Norman Swan: Hello, Norman Swan here. Today want to share with you another program from RN because I think you'll find it particularly interesting. It's an episode of Science Friction presented by Natasha Mitchell, and it's about a procedure at the leading edge of medical science; the uterus transplant. Only a handful of babies worldwide have been born via uterus transplant, but there are more on the way. And there are huge ethical questions to be answered in this field, questions that could shape the future of human reproduction. Here's Natasha Mitchell with Science Friction.
Natasha Mitchell: Welcome to Science Friction, and to Future Uterus, this miniseries of ours taking a womb's eye view of the future of reproduction. Hi, I'm Natasha Mitchell.
When Lolita was 14, she felt this strange pain in her middle.
Lolita: So I went to the doctor.
Natasha Mitchell: The doctor examined her but detected something surprising and went and got a colleague for a second opinion. She was asked to come back for a more thorough examination.
Lolita: They had to put me to sleep and do an exam with a camera. And when I woke up the doctor was sitting there with a paper and pen and he was drawing and said that the uterus can look a lot different from woman to woman. And I asked him, 'Well, what does mine look like?' And he simply said that, 'You don't have any.'
Natasha Mitchell: You don't have a uterus?
Lolita: No.
Natasha Mitchell: So at age 14 in 1994, Lolita was told for the first time that she'd been born without a womb.
Lolita: I felt like a freak. I didn't know what I was. Because you've always been told that a woman is going to get their period and you're going to have a baby and all that. And I always loved children and I always wanted children. What was I now? I was heartbroken. The day after I came home I wrote in my diary, 'Please can somebody give me a uterus.'
Natasha Mitchell: Which makes what happened to Lolita 18 years later all the more extraordinary. In the last show we imagined a world where babies are created in artificial worms, where society has opted for portable baby pouches instead of pregnancy. That was all pure sci-fi of course. What you'll hear today though is real frontier science, transforming and in fact creating real lives. But provoking all sorts of ethical questions too, which are front and centre for bioethicist Dr Nicola Williams from Lancaster University.
Nicola Williams: So I suppose the uterus is different in that it's a symbolic organ of womanhood, and that's why it's quite important to many women with absolute uterine factor infertility because they don't feel whole sometimes.
Natasha Mitchell: And this potent symbolism of the uterus might explain why Lolita says she felt an inexplicable shame about the secret she carried inside her body. The condition she was born with is called Mayer-Rokitansky-Kuster-Hauser Syndrome. It's just one cause of absolute uterine factor infertility.
Lolita: And just to meet boys was difficult. I know that boys that age don't think about kids.
Natasha Mitchell: But Lolita just always felt like she had to let them know that she didn't have a womb, and you can imagine how awkward that conversation would have been, talking babies with teen boys.
Lolita: But I always felt I have to be two steps ahead.
Natasha Mitchell: Your sister's reaction at the time when you were 14 and received this news was really interesting. What happened? Tell us.
Lolita: Well, she said that, 'You can have my uterus, I don't kids, so you can have mine.'
Natasha Mitchell: How old was she? This is your older sister.
Lolita: Yes, she was 18.
Natasha Mitchell: Life had other plans for Lolita's sister, she went on to have four children, but her pledge to her little sister remained. Attempts to transplant one woman's uterus into another in fact started with the case of a pioneering transgender woman.
Nicola Williams: The first uterus transplant took place in 1930 for the Danish artist Lili Elbe.
Natasha Mitchell: You may have seen the film about Lili, called The Danish Girl.
[Excerpt from The Danish Girl]
Nicola Williams: Unfortunately the transplant fails and it causes her death, which is unsurprising given that immunosuppressants weren't even discovered until the mid 1970s, and there was very little knowledge about proper organ retrieval and storage procedures.
Natasha Mitchell: But 80 years later, scientists and surgeons were more confident.
Liza Johannesson: I mean, in the beginning they thought we were crazy, to be honest…
Natasha Mitchell: Did they?
Liza Johannesson: Yes, they thought we were nuts doing this.
Natasha Mitchell: Dr Liza Johannesson is a gynaecologist obstetrician who heads up the uterus transplant program at Baylor University Medical Centre in Dallas Texas. But she started out as a member of a trailblazing Swedish team, leaders in developing the procedure.
