"18 Ways to Make a Baby"PBS Airdate: October 9, 2001 NARRATOR: Frozen at minus-380 degrees Fahrenheit, a human embryo is selected to be thawed, resulting in the birth of Melina, now four years old. Her brother Luc was created in the same way. Their parents are Will, a lawyer in Los Angeles, and Marcellin who's a surgeon. They've been able to have children because of a discovery made in 1978—that by bringing together a man's sperm and a woman's egg in a laboratory, a baby could start its life outside the human body. It's called "in vitro fertilization." WILL: Marcellin was the sperm donor for one and I was the sperm donor for the other. But we don't tell the public or even our close friends or family who that is. But our children will know. Marcellin is from a very large family; he's the youngest of twenty. I am an only child, so I sort of always idealized family life in a big family. To me, it was just a basic human desire to want to have children. NARRATOR: Since neither Will nor Marcellin could carry their baby, they searched for a woman willing to serve as a surrogate mother. WILL: Many of the women we knew who wanted to help us didn't really want to carry a child that they were biologically related to. And with IVF, our friend said, "Okay, if the egg's not from me, I would feel comfortable carrying the child." NARRATOR: In vitro fertilization has enabled thousands of couples to create the family they desperately want. It has also opened a gateway to a brave new world—where a child can have five parents, or be born to a mother in her sixties; where a baby can have its sex determined before conception or be created with borrowed DNA; where an embryo, no larger than a speck of dust, can have its genes scanned for diseases, or one day be designed with new strengths and talents. LEE SILVER (Princeton University): What IVF does is it takes the process of reproduction out of the darkness of the womb, into the light of the laboratory. And all of the sudden you can do anything you want with these human embryos and eggs, which couldn't be done before. NARRATOR: A new revolution in making babies is underway, one that could allow us to influence and even shape the genetic fate of our children. Major funding for NOVA is provided by the Park Foundation, dedicated to education and quality television. This program is funded in part by the Northwestern Mutual Foundation. Some people already know Northwestern Mutual can help plan for your children's education. Are you there yet? Northwestern Mutual Financial Network. Scientific achievement is fueled by the simple desire to make things clear. Sprint PCS is proud to support NOVA. And by the Corporation for Public Broadcasting and by contributions to your PBS Station from viewers like you. Thank you. ANNE: I think it's very difficult for anybody to explain why they want a child. And the thing that I always felt so strongly about—why, as an infertile person, do I have to explain why I want a child, where somebody who's not infertile doesn't? And it's something nobody is prepared for. Nobody is prepared for somebody to sit across a desk from them and say, "I'm sorry, but you can't have a child." NARRATOR: One out of every six couples struggles with infertility. ILYSA: You come to realize how lucky so many other people are that they don't have a situation like this. And there are worse things, I definitely agree. But to us...we were devastated. NARRATOR: For many, in vitro fertilization is their last hope for a child, despite the stark reality that it fails 70 percent of the time. JAMES GRIFO (NYU School of Medicine): These patients have often gone through years of trying to get pregnant. They're really stressed just from that alone, and often by the time they reach the office of the specialist are depressed because of this illness. And not many people view this as an illness, but infertility is a rotten, horrible disease. And, no, it's not a disease that will kill you, but it wreaks havoc in these patients' lives. It is not a cosmetic illness. NARRATOR: The disease of infertility once seemed incurable—until the miraculous birth of Louise Brown in 1978. Her arrival marked an historic moment, for Louise was the first human baby ever conceived outside a mother's womb. British doctors Robert Edwards and Patrick Steptoe had labored for years trying to help women with blocked fallopian tubes. They could surgically remove their eggs and fertilize them in the lab, yet they couldn't figure out why the embryos failed to develop into pregnancies once they were returned to the mother. ROBERT EDWARDS (Bourne Hall Clinic): We had got all the techniques ready, right up to the point of implantation—beautiful embryos—and checked out the chromosomes and everything about them. And it was clear this method had to work. There was too much knowledge already in mice and rabbits and goats. Mind you, the techniques we were doing were in advance of those, so we felt that the human was not so different...that the method could not not work. NARRATOR: The breakthrough came when Steptoe and Edwards decided to transfer the embryo earlier, allowing it to divide only three times before placing it in the womb. ROBERT EDWARDS: I can see the embryo beautifully. We were trying to come earlier and earlier, really to avoid long-term cultures. That was my primary aim. And so suddenly the system started to work and we were there. NARRATOR: Three years later, NOVA filmed the birth of America's first "test tube" baby, Elizabeth