Bob Edwards, Father of Five Million
The Nobel laureate died yesterday at age 87, feted as the technological father of millions of babies around the world -- the oldest of whom is 36-year-old Louise Brown. He is responsible for in vitro fertilization, which in the 1970s was as controversial as embryonic stem cell research is today.
Additional background notes on his work appear at the end of this piece.
When I looked out from the top floor of the Willard Hotel at 6 a.m., a few taxis were moving slowly down Pennsylvania Avenue like blood cells through a vein. It was a fall morning in 2004, the chandeliers were blazing in the Crystal Room, and tables had been set up for an erudite bunch of guests who would soon be arriving.
I was here early to watch as the room filled up with an assortment of political pundits, lobbyists, scientific leaders, and staffers from a range of House and Senate subcommittees.
I'd returned recently from my visit with you at Cambridge, and could not dismiss the thought that the current fray would not be unfolding if not for your work with embryonic cells.
The circus could not have been set on a better stage.
You would have gotten a kick out of the place. The elegant Willard -- which, in civil war times, Nathaniel Hawthorne had described as "more the center of Washington than the White House" -- was not unaccustomed to the most impolite of battles. Within its walls, many social and political gales (and wails) had been unleashed over the decades.
It was here that president-elect Abraham Lincoln had been smuggled in 1861, hiding from assassination threats. Julia Ward Howe wrote The Battle Hymn of the Republic in her room here, and President Ulysses S. Grant coined the term "lobbyist" here, for all the pesky, influence-mongers who interrupted his end-of-day brandy and cigar in the Willard lobby.
It was Elias Zerhouni's turn. President Bush's health tsar had arrived for a sparring match with the angels and arch-angels of stem cell research.
By 8:00 a.m. the room was simmering.
I'd just come back from visiting embryonic stem cell labs around the world. I'd been decontaminated in an air shower with the fraudulent Dr. Hwang at his Seoul lab; got a glimpse into Teru Wakayama's dream experiment in Kobe, Japan; saw future Nobel laureate Shin-Ichi Nishikawa's gene analysis of embryonic stem cells; viewed Noce's mind-boggling results forging tail-less sperm cells from stem cells in a lab dish in Tokyo; saw rats with Alzheimer's being treated with stem cells at the Lund, Sweden lab of Patrik Brundin; and sat with Henrik Semb, who'd single-handedly generated most of the Bush administration's approved cell lines. I'd visited the Vatican in Rome, and pored over the theological texts concerning the "gospel of life."
We'd talked about these troublemakers, and your eyes sparkled as I told you what I'd managed to see. In Stockholm, at the Karolinska Institute, Jonas Frisen was devising a way to measure the age of stem cells in the body with carbon dating -- to determine the real effectiveness of adult stem cells. In Berlin, at an out-of-the-way beer garden, I'd had a rendezvous with a Chinese stem cell scientist who'd recently fled an unscrupulous but high-profile lab in Beijing, and was being hounded by Communist party leaders. I'd also witnessed the astounding birth of an endangered animal cloned from a creature that had been dead for more than 20 years. I'd interviewed patients, including Christopher Reeve at his home on a horse farm in New York a few months before he died; a Chicago man in his 40s dying of ALS ("Lou Gehrig's disease") who'd traveled to Kiev and paid tens of thousands of dollars desperate for any kind of stem cell treatment; and a Boston policeman, Fran Ford, who was looking to embryonic stem cell scientists save his son's precious eyesight. At Cambridge, I got the low-down from former USCF researcher Roger Pederson on how things were going for him as an ex-pat at Tony Blair's new stem cell center.
And I was still thinking about you, now, as Senator Brownback, Republican from Kansas, came strolling down the Willard Hotel's Peacock Alley. Brownback back then had sponsored the bill known as S. 245, which would make all forms of human embryonic stem cell cloning illegal and even criminalize American patients who sought therapeutic treatments based on this technology abroad.
