Science

‘Parents can look at their foetus in real time’: are artificial wombs the future?


The lamb is sleeping. It lies on its side, eyes shut, ears folded back and twitching. It swallows, wriggles and shuffles its gangly legs. Its crooked half-smile makes it look content, as if dreaming about gambolling in a grassy field. But this lamb is too tiny to venture out. Its eyes cannot open. It is hairless; its skin gathers in pink rolls at its neck. It hasn’t been born yet, but here it is, at 111 days’ gestation, totally separate from its mother, alive and kicking in a research lab in Philadelphia. It is submerged in fluid, floating inside a transparent plastic bag, its umbilical cord connected to a nexus of bright blood-filled tubes. This is a foetus growing inside an artificial womb. In another four weeks, the bag will be unzipped and the lamb will be born.

When I first see images of the Philadelphia lambs on my laptop, I think of the foetus fields in The Matrix, where motherless babies are farmed in pods on an industrial scale. But this is not a substitute for full gestation. The lambs didn’t grow in the bags from conception; they were taken from their mothers’ wombs by caesarean section, then submerged in the Biobag, at a gestational age equivalent to 23-24 weeks in humans. This isn’t a replacement for pregnancy yet, but it is certainly the beginning.

The team who made these artificial wombs say they are driven only by the desire to save the most vulnerable humans on Earth. Emily Partridge, Marcus Davey and Alan Flake are neonatologists, developmental physiologists and surgeons who work with extremely premature babies at the Children’s Hospital of Philadelphia (CHOP). After three years of tweaking, their latest prototype is designed to give babies born too soon a greater chance of survival than ever before.

L-r: Alan W. Flake, Emily A. Partridge, and Marcus G. Davey, the team that led the artificial womb research at Children’s Hospital of Philadelphia. Credit: Children’s Hospital of Philadelphia



From left: Alan Flake, Emily Partridge, and Marcus Davey, creators of the Biobag. Photograph: Children’s Hospital of Philadelphia

The Biobag was born into public consciousness in April 2017, when the CHOP team published their research in the journal Nature Communications. They had found a way to gestate sheep foetuses outside maternal bodies; foetuses that would eventually become lambs no different from those that had grown in ewes’ wombs. (Sheep are the go-to animals in obstetric research because they have a long gestation period and the foetuses are around the same size as ours.)

Their invention consists of a replacement placenta: an oxygenator plugged into the lamb’s umbilical cord, which also removes carbon dioxide and delivers nutrients. Blood is pumped entirely by the beating of the foetus’s heart, just as it would be in the womb. The bag acts like an amniotic sac filled with warm, sterile, lab-made fluid that the lamb breathes and swallows, just as a human foetus would.

CHOP’s communications department released a very slick short film, Recreating The Womb, to coincide with the paper’s release. There is not a foetus in sight. Instead there are neat diagrams of lambs in Biobag systems, slightly awkward footage of Partridge, Flake and Davey pretending to do lambless lamb research in a pristine lab and heartbreaking clips of impossibly small super-premature babies. Then there are carefully edited interviews with the team. “In the future, we envision the system will be in the neonatal intensive care unit and will look pretty much like a traditional incubator,” Davey says. The Biobags would be kept in a darkened environment to mimic the human womb, but the babies would be visible as never before: “Parents can actually look at their foetus in real time,” Flake adds.

Normal human pregnancy is 40 weeks; any baby born before 37 weeks is considered premature. The 23-24-week period is the border of viability, after which modern medicine currently has a hope of keeping babies alive, and doctors will attempt to resuscitate a newborn. To the NHS, a baby born dead at 24 weeks is classed as a stillbirth, whereas a dead baby born at 23 weeks and six days is a miscarriage. It is a brutal boundary.

A lamb at 10 days’ gestation, on day four in a Biobag

A lamb at 10 days’ gestation, on day four in a Biobag. Photograph: nature.com/Children’s Hospital of Philadelphia

In countries with good hospitals, there is a 24% chance of keeping a baby born at 23 weeks alive. But 87% of those who make it will experience major complications, such as lung disease, bowel problems, brain damage and blindness. While more extremely premature babies are surviving in wealthier countries, the number growing up with chronic conditions has also increased dramatically. Preterm birth is the greatest cause of death and disability among children under five in the developed world.

Incubators deal with some of the functions a premature newborn needs help with, but they don’t allow for the process of gestation to continue; the Biobag does, treating the baby as a foetus who has not yet been born. Women at risk of going into very early labour could have their babies transferred into an artificial womb. It sounds extreme, but if it could mean a healthy future instead of illness and disability, who could deny it to them?