Liza Johannesson: So we started in small animals like rodents, mice and rats. We did transplants in them and we had successful deliveries in rats and mice. We went through phases where we tried the surgery in sheep, in pigs. And then as a final step we even did it in nonhuman primates, just to mimic the conditions with humans as much as we could.
Natasha Mitchell: So in baboons?
Liza Johannesson: Yes, in baboons.
Natasha Mitchell: And what were the challenges as you developed that technique, as you developed the procedure? I mean, this is an organ transplantation, so rejection of that transplanted uterus is a big issue.
Liza Johannesson: It seems like it's not that big of an issue that we thought it was in the beginning. But when we did the trials in the baboons, that was certainly challenging because baboons don't necessarily take medications as you would want them to. So we struggled with rejections in the baboons and medical administration. But when it comes to humans, it actually looks like the uterus is fairly resistant to rejection, and no one has lost a uterus due to rejection so far.
Natasha Mitchell: When Lolita was 19 she saw media reports about those scientists and their animal experiments, and she even rang Mats Brännström, head of the team, to ask if they could help her.
Lolita: Yes. I don't know, I think he was surprised and I guess he was just in the beginning of something.
Natasha Mitchell: But they were only doing studies in mice at that very early stage.
Fast-forward a decade on, and by now Lolita had met and married her husband and she desperately wanted a child. The science had advanced dramatically too. The Swedes had approval for a human clinical trial, and that caught the world's attention.
Evie Kendal: It is an extraordinary development.
Natasha Mitchell: Dr Evie Kendal is a bioethicist at Deakin University with a focus on reproductive technology.
Evie Kendal: I'm a little concerned about some of the ramifications of uterine transplants, partly because it is quite risky. All transplantation, all surgery has its risks of course. We have risks to donors if they are living donors, and we have the usual transplant risks to recipients. But what we don't have are the same justifications as we have for life-saving transplants. So if you desperately need a heart transplant, of course those risks have to be balanced against those benefits, so a life-saving transplant is a lot easier to justify in many ways.
Liza Johannesson: In the beginning when we did this in animals, a lot of the criticism we had was that is this even doable, can you do this in humans? You're doing it in rats, but can you do it in humans? So a lot was focused around the procedure itself. And now the latest thing is is this doable from a cost perspective? Who are we going to replace this procedure with? Who's not going to get access to healthcare? Because we pay for the uterus transplants.
Nicola Williams: Uterus transplants are difficult and thorny ethically, scientifically, socially. Uterus transplantation is quite interesting because it has a dual status as both a transplant and a reproductive technology.
Natasha Mitchell: Dr Nicola Williams. Her work centres around the ethics and economics of uterus transplants.
Nicola Williams: And because of this, it's the most expensive reproductive technology available, and also the riskiest.
Evie Kendal: But you will leave the clinic either way infertile again. And I think one of the issues I'm having with uterine transplantation is it might serve as a distraction to better cures for infertility. And the reason I think it might be a dangerous distraction from the development of bioengineered wombs or actually fixing the womb injury that might have happened to a woman that is preventing pregnancy is because when IVF was found to be successful, work on actually unblocking fallopian tubes, one of the major causes of infertility that IVF does circumvent was actually abandoned for the most part. So women are now dependent on an industry that they go in and pay lots of money for to go around their body rather than actually giving them the experience that they want.
Natasha Mitchell: And so back to that Swedish trial and Lolita's story.
Lolita: Back in 2011, the spring time, there was an article in the newspaper saying that they were ready to take the next step and try this on a human.
Liza Johannesson: People reached out to us. They heard about our animal experiments, and we didn't advertise at all. These were people who came to us and we screened them.
Natasha Mitchell: Including the Lolita and her sister.
Liza Johannesson: I remember they were three sisters in that family and the older one wanted to donate her uterus. And she had already given birth to four kids of her own and she felt that she was done with her uterus, so she wanted to give it to her little sister.
Natasha Mitchell: And that little sister's one number one goal was to be able to carry her own baby.
Lolita: For me, it's always been important to be able to carry my own child.