Senator Dick Durbin, ducking behind one of the blue marble pillars, took his seat. He was cosponsor of a rival bill.
Taking his seat among the pundits was David Prentice, the senior fellow for life sciences at the Family Research Council's Center for Human Life and Bioethics, an opponent of embryonic stem cell research.
Durbin poured himself a glass of water from the tall silver pitcher, and took a long drink.
Two seats next to him, William Hurlbut, a member of the President's Council on Bioethics from Stanford University, was going on about a recent trip to the Vatican. It seemed to be a pretty popular place for U.S. politicians lately.
Arguments raged.
All over the world, parents who had undergone fertility treatments and had ended up with more embryos than they needed were getting letters from IVF clinics. What did they want to do with their leftover frozen embryos? Hundreds of thousands of them created thanks to you.
Insurance companies in the U.S. would sometimes pay for fertility treatments and the cost of storing the embryos created, but after a certain time period, the parents had to cover the costs -- usually about $500 a year, but eventually a decision would have to be made. It would be of no use to keep them frozen forever.
Hundreds of thousands were faced with the decision of discarding them, continuing to keep them frozen -- and paying the expenses involved -- or implanting them in the mother's womb to have more offspring.
These embryos were usually 5-8 days old, optimal for deriving embryonic stem cells for research. They were about the size of the dot of this "i," and, in the U.S. alone, at the time, about 400,000 sat languishing in freezers -- their fates to be determined.
The vast majority of excess embryos were being thrown out as medical waste, placed in an orange biohazard bag and thrown in a dumpster.
The debate was getting fierce, but Zerhouni was holding his ground. Medical progress took time. In the 16th and 17th centuries, he pointed out, scientists had to perform dissections in secret "or you'd be hanged."
***
On the way to your place, the purple flowers spilled out across the fields of Dry Drayton just outside of Cambridge. The Presidential election was approaching in America. Droves of scientists were leaving the U.S. for less restrictive research environments in Europe and Asia, eager to enter a new era of biology, medicine, and -- some would say -- human evolution.
You and I had talked several times by phone, and you invited me to Louise Brown's 25th birthday party the next day. First we would spend some time at your home in the countryside.
Getting off at the train station, I hailed a cab. Down a winding road, a white house surrounded by a white picket fence and a series of old brown stables formed a small square at the center of Duck End Farm. I was let off near the stables, then headed toward the last one, which had been turned into your cluttered office. One of your assistants greeted me.
"He's waiting for you at the house," she said, and I walked back to see you with your thick white hair, looking two decades younger than your 77 years, grinning and walking toward me.
We shook hands.
"We can sit outside, or in here," you said, leading me to a sun room at the back of the house. Beyond the windows, a willow tree and pots of red flowers dotted the yard.
We sat across from each other in those wicker chairs. Your voice was deep and undulated with each turn of phrase, growing soft and then vibrant.
You told me of the surprises along the way. Oddly, pig eggs mature in 37 hours just like humans (the only species with such a similarity). You also had a secret supply of human eggs in the 1960s and the 70s that allowed you to keep at your work.
In the 1960s, experimenting with super ovulation, you happened upon stem cells and their amazing ability to become a wide variety of tissue. It was not your focus and you did not ever say much about it, and so were never recognized for isolating stem cells. Though you documented them in detail in your lab reports at the time.
Speaking of these things, you became cheerfully agitated. It is widely believed stem cells were a discovery made only in the past five years, with Thomson and Gearhart, you said.
Did you ever confront Thomson about this, I asked.
"No," you said. "Would you do that for me?"
We both laughed, and I agreed to ask Thomson about it. I'm sorry I never got around to it.
The next day, in the midst of Louise's party at Bourne Hall, your Jacobean mansion and fertility clinic, you were in rare form as we continued our talk.
Nature isn't so damned impressive, you insisted. We all know it's actually quite imperfect. Indeed, you believed scientists have the upper hand over "god" and made no apologies about your philosophies.
