Got designs on a designer baby? Egg sharing? Intra-cytoplasmic sperm injection? Meet the citizens panel that's more than happy to make your reproductive choice for you.
For Alan and Louise Masterton, the death of their daughter, Nicole, had a uniquely cruel twist. It was terrible enough that the 3-year-old succumbed to burns suffered in an accident at the family's Monifieth, Scotland, home in 1999. But for the Mastertons, Nicole was more than just a cherished child - she was a chromosomal miracle. The couple had spent 15 years trying to conceive a girl, bearing four sons in the process. When Nicole finally arrived in 1995, the Mastertons considered their prayers answered and their family complete. Louise had her tubes tied.
A month after Nicole's death, a heartbroken Alan began posting messages on Usenet's fertility groups. "We know that if we had another 100 children, none could replace Nicole," he wrote. "But she has left such a huge emptiness in all our hearts, we feel (possibly selfishly) desperate to have another little girl to love and cherish, to let her live the life that Nicole was so cruelly denied." The Mastertons wanted another go at parenthood, provided they could be guaranteed a female child. The note ended with an appeal for leads on in vitro fertilization clinics that could identify an embryo's sex prior to implantation in the womb.
Had the Mastertons lived in the United States, the Wild West of reproductive medicine, their quest would have sparked little outcry. Fertility clinics in the US aren't subject to government licensing - unlike, say, tattoo parlors, veterinary hospitals, and, of course, individual doctors. Any family with $30,000 to spend can order a lab-concocted boy or girl.
The British, however, are more cautious about meddling in Nature's affairs. In the United Kingdom, a government panel known as the Human Fertilization and Embryology Authority tightly regulates the fertility industry. The HFEA, the world's first official overseer of reproductive technology, forbids human bioengineering for "social purposes," a catchall ban that largely disallows gender selection. If the Mastertons wished to proceed, they would need to change the HFEA's mind.
Currently, the HFEA is unique to Britain - but not for long. Canada's national health service, Health Canada, is considering a biotech jury based on the HFEA. Japan, Australia, and several European nations also have inquired about transplanting the authority's model. Ruth Deech, the HFEA's chair, spent last October in Japan, lecturing on the finer points of IVF regulation. There has even been a spark of interest in the freewheeling US: James Childress, a bioethicist from the University of Virginia, lauded the HFEA at a September Senate hearing, noting that "Congress might consider that model for our society as well."
Much of the admiration stems from the HFEA's willingness to confront even the stickiest moral quandaries with a cold, rational eye. As Britain's de facto guardian of the human blueprint, the HFEA takes seriously its obligation to look past emotional appeals in the interest of the big picture. "We are sympathetic to the difficulties of these couples, of course," says Jane Denton, a former nurse and one of the authority's 21 members. "But we do have to look at the overall principle of whether or not it's appropriate to allow some of these techniques. Because if it goes ahead in one particular case, it is eventually going to become widespread."
Most of all, the HFEA fears the slippery slope, a long-debated Ethics 101 concept best summed up in this case as "Today sex-specific children, tomorrow a bioengineered master race." Perhaps allowing the Mastertons to manufacture a substitute daughter would be a first step toward a Gattaca -like future of made-to-order babies, scrubbed clean of diseases and endowed with sparkling blue eyes - a world in which eugenics is just another branch of science.
Alan Masterton was primed for the challenge of persuading the HFEA. A feisty Scot who bears more than a passing resemblance to tough-guy actor Brian Dennehy, Masterton likes to point out his family's motto: Ea quibus credimus defendimus, dum ceciderit ultimus, or "We fight for what we believe in, until the last of us falls." In the past, the HFEA has approved sex selection, but only in rare cases involving genetic diseases that strike a particular gender. Families with a history of hemophilia, for example, are given permission to specify female, because only males are afflicted with the illness. To Masterton, making a similar exception for mental-health reasons didn't seem like much of a stretch. "The void that Nicole has left in our home and in our hearts can never be filled," he says. "But another female child would help us all heal a little bit better."
A Dundee University law student at the time, Masterton spent three months compiling a 30-page pamphlet containing his point-by-point argument in favor of sex selection. On the cover was a picture of a smiling, pigtailed Nicole and an inscription: "The joy and happiness she brought into our lives, her spirit, her place in our family and our hearts are the driving force behind this appeal." Masterton had 21 copies bound - one for each HFEA member - and sent them to London, hoping that the snapshot of a smiling Nicole would melt some hearts.
