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Albert Lasker
Clinical Medical Research Award

The publication of The Origin of Species in 1858 and the birth of the first test-tube baby in 1978 are defining events in the history of human society. These events are defining because they forced us to confront some of the most fundamental ideas about being human. The instigators of these revolutionary events, Charles Darwin and Robert Edwards, share several attributes. Both owe their intellectual origins to Cambridge University in England. Darwin, the father of evolution theory, was a student at Cambridge where he was introduced to biology, geology, and natural history. Edwards, the father of in vitro fertilization, was a professor of physiology at Cambridge from 1963–1989. At Cambridge, he performed the experiments with human eggs that we honor today. His experiments were truly seminal—literally as well as figuratively.
As one might expect, when we challenge our conception of humanity, we arouse controversy. Indeed, The Origin of Species and the first test-tube baby ignited two of the most violent controversies in the history of biology and medicine. If the human species evolved by natural selection instead of by Divine creation, then the Bible cannot be literally true. If human beings can be conceived in test tubes by scientists, then the act of conception has lost much of its mystery. As instigators of revolutionary science, Darwin and Edwards were subjected to vitriolic personal criticisms. But both of them, befitting their British gentlemanliness, conducted themselves with dignity and forthrightness, much to the admiration of their scientific comrades.
Most of you are familiar with Darwin's story, but many of you may not be so familiar with the Edwards's story. Who is Robert Edwards and what led him to develop in vitro fertilization, known to the world as IVF? Edwards was born in a small Yorkshire town, grew up in Manchester, served four years in the British army during World War II, and then entered universities in Wales and Edinburgh, where he took courses in agriculture and zoology and became fascinated with reproduction and embryology. He obtained a Ph.D. in 1957 from the Institute of Animal Genetics in Edinburgh. Here, he worked out a method for treating female mice with hormones so that scientists could precisely control the time of ovulation and the number of eggs produced. This classic study was done in collaboration with his future wife, Ruth Fowler. The Fowler-Edwards method for controlled superovulation made the mouse the animal of choice for studying early events in reproduction. Edwards no longer had to come into the lab in the middle of the night to harvest immature eggs. He could now decide exactly the time the eggs would be produced. His next goal, like that of many reproductive biologists in the 1950s, was to learn how to mix eggs with sperm so that fertilization would occur in vitro outside the womb of the mother.
Meanwhile, across the Atlantic, scientists in the U.S. were furiously trying to fertilize human eggs in the test tube. Although several claimed reproductive success, their results could not be reproduced. The first major breakthrough came not with human eggs, but with rabbit eggs. In the early 1960s, Min Chang, a scientist at the Worcester Foundation in Shrewsbury, Massachusetts, took eggs from a black rabbit, fertilized them with sperm from a black rabbit, transferred the embryo to the uterus of a white rabbit, and produced a litter of black pups. This was the first unequivocal demonstration of in vitro fertilization.
Spurred by Chang's success in the rabbit, Edwards began to fertilize the eggs of many different species of mammals, and in 1965 he first attempted the fertilization of human eggs. In developing IVF for humans, Edwards had to overcome formidable technical problems—problems that were orders of magnitude more difficult in humans than in animals confined to a cage. Edwards's story is one of courage—technical and moral. He had to learn how to induce ovulation in women, how to harvest their eggs from the ovary at the perfect moment, how to incubate them in a test tube with sperm so that normal fertilization would occur, and how to implant the embryos into the mother's uterus so that a normal baby would be born. All of this had to be carried out without doing harm to the woman or her baby. The most technically demanding step was finding a way to obtain eggs from the ovaries of women without having to subject them to open abdominal surgery. This problem was especially challenging to Edwards because he was a Ph.D. with no experience in clinical research.
As luck would have it, in 1967 Edwards read a paper in The Lancet that described a new procedure called laparoscopy. The author was a gynecologic surgeon named Patrick Steptoe who was affiliated with a small hospital in Oldham near Manchester. Steptoe reported that he could visualize the organs of the female reproductive tract by making a tiny keyhole-sized incision near the navel through which he inserted a long thin telescope equipped with a fiber-optic light. This newfangled instrument was called a laparoscope. Although Steptoe did not invent the laparoscope, he was the first English-speaking surgeon to learn the procedure firsthand from its inventors in France and Germany. In 1967, Steptoe published the first book in English to describe laparoscopy. The book became an instant surgical classic on both sides of the Atlantic.