It is hard to imagine it was a decade ago. That was seven year's before you were awarded the Nobel Prize, and just before you began to have symptoms of Alzheimer's.
I stood in the middle of the sprawling green at Bourn Mansion, surrounded by hundreds upon hundreds of chubby-cheeked cherubs all giggling, screaming, bawling, shouting, whining, and squealing to the strains of a 50-piece brass band.
Twin baby girls in a double stroller -- in matching pink dresses and headbands -- squirmed to get out of their stroller and into the action. Faces were being painted, henna tattoos applied; there is bouncing to be done on a huge inflated castle, and a tiny motorized train to ride around and around down the gravel pathways surrounding the Jacobean mansion.
A kid with a hotdog in his fist stood clinging to the trouser leg of his hamburger-devouring father. Two little fellows dressed in blue whiz by in yet another double stroller. There were more sets of twin here than I had ever observed in one setting.
To my right, an angelic baby slept. Smirking imps rode on their fathers' shoulders. A tiny fellow in blue-and-white checked overalls toddled by and then fell. A baby in a red dress and white bonnet was passed between her doting parents.
Babies and toddlers everywhere, of many nationalities, spilling juice on their mothers, crawling up the hillside, pleading for more ice cream.
Shards of sentences drifted by in the summer air.
"I'll put you down because you're getting heavy now."
"Sit down, Daddy's got some water for us to drink."
"She's a monkey."
"I don't know if he might just start walking instead of crawling."
Camera crews were now swarming around the place, and positioning themselves on the roof of the mansion for an aerial view.
Clearly, this was no ordinary family outing. All of these children were "test-tube babies," given life thanks to assisted reproduction.
At the time, we were celebrating Louise's birthday with about 1,000 IVF offspring and their parents, out of about three million in existence worldwide.
By 2013, more than 5 million IVF babies had been born.
***
In the U.S., as the politicians and scientists warred at the Willard Hotel, that same evening a reception unfolded in the upstairs atrium of the Rayburn House Office Building. Members of Congress were present to discuss stem cell research and talk with lobbyists and patient groups like the Coalition for the Advancement of Medical Research.
You'll be happy to know, amidst the crowd, Senator Dana Rohrabacher, Republican from California, was passing out photos of his new IVF triplets. "If science can create such beautiful children, it can help us also improve their lives," Rohrabacher said as his colleagues admired his beaming babies.
"He's about as right-wing as they come, but he's on our side," said Daniel Perry, head of CAMR.
Don't you think it ironic that IVF was the technology that had changed Rohrabacher's mind? Rohrbacher had become an important ally for patient groups like CAMR and the Juvenile Diabetes Foundation, both powerful lobbying forces when it came to medical issues.
That night, smiling senators and members of Congress sipped their drinks and passed around the photos of the beautiful babies.
IVF had been the watershed.
This is how it all really started.
Without IVF, and the ability to grow an embryo in a laboratory dish, the current discoveries about embryonic stem cell research would never have been made. Your breakthrough made it possible for human embryos to be generated in vitro, able to thrive outside the body. And without your technique of mixing eggs with sperm in a lab dish, there would be no blastocysts, or early stage embryos, to produce stem cells.
***
When I wandered from the lawn of 1,000 babies into a crowded hallway of the Bourne Hall mansion, a young man you knew well told me his story.
"Can you climb glass? The kids asked me 'Can you climb glass?" he said. He was 24-year-old Alistair Macdonald, one of your celebrities here, the world's second test tube baby and first boy created in vitro. As we talked, dozens of tiny children swirled around us.
In vitro is Latin for "in glass," versus in vivo, or in the body. IVF of course involves mixing eggs and sperm in a lab dish, where, with any luck, they turn into dividing embryos. It's one form of assisted reproduction. More involved techniques are also used routinely these days, including ICSI, a process where a sperm is injected into an egg.
As a kid, Macdonald said, he wasn't teased all that much, but he did remember being asked how he got out of the test tube. "They asked me. 'Can you climb glass!" he said cheerfully, still getting a kick out of the story.
