Artificial Wombs Are Getting Closer to Reality for Premature Babies
In 2017, researchers at the Children's Hospital of Philadelphia grew extremely preterm lambs from hairless to fluffy inside a "biobag," a dark, fluid-filled bag designed to mimic a mother's womb.
"There could be quite a lot of infants that would benefit from artificial womb technologies."
This happened over the course of a month, across a delicate period of fetal development that scientists consider the "edge of viability" for survival at birth.
In 2019, Australian and Japanese scientistsrepeated the success of keeping extremely premature lambs inside an artificial womb environment until they were ready to survive on their own. Those researchers are now developing a treatment strategy for infants born at "the hard limit of viability," between 20 and 23 weeks of gestation. At the same time, Dutch researchers are going so far as to replicate the sound of a mother's heartbeat inside a biobag. These developments signal exciting times ahead--with a touch of science fiction--for artificial womb technologies. But is there a catch?
"There could be quite a lot of infants that would benefit from artificial womb technologies," says Josephine Johnston, a bioethicist and lawyer at The Hastings Center, an independent bioethics research institute in New York. "These technologies can decrease morbidity and mortality for infants at the edge of viability and help them survive without significant damage to the lungs or other problems," she says.
It is a viewpoint shared by Frans van de Vosse, leader of the Cardiovascular Biomechanics research group at Eindhoven University of Technology in the Netherlands. He participates in a university project that recently received more than $3 million in funding from the E.U. to produce a prototype artificial womb for preterm babies between 24 and 28 weeks of gestation by 2024.
The Eindhoven design comes with a fluid-based environment, just like that of the natural womb, where the baby receives oxygen and nutrients through an artificial placenta that is connected to the baby's umbilical cord. "With current incubators, when a respiratory device delivers oxygen into the lungs in order for the baby to breathe, you may harm preterm babies because their lungs are not yet mature for that," says van de Vosse. "But when the lungs are under water, then they can develop, they can mature, and the baby will receive the oxygen through the umbilical cord, just like in the natural womb," he says.
His research team is working to achieve the "perfectly natural" artificial womb based on strict mathematical models and calculations, van de Vosse says. They are even employing 3D printing technology to develop the wombs and artificial babies to test in them--the mannequins, as van de Vosse calls them. These mannequins are being outfitted with sensors that can replicate the environment a fetus experiences inside a mother's womb, including the soothing sound of her heartbeat.
"The Dutch study's artificial womb design is slightly different from everything else we have seen as it encourages a gestateling to experience the kind of intimacy that a fetus does in pregnancy," says Elizabeth Chloe Romanis, an assistant professor in biolaw at Durham Law School in the U.K. But what is a "gestateling" anyway? It's a term Romanis has coined to describe neither a fetus nor a newborn, but an in-between artificial stage.
"Because they aren't born, they are not neonates," Romanis explains. "But also, they are not inside a pregnant person's body, so they are not fetuses. In an artificial womb the fetus is still gestating, hence why I call it gestateling."
The terminology is not just a semantic exercise to lend a name to what medical dictionaries haven't yet defined. "Gestatelings might have a slightly different psychology," says Romanis. "A fetus inside a mother's womb interacts with the mother. A neonate has some kind of self-sufficiency in terms of physiology. But the gestateling doesn't do either of those things," she says, urging us to be mindful of the still-obscure effects that experiencing early life as a gestateling might have on future humans. Psychology aside, there are also legal repercussions.
The Universal Declaration of Human Rights proclaims the "inalienable rights which everyone is entitled to as a human being," with "everyone" including neonates. However, such a legal umbrella is absent when it comes to fetuses, which have no rights under the same declaration. "We might need a new legal category for a gestateling," concludes Romanis.
But not everyone agrees. "However well-meaning, a new legal category would almost certainly be used to further erode the legality of abortion in countries like the U.S.," says Johnston.
The "abortion war" in the U.S. has risen to a crescendo since 2019, when states like Missouri, Mississippi, Kentucky, Louisiana and Georgia passed so-called "fetal heartbeat bills," which render an abortion illegal once a fetal heartbeat is detected. The situation is only bound to intensify now that Justice Ruth Bader Ginsburg, one of the Supreme Court's fiercest champions for abortion rights, has passed away. If President Trump appoints Ginsburg's replacement, he will probably grant conservatives on the Court the votes needed to revoke or weaken Roe v. Wade, the milestone decision of 1973 that established women's legal right to an abortion.