Unlike the US, Britain was relatively well prepared for the genetics revolution. The UK was the site of the first test-tube baby, Louise Brown, in 1978, and ever since has been trying to divine the murky implications of bioengineering. In 1984, the government-appointed Warnock Committee released a prescient report on the long-term problems that might arise from reproductive technology, everything from snake-oil treatments and dangerous implantation procedures to the ethics of designer kids. "And then that committee suggested setting up another committee, which tends to be a very British way of doing things," says Deech, the HFEA's chair since '94 and an Oxford University administrator. The bioethics panel was created in 1991 to license and inspect IVF clinics, with an eye toward preventing rogue experimentation. Fertility doctors who are discovered engaging in unapproved practices - implanting too many embryos in patients, skirting the rules on sex selection - risk losing their licenses. Those who dare soldier on without licenses risk prison terms.
The wielders of this extraordinary power are, for the most part, ordinary folks. The HFEA's charter requires that at least half of the panel's members come from outside the medical community. And neither the chair nor vice chair can have any connection to the fertility industry. Current ranks include a journalist, an Anglican bishop, an accountant, a social worker, and a retired customs official. "People know we're not just a bunch of mad, profit-seeking doctors running around in white coats," says Sara Nathan, an ex-BBC producer and a member since 1998. "The laypeople are there to make sure the doctors don't let science run ahead of what society wants."
Members are recruited via newspaper ads, and hundreds of applications flood the national Department of Health. A rigorous interview process follows, designed to weed out the merely curious from the passionate. "Sometimes we feel we need a child psychologist, or someone with experience in counseling, or an ethicist, or a philosopher, or a clergyman," says Deech, who assists in the selection process. "We also look for people who do not have any sort of emotional baggage - I think it would be a mistake to have a member who would be crusading for a particular point of view."
Those who are accepted receive three-year, renewable terms, along with a packed schedule of committee powwows and inspection tours. Though most members work full-time at other jobs, they are expected to dedicate at least one day per week to their HFEA duties. The panel meets monthly at the agency's headquarters near London's Liverpool Street.
Passions often flare around the huge oval table, as on this day, when members debate whether new fertility treatments merit the HFEA's seal of approval. The gatherings are closed to the public; only skeletal minutes are published, and individual comments are not recorded. Nathan admits "the meetings can get heated." She recalls her first one, which focused on egg sharing, an arrangement by which an infertile (usually wealthy) woman offers to pay for another woman's IVF procedure in exchange for a few spare ova. Skeptics at the table argued that such arrangements violated a fundamental principle of egg donation - that it should be altruistic - and could pave the way for a black market in gametes. "We spent a long time drawing up egg-sharing guidelines," says Nathan, "to protect women from overly enthusiastic medical staff."
In addition, members supervise inspection teams, which monitor the nation's 74 licensed fertility clinics. At least once a year, an HFEA squad will visit each clinic to see that records are up-to-date and gametes are safely stored. The inspectors also make sure the clinic isn't inflating its success rate to impress potential clients. Even under the best of circumstances, only 25 percent of infertility patients will ever give birth.
The HFEA's task was difficult enough during its early-'90s infancy, when the fertility industry was a rather simple affair. But as the number of British couples seeking treatment doubled over the decade to more than 30,000 annually, the panel's scope broadened. Few Britons had heard of the authority before 1995, the year a man named Stephen Blood contracted a fatal case of meningitis. Moments before his death, his wife, Diane, persuaded doctors to use a technique known as electro ejaculation to extract his sperm. She insisted the couple had talked of starting a family, and she hoped to create his children posthumously. But because Diane was unable to obtain explicit consent from her comatose husband, the HFEA tried to block her reproductive efforts, forbidding any UK clinic to impregnate her with the frozen sperm.
"Here was a man in a coma, at death's door," says Deech. "He didn't know that his sperm was being taken from himä. If there is one fundamental principle in common law, it is that you never do anything to a person when they are unconscious and without consent." Diane Blood's plight generated a tremendous amount of public sympathy, and she contested the HFEA's decision according to a European treaty that permits freedom of movement for medical reasons. She was eventually allowed to take her husband's gametes to Belgium, where she was impregnated.
Deech views the Blood case as emblematic of the fertility industry's evolution and of the HFEA's as well. "When IVF started, I think it was imagined that we would be dealing with infertile couples who needed a baby to complete their families," says Deech. "But around about the early to mid-'90s, it began to move beyond that. Clinicians and patients could see the possibilities of extending fertility beyond menopause, of freezing sperm or embryos, posthumous babies, and so on. And it moved away from just treatment of infertility to, if you like, matters of convenience."
