Why Don’t We Have Artificial Wombs for Premature Infants?
Ectogenesis, the development of a baby outside of the mother's body, is a concept that dates back to 1923. That year, British biochemist-geneticist J.B.S. Haldane gave a lecture to the "Heretics Society" of the University of Cambridge in which he predicted the invention of an artificial womb by 1960, leading to 70 percent of newborns being born that way by the 2070s. In reality, that's about when an artificial womb could be clinically operational, but trends in science and medicine suggest that such technology would come in increments, each fraught with ethical and social challenges.
An extra-uterine support device could be ready for clinical trials in humans in the next two to four years, with hopes that it could improve survival of very premature infants.
Currently, one major step is in the works, a system called an extra-uterine support device (EUSD) –or sometimes Ex-Vivo uterine Environment (EVE)– which researchers at the Children's Hospital of Philadelphia have been using to support fetal lambs outside the mother. It also has been called an artificial placenta, because it supplies nutrient- and oxygen-rich blood to the developing lambs via the umbilical vein and receives blood full of waste products through the umbilical arteries. It does not do everything that a natural placenta does, yet it does do some things that a placenta doesn't do. It breathes for the fetus like the mother's lungs, and encloses the fetus in sterile fluid, just like the amniotic sac. It represents a solution to one set of technical challenges in the path to an artificial womb, namely how to keep oxygen flowing into a fetus and carbon dioxide flowing out when the fetal lungs are not ready to function.
Capable of supporting fetal lambs physiologically equivalent to a human fetus at 23 weeks' gestation or earlier, the EUSD could be ready for clinical trials in humans in the next two to four years, with hopes that it could improve survival of very premature infants. Existing medical technology can keep human infants alive when born in this 23-week range, or even slightly less —the record is just below 22 weeks. But survival is low, because most of the treatment is directed at the lungs, the last major body system to mature to a functional status. This leads to complications not only in babies born before 24 weeks' gestation, but also in a fairly large number of births up to 28 weeks' gestation.
So, the EUSD is basically an advanced neonatal life support machine that beckons to square off the survival curve for infants born up to the 28th week. That is no doubt a good thing, but given the political prominence of reproductive issues, might any societal obstacles be looming?
"While some may argue that the EUSD system will shift the definition of viability to a point prior to the maturation of the fetus' lungs, ethical and legal frameworks must still recognize the mother's privacy rights as paramount."
Health care attorney and clinical ethicist David N. Hoffman points out that even though the EUSD may shift the concept of fetal viability away from the maturity of developing lungs, it would not change the current relationship of the fetus to the mother during pregnancy.
"Our social and legal frameworks, including Roe v. Wade, invite the view of the embryo-fetus as resembling a parasite. Not in a negative sense, but functionally, since it obtains its life support from the mother, while she does not need the fetus for her own physical health," notes Hoffman, who holds faculty appointments at Columbia University, and at the Benjamin N. Cardozo School of Law and the Albert Einstein College of Medicine, of Yeshiva University. "In contrast, our ethical conception of the relationship is grounded in the nurturing responsibility of parenthood. We prioritize the welfare of both mother and fetus ethically, but we lean toward the side of the mother's legal rights, regarding her health throughout pregnancy, and her right to control her womb for most of pregnancy. While some may argue that the EUSD system will shift the definition of viability to a point prior to the maturation of the fetus' lungs, ethical and legal frameworks must still recognize the mother's privacy rights as paramount, on the basis of traditional notions of personhood and parenthood."
Outside of legal frameworks, religion, of course, is a major factor in how society reacts to new reproductive technologies, and an artificial womb would trigger a spectrum of responses.
"Significant numbers of conservative Christians may oppose an artificial womb in fear that it might harm the central role of marriage in Christianity."
Speaking from the perspective of Lutheran scholarship, Dr. Daniel Deen, Assistant Professor of Philosophy at Concordia University in Irvine, Calif., does not foresee any objections to the EUSD, either theologically, or generally from Lutherans (who tend to be conservative on reproductive issues), since the EUSD is basically an improvement on current management of prematurity. But things would change with the advent of a full-blown artificial womb.