"A gestateling with intermediate status would almost certainly be considered by some in the U.S. (including some judges) to have at least certain legal rights, likely including right-to-life," says Johnston. This would enable a fetus on the edge of viability to make claims on the mother, and lead either to a shortening of the window in which abortion is legal—or a practice of denying abortion altogether. Instead, Johnston predicts, doctors might offer to transfer the fetus to an artificial womb for external gestation as a new standard of care.
But the legal conundrum does not stop there. The viability threshold is an estimate decided by medical professionals based on the clinical evidence and the technology available. It is anything but static. In the 1970s when Roe v. Wade was decided, for example, a fetus was considered legally viable starting at 28 weeks. Now, with improved technology and medical management, "the hard limit today is probably 20 or 21 weeks," says Matthew Kemp, associate professor at the University of Western Australia and one of the Australian-Japanese artificial womb project's senior researchers.
The changing threshold can result in situations where lots of people invested in the decision disagree. "Those can be hard decisions, but they are case-by-case decisions that families make or parents make with the key providers to determine when to proceed and when to let the infant die. Usually, it's a shared decision where the parents have the final say," says Johnston. But this isn't always the case.
On May 9th 2016, a boy named Alfie Evans was born in Liverpool, UK. Suffering seizures a few months after his birth, Alfie was diagnosed with an unknown neurodegenerative disorder and soon went into a semi-vegetative state, which lasted for more than a year. Alfie's medical team decided to withdraw his ventilation support, suggesting further treatment was unlawful and inhumane, but his parents wanted permission to fly him to a hospital in Rome and attempt to prolong his life there. In the end, the case went all the way up to the Supreme Court, which ruled that doctors could stop providing life support for Alfie, saying that the child required "peace, quiet and privacy." What happened to little Alfie raised huge publicity in the UK and pointedly highlighted the dilemma of whether parents or doctors should have the final say in the fate of a terminally-ill child in life-support treatment.
"In a few years from now, women who cannot get pregnant because of uterine infertility will be able to have a fully functional uterus made from their own tissue."
Alfie was born and, thus had legal rights, yet legal and ethical mayhem arose out of his case. When it comes to gestatelings, the scenarios will be even more complicated, says Romanis. "I think there's a really big question about who has parental rights and who doesn't," she says. "The assisted reproductive technology (ART) law in the U.K. hasn't been updated since 2008....It certainly needs an update when you think about all the things we have done since [then]."
This June, for instance, scientists from the Wake Forest Institute for Regenerative Medicine in North Carolina published research showing that they could take a small sample of tissue from a rabbit's uterus and create a bioengineered uterus, which then supported both fertilization and normal pregnancy like a natural uterus does.
"In [a number of] years from now, women who cannot get pregnant because of uterine infertility will be able to have a fully functional uterus made from their own tissue," says Dr. Anthony Atala, the Institute's director and a pioneer in regenerative medicine. These bioengineered uteri will eventually be covered by insurance, Atala expects. But when it comes to artificial wombs that externally gestate premature infants, will all mothers have equal access?
Medical reports have already shown racial and ethnic disparities in infertility treatments and access to assisted reproductive technologies. Costs on average total $12,400 per cycle of treatment and may require several cycles to achieve a live birth. "There's no indication that artificial wombs would be treated any differently. That's what we see with almost every expensive new medical technology," says Johnston. In a much more dystopian future, there is even a possibility that inequity in healthcare might create disturbing chasms in how women of various class levels bear children. Romanis asks us to picture the following scenario:
We live in a world where artificial wombs have become mainstream. Most women choose to end their pregnancies early and transfer their gestatelings to the care of machines. After a while, insurers deem full-term pregnancy and childbirth a risky non-necessity, and are lobbying to stop covering them altogether. Wealthy white women continue opting out of their third trimesters (at a high cost), since natural pregnancy has become a substandard route for poorer women. Those women are strongly judged for any behaviors that could risk their fetus's health, in contrast with the machine's controlled environment. "Why are you having a coffee during your pregnancy?" critics might ask. "Why are you having a glass of red wine? If you can't be perfect, why don't you have it the artificial way?"
Problem is, even if they want to, they won't be able to afford it.
In a more sanguine version, however, the artificial wombs are only used in cases of prematurity as a life-saving medical intervention rather than as a lifestyle accommodation. The 15 million babies who are born prematurely each year and may face serious respiratory, cardiovascular, visual and hearing problems, as well as learning disabilities, instead continue their normal development in artificial wombs. After lots of deliberation, insurers agree to bear the cost of external wombs because they are cheaper than a lifetime of medical care for a disabled or diseased person. This enables racial and ethnic minority women, who make up the majority of women giving premature birth, to access the technology.
