of-the-century institution called Dr. Kershaw’s Cot age Hospital, amid green fields about a mile from the hospital where Mrs. Brown awaits the birth. Steptoe has done much of his fertilization work there, using four rooms, plus a small adjoin theater, that are all protected by locks, sliding doors and a red warning light.

Ironically, Steptoe is able to pursue his expensive fertility work in part because of his earnings from legal abortions. He soon hopes to move to larger facilities and dreams of eventually building a center for reproductive studies.

From the very start, the efforts to give Lesley Brown a child went extremely well. As the pregnancy progressed, Steptoe and Edwards apparently even determined its sex from chromosomal examination. Lesley, however, is said to have insisted on not being told. She explained: “I’ve been waiting too long for this to be denied the surprise of learning whether the baby is a boy or girl at birth.” Late in her pregnancy, Mrs. Brown was sent to the spacious and well-equipped maternity wing at Oldham. There she presumably underwent all the most advanced testing: ultrasonic scanning to check the position, size and bodily shape of the fetus as it developed; monitoring of hormone levels and fetal heart beat; and perhaps withdrawal of amniotic fluid from the womb to determine whether the child had Down’s syndrome (mongolism), the congenital malformation called spina bifida or any number of other genetic defects. Had the doctors detected any serious problems, Lesley Brown could have quickly received an abortion. Observed Dr. Stuart J. Steele of London’s Middlesex Hospital Medical School: “Mrs. Brown would have had all the very close medical supervision that one would expect in a particularly precious pregnancy.”

How that precious pregnancy turns out will shortly be known; one estimated due date is Aug. 4, but a swing of two weeks on either side is perfectly normal. Steptoe and Edwards, for their part, must surely feel highly confident; otherwise these experienced researchers would never have allowed the pregnancy to go so far. Yet on the eve of what may well be the most awaited birth in perhaps 2,000 years, there are also still many unanswered questions. For the Brown family, it is whether their test-tube child is healthy and can ever hope to have anything resembling a normal life. For the doctors, it is whether they have pushed medicine to a new frontier or set it dramatically back by creating a medical disaster. For the world at large, it is whether doctors should be free to continue such daring exploits or whether new restraints should be posted to keep them from poaching on nature’s domain. There is a very large gathering in the waiting room for Baby Brown. ∙