In vitro fertilization pioneer wins Nobel Prize

The Nobel prize in physiology or medicine has been awarded this year to Robert G. Edwards, an English biologist who with a physician colleague, Patrick Steptoe, developed the in vitro fertilization procedure for treating human infertility.

Since the birth of the first test tube baby, Louise Brown, on July 25, 1978, some 4 million babies have been conceived by mixing eggs and sperm outside the body and returning the embryo to the womb to resume the normal development. The procedure overcomes many previously untreatable causes of infertility and is used in 3 percent of all live births in developed countries.

Advances in human reproductive technology arouse people’s deepest concerns and often go through a cycle, first of outrage and charges of playing God, then of acceptance. In vitro fertilization proved no exception.

“We know that IVF was a great leap because Edwards and Steptoe were immediately attacked by an unlikely trinity — the press, the pope and prominent Nobel laureates,” biochemist Joseph Goldstein said in presenting the Lasker Award to Edwards in 2001.

Research with human embryonic stem cells, made possible by Edwards’ development of in vitro fertilization, has evoked a similar outcry, but so far there are no offsetting practical benefits like the birth of healthy babies to eager parents. Because of the difficulty of stem cell research, such benefits may not be seen for many years, if ever.

Edwards, a physiologist who spent much of his career at Cambridge University in England, devoted more than 20 years to solving a series of problems in getting eggs and sperm to mature and unite successfully outside the body. His colleague, Steptoe, was a gynecologist and pioneer of laparoscopic surgery, the method he used to extract eggs from the prospective mother.

Steptoe, who presumably would otherwise have shared the prize, died in 1988 (the Nobel prize is not awarded posthumously). Edwards, 85, has retired as head of research from the Bourn Hall Clinic in Cambridge, which he and Steptoe founded as one of the world’s first centers for in vitro fertilization.

Because of health issues, Edwards himself was not available to reflect on his research career or the children alive because of his achievement.

“Unfortunately he is not in a position to understand the honor he has received today,” said Dr. Michael Macnamee, director of the Bourn Hall clinic and a longtime colleague of Edwards. “He remembers the past very well but not the present.”

The deliberations of the prize-giving committee at the Karolinska Institute in Sweden are confidential, and it is unclear why it took so long to acknowledge Edwards’ achievement.

The Swedish committee is believed to avoid controversial people and issues. The ethical objections to in vitro fertilization may have been one reason for the delay. Scientists speculated that Edwards’ political views — he has been a committed socialist — may have been another.

The committee routinely ignores the stipulation in Alfred Nobel’s will that the prize should be awarded for a discovery made the preceding year, because it takes longer than that to evaluate most scientific claims, but delays of 30 years or more are unusual. The Lasker Foundation in New York, whose jurors often anticipate the Nobel prize committee, awarded Edwards its prize nine years ago, although it, too, failed to act in time to honor Steptoe.

Although in vitro fertilization is now widely accepted, the birth of the first test tube baby was greeted with intense concern that the moral order was being subverted by unnatural intervention in the mysterious process of creating a human being. Edwards was well aware of the ethical issues raised by his research and took the lead in addressing them.

The objections gradually died away — except on the part of the Roman Catholic Church — as it became clear that the babies born by in vitro fertilization were healthy and that their parents were overjoyed to be able to start a family. Long-term follow-ups have confirmed the essential safety of the technique.

Edwards’ research proved too controversial for the Medical Research Council, a government funding agency that is the British equivalent of the National Institutes of Health. In 1971 the council rejected an application from Edwards and Steptoe to work on in vitro fertilization, but they were able to continue with private funds.

Both Edwards and Steptoe had to endure an unremitting barrage of criticism while developing their technique. Steptoe “faced immense clinical criticism over his laparoscopy, even being isolated at clinical meetings in London,” Edwards wrote in the journal Nature Medicine in 2001 after receiving the Lasker award. “Ethicists decried us, forecasting abnormal babies, misleading the infertile and misrepresenting our work as really acquiring human embryos for research.”

Edwards fought back, forming alliances with ethicists in the Church of England and filing libel actions — eight in one day — against his critics.

“I won them all, but the work and worry restricted research for several years,” he wrote.

Even after the birth of Louise Brown, the government refused to support his work, which was delayed for 2 1/2 years, Edwards wrote, until he secured private funds.

“There was at one time a possibility that Steptoe and Edwards would emigrate to the United States,” said Macnamee.

In parallel with defending his work in public, Edwards had to surmount one daunting problem after another in his laboratory. It sounds easy — mix eggs and sperm in a Petri dish and let nature do the rest. But the opposite is the case.

At the outset of his research, Edwards wasted two years trying to get eggs to mature outside the body, based on a report that human eggs matured in 12 hours. Eventually he learned that at least 25 hours is required.

Needing a reliable supply of human eggs, he approached Steptoe at the Oldham and District General Hospital because of his expertise at retrieving unfertilized eggs from the ovary through minute incisions in the patient’s skin. The two agreed to work as equals, to halt their work if danger emerged to patients or children and to ignore all religious and political criticism they deemed frivolous. The partnership lasted 20 years, until Steptoe’s death.

The two began transferring fertilized eggs to the womb in 1972, assuming that the rate of implantation would be as high as with farm animals. Their hopes were dashed. At first, the hormones given the mother to induce ovulation interfered with the growth of the embryo. Edwards and Steptoe then injected mothers with extra hormones, but these turned out to induce abortions.

They persisted through more than 40 embryo transfers before obtaining their first pregnancy. Unfortunately it was ectopic and had to be aborted. Louise Brown was born from the second pregnancy.

“It required grit and determination to keep going,” Macnamee said of his colleague. “But he had the conviction of his research work and he wanted to see it delivered to the people who needed it.”

Despite the ethical objections leveled at his work — some of which persist today, over the disposal of unused embryos and the high risk of multiple births — Edwards was nonetheless allowed to develop the technique over many years.

“It would be very difficult to develop in vitro fertilization now because the ethical committees would have stopped his research,” Macnamee said.

The ability to fertilize eggs in a dish made possible several other significant advances in reproductive technology, such as pre-implantation diagnosis of genetic diseases and the culturing of embryonic stem cells.

Edwards was keenly interested in human embryonic stem cells and started work toward developing them in the 1980s. He published an article in Science in 1984 reporting the culture of human blastocysts, the pre-implantation embryos from which stem cells are derived. But he discontinued the work because of the controversy it aroused in England.

“It was a very touchy subject in the early 1980’s. Bob was continually involved in lawsuits,” said Kay Elder, a colleague at the Bourn HallClinic.

Human embryonic stem cells were later derived by James Thomson of the University of Wisconsin in 1998.