Now, with the human genome a more or less open book, Deech foresees the HFEA grappling with a new era. "We have now just moved on to a third phase, which is genetic engineering," she says. "Are these techniques going to be used for the improvement - or, some would say, the manipulation - of babies?"
Fertility technology is developing at a relentless pace. Ten years ago, an infertile male's odds of siring children were nil. Now, a procedure known as intra-cytoplasmic sperm injection, in which a single sperm is directly injected into an egg, gives 95 percent of those afflicted a shot at genetic fatherhood. With improved hormonal regimens, IVF enables women in their fifties, even their sixties, to bear children. A few mavericks are freezing the testicular or ovarian tissue of terminally ill prepubescents, in the hope that technology might someday allow for the creation of sex cells.
The struggle to overcome infertility has brought researchers to the cusp of altering humanity's genetic heritage. As academics bicker over cloning, more efficacious technologies are quietly changing the rules of reproduction. One such method is cytoplasmic transfer, a process by which the damaged eggs of older women are repaired with injections of cytoplasm - the "jacket" that surrounds the egg - harvested from younger women. Since cytoplasm contains mitochondrial DNA, the resultant child inherits genetic material from several sources - the father, the mother, and the cytoplasm donor (or donors). Jacques Cohen, a researcher at the Institute for Reproductive Medicine and Science of Saint Barnabas, a New Jersey fertility clinic, has supervised the creation of 15 such multiparent babies over the past three years. In the March 2001 issue of the journal Human Reproduction, he boasted that his experiment was "the first case of human germline genetic modification resulting in normal, healthy children." He failed to note that cytoplasmic transfer negates the most basic equation of mammalian reproduction - one male plus one female equals offspring.
Then there are the rodents. In March 2000, Japanese and American researchers announced that they had transplanted human ovaries into mice. Their goal was to "create an egg bank for patients suffering from infantile cancer who may survive into adulthood and want to have a child," explains project leader Akiyasu Mizukami. The breakthrough followed the 1999 claim of Nikolaos Sofikitis, a Greek doctor, who said he'd grown human sperm in rat testes.
Some bioethicists fear these pioneers are pushing humanity down that infamous slippery slope. One nightmare scenario was popularized by Princeton University molecular biologist Lee Silver in his 1998 book Remaking Eden: How Genetic Engineering and Cloning Will Transform the American Family. Silver predicted that wealthy families would have their offspring crafted in IVF clinics, where the tykes would be outfitted with genes that confer advantages in intelligence, health, and appearance. These "GenRich" would lord over the unendowed masses, the "Naturals," who would provide menial labor. "The GenRich class and the Natural class will become entirely separate species with no ability to crossbreed," Silver prophesied, "and with as much romantic interest in each other as a current human would have in a chimpanzee."
That split seems distant, but inklings of a remade Eden are beginning to appear. Last January, scientists at the Oregon Regional Primate Research Center reported that they'd succeeded in endowing a rhesus monkey, nicknamed ANDi, with jellyfish genes. They did so by injecting viruses laden with jellyfish DNA into the mother's unfertilized eggs. ANDi was a first, small step toward allowing doctors to imbue human eggs with genes that confer disease resistance, or even enhanced mental and physical traits.
The standard media reaction to ANDi's birth was horror - a Saturday Night Live sketch joshed that the discovery would "be reported in the New England Journal of Evil." But what loving parents wouldn't resist the chance to enhance their child's prospects for health and happiness? Lori Andrews, author of Future Perfect: Confronting Decisions About Genetics, cites a Boston University Medical School study that found that 12 percent of women say they would abort a fetus with a genetic predisposition to obesity. And American IVF clinics are attracting well-heeled clients by selling gametes derived from Nobel laureates or Yale graduates, services that could conjure up a new tort. "If a woman gets sperm from a Nobel sperm bank," says Andrews, "and E=mc² isn't the first thing out of the child's mouth, will they sue?"
That legal question is typical of the Solomonic dilemmas wrought by the new technology. One of the HFEA's prime directives, for example, states that authority decisions must take into account both the welfare of the embryo and the welfare of existing children. But things get murky when those two obligations conflict, as is the situation with Raj and Shahana Hashmi, a couple whose case is being reviewed by the HFEA. Their 2-year-old son, Zain, suffers from beta thalassemia major, a rare blood disorder that is invariably fatal. Zain endures a harsh treatment regimen of four blood transfusions and five marathon drug-infusion sessions per week. Yet his condition is worsening, and he'll soon die without a stem-cell transplant.
