The New Origins of Life

By Claudia Wallis

The age of the test-tube baby is fast developing. Already science has produced an array of artificial methods for creating life, offering solutions to the growing problem of infertility. In these stories, TIME explores the startling techniques, from laboratory conception to surrogate mothers, and examines the complex legal and ethical issues they raise.

COVER STORIES

A group of women sit quietly chatting, their heads bowed over needlepoint and knitting, in the gracious parlor at Bourn Hall. The mansion's carved stone mantelpieces, rich wood paneling and crystal chandeliers give it an air of grandeur, a reflection of the days when it was the seat of the Earl De La Warr. In the well-kept gardens behind the house, Indian women in brilliant saris float on the arms of their husbands. The verdant meadows of Cambridgeshire lie serenely in the distance. To the casual observer, this stately home could be an elegant British country hotel. For the women and their husbands, however, it is a last resort.

Each has come to the Bourn Hall clinic to make a final stand against a cruel and unyielding enemy: infertility. They have come from around the globe to be treated by the world-renowned team of Obstetrician Patrick Steptoe and Reproductive Physiologist Robert Edwards, the men responsible for the birth of the world's first test-tube baby, Louise Brown, in 1978. Many of the patients have spent more than a decade trying to conceive a child, undergoing tests and surgery and taking fertility drugs. Most have waited more than a year just to be admitted to the clinic. Some have mortgaged their homes, sold their cars or borrowed from relatives to scrape together the $3,510 fee for foreign visitors to be treated at Bourn Hall (British citizens pay $2,340). All are brimming over with hope that their prayers will be answered by in-vitro fertilization (IVF), the mating of egg and sperm in a laboratory dish. "They depend on Mr. Steptoe utterly," observes the husband of one patient. "Knowing him is like dying and being a friend of St. Peter's."

In the six years that have passed since the birth of Louise Brown, some 700 test-tube babies have been born as a result of the work done at Bourn Hall and the approximately 200 other IVF clinics that have sprung up around the world. By year's end there will be about 1,000 such infants. Among their number are 56 pairs of test-tube twins, eight sets of triplets and two sets of quads.

New variations on the original technique are multiplying almost as fast as the test-tube population. Already it is possible for Reproductive Endocrinologist Martin Quigley of the Cleveland Clinic to speak of "oldfashioned IVF" (in which a woman's eggs are removed, fertilized with her husband's sperm and then placed in her uterus). "The modern way," he notes, "mixes and matches donors and recipients" (see chart page 49). Thus a woman's egg may be fertilized with a donor's sperm, or a donor's egg may be fertilized with the husband's sperm, or, in yet another scenario, the husband and wife contribute their sperm and egg, but the resulting embryo is carried by a third party who is, in a sense, donating the use of her womb. "The possibilities are limited only by your imagination," observes Clifford Grobstein, professor of biological science and public policy at the University of California, San Diego. Says John Noonan, professor of law at the University of California, Berkeley: "We really are plunging into the Brave New World."

Though the new technologies have raised all sorts of politically explosive ethical questions, the demand for them is rapidly growing. Reason: infertility, which now affects one in six American couples, is on the rise (see box page 50). According to a study by the National Center for Health Statistics, the incidence of infertility among married women aged 20 to 24, normally the most fertile age group, jumped 177% between 1965 and 1982. At the same time, the increasing use of abortion to end unwanted pregnancies and the growing social acceptance of single motherhood have drastically reduced the availability of children for adoption. At Catholic Charities, for instance, couples must now wait seven years for a child. As a result, more and more couples are turning to IVF. Predicts Clifford Stratton, director of an in-vitro lab in Reno: "In five years, there will be a successful IVF clinic in every U.S. city."

It is a long, hard road that leads a couple to the in-vitro fertilization clinic, and the journey has been known to rock the soundest marriages. "If you want to illustrate your story on infertility, take a picture of a couple and tear it in half," says Cleveland Businessman James Popela, 36, speaking from bitter experience. "It is not just the pain and indignity of the medical tests and treatment," observes Betty Orlandino, who counsels infertile couples in Oak Park, Ill. "Infertility rips at the core of the couple's relationship; it affects sexuality, self-image and selfesteem. It stalls careers, devastates savings and damages associations with friends and family."