Natasha Mitchell: Adoption or surrogacy could well have been an option for Lolita and her husband, although surrogacy is legally complex in Sweden.
Lolita: I was dying inside. This feeling like all this shame and depression, it's so destroying, it's just breaking you down.
Natasha Mitchell: Which makes the stakes very high if none of this was to work. This could make it even more profound, that feeling of despair for you.
Lolita: But for me it was important.
Liza Johannesson: And we thought this, Lolita and her sister, was a really, really good couple.
Natasha Mitchell: So this was very early on. Essentially they are part of this incredible experiment.
Liza Johannesson: Yes, in a way they were.
Natasha Mitchell: How do you communicate that to them?
Liza Johannesson: At that time it was even harder because that was before we even had the first birth in the world, so we didn't know what we were consenting them for, we didn't know what the results might be, and they trusted us, they wanted to go through this, and we told them about the risks, we told them that it's highly likely that this will not succeed, the uterus will never carry a pregnancy, but they anyway wanted to be part of this.
Natasha Mitchell: Lolita was one of nine women in the University of Gothenburg trial in 2012, the first substantial human trial of uterus transplant surgery. Previous efforts—in Saudi Arabia in 2000, and Turkey in 2011—hadn't been successful.
So the first step in the process, to source the uterus, either from a living or dead donor. Luckily, Lolita had her sister.
Lolita: I don't know, maybe it sounds crazy, but for us it was just like I was borrowing a sweater from her. I know it sounds crazy but…
Natasha Mitchell: Borrowing a sweater?
Lolita: …it's always been so natural.
Natasha Mitchell: Oh, uterus, a sweater, what's the difference?
Lolita: Exactly.
Natasha Mitchell: You didn't really even have to have the conversation it seems.
Lolita: No.
Natasha Mitchell: I wonder what it would have been like to have had that conversation?
Lolita: I imagine that would be difficult and hard, and today it's just so normal. She is the same aunt, just so normal, and I don't feel like I owe her anything.
Natasha Mitchell: You don't owe her anything.
Lolita: No.
Evie Kendal: It's not just the potential recipient, we have to be concerned about the rights of the donors as well.
Natasha Mitchell: Bioethicist Dr Evie Kendal:
Evie Kendal: I am concerned with the kind of pressure that might be placed on, say, a mother or a sister to donate their uterus to a sister or a daughter who is desperate to be pregnant. Those pressures already exist for all live donors. So one concern of course, and this goes back to the idea of sexual equality, we know that more mothers donate their kidneys to their children than fathers, and we know that perhaps there is a social pressure on women to be more selfless and to donate in a way that might actually be fairly toxic in this situation. It is not justified by 'you're saving the life of your child', it's 'you are providing the means to grow your own grandchild', which is quite different in terms of outcomes.
Natasha Mitchell: Toxic? Why would the potential outcome be toxic if there is a successful pregnancy, and a mother or sister has actively, proactively, voluntarily surrendered their own uterus to the process?
Evie Kendal: If it's involuntary and informed, then again it is the business of the people involved, I'm not here to tell people what risks are acceptable to them. It's toxic if it's coming from social pressure, particularly if that's of a very gendered nature.
Lolita: I had the luxury to have two donors, because me and my sister had to match, have the same blood type, and we did, but if we wouldn't I always had my mum, my mum would donate it too.
Natasha Mitchell: This is our Future Uterus miniseries here on Science Friction on ABC RN with me, Natasha Mitchell. And I'm going to come back to the use of dead donors rather than living later on because they raise really gritty ethical questions for uterus transplantation.
But the next step for Lolita and her husband was to undergo IVF to be sure they could create viable embryos together before her sister underwent the whole palaver of major transplant surgery. But then, finally, the day came.
Lolita: Me and my sister went down to Gothenburg the day before.
Liza Johannesson: We always start with the donor surgery.
Lolita: And so they started with her, and I was still at the hotel.
Liza Johannesson: And the donor surgery to remove the uterus together with their vessels that feeds, takes blood away from the uterus, and you also take a part of the vagina, and that's the structure you put into the recipient.
Lolita: I thought time has never passed so slow.
