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.
Autonomous, indoor farming gives a boost to crops
The glass-encased cabinet looks like a display meant to hold reasonably priced watches, or drugstore beauty creams shipped from France. But instead of this stagnant merchandise, each of its five shelves is overgrown with leaves — moss-soft pea sprouts, spikes of Lolla rosa lettuces, pale bok choy, dark kale, purple basil or red-veined sorrel or green wisps of dill. The glass structure isn’t a cabinet, but rather a “micro farm.”
The gadget is on display at the Richmond, Virginia headquarters of Babylon Micro-Farms, a company that aims to make indoor farming in the U.S. more accessible and sustainable. Babylon’s soilless hydroponic growing system, which feeds plants via nutrient-enriched water, allows chefs on cruise ships, cafeterias and elsewhere to provide home-grown produce to patrons, just seconds after it’s harvested. Currently, there are over 200 functioning systems, either sold or leased to customers, and more of them are on the way.
The chef-farmers choose from among 45 types of herb and leafy-greens seeds, plop them into grow trays, and a few weeks later they pick and serve. While success is predicated on at least a small amount of these humans’ care, the systems are autonomously surveilled round-the-clock from Babylon’s base of operations. And artificial intelligence is helping to run the show.
Babylon piloted the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off.
Imagine consistently perfect greens and tomatoes and strawberries, grown hyper-locally, using less water, without chemicals or environmental contaminants. This is the hefty promise of controlled environment agriculture (CEA) — basically, indoor farms that can be hydroponic, aeroponic (plant roots are suspended and fed through misting), or aquaponic (where fish play a role in fertilizing vegetables). But whether they grow 4,160 leafy-green servings per year, like one Babylon farm, or millions of servings, like some of the large, centralized facilities starting to supply supermarkets across the U.S., they seek to minimize failure as much as possible.
Babylon’s soilless hydroponic growing system
Courtesy Babylon Micro-Farms
Here, AI is starting to play a pivotal role. CEA growers use it to help “make sense of what’s happening” to the plants in their care, says Scott Lowman, vice president of applied research at the Institute for Advanced Learning and Research (IALR) in Virginia, a state that’s investing heavily in CEA companies. And although these companies say they’re not aiming for a future with zero human employees, AI is certainly poised to take a lot of human farming intervention out of the equation — for better and worse.
Most of these companies are compiling their own data sets to identify anything that might block the success of their systems. Babylon had already integrated sensor data into its farms to measure heat and humidity, the nutrient content of water, and the amount of light plants receive. Last year, they got a National Science Foundation grant that allowed them to pilot the use of specialized cameras that take pictures in different spectrums to gather some less-obvious visual data about plants’ wellbeing and alert people if something seems off. “Will this plant be healthy tomorrow? Are there things…that the human eye can't see that the plant starts expressing?” says Amandeep Ratte, the company’s head of data science. “If our system can say, Hey, this plant is unhealthy, we can reach out to [users] preemptively about what they’re doing wrong, or is there a disease at the farm?” Ratte says. The earlier the better, to avoid crop failures.
Natural light accounts for 70 percent of Greenswell Growers’ energy use on a sunny day.
Courtesy Greenswell Growers
IALR’s Lowman says that other CEA companies are developing their AI systems to account for the different crops they grow — lettuces come in all shapes and sizes, after all, and each has different growing needs than, for example, tomatoes. The ways they run their operations differs also. Babylon is unusual in its decentralized structure. But centralized growing systems with one main location have variabilities, too. AeroFarms, which recently declared bankruptcy but will continue to run its 140,000-square foot vertical operation in Danville, Virginia, is entirely enclosed and reliant on the intense violet glow of grow lights to produce microgreens.
Different companies have different data needs. What data is essential to AeroFarms isn’t quite the same as for Greenswell Growers located in Goochland County, Virginia. Raising four kinds of lettuce in a 77,000-square-foot automated hydroponic greenhouse, the vagaries of naturally available light, which accounts for 70 percent of Greenswell’s energy use on a sunny day, affect operations. Their tech needs to account for “outside weather impacts,” says president Carl Gupton. “What adjustments do we have to make inside of the greenhouse to offset what's going on outside environmentally, to give that plant optimal conditions? When it's 85 percent humidity outside, the system needs to do X, Y and Z to get the conditions that we want inside.”
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen.
Nevertheless, every CEA system has the same core needs — consistent yield of high quality crops to keep up year-round supply to customers. Additionally, “Everybody’s got the same set of problems,” Gupton says. Pests may come into a facility with seeds. A disease called pythium, one of the most common in CEA, can damage plant roots. “Then you have root disease pressures that can also come internally — a change in [growing] substrate can change the way the plant performs,” Gupton says.
AI will help identify diseases, as well as when a plant is thirsty or overly hydrated, when it needs more or less calcium, phosphorous, nitrogen. So, while companies amass their own hyper-specific data sets, Lowman foresees a time within the next decade “when there will be some type of [open-source] database that has the most common types of plant stress identified” that growers will be able to tap into. Such databases will “create a community and move the science forward,” says Lowman.
In fact, IALR is working on assembling images for just such a database now. On so-called “smart tables” inside an Institute lab, a team is growing greens and subjects them to various stressors. Then, they’re administering treatments while taking images of every plant every 15 minutes, says Lowman. Some experiments generate 80,000 images; the challenge lies in analyzing and annotating the vast trove of them, marking each one to reflect outcome—for example increasing the phosphate delivery and the plant’s response to it. Eventually, they’ll be fed into AI systems to help them learn.
