Seven ways IVF changed the world – from Louise Brown to stem-cell research

Guardian Web |

It sounds rather perverse and archaic today to call a child born by IVF a “test-tube baby”. The technique of assisted reproduction has become so widespread and normalised, more than 6 million babies down the road, that there’s nothing so remarkable or stigmatising in having been conceived in a petri dish (“in vitro”means in glass, although test tubes were never involved). In many countries worldwide, 3-6% of all children are now conceived this way.

Given how much scepticism and opposition IVF faced when it was still an untried and somewhat speculative field of research in the late 1960s, it’s surprising how quickly it became accepted. The technique was pioneered by the Cambridge physiologist Robert Edwards, working with obstetrician Patrick Steptoe of Oldham general hospital, who first reported successful fertilisation of a human egg cell in vitro in 1969. The pair faced immense opposition. Eminent biologists and doctors, including Nobel laureates, dismissed their work as scientifically worthless, unnecessary and ethically questionable, and the Medical Research Council would not fund it. Physiologist Martin Johnson, Edwards’s graduate student in the 1960s, admitted that he was initially reluctant to join him and Steptoe because “it was quite unsettling … to see the sheer level of hostility to their work”. Nevertheless, after achieving conception in a petri dish, the researchers refined the method for clinical use, culminating in the birth of Louise Brown in Oldham on . Edwards was awarded the Nobel prize in medicine or physiology for his work in 2010, but Steptoe died in 1988.

The birth of Louise Brown transformed public opinion. People could now see that a “test-tube baby” was like any other. Newspapers that had previously warned how IVF threatened human welfare and dignity suddenly became sentimental baby-worshippers, announcing the “baby of the century”. “She’s beautiful”, said the Daily Express, “ – that’s the test tube baby.” After their dystopian forecasts, the media was confused by the normality of it all. Witness the cognitive dissonance in Newsweek ’s headline: “She was born at around with a lusty yell, and it was a cry round the brave new world.”

As Edwards and Steptoe established the first IVF clinic at Bourn Hall near Cambridge, it soon became clear that fertility treatment was going to be big business. At last there was hope for people who had been expected previously to suffer their infertility in silence, and there was no shortage of clients. The procedure needed regulating.

But given how controversial it still was, politicians were reluctant to get involved. It wasn’t until 1982 that the British government appointed a committee to recommend regulatory guidelines, headed by the moral philosopher Mary Warnock. The Warnock report was delivered in 1984, but still the government prevaricated, taking another three years to draw up a white paper. This eventually became the Human Fertilisation and Embryology Act of 1990. It created the Human Fertilisation and Embryology Authority (HFEA) to adjudicate and license all work on human embryos, whether for IVF or for scientific study.

Today, the HFEA is responsible for overseeing a vast range of research well beyond the boundaries of what was initially envisaged for IVF. It has taken a permissive stance that has made the UK a world leader in embryology and related research – showing that, if done with care and sensitivity to balance welfare and social concerns against the importance of medical advance, strong regulation enables research. “Parliament has decided that the regulation of IVF and research involving human embryos in the UK is, in effect, a bargain between science and society,” says HFEA chief executive Peter Thompson. “Our regulatory oversight protects patients and provides the essential conditions for public trust, which in turn allows clinicians and scientists to innovate responsibly.”

By creating more fertilised eggs than are generally reimplanted in the uterus, IVF produces “spare embryos” that may be used, with consent, for scientific research. This notion of “spares” that might have the potential to become a human being (though many do not) still seems morally repugnant to some people. Others accept that “excess” embryos are inevitable if IVF is to achieve good success rates, and feel there is justification for using them to advance scientific understanding and bring medical benefits, rather than discarding them. In any event, IVF has made possible an entire field of human embryo research.

Such studies not only might help to improve IVF itself but may lead to insights into, for example, the causes of early miscarriage or growth defects. “Research on human embryos has changed our fundamental understanding of the genetics of cell biology,” says Alison Murdoch, professor of reproductive medicine at Newcastle University. “As well as helping us understand why fertility of the human species is so uniquely bad, the research has extended applications of human embryology beyond the clinical treatment of infertility into prevention of other medical problems.”

The HFEA places strict limits on what can be done with human embryos. The Warnock report advised that they should not be used in research beyond 14 days from fertilisation – a cutoff that was always acknowledged as somewhat arbitrary, although it was chosen partly because there is a clear biological marker. At this stage, embryos develop the “primitive streak”, the first sign of what will become the spinal column, after which they can no longer potentially become twins. So in a crude sense, after 14 days the “personhood” of the embryo becomes determined. But recent advances have made it possible in principle to keep embryos viable in vitro for longer than 14 days, reopening discussion about whether the 14-day rule should be extended. Currently there are no plans to do so.