The CHOP researchers want their device to be seen as ethically unremarkable. “Our goal is not to extend the limits of viability, but to offer the potential for improved outcomes for those infants already being routinely resuscitated,” their paper says. Extending the current limits of a foetus’s viability would create an ethical minefield. The legal abortion limit in the UK was brought down from 28 to 24 weeks in 1990 because advances in neonatal care meant foetuses born then were more likely to live. If artificial wombs help ever smaller babies survive, that could have profound implications for women. But women are not mentioned in CHOP’s work.

The application to patent the Biobag, filed in 2014, is revealing. There’s no coyness about extending the limits of human viability here: it explicitly says possible “subjects” include “pre-viable foetuses (eg 20–24 weeks)”.

I am not allowed to go to Philadelphia to see the team’s work. I so nearly was: Flake told me I was welcome, and we fixed a date. But then I was suddenly unwelcome. They want to be able to put human babies inside the Biobag within a couple of years, and the prospect of my visit had made the legal department twitchy. “There is a lot of caution to do anything that could jeopardise FDA approval,” a press officer told me.

***

“This is not a new field,” says Matt Kemp, wearily. He runs the perinatal lab at the Women & Infants Research Foundation (WIRF) in Western Australia, and his team’s artificial womb, Ex-Vivo Uterine Environment or EVE therapy, reported its first great successes in a paper published a few months after CHOP’s. The Biobag stole EVE’s thunder, and though Kemp makes little reference to it, he does sound somewhat narked.

“The Karolinska Institute in Sweden published a paper in 1958 showing the use of this sort of platform with pre-viable human foetuses,” he says. “Groups in Canada in the early 60s experimented with sheep using this system. As early as 1963, the Japanese did seminal work in the field… Anyone who tells you they have done this for the first time is being disingenuous.” He doesn’t name names.

There is no patent application for EVE (“It’s not patentable,” Kemp says, exasperated, “this has all been in the public domain since 1958”), so he is happy to answer questions – unless they are about the reason he decided to name his artificial womb after the first woman and the mother of mankind. He doesn’t want to get drawn into discussions about the symbolism of his work: “It was just a convenient way of describing it, I guess.”

Kemp has been developing EVE since 2013, with researchers at Tohoku University hospital in Sendai, Japan. No official images have been released, but I found a YouTube video uploaded to the WIRF channel. It looked as if it wasn’t supposed to be online (and has since been removed): it was clearly filmed on a phone and had had only 56 views in a year. After CHOP’s carefully sanitised images, this 44-second clip made my jaw drop.

It begins with beeping monitors in a neonatal intensive care unit; a healthy heartbeat thumping in red on a black screen. The camera pans to an incubator beside it and instead of a baby there is a lamb, its chest rising and falling, lying in yellowish fluid in a transparent bag from which protrudes a mass of tubes, like veins filled with blood. This is what an artificial womb really looks like.

Illustration of a baby's hand in a fake womb



‘Incubators deal with some of the functions a premature newborn needs help with, but they don’t allow for the process of gestation to continue.’ Photograph: Liz McBurney/The Guardian

The big difference between the work of WIRF and CHOP is the age of the lambs. The youngest foetus put into the Biobag was 106 days; EVE’s was 95. Kemp is cautious about translating this into human terms, but it’s between 21 and 23 weeks. No one else has ever reported working with foetuses this young. And while CHOP grew their lambs for several weeks, often to term, and let some live, Kemp’s team kept them in the artificial womb for a week, then killed all of them to analyse their organs. He says they could easily have kept them alive for longer: “These are stable, healthy animals.”

Even in a week, the lambs change dramatically, putting on weight and flexing and swallowing. “I’ve never been pregnant,” Kemp says, “but my wife says a foetus does those movements. It kicks, has a wee wiggle and goes back to sleep.”

But clinical trials involving human babies are a long way off. “Anyone who tells you they are going to be doing this in two years either has a wealth of data that is not in the public domain or is being a bit sensationalist.”

Is he talking about anyone in particular?

“I am not,” he says firmly. “All the experiments to date have been done on foetuses that come from healthy pregnancies. That’s simply not the case for a 21- or 22-week human foetus. These are not going to be healthy babies. Getting this into clinical use is going to be incredibly difficult. To create an argument an ethical committee will buy, you’ve got to have an odds-on chance of delivering an outcome far better than the technology currently in use,” he says. “What is the likely first demographic? A very sick 21-week foetus.”