For all the enthusiasm surrounding this technology, it’s not without downsides. Training just one AI system can emit over 250,000 pounds of carbon dioxide, according to MIT Technology Review. AI could also be used “to enhance environmental benefit for CEA and optimize [its] energy consumption,” says Rozita Dara, a computer science professor at the University of Guelph in Canada, specializing in AI and data governance, “but we first need to collect data to measure [it].”
The chef-farmers can choose from 45 types of herb and leafy-greens seeds.
Courtesy Babylon Micro-Farms
Any system connected to the Internet of Things is also vulnerable to hacking; if CEA grows to the point where “there are many of these similar farms, and you're depending on feeding a population based on those, it would be quite scary,” Dara says. And there are privacy concerns, too, in systems where imaging is happening constantly. It’s partly for this reason, says Babylon’s Ratte, that the company’s in-farm cameras all “face down into the trays, so the only thing [visible] is pictures of plants.”
Tweaks to improve AI for CEA are happening all the time. Greenswell made its first harvest in 2022 and now has annual data points they can use to start making more intelligent choices about how to feed, water, and supply light to plants, says Gupton. Ratte says he’s confident Babylon’s system can already “get our customers reliable harvests. But in terms of how far we have to go, it's a different problem,” he says. For example, if AI could detect whether the farm is mostly empty—meaning the farm’s user hasn’t planted a new crop of greens—it can alert Babylon to check “what's going on with engagement with this user?” Ratte says. “Do they need more training? Did the main person responsible for the farm quit?”
Lowman says more automation is coming, offering greater ability for systems to identify problems and mitigate them on the spot. “We still have to develop datasets that are specific, so you can have a very clear control plan, [because] artificial intelligence is only as smart as what we tell it, and in plant science, there's so much variation,” he says. He believes AI’s next level will be “looking at those first early days of plant growth: when the seed germinates, how fast it germinates, what it looks like when it germinates.” Imaging all that and pairing it with AI, “can be a really powerful tool, for sure.”
Scientists make progress with growing organs for transplants
Story by Big Think
For over a century, scientists have dreamed of growing human organs sans humans. This technology could put an end to the scarcity of organs for transplants. But that’s just the tip of the iceberg. The capability to grow fully functional organs would revolutionize research. For example, scientists could observe mysterious biological processes, such as how human cells and organs develop a disease and respond (or fail to respond) to medication without involving human subjects.
Recently, a team of researchers from the University of Cambridge has laid the foundations not just for growing functional organs but functional synthetic embryos capable of developing a beating heart, gut, and brain. Their report was published in Nature.
The organoid revolution
In 1981, scientists discovered how to keep stem cells alive. This was a significant breakthrough, as stem cells have notoriously rigorous demands. Nevertheless, stem cells remained a relatively niche research area, mainly because scientists didn’t know how to convince the cells to turn into other cells.
Then, in 1987, scientists embedded isolated stem cells in a gelatinous protein mixture called Matrigel, which simulated the three-dimensional environment of animal tissue. The cells thrived, but they also did something remarkable: they created breast tissue capable of producing milk proteins. This was the first organoid — a clump of cells that behave and function like a real organ. The organoid revolution had begun, and it all started with a boob in Jello.
For the next 20 years, it was rare to find a scientist who identified as an “organoid researcher,” but there were many “stem cell researchers” who wanted to figure out how to turn stem cells into other cells. Eventually, they discovered the signals (called growth factors) that stem cells require to differentiate into other types of cells.
For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells.
By the end of the 2000s, researchers began combining stem cells, Matrigel, and the newly characterized growth factors to create dozens of organoids, from liver organoids capable of producing the bile salts necessary for digesting fat to brain organoids with components that resemble eyes, the spinal cord, and arguably, the beginnings of sentience.
Synthetic embryos
Organoids possess an intrinsic flaw: they are organ-like. They share some characteristics with real organs, making them powerful tools for research. However, no one has found a way to create an organoid with all the characteristics and functions of a real organ. But Magdalena Żernicka-Goetz, a developmental biologist, might have set the foundation for that discovery.
Żernicka-Goetz hypothesized that organoids fail to develop into fully functional organs because organs develop as a collective. Organoid research often uses embryonic stem cells, which are the cells from which the developing organism is created. However, there are two other types of stem cells in an early embryo: stem cells that become the placenta and those that become the yolk sac (where the embryo grows and gets its nutrients in early development). For a human embryo (and its organs) to develop successfully, there needs to be a “dialogue” between these three types of stem cells. In other words, Żernicka-Goetz suspected the best way to grow a functional organoid was to produce a synthetic embryoid.
As described in the aforementioned Nature paper, Żernicka-Goetz and her team mimicked the embryonic environment by mixing these three types of stem cells from mice. Amazingly, the stem cells self-organized into structures and progressed through the successive developmental stages until they had beating hearts and the foundations of the brain.
“Our mouse embryo model not only develops a brain, but also a beating heart [and] all the components that go on to make up the body,” said Żernicka-Goetz. “It’s just unbelievable that we’ve got this far. This has been the dream of our community for years and major focus of our work for a decade and finally we’ve done it.”
If the methods developed by Żernicka-Goetz’s team are successful with human stem cells, scientists someday could use them to guide the development of synthetic organs for patients awaiting transplants. It also opens the door to studying how embryos develop during pregnancy.