Jordan Carr. Although Louise Brown was healthy at birth, many feared that IVF babies could well be abnormal. Ultrasound had shown that Elizabeth was small, and the doctors that created her, Georgeanna and Howard Jones were extremely worried. HOWARD JONES (Jones Institute for Reproductive Medicine): I had written out a press release that said that we'd been disappointed at birth that the child was abnormal, but that we did have a couple of other pregnancies coming along behind that. And we would hope that the others were perfectly okay. And fortunately, I didn't have to use that. PEDIATRICIAN: "All right, ladies, here she is—Elizabeth! That's right. I knew you would like it to be a girl." ARTHUR CAPLAN (Center for Bioethics, University of Pennsylvania): I think the major moral concern was, "Were you going to have a child born who had birth defects? Were you going to have developmental abnormalities? Would something go wrong later in the life of that person?" And I think the terror was that, somehow, doing something in a dish was going to create a person that was less than healthy. NARRATOR: But the terror faded quickly. As the press followed Louise Brown and Elizabeth Carr, it was clear that the girls who had made medical history were growing up to be perfectly normal. ELIZABETH CARR (First American to be conceived through IVF): Every year people pop up and say, "Oh, we'd like to do an update on Elizabeth." And every year I say, "Well, I'm the same as I was last year, just a year older. That's it." It's kind of like they expect a wonderful answer like, "Oh yes, I feel so different. I feel so special. And I don't." NARRATOR: Initially, IVF could only help a small percentage of infertile couples. Today, it has become the starting point for treating almost every cause of infertility as defective eggs, weak sperm, or abnormal chromosomes—once insurmountable obstacles—are overcome. Radical new techniques have proven that life on the cellular level is easier to manipulate than ever imagined. But for those who embark on this high-tech process, IVF remains a grueling ordeal. The first hurdle is to endure daily injections of powerful drugs to force the ovary to produce more than one egg. DARREN: Ilysa had gone through three weeks of taking shots, you know? All over her body bruises...getting up every morning at six in the morning to go to give blood. And you have a lot of guilt seeing your spouse go through all this stuff, knowing that if I didn't have this problem she wouldn't have to do this. She's very fertile. I mean that's the best part. NARRATOR: Infertility was often seen as a woman's curse, but in fact 40 percent of cases can be attributed to male problems like Darren's. DR. ZEV ROSENWAKS (New York-Weill Cornell Medical Center): The sperm count is very, very low. And when you have such low sperm count, the challenge is to select a normal sperm, or what looks like a normal sperm, and to get fertilization. However, so long as we have some sperm and they're alive, we can allow the sperm to get to the egg. NARRATOR: Because Darren's sperm are too weak to reach Ilysa's eggs, her eggs must be surgically retrieved. Using a long thin needle, Rosenwaks probes her ovary. One by one the tiny eggs are sucked out into test tubes and taken to the lab. It is the quality and number of the eggs and sperm that will determine the outcome. DR. ZEV ROSENWAKS: We had fifteen mature eggs, and there are several motile sperm, but very, very few. So they are looking...they have to search out quite a bit. And the hope is, of course, to get at least an equal number of sperm to the number of eggs we have. And this is the kind of situation we're dealing with here. NARRATOR: A fertile man will produce millions of sperm. Today the doctors have found only 12 of Darren's to work with. Using a thin glass needle, one sperm is grabbed by its tail. Then Ilysa's egg is placed into position. It was only by accident that scientist Gian Palermo discovered he could inject a sperm into an egg without damaging it. GIANPIERO PALERMO (New York-Weill Cornell Medical Center): Well I was placing sperm around the egg, underneath the shell, then, accidentally, I perforated the membrane of the egg. And then one sperm went inside. Ironically, I didn't pay much attention. I thought the egg would not survive the procedure. And I put a question mark to it because I thought it was going to die. But that was the only egg that fertilized. It finally was transferred to the patient, and this became the first ICSI baby. NARRATOR: Palermo called his discovery "ICSI" for intracytoplasmic sperm injection. Amazingly, creating a human being through the manual injection of sperm proved to be just as effective as natural fertilization. The only known safety risk seemed to be the possibility of passing on the gene for male infertility. ICSI's success would push forward a new frontier of reproductive biology. If a fragile human egg could be penetrated without harm, perhaps a human embryo might be manipulated in any number of ways. These new techniques would open up uncharted territory for another couple, Anne and Michael, as conventional treatments failed them. ANNE: People that are faced with infertility don't have the same decisions as people that aren't. And these decisions, they're not what we would want. These are the choices we're left with. If I could make a choice, I would like it if my husband and I could get pregnant on our own. And it's easy to sit there and say what