When Louise Joy Brown, with curly brown hair, her parents’ blue eyes and two gold studs in each ear, celebrated her 19th birthday this summer in Bristol, England, she as usual received greetings from her creator. Embryologist Robert Edwards has known “Baby Louise” since she consisted of only a few cells in a lab dish, dividing in a stately gavotte, blithely pursuing their own destiny–the first human to be conceived outside the mother’s womb.
The 1978 medical breakthrough by the Cambridge University physiologist and his partner, gynecologist Patrick Steptoe, changed the course of human reproduction and brought hope to scores of infertile couples–an estimated 200,000 in-vitro babies have been born worldwide. Edwards’ technique, which is regarded as last-resort therapy, has contributed to the wave of multiple births. It permits women to freeze their eggs when young and have children later. It also has led society to preselecting embryos that are clear of genetic diseases and could lead to selecting them for genetic traits–perhaps even to human cloning, a notion Edwards once dismissed as “clowning.”
An engaging, self-described “truculent Yorkshireman” who was interviewed recently in Chicago during a genetics conference, Edwards discusses the ramifications of his work and reflects on his struggle against ignorance, heartbreak and defeat, as nature only grudgingly has revealed to him the secrets about the beginnings of life.
Q: Classically speaking, in-vitro fertilization involves removing a woman’s eggs after priming her with fertility drugs, manually fertilizing the eggs with sperm, cultivating the embryos, then at the proper moment placing the hardiest candidates into the uterus in hopes at least one will implant. Your technique always has been equal parts science, medicine and magic. Has it become more scientific?
A: Yes, in that treatment of low sperm counts, which account for the largest single cause of infertility–about a third of all cases–has been revolutionized by intracytoplasmic sperm injection, or the injection of a single sperm in an egg. That means men who produce only 20 or 30 sperms can have 20 or 30 embryos. In-vitro fertilization used to need 500,000 sperms per egg. We needn’t anymore rely on ejaculated spermatozoa. We can go and get them, or even the progenitor cells that give rise to them, with a fine needle–it sounds awful, but it’s done very quickly and easily.
So that’s been a major breakthrough. It brings men to equal terms with women.
Q: You have always “superovulated” women, using hormones to make their ovaries overproduce eggs for you to try to fertilize. How many do you need now?
A: Endocrine techniques have been revolutionized. Now, we take control of the woman’s endocrine system completely. We stop it in its tracks, then start it when we want to. So she can come into the clinic on a specific day, and we can extract 50 eggs, say, per attempt. That’s enough, I think.
Q: But you need far fewer embryos than you used to. Correct?
A: Right. This is controversial, but in my view we want to transfer only two embryos to avoid multiple births. We used to implant three, and that’s still the limit in England, but in a good clinic the multiple pregnancy rate was about 25 to 30 percent. Nearly a third of the parents had a multiple birth, often their first pregnancy. That was not satisfactory. Most women can handle twins, but with triplets, the mother is stressed, the babies are small. Fetal morbidity goes up.
Overall, I think the field has been striving to use very low hormone levels, then to use fewer eggs but use them better, and to nourish the embryos to the best of our ability.
Q: But then when you gently squirt them back into the womb, it’s a shot in the dark. That hasn’t changed, has it?
A: Not really. Our problem is that the implantation rate per embryo is still only about 15 percent. The implantation part of in-vitro fertilization still is a black box. Why can’t humans be more like mice or goats? When I went into this, every species I tried had high implantation rates–90 percent. I’d get twins and triplets all over the place.
Eventually, when I could work with beautiful human embryos, I’d transfer them very carefully and still get only 12.5 percent pregnancies–4 out of 32. That bewildered me. It had to be something wrong in the lab. Then I started to look at natural conception and found that wasn’t much better than what we were getting.
Q: How do the numbers break down?
A: With two embryos, we’re talking about a 40 percent pregnancy rate. But then comes a lot of fetal death, just as happens in natural pregnancies. So we’ll certainly lose 10 to 15 percent of those, maybe more, and end up with 25 percent take-home babies. Our best estimate is that a woman has a 22 percent chance of getting pregnant in a natural cycle. The same thing seems to occur in vivo (in the body) as occurs in vitro.
In other words, we may be facing an evolutionary situation in which the strict controls that lead to high pregnancy rates in animals have relaxed in the human species.
I wonder if over eons humans have been so fertile that the need for big litter sizes has diminished and the genes that produce them have switched off. Today, most people want only two children; in the old days, we’d have five and three would die. So it’s possible that human evolution still may affect us.
Q: Because of the expense of in-vitro fertilization (thousands of dollars per attempt), you would want to do better, correct?
A: A valid point. Our goal with in-vitro fertilization going back to the 1960s was to someday be able to equal nature, but if we have to beat nature, we’re in trouble. The cause of the low birthrate with in-vitro fertilization may have nothing to do with us; it’s just a fact of life we must learn to control. We control nature all the time. Hip replacements beat nature–why, even eyeglasses do–but to me, the last 10 years have made it clear that seeking a higher rate of natural human fertility may now find us staring directly at evolution.
Q: If humans were ever to be cloned, specialists like you would do it. What do you think about the possibility?
A: Any of us could have tried over the last 10 years if we’d wanted to. The techniques are not difficult–the same things we do for intracytoplasmic sperm injection could be used for cloning. Any of us could have cloned. No one has.
Q: Would a human cell nucleus respond as the sheep nucleus reportedly taken from an adult mammary gland cell was said to have responded? Baby Louise occurred only after 70 failures; Dolly the sheep resulted after 400. Are human eggs likely to be amenable?
A: Possibly. We need a few more clones. We want to know in animals what’s really going on. But even if it turns out to be possible, all of us seem to have reacted to the idea of transferring it to humans . . . not with revulsion, but with distaste.
Q: You’ve been battling taboos your entire career. What’s different about this?
A: All of us say we would never clone a human just for the hell of it. On the other hand, if a woman has no eggs, maybe we could make a copy of her to cure her infertility. Or it might be possible to take one embryo, divide it and put it in four eggs. That would give us identical quadruplets.
It must be pointed out that cloning embryos–which have genes from both parents–is not the same as cloning an individual person. Yet we already know that if we take out two cells from eight embryonic cells to analyze them for genetic defects (preimplantation genetics), the embryo learns to reconstruct itself and keep on growing. That means the cells must talk to each other somehow. They indeed do have the capacity to go back and start over.
Q: The human egg has turned out to be a lot tougher and more resilient than you ever imagined, right?
A: It’s amazing, really. And in the last year, breakthroughs have been coming very fast. We’re learning how genes switch on and off to give the embryo its shape–why our heads are at the top and feet at the bottom, how we develop right and left sides. Suddenly, we’re ready for a huge stride forward.
Q: Your partner, Dr. Steptoe, died in 1988, but the two of you lived to see your work change things as few other scientists have done. How does that make you feel?
A: Clearly, I enjoy everything about it, particularly meeting the families all over the world. But I have not lost my drive, and I am passionately in favor of a man and a woman having the right to establish their family. That applies also to people who are post-menopausal. I firmly believe that merely because a woman has been unable to conceive for 30 years is no reason for us to refuse to help her now. She’s 55 years old and wants to have a baby. I don’t think it’s up to me to say no.
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An edited transcript