The national registry contains no suitable donors, so the Hashmis are considering a revolutionary IVF procedure to help their son. Using a pre-implantation genetic diagnosis, a doctor would select an embryo with compatible tissue from among Shahana's many fertilized eggs, and then harvest the stem cells for Zain from the resulting child's umbilical cord. This seems to have worked for a Colorado couple, the Nashes, whose daughter, Molly, suffers from Fanconi anemia, a blood disease that leads to bone marrow failure. The Nashes used in vitro fertilization and PGD to select a tissue-matched son, Adam, who was born last October; an infusion of stem cells from her brother has given Molly a 90 percent chance of survival.
Despite the time-sensitive nature of the case, the HFEA is being judicious. Panelists consider the Hashmi decision fraught with ethical perils, most of them related to a frightful vision of babies rolling off a conveyor belt and being stamped SPARE PARTS. "If the first child needed a bone marrow transfusion, for example, or needed another organ, would compatibility mean the second child was always expected to provide these things?" asks the Right Reverend Michael Nazir-Ali, an HFEA member and the bishop of Rochester. One potential solution the HFEA has considered is making the tissue-matched offspring a ward of the court, thereby curtailing the parents' harvesting powers. A final decision is expected early this year, but in the meantime, the HFEA has denied the Hashmis' request to freeze eggs in anticipation of the ruling.
Though no polls have been taken, panel members claim that the majority of Britons support their go-slow approach. "What we do is certainly made easier by the fact that we have so much support from the general public," says Peter Mills, a spokesperson for the HFEA and one of 34 full-time staffers assigned to it. Clinicians, however, frequently rail against the panel, saying it's overly timid. Doctors howled when the authority held up the approval of intra-cytoplasmic sperm injection due to anecdotal evidence that the ensuing babies are prone to chromosomal abnormalities (likely inherited from their infertile fathers). The HFEA tarried despite the procedure's acceptance in the US and Europe, which played host to hundreds of British "fertility tourists" throughout the 1990s. "The problem with the HFEA is that they have to be certain everything is safe before it is used," grumbles Simon Fishel, director of the Nottingham-based Centres for Assisted Reproduction. "If everybody else was inhibited in the same way, no progress would be made. Indeed, some would argue that Louise Brown would never have come into existence with the current act."
The HFEA's influence over a controversial field of medicine, coupled with the secrecy of its deliberations, has made it a particularly inviting target in the press. Tom Utley, a popular Daily Telegraph columnist, wrote in November 1999: "It is hardly an exaggeration to say that, every time these 21 people meet, they are required to make decisions that in an earlier age were left to God."
The Fleet Street tabs were similarly unkind to the Mastertons, accusing the couple of reviving Nazi eugenics and treating kids like consumer items. "How long before every child born in Britain is as, one to another, a foil-wrapped pack of tomatoes?" wrote one Daily Mail scribe. Alan Masterton couldn't understand the fuss - he's heard of cases in which Britons discovered a fetus' gender via amniocentesis and then aborted. Why should Louise be denied the opportunity to select the sex of her child merely because she required IVF?
Alan made repeated requests - 26 by his count - to state his case in person. HFEA rules bar public participation at the panel's meetings, but chief executive Suzanne McCarthy assured him that his case would be considered. Finally, in January 2000, the issue came up at the authority's monthly conclave. The committee decided, in effect, not to hear the case at all. If the Mastertons wanted the HFEA to reconsider the use of PGD for sex selection, they would have to persuade a British clinic to file a licensing application on their behalf. "We sorted out the law," says Deech, "which was that they should really make their case to a clinic. And if a clinic really wants to espouse it, they should apply to us."
The decision left the Mastertons in a tight spot. They needed to find a clinic willing to challenge the HFEA's ruling. However, obtaining a license is an arduous process that few clinics would undertake without being fairly certain their application would be accepted - and, in this case, such an outcome was highly unlikely. Alan Masterton was enraged. "I was promised right up to the day before the meeting that my case would be seen by all 21 members of the committee," says Masterton, who accuses Deech of making the decision unilaterally. She denies this. With no formal appeals process, the family's options were limited. They requested a parliamentary investigation, and last May an ombudsman concluded that the HFEA did err in promising the Mastertons that an individual appeal would be heard. But the ombudsman has no power to force reconsideration.