you would or wouldn't do when you're not in those shoes. DAVID SABLE (Saint Barnabas Medical Center): She'd been trying for over four years. And she had done several treatments. She'd done some of the more...kind of low-key treatments, you know? Medication by itself, medication with insemination using her husband's sperm. She had had the full battery of diagnostic tests, none of which really revealed a smoking-gun cause as to why she was having difficulty. And she was climbing the ladder from least aggressive to most aggressive treatment. NARRATOR: During Anne's first IVF cycle, her doctors retrieved 35 eggs—an astounding number. Yet once the eggs were fertilized in the lab and began dividing, embryologist Jacques Cohen noticed fragments, little pieces of cells that are left behind when embryos divide inefficiently. JACQUES COHEN (Saint Barnabas Medical Center): And normally they're not really a hindrance to further development and pregnancy, because they occur in about 85 percent of all embryos. But when you have a lot of them, it interferes with normal development. The cells then cannot interact. And that's what happened in their case. There were so many of them that you couldn't even count the number of cells. Let's say you had a four-cell embryo or an eight-cell embryo. You couldn't make a count, which you normally can. ANNE: So on the one hand, I have an answer which is finally...after like three years...I finally have an answer of why I'm not getting pregnant. Then, on the other hand I have this news that I don't know if this is going to be fixable. This may be a permanent problem that we could never fix. NARRATOR: For decades, no one dared to invade the inner sanctum of an embryo for fear of harming it. But in 1990, Cohen began piercing the shells of fertilized eggs that appeared brittle to help them hatch. Today, he uses this technique to enter Anne's embryos and remove their fragments. This plastic surgery is now routine in many IVF clinics, in order to boost a poor quality embryo's chance of implanting. DAVID SABLE: To be honest, in the beginning I don't think we were sure whether we were just making the embryos look better, or whether we were actually helping them to develop. And then when we put the data together, it turned out that, yes, indeed there's a window of accumulation of fragments from about 15 to about 30 percent of the embryo. Previously, that embryo didn't have much of a chance of implanting and turning into a pregnancy. But if you remove those fragments, they had a very good chance of turning into a pregnancy. NARRATOR: Five of the best quality embryos were transferred back to Anne. Although she became pregnant, six weeks later, she lost the baby. ANNE: During all this time, we were surrounded by people that were getting pregnant. And here we were putting our financial savings into this. A typical IVF cycle in this area costs 12 to 15 thousand dollars. And you would invest your time, emotions, and your money. And to have a result like this...you just feel like you've been beaten. NARRATOR: Anne endured one more IVF cycle. Once again she conceived and then miscarried. Although she was only 29 years old, it seemed unlikely that she would get pregnant using her own eggs. Failure is not the only risk of IVF. For those patients lucky enough to become pregnant, one-third will deliver more than one baby. Laura and David May became the parents of triplets after three of their four embryos implanted. Although they were desperate to have children, they were not prepared for the high risk of a multiple pregnancy. LAURA MAY: I had to go into the hospital and they had, like, a little pump that they installed to help control the contractions. I just ballooned. And the most painful part was I no longer had ankles. DAVID MAY: We gave her six meals a day to make sure that all the nutrients and everything that she needed, and the children needed, were there. LAURA MAY: We had the option to abort some to increase the odds of the other ones being healthy. But we had tried five years and there was no question in our minds. We were going for the multiple. NARRATOR: Fortunately, Laura May delivered three healthy children. But not every family is as lucky. Most triplets and higher order multiples are born prematurely. Thirty percent will weigh less than two pounds. ARTHUR CAPLAN: And the data that we have on that shows that about one in four of those babies is going to have serious disability—not mild disability, but real developmental handicaps in life. NARRATOR: Given the enormous risks, why not limit the number of embryos transferred back to the mother? JAMES GRIFO: When a patient goes through an IVF cycle, and goes through all of what's involved, they want the best possible chance. Now how do you give them the best possible chance? By putting back more embryos. And how are clinics compared? People look at success rates. Even though they don't understand the nuances and differences between patient populations, they want the one with the best percentage. So there is this incredible pressure on us to have high pregnancy rates. NARRATOR: Because 70 percent of all embryos fail to develop, doctors transfer back several in the hope that at least one will turn into a baby. DOUG POWERS: You know, when you look at an embryo under the microscope, as beautiful as it is on the first day after fertilization, when they're single cells, they just almost all look the same. You can't pick out the highest quality embryo on