Thursday, October 7, 2010

Robert Edwards: The father of test tube babies

Now his work has been widely recognized and utilized, leading to four million lives that would not come at all without his work, although the church still criticizes him. It reminds how hard for new things to develop. It is the normal minds, which makes the biggest number, that impedes the few great ones. When new things come, these mediocre automatically try to crush them, rather than to rethink about their current situations and see if they can adapt. Such intolerance must have painful to Edwards.

Very few scientists can say that four million people are alive because of their work, but Robert Edwards is one of those few. His development of the technique at the heart of that claim — in vitro fertilization (IVF) — has won him this year's Nobel Prize in Physiology or Medicine.

To make IVF possible, Edwards had to solve numerous problems in basic biology — some of which opened the door for embryonic stem-cell research — while facing bitter opposition from churches, politicians and even some of his eminent colleagues at the University of Cambridge, UK. An outgoing yet thoughtful personality who eagerly engaged in public debate, Edwards was hurt by charges that his work was unethical.

But thanks also to his collaboration with another outsider, Patrick Steptoe, an obstetrician at the Oldham and District General Hospital, the world's first test-tube baby, Louise Brown, was born in 1978. Within five years, 150 test-tube babies had been born worldwide. Since then, IVF has become mainstream, and Edwards and Steptoe have been lauded for helping give life to millions. Had he not died in 1988, Steptoe would probably have shared the prize.

In 2001, Edwards won a Lasker award, which often presages the Nobel. Two years ago he celebrated the 30th anniversary of IVF at a symposium where the impact of this work on many levels of society — biology and medicine, but also law, ethics, the arts and social anthropology — was discussed. At 85, Edwards is now too frail to give interviews, but his wife told the Nobel Foundation of his happiness at receiving the prize. "No other scientist could have transformed so many aspects of our society," says Martin Johnson, one of Edwards's first graduate students and now professor of reproductive sciences at the University of Cambridge.

Edwards began his research career in the early 1950s working on the reproductive biology of mice. After harvesting eggs from female mice, he learned how to coax them, and eggs from other species, to mature and be fertilized in a test tube. He also worked out how to control the timing of the rodents' ovulation — which annoyingly tended to happen at night — by administering certain hormones.

Soon after he joined the National Institute for Medical Research in London in 1958, Edwards began applying his findings, and those of other groups working on reproductive biology, to humans. He acquired slices of human ovaries from surgeons, and from these he isolated immature eggs. He spent two disappointing years failing to coax them to mature in vitro, until he realized that the process required at least 24 hours of incubation, not the 12 hours that rodent eggs required. "It is these empirical observations that move science forward," says Ian Wilmut of the MRC Centre for Regenerative Medicine at the University of Edinburgh, UK, who also had to modify the conventional timing of cell incubation to create the first cloned mammal, Dolly the sheep. "These things seem very small in retrospect, but they are critical."

By 1968, Edwards had fine-tuned the maturation of human eggs, learning how to fertilize them with the potential father's sperm and to prod them into forming embryos that could be implanted. Having moved to the University of Cambridge he needed a collaborator to help him apply these techniques in human patients. Having read about Steptoe's pioneering work on laparoscopy — the placement of a fibre-optic endoscope into the abdomen to view internal organs — in his small hospital in northern England, Edwards picked up the phone. Steptoe was already using the method to withdraw fluid from the reproductive tract and agreed that he could also use it to extract eggs. Working as equal partners, the pair set out their own ethical guidelines, agreeing to stop if patients or children were endangered, but not in deference to what Edwards called "vague religious or political reasons".

The UK Medical Research Council refused to fund their work, believing it could lead to babies with severe abnormalities, and disapproving of the pair's high profile in the media (M. H. Johnson et al. Hum. Reprod. 25, 2157–2174; 2010).

Johnson recalls the "strange atmosphere" in the 1960s and 1970s, when the prospect of overpopulation seemed to be a bigger societal concern than infertility. "There was no awareness then of the personal pain of infertility," he says. "I remember eminent Cambridge scientists would tell us that our PhD supervisor was off his rocker." He also recalls Max Perutz and James Watson, both Nobel laureates at Cambridge, telling him it was irresponsible to interfere with the beginning of life. "Often people refused to speak to us in the tea room because they disapproved of what we were doing." Johnson stuck by Edwards though, finding him "inspirational and visionary".

The technique has not only benefitted infertile couples — it can also help parents to avoid passing on serious inherited diseases such as cystic fibrosis or Huntington's disease to their children, by selecting embryos that are free of dangerous mutations for implantation.

In addition, it has enabled the field of human embryonic stem-cell research. Reproductive biologist Outi Hovatta of the Karolinska Institute's IVF clinic in Stockholm, where new human embryonic stem-cell lines are derived from spare embryos, says that Edwards was the first, in 1984, to publicly discuss the benefits of such cells to medical research, and the ethical dilemmas that would inevitably accompany them. He was equally prescient on the need for oversight of his powerful technique, advocating in 1971 that a legal authority should be established to control IVF. The UK Human Fertilisation and Embryology Authority was founded 20 years later.

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