The HFEA based its ruling on a technicality, but it's clear that many members harbored qualms about the Masterton case. Nazir-Ali believes the sex-selection boundary is best left uncrossed. "There's a fear that sex selection for social purposes will discriminate against women, in effect," he says. "There is also the fear that a child may be treated as a means to an end, rather than an end in itself, particularly if that child is seen as replacing a child who died in tragic circumstances. It's a heavy burden to bear if you're there as a replacement, not for your own sake."
Still desperate for a daughter, the Mastertons joined the hordes of British fertility tourists who go elsewhere for treatments deemed too risky or offensive back home. The richest travel to the United States; those of lesser means head to Italy, also an unregulated frontier of reproductive medicine. In July of 2000, with £6,000 borrowed from friends, the Mastertons visited Biogenesi, a Roman clinic, where doctors removed three eggs from Louise's ovaries. Two of the eggs were immature so they couldn't be used - a common complication for a woman in her forties. The surviving ovum was successfully fertilized with Alan's sperm, and then screened to ensure that the telltale Y chromosome was absent.
No dice. It was a male. And it was the last straw.
Lacking funds for another treatment cycle, the Mastertons donated the embryo to an infertile couple. And then they headed home, exhausted and broke. They've retained a London lawyer to research whether the family can file an appeal in accordance with Britain's Human Rights Act, which guarantees a fair judicial review. Alan knows it's a long shot, and his natural optimism has been supplanted with bitterness. "These people are coldhearted, uncaring bastards," he says, his Scottish brogue thickening with anger. "They look after their own asses and care not a jot for anyone else. Because of the shabby way my family has been treated by these deceitful people, I will crusade against the way this organization operates until it is changed to be more people-friendly and accountable."
The HFEA's handling of the Masterton case still riles Simon Fishel too, who favors a regulatory body staffed by more seasoned scientists in addition to laypersons. "If you and your medical practitioner want to do some chemical jiggery-pokery for you to have the gift of your own child, who else should have a say in that decision?" he asks. "Does it matter that your next-door neighbor has an opinion on how you reproduce?"
Absolutely, says HFEA member Sara Nathan. "Fertility doctors are not just curing somebody's arm ache - they're creating new people," she says. "And those people are going to live in society, and they'll have mutual responsibilities with society. That's why we need regulation that is both scientific and ethical."
The next big test for that credo will likely be the use of PGD for science beyond sex selection. By analyzing a sliver of embryonic cells, doctors can now determine whether an embryo contains genetic flaws, and then refrain from implanting it in the womb. Of the 10,000 or so genetic disorders that can afflict an embryo, only a few are currently subject to tests - primarily grave conditions such as cystic fibrosis or Duchenne's muscular dystrophy. But if the evolution of pre-implantation genetic diagnosis mirrors that of other reproductive technologies, doctors could soon be able to identify whether a child is predisposed to middle-aged cancer, late-onset deafness, or even premature baldness.
Nevertheless, if there were a test developed that could detect a propensity for severe late-onset diseases, the ever-cautious HFEA would be disinclined to approve its use. "By the time a person is 45, there might be a cure for heart disease, or that person may be a Beethoven who's written I don't know how many symphonies, or married and had beautiful children who are free of heart disease," says Deech. "People are fearful of the search for perfection, and in the public's mind there is a broad distinction between avoidance of a very serious disease that a parent would dread, and trying to choose an embryo who will be perfect."
That philosophy baffles Simon Fishel. "You either have to be on the side of medicine and scientific development, or on the side of natural selection. You cannot just say, well, with regard to appendicitis, it's OK to intervene, but in regard to human reproduction, we should just leave it up to divine providence." If bioengineering can spare a human the burden of, say, diabetes, Fishel cannot imagine a good reason for not taking action. And if this science can also be used to select a baby's gender, then so be it.
But what about sparing a toddler the dangers of asthma? Or an adult the horrors of clinical depression? The thorniness of these questions has opened a debate in the United States about whether to let fertility doctors act as sole arbiters of what's best for humanity. There are federal agencies that regulate airwaves, power plants, highways, even harbor buoys. Why not a biotech jury to safeguard life itself? It all seems so sensible.
Not to everyone, though. "I am aware that your government has been discussing possibly following the HFEA model," says Alan Masterton, turning a bit gruff. "My heartfelt advice, born of experience, is don't do it."