For women, the most common reason for infertility is a blockage or abnormality of the fallopian tubes. These thin, flexible structures, which convey the egg from the ovaries to the uterus, are where fertilization normally occurs. If they are blocked or damaged or frozen in place by scar tissue, the egg will be unable to complete its journey. To examine the tubes, a doctor uses X rays or a telescope-like instrument called a laparoscope, which is inserted directly into the pelvic area through a small, abdominal incision. Delicate microsurgery, and, more recently, laser surgery, sometimes can repair the damage successfully. According to Beverly Freeman, executive director of Resolve, a national infertility-counseling organization, microsurgery can restore fertility in 70% of women with minor scarring around their tubes. But for those whose tubes are completely blocked, the chance of success ranges from 20% to zero. These women are the usual candidates for in-vitro fertilization.

Much has been learned about the technique since the pioneering days of Steptoe and Edwards. When the two Englishmen first started out, they assumed that the entire process must be carried out at breakneck speed: harvesting the egg the minute it is ripe and immediately adding the sperm. This was quite a challenge, given that the collaborators spent most of their time 155 miles apart, with Edwards teaching physiology at Cambridge and Steptoe practicing obstetrics in the northwestern mill town of Oldham. Sometimes, when one of Steptoe's patients was about to ovulate, the doctor would have to summon his partner by phone. Edwards would then jump into his car and charge down the old country roads to Oldham. Once there, the two would remove the egg and mate it with sperm without wasting a moment; by the time Lesley Brown became their patient, they could perform the procedure in two minutes flat. They believed that speed was the important factor in the conception of Louise Brown.

As it happens, they were wrong. Says Gynecologist Howard Jones, who, together with his wife, Endocrinologist Georgeanna Seegar Jones, founded the first American in-vitro program at Norfolk in 1978: "It turns out that if you get the sperm to the egg quickly, most often you inhibit the process." According to Jones, the pioneers of IVF made so many wrong assumptions that "the birth of Louise Brown now seems like a fortunate coincidence."

Essential to in-vitro fertilization, of course, is retrieval of the one egg normally produced in the ovaries each month. Today in-vitro clinics help nature along by administering such drugs as Clomid and Pergonal, which can result in the development of more than one egg at a time. By using hormonal stimulants, Howard Jones "harvests" an average of 5.8 eggs per patient; it is possible to obtain as many as 17. "I felt like a pumpkin ready to burst," recalls Loretto Leyland, 33, of Melbourne, who produced eleven eggs at an Australian clinic, one of which became her daughter Zoe.

According to Quigley, the chances for pregnancy are best when the eggs are retrieved during the three-to four-hour period when they are fully mature. At Bourn Hall, women remain on the premises, waiting for that moment to occur. Each morning, Steptoe, now 71 and walking with a cane, arrives on the ward to check their charts. The husband of one patient describes the scene: "Looking at a woman like an astonished owl, he'll say, 'Your estrogen is rising nicely.' The diffidence is his means of defense against desperate women. They think he can get them pregnant just by looking at them."

When blood tests and ultrasound monitoring indicate that the ova are ripe, the eggs are extracted in a delicate operation performed under general anesthesia. The surgeons first insert a laparoscope, which is about 1/3 in. in diameter, so that they can see the target: the small, bluish pocket, or follicle, inside the ovary, where each egg is produced. Then, a long, hollow needle is inserted through a second incision, and the eggs and the surrounding fluid are gently suctioned up. Some clinics are beginning to use ultrasound imaging instead of a laparoscope to guide the needle into the follicles. This procedure can be done in a doctor's office under local anesthesia; it is less expensive than laparoscopy but may be less reliable.

Once extracted, the follicular fluid is rushed to an adjoining laboratory and examined under a microscope to confirm that it contains an egg (the ovum measures only four-thousandths of an inch across). The ova are carefully washed, placed in petri dishes containing a solution of nutrients and then deposited in an incubator for four to eight hours. The husband, meanwhile, has produced a sperm sample. It is hardly a romantic moment, recalls Cleveland Businessman Popela, who made four trips to Cambridgeshire with his wife, each time without success. "You have to take the jar and walk past a group of people as you go into the designated room, where there's an old brass bed and a couple of Playboy magazines. They all know what you're doing and they're watching the clock, because there are several people behind you waiting their turn."

The sperm is prepared in a solution and then added to the dishes where the eggs are waiting. The transcendent moment of union, when a new life begins, occurs some time during the next 24 hours, in the twilight of an incubator set at body heat. If all goes well, several of the eggs will be fertilized and start to divide. When the embryo is at least two to eight cells in size, it is placed in the woman's uterus. During this procedure, which requires no anesthetic, Steptoe likes to have the husband present talking to his wife. "The skill of the person doing the replacement is very important," he says. "The womb doesn't like things being put into it. It contracts and tries to push things out. We try to do it with as little disturbance as possible."