This floors me. I lost a baby at 20 weeks – a son, who would have been my second child. There was nothing wrong with him. He was perfect. I got appendicitis when I was nearly 19 weeks pregnant. I spent a week in hospital while obstetricians and gynaecologists scanned and poked, trying to work out why I was ill. And then I went into labour. It happens: if you are pregnant, a serious infection can cause your cervix to open. In between contractions, the obstetrician told me if I had been 24 weeks pregnant, everything would have been different. Even though my son was a proper baby, who was wrapped up and given to me to hold, he died while I was giving birth to him. A miscarriage, not a stillbirth.

This happened three years ago. Since then, I’ve had my appendix out, and had a daughter. But, like anyone who has lost a baby, I will always be haunted by what could have been done differently. If an artificial womb might save the life of a very sick 21-week-old foetus, could it also save a 20-week-old who was perfectly healthy, but unlucky enough to be inside a woman who was ill?

I swallow hard. “If the first time you put a human foetus in your system,” I say, “it will be one not viable otherwise, questions will come up about pushing the boundaries of viability. Can’t you imagine parents of even more premature babies wanting their child to have any chance an artificial womb might offer?”

“This is a really easy question,” he says. “This is a human – or a foetus, or a baby – that’s sick. If you had a three-year-old that was unwell and somebody was developing a new therapy, would you have any qualms about that?”

“Of course not.”

“So there you go. From our perspective, this is no different.”

In other words, so long as they have a chance to save a baby’s life, they will try to do it. But there are limits.

“We don’t think we are shifting the border of viability further and further: if you can’t get a catheter in and the heart is not sufficiently developed to drive blood through the system, it’s not going to work. So any concerns about harvesting eggs and putting them into these artificial devices are completely abrogated by that. It’s just not practically possible.”

Anna Smajdor, professor at Oslo university a bioethicist who believes that pregnancy is barbaric



Dr Anna Smajdor, a bioethicist at Oslo university who believes that pregnancy is barbaric. Photograph: courtesy of Anna Smajdor

As we get better at extending the lives of embryos outside the womb, and keeping ever more premature babies alive, there will come a time when those two points meet. The obstacles will be legal and ethical, not technological. IVF was once science fiction, then an ethical conundrum, then the cutting edge of assisted reproduction. Now it’s a normal part of making families. Once bags and tubes can replace a womb, pregnancy and birth will be fundamentally redefined. If gestation no longer has to take place inside a woman’s body, it will no longer be female. And the meaning of motherhood will also be changed, for ever.

“Pregnancy is barbaric,” Dr Anna Smajdor declares. “If there were any disease that caused the same problems, we would regard it as very serious.” I am sitting in her office at the University of Oslo, opposite a calendar featuring photographs of her cats. She is a bioethicist and associate professor of practical philosophy, but has the air of a mischievous teenager.

“The number of women who suffer tears and incontinence, and things that damage them for the rest of their lives is really high, yet it’s not adequately recognised,” she continues. “This is all tied up with the strong value we attach not just to motherhood, but to giving birth.”

I’ve been eager to meet Smajdor since I read her groundbreaking academic papers on artificial wombs. She argues that ectogenesis – reproduction outside the human body – would allow reproductive labour to be redistributed fairly in society, so there is a moral imperative for more research.

“There’s an unquestioned assumption that women will have babies, and a failure to notice how bizarre it is that we have to produce new human beings out of our own bodies. And how dangerous that is.”

To demonstrate her point, she tells me about a colleague having a wisdom tooth out. Smajdor suggested they film it, as a beautiful experience to savour: “Here it comes! And look, here’s the stitching! Wow – you did that without any painkillers!”

The comparison is completely perverse, but I can see her point. Our attitude to birth is very strange. There is blood, pain and stitching even if it all goes well, and we are meant to ignore it. Maternal mortality and stillbirth rates are going down globally, but Smajdor says that isn’t necessarily all good news. “The more medicine advances, the more women get scathed. I see a trajectory towards knowing so much about the foetus, and what’s good or bad for it, that women become almost ectogenetic gestators themselves, their whole function about maximising what’s good for the baby.”

I have definitely felt like an ectogenetic gestator. I have had to lie back while a 20cm needle was plunged into my belly so doctors could extract my son’s DNA because something on a scan made them think he might have Down’s syndrome. (He didn’t, but then I got appendicitis.) I have had to stop myself from gagging while forcing down a cloying glucose concoction because a late scan of my daughter showed I might have gestational diabetes. (I didn’t.) I have had to lie with my legs clamped apart while a surgeon stitched up my cervix because a scan showed I was at risk of going into another early labour. Being pregnant is a remarkable experience, and I loved carrying my first child, but I have never felt more like a thing, being acted upon purely because my very dedicated doctors knew too much about what might be going on inside me.

