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 scientists repeated 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.
Opioid prescription policies may hurt those in chronic pain
Tinu Abayomi-Paul works as a writer and activist, plus one unwanted job: Trying to fill her opioid prescription. She says that some pharmacists laugh and tell her that no one needs the amount of pain medication that she is seeking. Another pharmacist near her home in Venus, Tex., refused to fill more than seven days of a 30-day prescription.
To get a new prescription—partially filled opioid prescriptions can’t be dispensed later—Abayomi-Paul needed to return to her doctor’s office. But without her medication, she was having too much pain to travel there, much less return to the pharmacy. She rationed out the pills over several weeks, an agonizing compromise that left her unable to work, interact with her children, sleep restfully, or leave the house. “Don’t I deserve to do more than survive?” she says.
Abayomi-Paul’s pain results from a degenerative spine disorder, chronic lymphocytic leukemia, and more than a dozen other diagnoses and disabilities. She is part of a growing group of people with chronic pain who have been negatively impacted by the fallout from efforts to prevent opioid overdose deaths.
Guidelines for dispensing these pills are complicated because many opioids, like codeine, oxycodone, and morphine, are prescribed legally for pain. Yet, deaths from opioids have increased rapidly since 1999 and become a national emergency. Many of them, such as heroin, are used illegally. The CDC identified three surges in opioid use: an increase in opioid prescriptions in the ‘90s, a surge of heroin around 2010, and an influx of fentanyl and other powerful synthetic opioids in 2013.
As overdose deaths grew, so did public calls to address them, prompting the CDC to change its prescription guidelines in 2016. The new guidelines suggested limiting medication for acute pain to a seven-day supply, capping daily doses of morphine, and other restrictions. Some statistics suggest that these policies have worked; from 2016 to 2019, prescriptions for opiates fell 44 percent. Physicians also started progressively lowering opioid doses for patients, a practice called tapering. A study tracking nearly 100,000 Medicare subscribers on opioids found that about 13 percent of patients were tapering in 2012, and that number increased to about 23 percent by 2017.
But some physicians may be too aggressive with this tapering strategy. About one in four people had doses reduced by more than 10 percent per week, a rate faster than the CDC recommends. The approach left people like Abayomi-Paul without the medication they needed. Every year, Abayomi-Paul says, her prescriptions are harder to fill. David Brushwood, a pharmacy professor who specializes in policy and outcomes at the University of Florida in Gainesville, says opioid dosing isn’t one-size-fits-all. “Patients need to be taken care of individually, not based on what some government agency says they need,” he says.
‘This is not survivable’
Health policy and disability rights attorney Erin Gilmer advocated for people with pain, using her own experience with chronic pain and a host of medical conditions as a guidepost. She launched an advocacy website, Healthcare as a Human Right, and shared her struggles on Twitter: “This pain is more than anything I've endured before and I've already been through too much. Yet because it's not simply identified no one believes it's as bad as it is. This is not survivable.”
When her pain dramatically worsened midway through 2021, Gilmer’s posts grew ominous: “I keep thinking it can't possibly get worse but somehow every day is worse than the last.”
The CDC revised its guidelines in 2022 after criticisms that people with chronic pain were being undertreated, enduring dangerous withdrawal symptoms, and suffering psychological distress. (Long-term opioid use can cause physical dependency, an adaptive reaction that is different than the compulsive misuse associated with a substance use disorder.) It was too late for Gilmer. On July 7, 2021, the 38-year-old died by suicide.
Last August, an Ohio district court ruling set forth a new requirement for Walgreens, Walmart, and CVS pharmacists in two counties. These pharmacists must now document opioid prescriptions that are turned down, even for customers who have no previous purchases at that pharmacy, and they’re required to share this information with other locations in the same chain. None of the three pharmacies responded to an interview request from Leaps.org.
In a practice called red flagging, pharmacists may label a prescription suspicious for a variety of reasons, such as if a pharmacist observes an unusually high dose, a long distance from the patient’s home to the pharmacy, or cash payment. Pharmacists may question patients or prescribers to resolve red flags but, regardless of the explanation, they’re free to refuse to fill a prescription.
As the risk of litigation has grown, so has finger-pointing, says Seth Whitelaw, a compliance consultant at Whitelaw Compliance Group in West Chester, PA, who advises drug, medical device, and biotech companies. Drugmakers accused in National Prescription Opioid Litigation (NPOL), a complex set of thousands of cases on opioid epidemic deaths, which includes the Ohio district case, have argued that they shouldn’t be responsible for the large supply of opiates and overdose deaths. Yet, prosecutors alleged that these pharmaceutical companies hid addiction and overdose risks when labeling opioids, while distributors and pharmacists failed to identify suspicious orders or scripts.
Patients and pharmacists fear red flags
The requirements that pharmacists document prescriptions they refuse to fill so far only apply to two counties in Ohio. But Brushwood fears they will spread because of this precedent, and because there’s no way for pharmacists to predict what new legislation is on the way. “There is no definition of a red flag, there are no lists of red flags. There is no instruction on what to do when a red flag is detected. There’s no guidance on how to document red flags. It is a standardless responsibility,” Brushwood says. This adds trepidation for pharmacists—and more hoops to jump through for patients.