Even extremely premature babies, those babies (far) below the threshold of 28 weeks of gestation, half of which die, could now discover this thing called life. In this scenario, as the Australian researcher Kemp says, we are simply giving a good shot at healthy, long-term survival to those who were unfortunate enough to start too soon.
In 1962, the world was a remarkably different place: Neil Armstrong had yet to take his first steps on the lunar surface, John F. Kennedy was serving as president of the United States, and the Beatles were still a few years away from superstardom, having just recorded their first single.
The word “measles” was also a household name. Measles, which still exists in parts of the world today, is a highly contagious viral infection that typically causes fever, cough, muscle pain, fatigue, and a distinctive red rash. Measles was so pervasive around the world in 1962 that most children had gotten sick with it before the age of fifteen—but even though it was common, it was far from harmless. Measles killed around 400 to 500 people per year in the United States, and approximately 2.6 million people each year worldwide. Countless others suffered severe complications from measles, such as permanent blindness.
Tragedy hits home
Author Roald Dahl at his Buckinghamshire home with Olivia, daughter Chantal, and wife Patricia Neal in 1960.
Ben Martin / Getty Images
That year, British author Roald Dahl was beginning to make a name for himself, having just published his best-selling book James and the Giant Peach. Dahl, who would go on to write some of the most well-loved children’s books of the century, lived in southern England with his wife and three children. One day, Dahl and his wife, actress Patricia Neal, received word that there was an outbreak of measles at his daughters’ school.
While some parents quarantined their children, many others also considered measles a harmless childhood disease. Neal later recalled in her autobiography that a family member had advised her to “let the girls get measles,” thinking it would strengthen their immune systems and be “good for them.” Reluctantly, Dahl and Neal let their two school-aged children, Olivia and Chantal, continue school. Olivia, then aged seven, fell sick with the measles not long after that.
Neither Dahl nor Neal were terribly concerned about Olivia’s infection. Dahl would write later that it seemed to be taking its “usual course,” and the two would read and spend time together while Olivia rested. After a few days of fever and fatigue, Dahl wrote, Olivia seemed like she was “well on the road to recovery.”
But one afternoon, as the two sat on Olivia’s bed making animals out of pipe cleaners, Dahl noticed that Olivia’s “fingers and her mind were not working together.” When Dahl asked how she was feeling, Olivia replied, “I feel all sleepy.”
Within an hour, Dahl wrote, Olivia was unconscious. Within 12 hours, she was dead.
Olivia died of measles encephalitis, an inflammation of the brain caused by an infection. Approximately 1 in 1,000 people infected with measles develop encephalitis, and of those who develop it, between 10 and 20 percent will die.
Dahl was overcome with grief and wracked with guilt for being unable to prevent his daughter’s death. Mourning, Dahl threw himself into his writing and, in his spare time, spent hours lovingly constructing a rock garden on Olivia’s grave in a local churchyard.
After Olivia’s death, Dahl wrote sixteen novels and several collections of short stories, including Matilda, Fantastic Mr. Fox, and Willy Wonka and the Chocolate Factory, which garnered him worldwide acclaim. His most influential piece of writing, however, wasn’t written until 1986.
A father's plea
Roald Dahl and the open letter he wrote in 1986, encouraging parents to vaccinate their children against measles.
By 1986, measles was no longer the global health threat that it had been in the 1960s, thanks to a measles vaccine that became available just one year after Olivia had died. Still, in the United Kingdom alone, approximately 80,000 people every year were infected with measles. This bothered Dahl, especially since measles rates in the United States had dropped by 98 percent compared to pre-vaccine years. “Why do we have so much measles in Britain when the Americans have virtually gotten rid of it?,” Dahl was reported to have said.
So Dahl set out to prevent a tragedy like Olivia’s from happening again. With encouragement from several prominent public health activists, Dahl wrote an open letter addressed to parents in the UK. The letter recounted his daughter’s death from encephalitis and begged parents to protect their own children from measles:
“...there is today something that parents can do to make sure that this sort of tragedy does not happen to a child of theirs. They can insist that their child is immunised [sic] against measles. I was unable to do that for Olivia in 1962 because in those days a reliable measles vaccine had not been discovered. Today a good and safe vaccine is available to every family and all you have to do is to ask your doctor to administer it.”