Smajdor was “not very surprised” when she saw CHOP’s lambs. “Those people were clever in their – ” she chooses the word carefully – “marketing. And, of course, being unwilling to talk about ectogenesis is part of the PR approach.” Instead of pouring resources into saving premature babies, she says we should be growing them in artificial wombs from the start, “because it’s a trauma for the foetus, being removed from the uterus, even if it then goes into a Biobag and survives”.

Smajdor uses provocative ideas to raise difficult questions. It works: she has made me think about how messed up our notions of what “normal” childbirth, pregnancy and motherhood are.

If perfect ectogenesis could ever exist, there is a long list of women who would want to use it: women with epilepsy, bipolar disorder or cancer, for whom pregnancy would mean risking either their own or their foetuses’ lives by stopping or starting medication; women who have had their wombs removed for medical reasons. Ectogenesis will also help women in circumstances much less likely to attract public sympathy: social surrogacy clients and older women, whose male equivalents have babies without a thought. You could conceive an embryo while you’re young and grow it in a bag after you retire.

But perhaps the people most likely to be emancipated by this technology are those not born female: single men, gay men and trans women desperate for their own biological children. I ask Smajdor about the benefits of ectogenesis for them.

“I don’t support anyone’s right to have a child. I support people’s right not to have their body interfered with.” Then she leaves the world of philosophical logic for a moment. “Assuming we could get perfect ectogenesis, it seems like a thing we should do, in a fully just society. The problem is that our societies are not fully just. In a society that believes natural reproduction is the most amazing part of a woman’s life, ectogenesis is going to be very problematic, and more likely to be used in ways that are detrimental to women.”

“What kind of ways?”

“When we talk about rescuing very premature babies, there’s a risk of a desire to rescue babies because their mother is not fit to carry the foetus,” Smajdor says. Across the world, inappropriate behaviour during pregnancy is increasingly viewed as child abuse. Since the 50s, dozens of US states have prosecuted women for using drugs while pregnant. If you can save a baby from the dangers of premature birth, would you not be prepared to save it from a reckless mother?

It’s easy to imagine a future where the kind of “help” already offered by employers in Silicon Valley and beyond, enabling staff to freeze their eggs so they can focus on their careers, might include the option to grow their babies in an artificial womb. Using a real womb, inside the body, could ultimately become a sign of poverty, of chaotic lives, of unplanned pregnancy, or of being a borderline-dangerous “freebirther”, choosing to have a baby without any medical input.

The greatest existential threat faced by unborn babies today doesn’t come from women “unfit” to be pregnant, but from unwilling mothers. Once a woman’s body is no longer the incubator, abortion can be both pro-choice and pro-life. In the ectogenetic future, foetuses aborted by mothers who didn’t want them to exist could be “rescued” and adopted. In that world, some women might seek out backstreet abortions that would end their babies’ lives, rather than legal ones that would allow them to live. It’s a horrifying thought. But it could happen if the foetus’s right to life trumps that of a woman to refuse to become a mother.

Artificial wombs will be an incredibly powerful new technology. How that power will manifest itself depends on who is demanding, making, controlling and paying for the technology. Once IVF became mainstream, research into treating fertility problems such as blocked fallopian tubes all but stopped. Why bother, if the problem can be circumvented by assisted reproduction? The same could happen with research that makes it easier and safer for women to have babies without being sliced, probed and torn. What’s the point, if the solution is already there?

Women gain so much more than we lose by bearing children: the creative power of being a mother, the right to choose whether to become a parent at all. Can the freedom to have babies without being pregnant be worth sacrificing any of this?

Full ectogenesis will not exist for decades, but artificial wombs are coming. We need to ensure that, when they do arrive, it’s in a society that values women for more than just their reproductive capacity, and that they are put to use for the benefit of people who can’t be pregnant for biological rather than social reasons. We do still have time. But the race to innovate means maybe not enough.

“This certainly is a project that would have sounded more like science fiction,” Emily Partridge says at the end of the CHOP video. “But over three years of doggedly pursuing it, it has become very real.”

This is an edited extract from Sex Robots & Vegan Meat: Adventures At The Frontier Of Birth, Food, Sex & Death, by Jenny Kleeman, published on 9 July by Picador at £16.99. To order a copy for £14.61, go to guardianbookshop.com.



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