Liza Johannesson: It's almost the size of a hand, you could say, and then it's attached in the body to the fallopian tubes and, in a way, to the ovaries as well. But we always leave the ovaries, the ovaries are the ones that produces hormones that the women need up until they are postmenopausal for their bones and their cardiovascular disease risk and all of those things. We always leave those. And then we suture the vagina back together. So afterwards they look the same but they don't have the uterus there anymore.
Lolita: And the nurse was holding my hand, so the last thing I remember, her holding my hand and was like, 'Sleep well.'
Liza Johannesson: And then we put the organ on ice. We look at it very carefully because we want to make sure that this uterus is going to work, and in doing that we look at the uterus, we look at the cavity which is inside the uterus and we look at the vessels. And then we bring the uterus in and we attach it. It's like plumbing, you attach the vessels, you attach the vagina…
Natasha Mitchell: And stitch them into place.
Liza Johannesson: We stitch them into place. And the amazing thing is that afterwards it looks like the uterus has been there forever.
Natasha Mitchell: So you are lying side by side in the recovery after the surgery, and she no longer has her uterus, her uterus is inside you. How did that feel?
Lolita: It was amazing. It was so unreal. I was so happy. Of course I was in a lot of pain, but the people taking care of us were beautiful. The day I got the uterus, I became whole as a person, as a human being. I wasn't whole before, I was in pieces.
Natasha Mitchell: And we'll come back to Lolita and her sister in the recovery room.
But the very idea of transplanting a uterus between two women, sisters or a mother and daughter, makes some people feel really squeamish.
Nicola Williams: They find it quite hard to imagine that a woman's child could be gestated in the womb of their mother. And this is a similar concern that they've had regarding mothers who have acted as surrogates for their daughter. I don't think it has much of a rational basis.
Natasha Mitchell: Yes, a womb is a womb is a womb, but then something about it, taking their womb from your mother, the womb that gave birth to you, and then creating a child of your own and gestating a child in that very same womb.
Nicola Williams: Well, there have been a lot of meanings accorded to the womb throughout history, haven't there, and so I think that perhaps our unease with transplanting this organ stems from that perhaps.
Natasha Mitchell: But let's come back to Lolita and her sister recovering after their big operations. Lolita was put on immunosuppressant drugs to prevent her body from attacking and rejecting her sister's uterus inside her, and these drugs have their own side-effects.
Liza Johannesson: That's why we tried to minimise the time of the uterus being in the person as much as we can because we don't want to expose them to unnecessary drugs. So what we monitor is the levels obviously of the immunosuppressant and we also monitor cervical biopsies, so we take biopsies from the uterus at certain time points to see how the uterus is doing.
Natasha Mitchell: What can go wrong at this stage? Have you or other teams had situations where the uterus has been altogether rejected or has started to vitrify, to die?
Liza Johannesson: Early experiments that was done even before the Swedish trial, in Saudi Arabia, where they had necrosis of the uterus, meaning that the uterus started to die, but that was due to the vessels and poor blood flow. We had rejection episodes. But if you see those rejection episodes early, and you do if you do the cervical biopsies, you can treat them and they go away.
Natasha Mitchell: Is it too early to be doing these in humans?
Liza Johannesson: I don't think so. I mean, we have very promising results, and even if we have failures and even if we have complications, they are not so severe that it would make us not do the procedure.
Natasha Mitchell: When a transplanted uterus settles into its new home, it just seems to start doing what a uterus does. And in fact that's what most spooked Lolita.
Lolita: Yes, I wasn't afraid to die but I was terrified to get my first period.
Natasha Mitchell: First period. I guess because it you'd never had one before, ever.
Lolita: Yes, I'd never had one.
Natasha Mitchell: And here you were…
Lolita: I was so scared, it's like blood was supposed to come out of me. Would I know when it was going to come? Going to the grocery store and just pick out a pad, that is amazing, so much to choose. So it was hard.
Liza Johannesson: So everything is amazingly normal. So they start with menstrual periods about 3 to 7 weeks after their surgery. The first time they are terrified.
Lolita: It started the night before. I was having bad pain in my back and my ovaries and I didn't understand what it was, I thought something was wrong.
Liza Johannesson: Because it's bleeding and they think it's a rejection and they call us and they're horrified. And we were in the beginning too, but now we realise that it's just proving to work.