Louise Brown stood a few feet away in a beige summer suit, her blonde hair pulled back in a ponytail.
Standing on the mansion steps beside her, you were particularly animated, passing out hugs and kisses to all your former patients, and particularly to Louise and Alistair, who grew up knowing you as Uncle Bob.
When Louise was born, at 13 minutes to midnight on July 25, 1978, she was a 5 pound, 12 ounce bundle of controversy. You kept the details and location of her birth secret, leading to suspicions the whole scenario was a fraud. (The parents had negotiated exclusive rights to the first baby pictures with the London Daily Mail for more than $500,000. Newspapers that bought reprint rights were guaranteed a 40 percent discount if the baby died within the first week.)
Who told her she was a test tube baby? Her mother and father, just before she went to school, she told me as she posed on the mansion steps with you and two IVF twins, one in each arm.
Alistair Macdonald had regarded you and your colleague Patrick Steptoe (you affectionately call him Steppy), as uncles. While you remained close friends with the Macdonald family, Alistair was never told that you were responsible for his birth.
"I saw Steptoe on TV when he died," Alistair told me. "And I saw pictures of Louise on TV with him. I figured I must also be a test tube baby. I went running to my mother and said, 'Mom. I know why I'm special."
"My mum was flabbergasted that I worked that out," he said.
I asked Grace Macdonald, Alistair's mother, if she failed to tell her son he was a test tube baby for fear he would be stigmatized.
"Certainly not," she said. "I thought I'll wait till he's about 10 and I'll show him all of the ... the leaflets, everything that had been written so I could explain it all to him in a way that he would really appreciate. It was a big responsibility for him to have to live with. And I wanted him to appreciate just how important it was. When he was younger I thought he's not ready yet. "
Alistair, who stood with us, blurted out with a smirk, " I was way ahead of my time."
His mother laughed and enjoyed telling the story. "He came in to me, I was half asleep. I said what are you talking about Alistair? He said I just saw Louise and Mr. Steptoe on the television. Of course he was upset as well because we just found out that Patrick had died. That was upsetting. At the same time, I thought well I've got to fill you in on the gaps. A precocious 9-year-old ... he said "Well I get most of it, mom!" Grace Macdonald laughs and says, "He took it all in his stride."
"I didn't know them as doctors at all. Uncle Patrick and Uncle Bob," he said.
We all exchanged email addresses and then Grace asked her son if he wanted to go out for an ice cream.
"If I have one, will it shut you up Mom?" he asked.
They were no different, it seemed, than other mothers and sons.
***
Castel Gandolfo, summer residence of the Pope, shimmered on the outskirts of Rome. Perhaps you were serenely gazing at the trees at Duck End Farm, and so were spared from the rodeo.
In 2010, the Roman Catholic church denounced your Nobel prize, and the next year you were knighted by Queen Elizabeth II.
If you were to go to the Pope's Castel, you would find an enormous archway that opens onto the vast, walled courtyard of the 17th century palace. Below, sun spills diamonds all over Lake Albano. And from the terrace of the Pope's small cottage, an oval shoreline surrounds the lake like an egg within its zona.
As you know, in human biology, the zona pellucida is a delicate membrane -- the perimeter of an oocyte. The malleable shell around a human egg.
Oocyte. That is the scientific term for egg. I always thought the word itself seemed to be a whimsical celebration of the zona -- a drawing of two round encircling membranes. It came from oion, the Greek word for egg, and kytos, a hollow space or container. The letter "o" was one.
I remember when, in the shimmering August heat in the Alban Hills, Pope John II held forth before the faithful, wavering and unsteady from the ravages of Parkinson's disease.
Over the lake, small hands of leaves gesticulated in the summer breeze.
For 17th century Catholic mystic Blaise Pascal, the realm of God was like an infinite sphere; for many scientists, within the microscopic sphere of the human egg was the mystery of the infinite regeneration of man. When fertilized -- or stimulated to divide like an embryo as if fertilized -- it was responsible for setting back the clock on aged body cells. You told me you were certain this would be perfected within two decades. You left too soon to find out.