The tension of the next two weeks, as the couple awaits the results of pregnancy tests, is agonizing. "Women have been known to break out in hives," reports Linda Bailey, nurse-coordinator at the IVF program at North Carolina Memorial Hospital in Chapel Hill. Success rates vary from clinic to clinic; some centers open and close without a single success. But even the best clinics offer little more than a 20% chance of pregnancy. Since tiny factors like water quality seem to affect results, both physicians and patients tend become almost superstitious about what else might sway the odds. Said one doctor: "If someone told us that painting the ceiling pink would make a difference, we would do it."

In recent years, IVF practitioners have discovered a more reliable way of improving results: transferring more than one embryo at a time. At the Jones' clinic, which has one of the world's highest success rates, there is a 20% chance of pregnancy if one embryo is inserted, a 28% chance if two are used and a 38% chance with three. However, transferring more than one embryo also increases the likelihood of multiple births.

For couples who have struggled for years to have a child, the phrase "you are pregnant" is magical. "We thought we would never hear those words," sighs Risa Green, 35, of Framingham, Mass., now the mother of a month-old boy. But even if the news is good, the tension continues. One-third of IVF pregnancies spontaneously miscarry in the first three months, a perplexing problem that is currently under investigation. Says one veteran of Steptoe's program: "Every week you call for test results to see if the embryo is still there. Then you wait to see if your period comes." The return of menstruation is like a death in the family; often it is mourned by the entire clinic.

Many couples have a strong compulsion to try again immediately after in vitro fails. Popela of Cleveland compares it to a gambling addiction: "Each time you get more desperate, each time you say, 'Just one more time.' " In fact, the odds do improve with each successive try, as doctors learn more about the individual patient. But the stakes are high: in the U.S., each attempt costs between $3,000 and $5,000, not including travel costs and time away from work. Lynn Kellert, 31, and her husband Mitchell, 34, of New York City, who tried seven times at Norfolk before finally achieving pregnancy, figure the total cost was $80,000. Thus far, few insurance companies have been willing to foot the bill, arguing that IVF is still experimental. But, observes Grobstein of UCSD, "it's going to be increasingly difficult for them to maintain that position."

Second and third attempts will become easier and less costly with the wider use of cryopreservation, a process in which unused embryos are frozen in liquid nitrogen. The embryos can be thawed and then transferred to the woman's uterus, eliminating the need to repeat egg retrieval and fertilization. Some 30% to 50% of embryos do not survive the deep freeze. Those that do may actually have a better chance of successful implantation than do newly fertilized embryos. This is because the recipient has not been given hormones to stimulate ovulation, a treatment that may actually interfere with implantation.

Opinion is sharply divided as to how age affects the results of IVF. Although most clinics once rejected women over age 35, many now accept them. While one faction maintains that older women have a greater tendency to miscarry, Quigley, for one, insists that "age should not affect the success rate." Curiously, the Joneses in Norfolk have achieved their best results with women age 35 to 40. This year one of their patients, Barbara Brooks of Springfield, Va., had a test-tube son at age 41; she can hardly wait to try again.

Doctors are also beginning to use IVF as a solution to male infertility. Ordinarily, about 30 million sperm must be produced to give one a chance of penetrating and fertilizing the egg. In the laboratory, the chances for fertilization are good with only 50,000 sperm. "In vitro may be one of the most effective ways of treating men with a low sperm count or low sperm motility, problems that affect as many as 10 million American men," says Andrologist Wylie Hembree of Columbia-Presbyterian Medical Center in New York City.

While most clinics originally restricted IVF to couples who produced normal sperm and eggs, this too is changing. Today, when the husband cannot supply adequate sperm, most clinics are willing to use sperm from a donor, usually obtained from one of the nation's more than 20 sperm banks. An even more radical departure is the use of donor eggs, pioneered two years ago by Dr. Alan Trounson and Dr. Carl Wood of Melbourne's Monash University. The method can be used to bring about pregnancy in women who lack functioning ovaries. It is also being sought by women who are known carriers of genetic diseases. The donated eggs may come from a woman in the Monash IVF program who has produced more ova than she can use. Alternately, they could come from a relative or acquaintance of the recipient, providing that she is willing to go through the elaborate egg-retrieval process.