that first day. NARRATOR: Since the early days of IVF, doctors have transferred fertilized eggs back to the mother when they reach the eight-cell stage. But recently, labs have been getting better at keeping embryos alive. DOUG POWERS (Boston IVF): The hope has been to let nature take its course and keep them in culture for a few more days—after the stage we call the blastocyst, when, really, the embryo proper starts developing. And the thought is, at that stage, nature will have selected, in our incubators, the best embryos. NARRATOR: By transferring back only two embryos at the blastocyst stage, doctors avoid the risks of multiples without diminishing the chance of a pregnancy. But not every embryo can make it to the fifth day. At Cornell University, Ilysa and Darren anxiously await news about their 13 fertilized eggs. Fortunately, eight have become viable blastocysts. Now the challenge is to pick the two that are most likely to survive. ILYSA: Yes, there is a possibility of having twins and I'd be ecstatic. I'd be, like,so happy. I even joked, you know, "Can I request them?" And they're like, "No." But you just want something to stick and hopefully it will work. But if it doesn't we would do it again. NARRATOR: Although more than half the couples going through IVF walk away childless, Darren and Ilysa hope that they will be the lucky ones who defy the odds. Back in the lab, their two embryos are located beneath the microscope and carefully sucked up in a catheter. Having live embryos transferred to her womb will be the closest Ilysa has ever come to being pregnant. But to become babies they must implant. DR. ZEV ROSENWAKS: With blastocyst transfer, we have a very high success rate. Nevertheless, it's age-dependent, and in the early thirties it's 50 percent. It's still 50-50. At the end of the day it's the biology and the competence of that embryo, and that depends on both the egg and the sperm, and their combination. DARREN: The most difficult part of IVF is everyday you're waiting for results on something—waiting to find out how much sperm and how many eggs there were. Then a day later you're waiting to see, "Hey, when are they going to inject them back into you?" And that was very stressful. That was four days of just waiting. And now you don't hear anything until you find out if you have a child or not. So now will be the greatest of all results, but you won't know for two weeks. NARRATOR: As technology advances, the treatment of infertility has been transformed from a small medical specialty into a four-billion-dollar-a-year industry. At this trade fair, sales teams from all over the world pitch their services to doctors, hospitals and couples desperate for a baby. The Center for Surrogate Parenting is in business to find surrogates and egg donors for infertile couples. WILLIAM HANDEL (Center for Surrogate Parenting): This field started with everybody thinking that it was ungodly, satanistic. I couldn't get a doctor to even talk to me when I first started. I was considered such a maverick. Doctors were afraid of being put in jail. I cannot think of any other field of medicine that in 20 years has gone from being a pariah to being considered mainstream this quickly. NARRATOR: Many clinics insist that egg donors remain anonymous, but Bill Handel has launched a thriving business finding applicants willing to reveal their backgrounds, and matching them with infertile couples. WILLIAM HANDEL: Our Internet site, EggDonor.Com, offers the profiles of 300 of our egg donors. NURSE: What are you looking for? WOMAN: Do you have Jewish donors? NURSE: Absolutely. WOMAN: In our area? NURSE: And your area is...? COUPLE: In California? NURSE: Yes, we do. COUPLE: Okay. Just click Jewish here? NURSE: Yes. COUPLE: Brown hair, brown eyes. WILLIAM HANDEL: You can go on "blond, blue-eyed, Caucasian, Christian woman," and it will then select everybody in our database that has those characteristics. NURSE: And we'll submit. NARRATOR: Bringing a third person into the reproductive process raises many troubling questions. For an infertility patient like Anne, turning to egg donation or even adoption meant forsaking a biological tie to her child. As she grappled with this dilemma, the research team at Saint Barnabas Hospital was pushing forward a new frontier of reproductive biology involving the exchanging of parts, from one egg cell to another. They offered Anne an experimental procedure called cytoplasmic transfer, designed to help women whose eggs divide inefficiently. DAVID SABLE: The reason that an egg might not be able to do its job very well is that it may have abnormal chromosomes inside. On the same hand there's a possibility that there's a defect in the ability of the egg to distribute its normal chromosomes. And we most suspect that that's true in younger women, who we believe still have genetically normal eggs, and in whom the usual in vitro fertilization techniques uniformly result in very poorly developing embryos. NARRATOR: The procedure would preserve the nucleus of Anne's eggs that contain over 99 percent of her chromosomes, the DNA or genetic material that makes her unique. She would borrow from a donor egg a portion of its cytoplasm, containing tiny cellular structures. Among them are thousands of mitochondria that provide energy for the cell to divide, and incidentally, carry DNA for a small number of genes. In theory, a deficiency in the cytoplasm might prevent an egg from developing normally. STEEN WILLADSEN (Saint Barnabas Medical Center): The idea behind it was that, if there were situations where it appeared that cytoplasm was damaged or insufficient in one way or another, even if one was unable to say precisely what it was that was wrong with it, one might be able to replace it with presumed normal cytoplasm. NARRATOR: Cohen and Willadsen experimented with animal models, mixing the cytoplasm from different mothers of the same species. As they had hoped, the babies appeared healthy and normal. Although the doctors felt confident enough to proceed, Anne struggled with the risks. ANNE: When you're left with these choices, egg donation or adoption, or doing this new procedure... Egg donation...you don't know who is donating this egg. It's all anonymous egg donation. You don't know any dispositions towards illnesses, whether it be mental or physical illnesses. And you don't know how your children are going to react to the news when they grow up that they are not genetically your child. With adoption, you have the same risks, except the adoptive mother could want this child back in their life. So you're looking at three options that are risky, and you have to decide emotionally, medically and financially which have the fewer risks. NARRATOR: Deciding to proceed with cytoplasmic transfer, Anne and a donor had their eggs harvested. Then Cohen removed the cytoplasm from the donor's egg, carefully avoiding it's nucleus. STEEN WILLADSEN: One could argue, as indeed some people are arguing, that all this is unnatural, and it shouldn't be done, and just leave it alone. But on the other hand, if we want to gain more insight that can be of benefit in the area of human reproduction, well then, every now and then the boundaries have to be moved a little bit. You simply cannot gain experience without experimenting. And it's as simple as that. NARRATOR: By using the fertilization technique of ICSI, donor cytoplasm can be safely injected into Anne's eggs along with her husband's sperm. Three days later, when the developing embryos were examined, they appeared less fragmented. Four were selected for transfer. JACQUES COHEN: I think looking at her pictures of the four embryos that were transferred in a final cytoplasmic attempt, and comparing them to the photographic material we have available from the previous attempt, there were more cells and the cells looked healthier. And therefore, my impression is that at least in one or two of the embryos there seemed to be a higher chance of development. NARRATOR: Unlike Anne, the majority of patients who turn to IVF are in their late thirties or early forties. Many find it difficult to get pregnant simply because of the age of their eggs. JAMES GRIFO: Our peak fertility is in the mid-twenties, early twenties. And yet most of us are delaying childbearing until the late thirties. Now it is clear that one of the reasons the older patients don't get pregnant with the same efficiency as the younger patients is that the embryos are chromosomally abnormal at a higher rate. And it all correlates with the egg and what happens to the egg. NARRATOR: During a woman's childbearing years, one egg is ovulated each month. If it is fertilized, it will replicate its chromosomes and then divide, splitting them in half. JAMES GRIFO: Now, when that process happens in a young woman's egg, it goes along just fine. When it happens in an older woman's egg, it doesn't. Chromosomes get lost or are missing and you make an unhealthy embryo from that. So the theory is that there's something in the machinery or the cytoplasm, not the nuclear portion of the egg, but the surrounding portion of the egg, that moves those chromosomes around that causes these defects in the older woman. NARRATOR: To avoid the possibility of chromosomal damage, Grifo went one step further than cytoplasmic transfer. He carefully took the nucleus from an older woman's egg and injected it into a younger donor egg that had had its nucleus removed. The reconstructed egg was then fertilized and allowed to divide using the machinery in the cytoplasm of the younger donor. JAMES GRIFO: And we were able to reconstruct an egg in that fashion—get it to fertilize and make embryos. And we did it in a couple patients and we transferred embryos and nobody got pregnant. We only transferred three or four embryos total in the experiment, but then we got into trouble. NARRATOR: Criticized for unacceptable human experimentation, Grifo returned to the lab. Nuclear transfer techniques had recently been used to clone animals. And although Grifo was not trying to clone a human being, some feared his work might take us one step closer. LEE SILVER: There's a lot of criticism of human reproductive biologists who are using all of these new technologies to allow people to have babies. Because as a scientist you do all of this background research, and you don't try anything until you're absolutely 100 percent confident. But in these cases we have women and men who are desperate to have children. And what the reproductive biologists are working on is the basic premise that if you do a manipulation, and you've manipulated it too far, you don't get a birth defect, you get no fetus or baby. NARRATOR: On December 20, 1998, Anne delivered a healthy baby girl named Katie. She was the third child born using cytoplasmic transfer. ANNE: This was my closure. This birth was closure to 5 years of infertility, and I really think this whole experience, when I look back on it, it makes me