“I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately,” Nicolson says.
“We now have about a dozen studies that show that actually ripping somebody off their medication increases their risk of overdose and suicide by three to five times, destabilizes their health and mental health, often requires some hospitalization or emergency care, and can cause heart attacks,” says Kate Nicolson, founder of the National Pain Advocacy Center based in Boulder, Colorado. “It can kill people.” Nicolson was in pain for decades due to a surgical injury to the nerves leading to her spinal cord before surgeries fixed the problem.
Another issue is that primary care offices may view opioid use as a reason to turn down new patients. In a 2021 study, secret shoppers called primary care clinics in nine states, identifying themselves as long-term opioid users. When callers said their opioids were discontinued because their former physician retired, as opposed to an unspecified reason, they were more likely to be offered an appointment. Even so, more than 40 percent were refused an appointment. The study authors say their findings suggest that some physicians may try to avoid treating people who use opioids.
Abayomi-Paul says red flagging has changed how she fills prescriptions. “Once I go to one place, I try to [continue] going to that same place because of the amount of records that I have and making sure my medications don’t conflict,” Abayomi-Paul says.
Nicolson moved to Colorado from Washington D.C. in 2015, before the CDC issued its 2016 guidelines. When the guidelines came out, she found the change to be shockingly abrupt. “I went into the doctor one day here and she said, ‘I'm going to stop prescribing opioids to all my patients effective immediately.’” Since then, she’s spoken with dozens of patients who have been red-flagged or simply haven’t been able to access pain medication.
Despite her expertise, Nicolson isn’t positive she could successfully fill an opioid prescription today even if she needed one. At this point, she’s not sure exactly what various pharmacies would view as a red flag. And she’s not confident that these red flags even work. “You can have very legitimate reasons for being 50 miles away or having to go to multiple pharmacies, given that there are drug shortages now, as well as someone refusing to fill [a prescription.] It doesn't mean that you’re necessarily ‘drug seeking.’”
While there’s no easy solution. Whitelaw says clarifying the role of pharmacists and physicians in patient access to opioids could help people get the medication they need. He is seeking policy changes that focus on the needs of people in pain more than the number of prescriptions filled. He also advocates standardizing the definition of red flags and procedures for resolving them. Still, there will never be a single policy that can be applied to all people, explains Brushwood, the University of Florida professor. “You have to make a decision about each individual prescription.”
This article is part of the magazine, "The Future of Science In America: The Election Issue," co-published by LeapsMag, the Aspen Institute Science & Society Program, and GOOD.
When COVID-19 cases were surging in New York City in early spring, Chitra Mohan, a postdoctoral fellow at Weill Cornell, was overwhelmed with worry. But the pandemic was only part of her anxieties. Having come to the United States from India on a student visa that allowed her to work for a year after completing her degree, she had applied for a two-year extension, typically granted for those in STEM fields. But due to a clerical error—Mohan used an electronic signatureinstead of a handwritten one— her application was denied and she could no longerwork in the United States.
"I was put on unpaid leave and I lost my apartment and my health insurance—and that was in the middle of COVID!" she says.
Meanwhile her skills were very much needed in those unprecedented times. A molecular biologist studying how DNA can repair itself, Mohan was trained in reverse transcription polymerase chain reaction or RT-PCR—a lab technique that detects pathogens and is used to diagnose COVID-19. Mohan wanted to volunteer at testing centers, but because she couldn't legally work in the U.S., she wasn't allowed to help either. She moved to her cousin's house, hired a lawyer, and tried to restore her work status.
"I spent about $4,000 on lawyer fees and another $1,200 to pay for the motions I filed," she recalls. "I had to borrow money from my parents and my cousin because without my salary I just didn't have the $7,000 at hand." But the already narrow window of opportunity slammed completely shut when the Trump administration suspended issuing new visas for foreign researchers in June. All Mohan's attempts were denied. In August, she had to leave the country. "Given the recent work visa ban by the administration, all my options in the U.S. are closed," she wrote a bitter note on Twitter. "I have to uproot my entire life in NY for the past 6 years and leave." She eventually found a temporary position in Calcutta, where she can continue research.
Mohan is hardly alone in her visa saga. Many foreign scholars on H- and J-type visas and other permits that let them remain employed in America had been struggling to keep their rights to continue research, which in certain cases is crucial to battling the pandemic. Some had to leave the country, some filed every possible extension to buy time, and others are stuck in their home countries, unable to return. The already cumbersome process of applying for visas and extensions became crippled during the lockdowns. But in June, when President Trump extended and expanded immigration restrictions to cut the number of immigrant workers entering the U.S., the new limits left researchers' projects and careers in limbo—and some in jeopardy.
"We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened."