Because of theological and ethical opposition to embryo research, stem cell research started long after IVF began in 1978. It really only began to take off after the isolation of human embryonic stem cells (HESCs) in 1998. “Suddenly all the funding agencies wanted to fund research, and clinics were encouraged to participate by asking their patients to donate surplus embryos,” says Murdoch.

In their earliest stages, embryos are made up of stem cells, which can develop into any tissue type in the body. Later generations of cells become specialised: heart cells, muscles, neurons and so on. Because of their versatility, HESCs can be used to grow tissues for regenerative medicine. Efforts to treat conditions such as heart disease or Parkinson’s by injecting stem cells into the respective tissues are now undergoing human clinical trials. In the US, such stem cell therapies have been hampered by the ruling of the George W Bush administration in 2001 that research using new HESC lines taken from IVF embryos could not be federally funded. Such uses of embryos were deemed unethical by Bush’s conservative bioethics advisory panel.

Despite such obstacles, says Murdoch, since 2000 “the science of HESCs made good progress, and the UK was prominent in this research”. Murdoch’s group at Newcastle has pioneered mitochondrial transfer techniques, the offspring of which are misleadingly dubbed “three-parent babies”, to combat heritable and debilitating mitochondrial diseases. “If we had not had the prior experience in [in vitro] human embryology and in the management of the ethical and regulatory challenges from HESC research, we would probably never have been able to achieve this,” she says. Such advances have been aided by the HFEA’s permissive but tight regulatory framework. “It is no accident that the UK is the first country in the world to license gene editing in research and mitochondrial donation in treatment,” says Thompson.

In 1990, shortly before the Commons debate of the Human Fertilisation and Embryology Bill, the British fertility experts Robert Winston and Alan Handyside revealed they had analysed embryos to determine their sex, raising the possibility of screening embryos for a serious disease specific to one sex. This helped to persuade some sceptics that embryo research did, after all, have sound medical motivation.

In fact more detailed genetic analysis of cells removed from embryos to look for disease-linked genes had already been reported. This method, called preimplantation genetic diagnosis (PGD), is now permitted by the HFEA to screen for around 400 serious diseases associated with single genes (such as cystic fibrosis), so that embryos carrying disease-related gene variants will not be implanted – eliminating the risk of passing on the condition for couples who know they are carriers of the gene. But the gene-screening technology also fuels fears of designer babies, selected not to avoid disease but because they have genes thought to be linked to desirable traits such as intelligence and athleticism. That practice is illegal in the UK, but there’s no binding international legislation.

The fertilisation of a human egg cell by a sperm was first observed under the microscope 99 years before Louise Brown was born, by the Swiss zoologist Hermann Fol. But it was only when the fertilised egg’s development could be sustained and followed, with the inception of IVF in 1969, that the human embryo, that suggestive little cluster of cells, became emblematic of the start of life. Few media stories on assisted reproduction are now complete without a photograph of one. The equally iconic image of a sperm being injected through a micropipette into the soft, yielding egg in the variant of IVF called intracytoplasmic sperm injection (ICSI) is itself a kind of stylised recapitulation of sexual intercourse. These pictures are displayed as miraculous images of hope – even while, paradoxically, confronting us with a view of human life deeply alien to our experience. Sociologist Sarah Franklin of the University of Cambridge says that micrographs of ICSI reconfigure our notion of life as something that may be technologically mediated. “Having passed through the looking glass of IVF, neither human reproduction nor reproductive biology look quite the same,” she says. “IVF has changed scientific understandings of what life is.”

The technique has changed traditional notions of family structure, too. Egg donation and surrogacy, the freezing of embryos, and techniques such as mitochondrial transfer and genome editing alter long-held views about biological relations, kinship and the constraints of time, space, gender and genetics on procreation.

So long as the embryo stayed out of sight, all kinds of narratives could be spun about its moral status – traditionally, for the Catholic church, revolving around the issue of when it acquired a soul. But when the biology was laid bare, new stories were required. As the political scientist Rosalind Petchesky has pointed out, anti-abortionists have increasingly framed these in biological terms. Is personhood a matter of unique genetic identity? (Identical twins pose problems there.) Is it granted when the sperm and egg combine? When the embryo begins to acquire shape in the process called gastrulation ? Implantation in the uterus? Formation of the nervous system?

The irony is that, even while biology becomes yoked to moral arguments, it shows our development as a series of contingent steps, none obviously more “fundamental” than the others. Thus the embryo’s moral status remains contentious.

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