appreciate my daughter and my family so much. And every day I look at her in amazement that she's here. And that she's my child. She knows her background, she knows her roots, and to me, that's important. NARRATOR: Katie has a mix of her parents' genes, as well as traces of mitochondrial DNA from the egg donor. But was cytoplasmic transfer responsible for her birth? DR. DON WOLF (Oregon Regional Primate Research Center): My problem with cytoplasmic transfer is I can't conceptualize very well what in fact is the significant component that is being transferred from the cytoplasm of a donor egg to the cytoplasm of the infertile woman's egg that's conferring upon that egg some kind of improvement in quality. If, in fact, that's happening. I mean, the numbers at this point don't allow us to say anything in terms of efficacy. And clearly they don't allow us to say much in terms of safety. LEE SILVER: There's no scientific proof that the genetic change brought about the development of this child, but there is scientific proof that this child has DNA from a source other than her parents. And so, this is the first instance of genetic engineering. Whether or not the genes themselves really had an impact on allowing this child to be born, the threshold has been crossed. We have already engineered embryos, and so people can't say, "Well we have to wait until a certain point." It's already been done. NARRATOR: With each new breakthrough in making babies, the limitations and randomness of nature are slowly being overcome. One of the most intractable barriers egg donation has pushed back is the limit of age. Back in 1980, when Arceli Keh got married, she was entering menopause and had no chance of becoming pregnant or even adopting a child. For years, she followed the development of IVF, hoping that new techniques might help her become a mother. She saw her chance with egg donation, and at age 60, decided to bend the rules. ARCELI KEH (Woman who gave birth at 63): I really lied about my age because they have this age limit of 55. So I think I will not qualify if I will not lie about my age. And I really want to have a baby. RICHARD PAULSON: She presented herself as someone who was fifty years old—well within our age guideline of 55—underwent the usual kinds of medical testing, including a treadmill test and a variety of other blood tests that we do on all the patients, and as far as we were concerned,we thought that she was just another routine patient. NARRATOR: Mrs. Keh took hormones to force the tissues lining the walls of her uterus to thicken. Within months, her womb returned to its pre-menopausal state, capable of sustaining a pregnancy. Then donated eggs, fertilized with her husband's sperm, were transferred back. After spending 40,000 dollars and enduring five IVF cycles, she gave birth to Cindy. At age 63, she was the oldest woman to ever have a baby. RICHARD PAULSON (USC Center for Infertility): The deception had been obvious. She knew that she had deceived us. She did it consciously, and successfully, because she had attained the goal that she had wanted to. What should I tell her? Scold her for being non-forthright? I congratulated her. ARCELI KEH: I feel very happy, actually. She changed our life for a better one. I just hope God will give me a much longer life, you know, to be around her. ARTHUR CAPLAN: When an older woman has a baby, it's very likely that her partner or mate may be old as well. And I think it's risky to create orphans. So, you might want to set an age limit, if not on the age of the woman, then at least on the couple. So that you do what we do in adoption, which is to say at some age, "We're nervous that you can't be around to make sure that the child's interests are protected." NARRATOR: The creation of families with borrowed eggs, sperm or wombs has raised a myriad of complex issues. One of the most difficult is explaining to children how they came to be. WILL: "Oh help! There is a mouse about the house!" MELINA: "That's okay." WILL: "And it gave Mrs. B a fright." MELINA: "That's okay." WILL: When we turned to IVF from traditional methods, such as artificial insemination, one of the things we did think about was what story we tell our children. Because when you start separating the functions of carrying the child versus donating the genetic material, then it becomes more complex. NARRATOR: Will and Marcellin created a birth book to explain to Melina why she doesn't have a mother in the traditional sense. WILL: It's a very simple story about how her daddy and papa met, fell in love, wanted a family. And how men don't have eggs and women have eggs and men can't carry children or deliver children, but women can. And papa and daddy searched the world to find two women who would help them. JAMES GRIFO: There's, like, 18 different ways to make a baby now, because of the technologies. And, you know, that makes us have to rethink, "What is a family?" Well, the fact is, what it means to be a family is to have a parent or two parents raise a child, and care for the child, and have an attachment to that child that nobody else has, and a responsibility to that child that no one else has. And that's really what matters. NARRATOR: Assisted reproduction began with the idealistic goal of helping infertile couples have babies. But increasingly, it has given parents greater control over their unborn offspring. At a leading infertility clinic in Virginia, a technology called "microsort" is enhancing the ability of