Rakesh Ramachandran, whose computational biology work contributed to one of the first coronavirus studies to map out its protein structures—is stranded in India. In early March, he had travelled there to attend a conference and visit the American consulate to stamp his H1 visa for a renewal, already granted. The pandemic shut down both the conference and the consulates, and Ramachandran hasn't been able to come back since. The consulates finally opened in September, but so far the online portal has no available appointment slots. "I'm told to keep trying," Ramachandran says.
The visa restrictions affected researchers worldwide, regardless of disciplines or countries. A Ph.D. student in neuroscience, Morgane Leroux had to do her experiments with mice at Gladstone Institutes in America and analyze the data back home at Sorbonne University in France. She had finished her first round of experiments when the lockdowns forced her to return to Paris, and she hasn't been able to come back to resume her work since. "I can't continue the experiments, which is really frustrating," she says, especially because she doesn't know what it means for her Ph.D. "I may have to entirely change my subject," she says, which she doesn't want to do—it would be a waste of time and money.
But besides wreaking havoc in scholars' personal lives and careers, the visa restrictions had—and will continue to have—tremendous deleterious effects on America's research and its global scientific competitiveness. "It's incredibly short-sighted and self-destructing to restrict the immigration of scientists into the U.S.," says Benjamin G. Neel, who directs the Laura and Isaac Perlmutter Cancer Center at New York University. "If they can't come here, they will go elsewhere," he says, causing a brain drain.
Neel in his lab with postdocs
(Courtesy of Neel)
Neel felt the outcomes of the shortsighted policies firsthand. In the past few months, his lab lost two postdoctoral researchers who had made major strides in understanding the biology of several particularly stubborn, treatment-resistant malignancies. One postdoc studied the underlying mechanisms responsible for 90 percent of pancreatic cancers and half of the colon ones. The other one devised a new system of modeling ovarian cancer in mice to test new therapeutic drug combinations for the deadliest tumor types—but had to return home to China.
"By working around the clock, she was able to get her paper accepted, but she hasn't been able to train us to use this new system, which can set us back six months," Neel says.
Her discoveries also helped the lab secure about $900,000 in grants for new research. Losing people like this is "literally killing the goose that lays the golden eggs," Neel adds. "If you want to make America poor again, this is the way to do it."
Cassidy R. Sugimoto at Indiana University Bloomington, who studies how scientific knowledge is produced and disseminated, says that scientists are the most productive when they are free to move, exchange ideas, and work at labs with the best equipment. Restricting that freedom reduces their achievement.
"Several empirical studied demonstrated the benefits to the U.S. by attracting and retaining foreign scientists. The disproportional number of our Nobel Prize winners were not only foreign-born but also foreign-educated," she says. Scientific advancement bolsters the country's economic prowess, too, so turning scholars away is bad for the economy long-term. "We have been a beneficiary of this flow of human capacity and resource investment for many generations—and this is now threatened," Sugimoto adds—because scientists will look elsewhere. "We are seeing them shifting to other countries that are more hospitable, both ideologically and in terms of health security. Many visiting scholars, postdocs, and graduate students who would otherwise come to the United States are now moving to Canada."
It's not only the Ph.D. students and postdocs who are affected. In some cases, even well-established professors who have already made their marks in the field and direct their own labs at prestigious research institutions may have to pack up and leave the country in the next few months. One scientist who directs a prominent neuroscience lab is betting on his visa renewal and a green card application, but if that's denied, the entire lab may be in jeopardy, as many grants hinge on his ability to stay employed in America.
"It's devastating to even think that it can happen," he says—after years of efforts invested. "I can't even comprehend how it would feel. It would be terrifying and really sad." (He asked to withhold his name for fear that it may adversely affect his applications.) Another scientist who originally shared her story for this article, later changed her mind and withdrew, worrying that speaking out may hurt the entire project, a high-profile COVID-19 effort. It's not how things should work in a democratic country, scientists admit, but that's the reality.
Still, some foreign scholars are speaking up. Mehmet Doğan, a physicist at University of California Berkeley who has been fighting a visa extension battle all year, says it's important to push back in an organized fashion with petitions and engage legislators. "This administration was very creative in finding subtle and not so subtle ways to make our lives more difficult," Doğan says. He adds that the newest rules, proposed by the Department of Homeland Security on September 24, could further limit the time scholars can stay, forcing them into continuous extension battles. That's why the upcoming election might be a turning point for foreign academics. "This election will decide if many of us will see the U.S. as the place to stay and work or whether we look at other countries," Doğan says, echoing the worries of Neel, Sugimoto, and others in academia.
Dogan on Zoom talking to his fellow union members of the Academic Researchers United, a union of almost 5,000 Academic Researchers.
(Credit: Ceyda Durmaz Dogan)
If this year has shown us anything, it is that viruses and pandemics know no borders as they sweep across the globe. Likewise, science can't be restrained by borders either. "Science is an international endeavor," says Neel—and right now humankind now needs unified scientific research more than ever, unhindered by immigration hurdles and visa wars. Humanity's wellbeing in America and beyond depends on it.
[Editor's Note: To read other articles in this special magazine issue, visit the beautifully designed e-reader version.]
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.