Not too long after your party at Bourne Hall, the Vatican was preparing a detailed internal theological paper, in which, among other things, it posed the question, "How far is man allowed to remake himself?"
That question of how far science should go has inspired fiery wars throughout the ages. James Watson, the father of DNA, had been dubbed "the Caligula of biology" by one of his colleagues.
I've always loved the origins of the word "cell." It's from Old English's "religious house," and Latin's celare, to conceal.
As a biologist, your 'religious house' was indeed the cell. From the earliest days of biology, with the first 18th century concept of the cell as a unit of life, these tiny chambers have only slowly revealed the miraculous workings of their mechanisms.
There is concern that genetic errors that may be introduced when human embryos are engineered in a lab. But nature herself flubs up as often, or more often, than scientists, you told me.
The unsolved conundrum remains: Why is human reproduction so inefficient?
Til the end, you puzzled over the problems of the human reproductive system -- like Einstein puzzled over the weirdness of the cosmos. You told me something must be fundamentally flawed with a reproductive system that allows only 20 percent of embryos to implant, even in younger couples. Why are so many human spermatozoa immotile or formed abnormally, you wanted to know, and why do up to one-half of embryos carry chromosomal anomalies?
Then I stopped for a moment to observe a group of toddlers crowded around in a circle observing live animals who had been brought here for party entertainment; two live falcons and an eagle glared back at them. It was an odd moment. Natural creatures stared down curiously at the human offspring that nature could not quite accommodate.
It is the responsibility of science and technology to finish the unfinished business of nature, you told me.
The party had been going on for hours now, and I turned to gaze into the grotesque face of a clown on stilts that hovered above me. Was this elongated harlequin an ominous specter, or was just I being melodramatic?
Now as then, the world is vibrating with the domino effects of technologies on top of technologies; and technology being used to clean up the inadvertent ills brought about in the first place by the application of technology.
I remember what Dr. Farber, a scientist who'd nurtured dozens of healthy cloned cows in an Iowa field, had said to me. He'd successfully helped a top stem cell scientist clone an endangered animal from cells that had been frozen for decades. "Technology is wonderful," he said. "But you do get in trouble when you layer too much technology on top of technology."
As I remembered the miraculous birth I'd witnessed in an Iowa field earlier that year, an IVF husband interrupted my thoughts. "It's a Pandora's box, isn't it?" he said.
He pointed out that he and his wife were given the option of having her placenta stored after the birth -- an option given by many hospitals in the US as well these days -- so that they would have a potential source of stem cells in the future, should their daughter have immune system problems, the incidence of which is higher in IVF babies.
"A hi-tech beginning can end up with a hi-tech end -- intensive care," he said. "And there's the controversy of who pays the medical costs."
I looked down again to peer into the eyes of two blue-eyed angels, and just to their right, the deep, dark eyes of twin girls born here to a Palestinian couple.
Those eyes of the children seemed to hover in the summer air, some deep presence, the tender fragility of what it is to be human.
***
Baby Orla was crawling up the hill toward the Bourn Hall mansion, and then sliding back down again. She just had her first birthday. Her parents, Eleanor and Ben O'Dwyer, told me they tried for five years and were about to give up when Orla was finally conceived.
The couple has leftover eggs from their procedures, which are frozen. "I hope we use them," she said. Bourn Hall also gives couples the option of donating leftover embryos for stem cell research, to labs such as the one headed by Roger Pederson.
Another couple strolls the grounds with their 3-year-old daughter Lauren, born by IVF after her parents tried to have a child naturally for twenty years. "It chokes you up. You walk into the hall and it chokes you up again. We came here in hope for a child, and then come back here with the end product," says Martin, Lauren's father, while Lauren's squealing interrupts him between sentences. "It's amazing. You can't put it into words. It's nice to come back."