"Significant numbers of conservative Christians may oppose an artificial womb in fear that it might harm the central role of marriage in Christianity," says Deen, who specializes in the philosophy of science. "They may see the artificial womb as a catalyst for strengthening the mechanistic view of reproduction that dominates the thinking of secular society, and of other religious groups, including more liberal Christians."
Judaism, however, appears to be more receptive, even during the research phases.
"Even if researchers strive for a next-generation EUSD aimed at supporting a fetus several weeks earlier than possible with the current system, it still keeps the fetus inside the mother well beyond the 40-day threshold, so there likely are no concerns in terms of Jewish law," says Kalman Laufer, a rabbinical student and executive director of the Medical Ethics Society at Yeshiva University. Referring to a concept from the Babylonian Talmud that an embryo is "like water" until 40 days into pregnancy, at which time it receives a kind of almost-human status warranting protection, Laufer cautions that he's speaking about artificial wombs developed for the sake of rescuing very premature infants. At the same time though, he expects that artificial womb research will eventually trigger a series of complex, legalistic opinions from Jewish scholars, as biotechnology moves further toward supporting fetal growth entirely outside a woman's body.
"Since [the EUSD] gives some justification to end abortion, by transferring fetuses from mother to machine, conservatives will probably rally around it."
While the technology treads into uncomfortable territory for social conservatives at first glance, it's possible that the prospect of taking the abortion debate in a whole new direction could engender support for the artificial womb. "Since [the EUSD] gives some justification to end abortion, by transferring fetuses from mother to machine, conservatives will probably rally around it," says Zoltan Istvan, a transhumanist politician and journalist who ran for U.S. president in 2016. To some extent, Deen agrees with Istvan, provided we get to a point when the artificial womb is already a reality.
"The world has a way of moving forward despite the fear of its inhabitants," Deen notes. "If the technology gets developed, I could not see any Christians, liberal or conservative, arguing that people seeking abortion ought not opt for a 'transfer' versus an abortive procedure."
So then how realistic is a full-blown artificial womb? The researchers at the Children's Hospital of Philadelphia have noted various technical difficulties that would come up in any attempt to connect a very young fetus to the EUSD and maintain life. One issue is the small umbilical cord blood vessels that must be connected to the EUSD as fetuses of decreasing gestational age are moved outside the mother. Current procedures might be barely adequate for integrating a human fetus into the device in the 18 -21 week range, but going to lower gestational ages would require new technology and different strategies. It also would require numerous other factors to cover for fetal body systems that mature ahead of the lungs and that the current EUSD system is not designed to replace. However, biotechnology and tissue engineering strategies on the horizon could be added to later EUSDs. To address the blood vessel size issue, artificial womb research could benefit by drawing on experts in microfluidics, the field concerned with manipulation of tiny amounts of fluid through very small spaces, and which is ushering in biotech innovations like the "lab on a chip".
"The artificial womb might put fathers on equal footing with mothers, since any embryo could potentially achieve personhood without ever seeing the inside of a woman's uterus."
If the technical challenges to an artificial womb are indeed overcome, reproductive policy debates could be turned on their side.
"Evolution of the EUSD into a full-blown artificial external uterus has ramifications for any reproductive rights issues where policy currently assumes that a mother is needed for a fertilized egg to become a person," says Hoffman, the ethicist and legal scholar. "If we consider debates over whether to keep cryopreserved human embryos in storage, destroy them, or utilize them for embryonic stem cell research or therapies, the artificial womb might put fathers on equal footing with mothers, since any embryo could potentially achieve personhood without ever seeing the inside of a woman's uterus."
Such a scenario, of course, depends on today's developments not being curtailed or sidetracked by societal objections before full-blown ectogenesis is feasible. But if this does ever become a reality, the history of other biotechnologies suggests that some segment of society will embrace the new innovation and never look back.
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