Natasha Mitchell: So the uterus is doing what it's meant to do.
Liza Johannesson: It's supposed to do that, so it's doing really well.
Natasha Mitchell: But after all that, a functional uterus is not the desired end point here, pregnancy is. So, four months after the transplant, it was time to implant an embryo. Would it work? It was touch and go for Lolita. One, two, three embryos, four, five, six embryos later, and then…
Lolita: My mum and my youngest sister were at my house, and I remember that I didn't want to tell them because I wanted my husband to be the first one to know, so I was standing in the bathroom and I was just crying, silent. My husband was at work, and after work he went to the gym and after the gym he went and saw friends, so when he got home I was so mad because I'd been waiting the whole day.
Natasha Mitchell: And three trimesters later, Lolita's obstetrician gynaecologist Liza Johannesson remembers it well.
Were you there when the baby was born?
Liza Johannesson: Yes, I was the one delivering him.
Lolita: It was a Thursday. I called my sister in the morning and I was like, yeah, I don't know if I'm peeing or if I'm leaking because I was dripping water…
Liza Johannesson: And she started to go into labour.
Lolita: I remember there were so many people in the surgery room. And then I heard my son.
Liza Johannesson: It's a miracle every time you deliver a baby, but these women, the stakes are so high, and you live so closely with them, so it feels like you're family.
Lolita: It was so beautiful, he was perfect.
Natasha Mitchell: Holding him for the first time. What was that like?
Lolita: Unbelievable, so worth every tears, every fear, every laugh, everything. It's been a hard journey of course, but I would do it in a heartbeat.
Natasha Mitchell: How did you feel saying goodbye to your sister's uterus? You had to have it removed.
Lolita: It was hard. For a few seconds it felt like I wasn't allowed to feel sad because people thought that I was ungrateful for the son I had but it had nothing to do with that, just that to be able to have more kids. I dreamt about it but at the same time I'm so happy for my son. And my sister said that after the surgery she feels more like a woman than she did before.
Natasha Mitchell: Why did she say that?
Lolita: I don't know, she feels like she did this for me and she did it for the other ladies in the world. She feels stronger, she feels more beautiful and she doesn't have her period anymore.
Natasha Mitchell: Lolita's son is a happy, active, three-and-a-half-year-old now, the fourth out of 13 children around the world in total, at last count at least, to be gestated in a transplanted uterus. More babies on the way this year, Dr Liza Johannesson tells me, and she says her Dallas team now receive hundreds of calls from women who want to donate their uterus to complete strangers. But it's early days, this is a novel procedure, so the clinicians are tracking children closely, both body and mind.
Liza Johannesson: They are for sure historical and they are for sure a population that we will follow closely. We're going to track them until they go to college probably.
Natasha Mitchell: Your sister's children and your little boy were born using the same uterus, they are cousins. Do you all think of their relationship a little differently because they were born using the one uterus transplanted between you?
Lolita: No, the only thing we say is that they are the 'bag cousins', and my sister is 'bag aunt' because my niece was only five years old, and to explain to her we told her that I was going to borrow her mum's baby bag, because how do you explain 'uterus' to a five-year-old.
Natasha Mitchell: 'Bag cousins' and 'bag aunts' because they shared a baby bag.
Lolita: Yes, the only one in the whole wide world.
Natasha Mitchell: That's great, because I've just read a science fiction novel where the whole premise is based on a future where we no longer have babies inside us in a uterus, we actually gestate them entirely in an artificial womb, which they call a baby bag.
Lolita: Wow. We were first, we were first with the expression!
Natasha Mitchell: Thanks so much to Lolita for sharing her experiences. The ethical concerns about uterus transplantations go really deep, so let me urge you to pick up the Science Friction podcast for that conversation at about 25 minutes. Could demand for uterus donations trigger an illegal global trade in uteri? Should donors get paid? What about dead donors? Are they a less ethically fraught source for uteri or not? Next step in Future Uterus, a scientist building an artificial womb. Talk to me on Twitter @NatashaMitchell. Thanks to Jane Lee and Ari Gross. Spread the word about the podcast, culture and science and spice is our thing here on Science Friction.