The couple conceived during their first trial, being the second ever to use ICSI, which Martin, Lauren's father, describes as "coming down the motorway with all your bits and bobs in a bucket, and putting it all together. It's tremendous."
ICSI involves injecting a single sperm into an egg, used for males with a low sperm count. In the case of Lauren, her father's sperm was manipulated at Bourn Hall and put in an incubator; his wife's eggs were removed at another hospital and put in an incubator. The ingredients were then driven to Bourn Hall and put together.
ICSI was also being used by stem cell scientists engaged in therapeutic cloning -- in hopes of creating healthy replacement cells that genetically match a patient's own body cells. The same machine is used, but instead of injecting sperm into an egg, it injects DNA from a donor once the egg is hollowed out.
Hundreds of couples being treated at Bourne Hall have been asked to donate their leftover eggs and embryos for such stem cell research. Of the 20 or so couples I talked to, only one said they would not be willing to donate them for research.
I watched as you gave Louise a huge kiss as she cut her birthday cake and the crowd sang happy birthday.
***
I never told you about my dinner with Roger.
The night after I left you, the cobbled streets of Cambridge, England were basked in a dwindling, golden light. A tall, slender American strolled down Trumpington Street, then ducked into the ancient eating establishment known as Fitzbillies; in the 1920s it would have been brimming with chaps in flannel trousers and blazers.
Roger Pederson sat with me in a grey suit; across the white linen tablecloth, a few local flowers stood in a vase on the small table.
I brought him kind regards from you. Pederson, as you know, left the U.S. in despair over lack of funding and the political wars surrounding his work.
Walking along Trumpington Street, we passed Little St. Mary's church, with a memorial to a former vicar, the Reverend Godfrey Washington, great-uncle of George Washington. The family coat of arms contains stars, stripes, and an eagle and is thought to be the origin of the American flag. America was still on Pederson's mind.
Will he ever return to work in a U.S. lab? He told me he had a soft spot in his heart for America, but the work he is doing now has "unlimited" support from the UK government. He considered America to be in the backwoods.
We began to talk about Cambridge University, which was founded in the eleventh century by disaffected academics from Oxford. Cambridge and Oxford are similar distances from London: Oxford lies to the west and Cambridge to the north.
Pederson told me a story about "the gowns and the town." Cambridge academics, who used to be required to wear gowns, would get beat up in Cambridge by commoners for going down the wrong street. This reminded him of America's relative unfriendliness to scholars and science. Stem cell scientists were getting pummeled.
Roger mused over the impact your IVF breakthrough might have had on current attitudes in the UK regarding embryo research. The debates regarding embryos have already been haggled over for decades here, because of it. "There were a couple of big public policy debates started in the aftermath of Louise Brown being born. That debate did in fact address a lot of these issues. I don't know what the opposition means. It intrigues me that people who are opposed to embryo research by and large have no idea what an embryo is."
I am fascinated by the tectonic nature of being human.
As I gazed upon the beautiful dimpled bouncing babies at Louise's party, I suddenly viewed them as little lava flows.
We are all continually renewing ourselves, on the cellular level. We're a tectonic, self-renewing species.
It is curious that the brain is a pretty static organ. There are few stem cells found there. Neurons in the brain stick around for a lifetime. That's why we have a concept of ourselves, a memory of our life. We use the brain to ponder who we are. Everything else is in flux.
Pederson had described it all to me. Like the tectonic earth, us humans are constantly being renewed from deep sources. And, somewhere there's something like subduction. Deep sources like those beneath the plates of earth that constantly renew the surface of the world until it's subducted, melted back into magma again.
I'd been taken on a wild ride of the soma. As you were and as we all are.
You opened a Pandora's box, as scientists often do. Once we were able to create embryos in a lab dish, what would be their fate if they never made it to the womb? Once IVF came along, the problem of the disposition of embryos was inevitable.
As seen in the swarms of gleeful and wailing children, humanity goes on, full blown, seemingly without a care for whether it generated in chemical soup created by scientists, or in-vivo by nature.