science to determine one of a child's most important traits—its sex. JOSEPH SCHULMAN (Genetics & IVF Institute): The commonest types of individuals that we help are families who are at risk for having children with x-link disorders. These are disorders that effect males and therefore microsort can be very helpful in producing disease-free, female offspring in these families. And the other largest group come to us for family balancing, where they already have a preponderance of children of one gender in the family and they wish to weight the odds in favor of the opposite gender. NARRATOR: Of the 23 chromosomes carried by the sperm, only one determines gender. Sperm carrying an X chromosome will produce a girl. Sperm carrying a Y chromosome will produce a boy. For $3200, sophisticated machines can detect the minute differences in size between male and female sperm and sort them. JOSEPH SCHULMAN: The chance of having a girl, when that is sought, exceeds ninety percent. And the chance of having a son exceeds seventy percent. ARTHUR CAPLAN: I think what's involved here is not the choice of boy or girl, it's the fear of sexism. If we knew the percentage of boys and girls would be about the same, I don't think anybody would care. So, I think the issue isn't choice of sex. It's actually, "Is it going to distort the make-up of the population or reinforce stereotypes about men and women?" NARRATOR: Sex selection has already led to an imbalance in India where there are an estimated 40 million fewer women, primarily because of the routine abortion of female fetuses. In China, the desire for boys at one point changed the sex ratio to 153 Chinese males for every 100 females. In contrast to the rest of the world, American parents are using microsort to have baby girls. JAMES GRIFO: I think if patients want to use it, and want to spend the amount of money that's required that's their choice. To me, it's the wrong message. To me, gender is not a disease, and I'm not going to select against it. You know, I want people to have healthy babies. And whether it's a healthy boy or a healthy girl, I don't care. NARRATOR: Choosing a baby's sex is a far cry from designing our children. But eventually, parents will have even more choices using a powerful technique called pre-implantation genetic diagnosis or PGD. From a single cell plucked from an embryo, doctors can analyze individual chromosomes and genes. This microsurgery rarely harms embryos, and helps doctors figure out which ones are disease-free. One of the earliest pioneers to use PGD was Barbara Nastro. BARBARA NASTRO: I had many chemical...what they refer to as chemical pregnancies. So that means that I would become pregnant, and then within a couple of weeks of holding the pregnancy, it would fizzle out. DAVID SABLE: When you see that, it's very suggestive that many of the fertilized eggs have abnormal chromosomes, and that nature is just doing its best to stop these abnormal pregnancies from developing. NARRATOR: At age 41, Barbara underwent IVF in order to use PGD to test her embryos. A single cell was plucked from each one and analyzed with fluorescent dyes targeted to bond with five specific chromosomes most prone to have either an extra copy or a missing one. Embryos with the correct number of chromosomes, like this one with matching pairs of color signals, could be transferred back. In contrast, this embryo is missing one if its red signals, and would not develop normally. Barbara had nine fertilized eggs to test. DAVID SABLE: And it turned out that four of them were chromosomally abnormal, including some of the embryos that looked very, very good—that typically, we would have transferred, and would have resulted in another miscarriage. And we subsequently transferred the normal embryos and a successful pregnancy occurred. NARRATOR: Barbara gave birth to healthy fraternal twins, Gabriel and Luke. Although PGD spared her repeated miscarriages, its cost, in conjunction with IVF, was almost prohibitive. BARBARA NASTRO: The pre-genetic determination test alone as I recall, is about $20,000. Plus...then when our babies were born early...premature...six weeks...they then had to spend three weeks in the NIC Unit. That alone, I believe, was somewhere around several hundred thousand dollars for them to be there for that length of time. It's an enormous amount of money—money that is inconceivable to most couples. NARRATOR: But for parents who risk passing on inherited diseases like cystic fibrosis, PGD offers the hope of having a healthy baby. At the moment, scientists can look for genes related to several dozen diseases. But our ability to screen embryos will improve exponentially as a result of the decoding of the human genome. LEE SILVER: And what's going to happen over the next decade is we're going to understand how those genes cause all sorts of diseases like asthma or juvenile diabetes, or severe depression, or predisposition to heart disease or Alzheimer's diseases. All of these diseases are going to be understood in terms of their genetic influence. NARRATOR: To exploit this knowledge, technology is emerging that allows DNA fragments containing thousands of genes to be analyzed with automated gene scanners. In the future, DNA computer chips may be able tell you every single form of the approximate thirty thousand genes that you've got. GATTACA CLIP: "They used to say that a child conceived in love has a greater chance of happiness." NARRATOR: Hollywood has already imagined