Dahl went on to say that although many parents still viewed measles as a harmless illness, he knew from experience that it was not. Measles was capable of causing disability and death, Dahl wrote, whereas a child had a better chance of “choking on a chocolate bar” than developing any serious complication from the vaccine. Dahl ended his letter by saying how happy he knew Olivia would be “if only she could know that her death had helped to save a good deal of illness and death among other children.”
Dahl’s letter was published in early 1986 and distributed to local healthcare workers, schools, and to parents of children who were particularly at risk. As the letter circulated, vaccination rates continued to climb year after year.
Thirty-one years after Dahl’s letter was published, and 55 years after Olivia’s death, the World Health Organization declared in 2017 that measles had officially been eradicated for the first time in the UK thanks to high rates of vaccination.
A small step back
As vaccination rates decline, measles is now making a strong comeback in the United States and elsewhere.
Today, vaccination rates for the measles are in decline, and countries like the UK and the US, who had once eradicated measles completely, are now seeing a comeback. The Centers for Disease Control and Prevention (CDC) recently reported that between December 1, 2023 and January 23, 2024, 23 cases of measles had been confirmed across multiple states. The majority of these cases, they reported, were among children and adolescents who had traveled internationally and had not yet been vaccinated even though they were eligible to do so.
Roald Dahl passed away in 1990, but fortunately, his writing continues to live on. While readers can explore fantastical worlds through his novels and short stories, they can also look back to a reality when tragic deaths like Olivia’s happened far too often. The difference is that today, thanks to modern science, we now have the tools to stop them.
Sarah Watts is a health and science writer based in Chicago.
On today’s episode of Making Sense of Science, I’m honored to be joined by Dr. Paul Song, a physician, oncologist, progressive activist and biotech chief medical officer. Through his company, NKGen Biotech, Dr. Song is leveraging the power of patients’ own immune systems by supercharging the body’s natural killer cells to make new treatments for Alzheimer’s and cancer.
Whereas other treatments for Alzheimer’s focus directly on reducing the build-up of proteins in the brain such as amyloid and tau in patients will mild cognitive impairment, NKGen is seeking to help patients that much of the rest of the medical community has written off as hopeless cases, those with late stage Alzheimer’s. And in small studies, NKGen has shown remarkable results, even improvement in the symptoms of people with these very progressed forms of Alzheimer’s, above and beyond slowing down the disease.
In the realm of cancer, Dr. Song is similarly setting his sights on another group of patients for whom treatment options are few and far between: people with solid tumors. Whereas some gradual progress has been made in treating blood cancers such as certain leukemias in past few decades, solid tumors have been even more of a challenge. But Dr. Song’s approach of using natural killer cells to treat solid tumors is promising. You may have heard of CAR-T, which uses genetic engineering to introduce cells into the body that have a particular function to help treat a disease. NKGen focuses on other means to enhance the 40 plus receptors of natural killer cells, making them more receptive and sensitive to picking out cancer cells.
Paul Y. Song, MD is currently CEO and Vice Chairman of NKGen Biotech. Dr. Song’s last clinical role was Asst. Professor at the Samuel Oschin Cancer Center at Cedars Sinai Medical Center.
Dr. Song served as the very first visiting fellow on healthcare policy in the California Department of Insurance in 2013.He is currently on the advisory board of the Pritzker School of Molecular Engineering at the University of Chicago and a board member of Mercy Corps, The Center for Health and Democracy, and Gideon’s Promise.
Dr. Song graduated with honors from the University of Chicago and received his MD from George Washington University. He completed his residency in radiation oncology at the University of Chicago where he served as Chief Resident and did a brachytherapy fellowship at the Institute Gustave Roussy in Villejuif, France. He was also awarded an ASTRO research fellowship in 1995 for his research in radiation inducible gene therapy.
With Dr. Song’s leadership, NKGen Biotech’s work on natural killer cells represents cutting-edge science leading to key findings and important pieces of the puzzle for treating two of humanity’s most intractable diseases.
- Paul Song LinkedIn
- NKGen Biotech on Twitter - @NKGenBiotech
- NKGen Website: https://nkgenbiotech.com/
- NKGen appoints Paul Song
- Patient Story: https://pix11.com/news/local-news/long-island/promising-new-treatment-for-advanced-alzheimers-patients/
- FDA Clearance: https://nkgenbiotech.com/nkgen-biotech-receives-ind-clearance-from-fda-for-snk02-allogeneic-natural-killer-cell-therapy-for-solid-tumors/Q3 earnings data: https://www.nasdaq.com/press-release/nkgen-biotech-inc.-reports-third-quarter-2023-financial-results-and-business