Are we ready for the artificial womb?
By John Lorinc
Two questions have intrigued both scientists and philosophers for centuries: What does it mean to be born? And, can we create life outside the womb?
Mike Seed (PGME ’11), an associate professor in Temerty Faculty of Medicine’s Departments of Paediatrics, Medical Imaging, and Obstetrics and Gynaecology, can pinpoint the moment when his team’s work — exploring the possibility of creating artificial placentas for premature babies — served up an aha moment.
Professor Seed, The Hospital for Sick Children’s head of cardiology, is working with a Toronto-based group who want to extend the ground-breaking 2017 work of a research team at the Children’s Hospital of Philadelphia.
The U.S. group developed a “biobag” for gestating sheep fetuses, using artificial amniotic fluid, an oxygenator and surgical techniques for swapping out the ewe’s placenta with a “circuit” of tubes designed to siphon in nutrients and gases, and draw out wastes. In effect, they created an artificial placenta.
The Toronto project, which involves graduate
students, is supported by the SickKids Foundation and the Canadian Institutes of Health Research. SickKids doesn’t have facilities for pregnant sheep, so Seed opted to work with mini-pig fetuses, which are closer in size to the extremely preterm humans that are the research target. The first 10 experiments failed: The pig fetuses died almost immediately.
Seed’s co-investigator, Christoph Haller (PGME ’17), an assistant professor in Temerty Medicine’s Department of Surgery and a surgeon-investigator at SickKids, knows how challenging it is to insert tubes carrying oxygen and nutrients into the umbilical cord. But the team succeeded in developing an approach to connect the fetus to the oxygenator circuit.
“At one point during one of our recent experiments, the heart rate came down and the blood flow around the circuit was normal,” says Seed. Yet he notes a qualifier: that pig fetus that succeeded had been slightly larger than the others. “That might have been what made the difference,” he allows. “Still, the most important moment for us was when we first managed to get an animal onto the system.”
Earlier this year, the SickKids team embarked on a new set of experiments. While Seed acknowledges there’s likely a long way to go before artificial womb technology can be used to gestate premature human babies, he and others in the field know what they’d like to achieve. They’d like to find a way to prevent the high risk of disability and death that imperils babies born very prematurely, around the threshold of viability, at about 22 or 23 weeks gestation.
These infants spend their first months in an incubator and run a high risk of respiratory, cardiac or cerebral injury. “The existing approach is pretty bad,” Seed says. With advances in fetal surgery, he adds that artificial placentas could enable procedures like cardiac surgery to be carried out more safely. “The artificial placenta could become a vehicle for delivering new experimental treatments such as gene therapy or stem cell therapy,” he says.
Developing mechanical and surgical techniques is only part of the discovery process. Cynthia Maxwell (PGME ’04) is a professor in Temerty Medicine’s Department of Obstetrics and Gynaecology who is participating in Seed’s project. She says the viability of artificial wombs poses critical questions about how health care practitioners work with pregnant people. Professor Maxwell, who is also a maternal fetal medicine specialist at Sinai Health and Women’s College Hospital, says advances in artificial womb techniques will require the development of “fetal ICUs” equipped and staffed to provide specialized care for fetuses. As Maxwell observes, developing this technology poses a fundamental question if there’s an option besides vaginal birth and C-sections. She asks, “What does it mean to be born?”
Bioethicists stress this research is raising important questions about whether the existence of artificial wombs will alter assumptions about pregnancy, uterine transplantation, surrogacy and even the rights of women to obtain an abortion. “In the short term, it may seem like this is about private decisions to be made by individual women with respect to their pregnancy and fetus,” says Françoise Baylis, a professor at Dalhousie University. “But it has broad societal implications, and that’s why it’s really important to involve non-scientists including bioethicists in frontier science.”
Elizabeth Chloe Romanis, an assistant professor in biolaw at Durham University in England, says it will be critical for researchers and university ethics boards around the world to recognize that such technology must not be seen as only an innovative form of clinical treatment if it’s tested on humans. “It will ultimately be an experiment when it’s first used,” she says.
Attempts to build an artificial womb go back to Sweden in the 1950s, and researchers have been picking away at the idea ever since. Artificial wombs, says Seed, “make total sense.”
Premature babies have underdeveloped lungs that are easily damaged. For a fetus, the placenta provides nutrients and hormones, as well as a continuous exchange of gases. “Placentas are unique in terms of that relationship,” says Maxwell.
The oxygenators used in neonatal cardiac surgery have become more sophisticated and similar in their performance to a real placenta, resulting in increasingly convincing artificial placenta experiments in animal models. (Research teams, including those in Michigan and Australia, are also working on artificial placentas.) Seed and Haller’s group discovered that the commercial neonatal oxygenators caused heart failure in their small pig fetuses so decided to add a pump to the circuit.
In a second series of experiments incorporating a pump, the fetuses were much more stable, with the animals surviving for up to a week. Yet the group is still seeing problems with heart failure in their animal subjects and is continuing to modify the circuit in an attempt to more faithfully reproduce the physiology of a real placenta.
Maxwell is focusing on post-procedural issues, such as what will be required in the fetal ICU, environmental issues such as temperature and lighting, and even techniques for mimicking the pregnant person’s movements. “The animal models are super promising,” she says. “The sheep model suggests that you can bring a baby lamb all the way to term, so I think it’s really a matter of time before that technology will be worked out in other animal models, and then we’re able to actually use that for human beings.”
The SickKids team doesn’t anticipate that the artificial placenta will alter the current threshold of fetal viability. “There are likely to be physical constraints in terms of vessel size and blood pressure that mean this approach will primarily be used in extremely preterm babies that currently receive conventional neonatal intensive care,” says Seed. “It’s going to be risky to support a baby on an artificial placenta, such that it will always be much safer for them to remain in utero whenever possible.”
The Big Questions
The research has raised important ethical questions about the role of this kind of technology in human reproduction. Romanis’ doctoral studies included several months working with Bernard Dickens, a University of Toronto Faculty of Law professor emeritus. Romanis predicts that it will be ethically challenging to organize clinical trials or obtain informed consent for participation in a clinical trial because pregnant people facing the risk of premature birth still have the option of neonatal intensive care, which is a well-established approach. “I think human trials are going to be really, really complicated,” she says.
Baylis cautions that such research tends to focus on solutions and benefits and neglect potential harms and misuses, such as whether the artificial womb technology could someday be used as an alternative to any pregnancy, and thus serve as a procedure that anti-abortion politicians might mandate as an alternative to ending a pregnancy.
Maxwell notes that the use of artificial womb technology could also pose questions about resource allocation in hospitals, and whether fetal ICUs may come at the expense of other services. But for now, that question may be a way off. “I don’t think we’re at that stage yet,” she says. ●