At Harbor Hospital in Torrance, Calif., which is affiliated with the UCLA School of Medicine, a team headed by Obstetrician John Buster has devised a variant method of egg donation. Instead of fertilizing the ova in a dish, doctors simply inseminate the donor with the husband's sperm. About five days later, the fertilized egg is washed out of the donor's uterus in a painless procedure called lavage. It is then placed in the recipient's womb. The process, which has to date produced two children, "has an advantage over IVF," says Buster, "because it is nonsurgical and can be easily repeated until it works." But the technique also has its perils. If lavage fails to flush out the embryo, the donor faces an unwanted pregnancy.

The most controversial of the new methods of reproduction does not depend on advanced fertilization techniques. A growing number of couples are hiring surrogate mothers (see box) to bear their children. Surrogates are being used in cases where the husband is fertile, but his wife is unable to sustain pregnancy, perhaps because of illness or because she has had a hysterectomy. Usually, the hired woman is simply artificially inseminated with the husband's sperm. However, if the wife is capable of producing a normal egg but not capable of carrying the child, the surrogate can be implanted with an embryo conceived by the couple. This technique has been attempted several times, so far without success.

The medical profession in general is apprehensive about the use of paid surrogates. "It is difficult to differentiate between payment for a child and payment for carrying the child," observes Dr. Ervin Nichols, director of practice activity for the American College of Obstetrics and Gynecology. The college has issued strict guidelines to doctors, urging them to screen carefully would-be surrogates and the couples who hire them for their medical and psychological fitness. "I would hate to say there is no place for surrogate motherhood," says Nichols, "but it should be kept to an absolute minimum."

In contrast, in-vitro fertilization has become a standard part of medical practice. The risks to the mother, even after repeated attempts at egg retrieval, are "minimal," points out Nichols. Nor has the much feared risk of birth defects materialized. Even frozen-embryo babies seem to suffer no increased risk of abnormalities. However, as Steptoe points out, "we need more research before we know for sure."

The need for research is almost an obsession among IVF doctors. They are eager to understand why so many of their patients miscarry; they long to discover ways of examining eggs to determine which ones are most likely to be fertilized, and they want to develop methods of testing an embryo to be certain that it is normal and viable. "Right now, all we know how to do is look at them under the microscope," says a frustrated Gary Hodgen, scientific director at the Norfolk clinic.

Many scientists see research with embryos as a way of finding answers to many problems in medicine. For instance, by learning more about the reproductive process, biologists may uncover better methods of contraception. Cancer research may also benefit, because tumor cells have many characteristics in common with embryonic tissues. Some doctors believe that these tissues, with their tremendous capacity for growth and differentiation, may ultimately prove useful in understanding and treating diseases such as childhood diabetes. Also in the future lies the possibility of identifying and then correcting genetic defects in embryos. Gene therapy, Hodgen says enthusiastically, "is the biggest idea since Pasteur learned to immunize an entire generation against disease." It is, however, at least a decade away.

American scientists have no trouble dreaming up these and other possibilities, but, for the moment, dreaming is all they can do. Because of the political sensitivity of experiments with human embryos, federal grant money, which fuels 85% of bio-medical research in the U.S., has been denied to scientists in this field. So controversial is the issue that four successive Secretaries of Health and Human Services (formerly Health, Education and Welfare) have refused to deal with it. This summer, Norfolk's Hodgen resigned as chief of pregnancy research at the National Institutes of Health. He explained his frustration at a congressional hearing: "No mentor of young physicians and scientists beginning their academic careers in reproductive medicine can deny the central importance of IVF-embryo transfer research." In Hodgen's view the curb on research funds is also a breach of government responsibility toward "generations of unborn" and toward infertile couples who still desperately want help.

In an obstetrics waiting room at Norfolk's in-vitro clinic, a woman sits crying. Thirty-year-old Michel Jones and her husband Richard, 33, a welder at the Norfolk Navy yard, have been through the program four times, without success. Now their insurance company is refusing to pay for another attempt, and says Richard indignantly, "they even want their money back for the first three times." On a bulletin board in the room is a sign giving the schedule for blood tests, ultrasound and other medical exams. Beside it hangs a small picture of a soaring bird and the message: "You never fail until you stop trying." Michel Jones is not about to quit. Says she: "You have a dream to come here and get pregnant. It is the chance of a lifetime. I won't give Up."

--By Claudia Wallis. Reported by Mary Cronin/London, Patricia Delaney/Washington and Ruth Mehrtens Galvin/Norfolk

With reporting by Mary Cronin, Patricia Delaney, Ruth Mehrtens Galvin, Norfolk