the implications of this powerful technology. GATTACA PROGENY (played by ETHAN HAWKE): I will never understand how my mother put her faith in God's hands rather than those of her local geneticist. Ten fingers, ten toes that's all that used to matter. Not now. Now only seconds old, the exact time and cause of my death was already known. GATTACA NURSE: Neurological condition, 60 percent probability; manic depression, 42 percent probability; A-D-D, 89 percent probability; heart disorder, 99 percent probability; life expectancy 30 point 2 years. LEE SILVER: The amazing thing about Gattaca is that it is scientifically right on the mark. Because it will be possible in the future to take a drop of blood from a child, and know the pre-dispositions to every kind of disease that this child is going to face in his or her life. DNA chips revolutionized our ability to look at human genes and it will be possible in the future to use a DNA chip on embryos. ARTHUR CAPLAN: What I envision in 20 years, is that someone will be able to go to the in vitro clinic who's very fertile, who has no infertility problems at all, but simply says, "If you can tell me a lot about the kind of child that I'm likely going to have, then I'm going to spend the money and use an artificial way to create a baby...to kind of get a better baby." LEE SILVER: And then what a couple would be able to do is to look at their computer screen and look at what the child's height would be, certainly; what the hair color would be; whether the child's going to go bald; whether the child's going to get asthma; whether the child's going to be a bit aggressive or shy. All of these things are going to come out of looking at a DNA chip profile from each of these embryos. NARRATOR: The limitation to pre-implantation genetic diagnosis is that parents can only select for genes that embryos already have. But scientists have begun inserting new genes into embryos, endowing thousands of animals with unusual traits. A specific gene from a jellyfish can make mammals glow in the dark. Molecules involved in learning and memory can be genetically augmented to create smarter mice. As reproductive biology and genetics merge, will parents of the future have the tools to design their children with new strengths and talents? JAMES GRIFO: Yes. These things could happen. Right now they don't. We don't know the genes for hair color, eye color or intelligence. We don't know how to select for them. We don't know how to analyze for them. So these fears, while based in the potential reality that they could occur, are really unfounded. ARTHUR CAPLAN: I think we'll see this happen. I think it's going to be very difficult to say to people, "You can't do this," because in a sense, today, we're already down that road.Some people do everything they can to environmentally advantage their kids. Do we say they're morally wrong? In fact, we say they're doing a morally good thing. It's good to give your child, in a competitive market society, the best shot at success. And I think that's the ethos that's going to carry us right straight into using pre-implantation genetic testing and new genetic knowledge to design our descendents. NARRATOR: In many ways, the brave new world of assisted reproduction promises far more benefits than perils. In the 21st century, newborn children will be spared lethal diseases that plagued past generations. As the mysteries of reproduction give way to knowledge, even infertility might be overcome. For Ilysa and Darren ICSI has paid off. They are now the elated parents of a healthy baby girl named Sarah, born January 29th, 2001. Anne's daughter, Katie appears to be healthy and developing normally. Although cytoplasmic transfer is still highly experimental, for the small group of patients that have turned to it, 36 percent have become pregnant. LEE SILVER: People are afraid of the unknown and most people, therefore, reject new technology. It takes the mavericks, the maverick scientists and the people who have some guts to work with the maverick scientists and clinicians to bring the technology into the public domain. JAMES GRIFO: There are risks to these things, but there's also risk to not treating disease. And people forget that. People forget how hard it is to live with infertility. People forget how devastating that is. And people don't understand why patients are willing to take these unknown kinds of risks to have that child, because they forget about the disease. Doctors today have a surprising number of ways to help make a baby. On NOVA's Web site, explore the more than 18 high-tech procedures now in use—on PBS.org or America Online, Keyword PBS. Educators can order this or any other NOVA program for $19.95 plus shipping and handling. Call WGBH Boston Video at 1-800-255-9424. NOVA is a production of WGBH Boston. Major funding for NOVA is provided by the Park Foundation, dedicated to education and quality television. Scientific achievement is fueled by the simple desire to make things clear. Sprint PCS is proud to support NOVA. This program is funded in part by the Northwestern Mutual Foundation. Some people already know Northwestern Mutual can help plan for your children's education. Are you there yet? Northwestern Mutual Financial Network. And by the Corporation for Public Broadcasting and by contributions to your PBS Station from viewers like you. Thank you. This is PBS. PRODUCTION CREDITS18 Ways to Make a Baby
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