Edwards was immediately struck by the potential of laparoscopy for retrieving eggs directly from the ovaries of women at just the right time in the ovulation cycle. He rang up Steptoe and proposed a collaboration. Edwards's colleagues in Cambridge raised their academic eyebrows, thinking he was mad to hook up with a non-academic surgeon in private practice in a backwater hospital who was fiddling around with a dangerous foreign device that should never have been allowed into England in the first place. But, the irrepressible Edwards had the vision to realize that he needed the technology that Steptoe could provide. Like many discoveries in medicine, the discovery of in vitro fertilization itself required fertilization—the cross-fertilization between a scientist and a physician.
For the next 10 years, from 1968 to 1978, Edwards traveled back and forth by car over bumpy country roads from Cambridge to Oldham and back to Cambridge, an arduous eight-hour journey. Edwards calculated that he traveled the world four times over in his decade of near-weekly commutes. Commuting may have been tiresome, but that was nothing to equal the scientific frustrations and disappointments that Edwards and Steptoe experienced during the first decade of their collaboration. Within 18 months, they had successfully harvested eggs from infertile women, fertilized them, and developed living human embryos. But, success was short-lived. In their first 40 patients the embryos failed to implant in the uterus of the mother. Then, in 1975 the 41st patient became pregnant. Steptoe and Edwards were exhilarated, but their jubilation was again short-lived: the pregnancy had to be terminated because the embryo implanted in the fallopian tubes rather than the uterus.
Edwards and Steptoe persevered despite overwhelming odds. To make a 10-year story short, 102 patients received embryo transfers without a single successful pregnancy. In the end, success turned out to be a matter of getting the hormones right so that the transferred embryos would implant properly in the uterus and normal pregnancy would ensue. The first test-tube baby was born on July 25, 1978—her name, Louise Joy Brown. July 25, 1978 also marked the beginning of joy for many, many infertile couples.
Infertility is a frequent medical problem. Throughout the world, infertility affects 1 in 6 couples. In the U.S right now, more than six million infertile couples desperately want to have children. Many infertile women produce normal eggs, but these eggs are unable to reach the uterus because of blockage in the fallopian tubes. That was the problem in the mother of Louise Brown. Since the birth of Louise Brown 23 years ago, nearly a million healthy babies have been born to infertile parents through IVF. Last year alone, more than 100,000 IVF babies were born, accounting for 1 in 200 births in the U.S. and more than 1 in 50 births in the U.K., France, Scandinavia, and Israel.
Edwards and Steptoe's breakthrough in IVF spawned five new fields of clinical investigation. The first spin-off is the preimplantation diagnosis of genetic diseases, which makes it possible to prevent the birth of embryos that are destined to develop serious inherited disorders like cystic fibrosis and Down's syndrome. The second spin-off is the freezing of human embryos (cryopreservation), which makes it possible for patients undergoing cancer chemotherapy to preserve their fertility. A third spin-off is a new treatment for male infertility, called ICSI, in which a single sperm from a man with a low sperm count is injected into the cytoplasm of the egg. The fourth spin-off is the new field of human embryonic stem-cell research, which holds great potential for treating many common disorders such as Parkinson's disease and juvenile diabetes. Without Edwards's technique of mixing eggs with sperm in the test tube, there would be no blastocysts to produce the stem cells. And finally, the birth of Louise Brown led to a new field of reproductive bioethics and law, which is especially timely in view of the current controversy surrounding stem-cell research.
Patrick Steptoe, Edwards's long-term clinical collaborator, died in 1988 at age 75, one week before he was to be knighted at Buckingham Palace by Queen Elizabeth II. Had Steptoe been alive today, he would have undoubtedly shared in this Lasker Award with Robert Edwards. Without cross-fertilization, there would be no in vitro fertilization.
Most advances in medicine proceed in small steps. A precious few are great leaps. 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! The passage of time—plus a million smiling babies full of joy—have vindicated Edwards. This millennial year, the UK issued four stamps to celebrate the most noteworthy British advances in clinical medicine over the last 1000 years. Those honored were: Edward Jenner for vaccination against smallpox (1796); Florence Nightingale for founding the field of nursing (1890); Alexander Fleming for penicillin (1928); and Robert Edwards for developing IVF (1978). If one picture is worth 1000 words, then one's picture on a millennial stamp should be worth 1000 Laskers!