We bid our farewells, and I wandered down the long driveway that leads from the expansive lawn surrounding Bourne Hall, and sat on the curb with a traffic cop while I waited for my cab to the train station. All the locals were abuzz about the party at Bourn Hall.
My cab pulled up. The taxi driver told me his four-year-old was created at Bourn Hall. He and his wife had success after three tries. "We were going to give up," he said. "Now, it's brilliant. I spend most of my time on my hands and knees playing with my daughter."
He'd just picked up a woman with a baby leaving the party. He tells me the child was very beautiful. "I asked her what test tube did you use? I want that test tube," he said.
How many citizens of this little town, I wonder, were engineered in a petri dish?
The blue night was deepening as we drove on, traversing the winding roads of Cambridgeshire.
***
Additional background on Edwards' work:
Edwards developed IVF with his colleague Patrick Steptoe (who died in 1988). They had to perfect inducing ovulation in women, incubating eggs in a test tube with sperm so that normal fertilization would occur, and implanting the embryos into a mother's uterus so that a normal baby would be born.
Edwards obtained a PhD in 1957 from the Institute of Animal Genetics in Edinburgh, where he devised a way to treat female mice with hormones to control the time of ovulation and the number of eggs produced. This was done in collaboration with his future wife, Ruth Fowler.
Louis Brown, the first test tube baby [AP]His next goal, like that of many reproductive biologists in the 1950's, was to learn how to mix eggs with sperm so that fertilization would occur in vitro outside the womb of the mother.
While Edwards was busy doing his work, back in the U.S. scientists were furiously trying to fertilize human eggs in the test tube. Although several claimed 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 demonstration of in vitro fertilization.
Spurred by Chang's success, Edwards began to fertilize the eggs of many different species of mammals, and in 1965 he first attempted the fertilization of human eggs. By 1969, he had succeeded, but his success was demonized and attacked on ethical grounds, and refusals to fund his work quickly followed.
In developing IVF for humans, Edwards had to overcome formidable problems that were orders of magnitude more difficult in humans than in animals confined to a cage.
What's more, to do his work in humans required collaboration with a physician. Edwards read about Dr. Patrick Steptoe's use of the laparoscope, a very controversial device at the time, in an article that appeared in The Lancet.
He believed laparoscopy could be used to retrieve eggs directly from the ovaries of women at just the right time in the ovulation cycle, and realized he needed to collaborate with Steptoe to make his in vitro fertilization possible in humans. Edwards' colleagues thought him mad to hook up with a non-academic surgeon in private practice in a backwater hospital who was tinkering with a dangerous foreign device that should never have been allowed into England in the first place.
From 1968 to 1978, Edwards traveled back and for his weekly commutes to work with Steptoe, and within 18 months, the two successfully harvested eggs from infertile women, fertilized them, and developed living human embryos.
With the first 40 patients, however, the embryos failed to implant in the uterus of the mother. Then, in 1975 the 41st patient became pregnant, but the pregnancy had to be terminated because the embryo implanted in the fallopian tubes rather than the uterus.
Steptoe and Edwards persevered, and finally after 10 years and 102 patients who received embryo transfers without a single successful pregnancy, success turned out to be a matter of getting the hormones right so that the transferred embryos would implant properly. Eventually they succeeded.
With the birth of Louise Joy Brown, Edwards' and Steptoe's breakthrough in IVF spawned five new fields of clinical investigation and biotechnology. PGD, the preimplantation diagnosis of genetic diseases -- now in routine use worldwide by fertility clinics and embryologists -- makes it possible to prevent the birth of embryos that are destined to develop serious inherited disorders like cystic fibrosis and Down's syndrome. Cryopreservation, also in universal use currently, is the freezing of human embryos, making it possible, for example, for patients undergoing cancer chemotherapy to preserve their fertility. Cryopreservation is also now crucial for the work of current embryonic stem cell researchers.