A group of clinicians and researchers in the US has taken a big leap toward developing an artificial womb for humans—by building and testing one designed to keep very premature lambs alive outside the bodies of their mothers.
The immediate goal is to develop a human-ready version of these "biobags" to provide desperately-needed help to the 30,000 pre-term babies born in the US every year, according to the researchers, who addressed the media in a phone conference on Monday. The statistics are grim for these preemies, babies who are born before 23 weeks: among this group, morbidity and mortality rates are high, and negative health effects can last into adulthood.
Incubators currently used to keep premature infants alive in a neonatal intensive care unit (NICU) swaddle them in nothing but air—unlike the warm, saline-like amniotic fluid that bathes them in utero. This fluid is crucial in warding off infections.
In addition, having babies breathe air instead of fluid can impede the development of lung tissue. Pre-term babies have higher rates of lifetime lung function loss due to factors like these.
Taking a cue from nature, Alan Flake, a researcher and neonatal surgeon at the Children's Hospital of Philadelphia, worked with his team to create a new type of incubator—one that mimics the fluid-filled interior of the mother's womb while still maintaining a connection to the outside world.
The technique has yet to be tested on humans—that requires government approval. And the idea of entirely artificial, womb-free reproduction is still science fiction. In this study, published Tuesday in Nature Communications, lambs were used to test out the biobag. These animals have been used for years in premature birth research: they have similar developmental milestones to humans, and undergo many of the same biological processes in the womb.
Flake's biobag resembles a big plastic sack with ports in the side and a few tubes going in and out. Inside is a pre-term baby lamb, at the equivalent developmental age of a 23-week-old human. It's a sealed system, so bacteria and viruses can't get inside. The lamb's umbilical cord is hooked up to an oxygenator circuit which provides vital gas (like oxygen) and scrubs out carbon dioxide.
Crucially, blood is not forced into the lamb's circulatory system, where the pressure could cause damage; the biobag is pumpless and the power to drive it comes only from the baby lamb's heart.
The eight lambs in this study were kept alive for four weeks in these biobags. Tests showed they were healthy and exhibited normal developmental progress. The only reason the experiments were stopped at the four-week mark was due to experimental protocols; there is every indication they could have gone on longer.
Despite the somewhat off-putting appearance of a lamb fetus swimming in a plastic pouch, future versions of the device designed for humans will closely resemble a traditional incubator found in a NICU. "It's not going to be fetuses hanging off the wall in bags," said Flake in a phone interview.
In addition to the lambs looked at in this study, a smaller group of four lambs who spent time in the bags as infants have been successfully "birthed" and are healthy and normal. One is a year old. "There's no intelligence test for lambs, but we think they're pretty smart," said Flake.
Now that these proof-of-concept experiments have shown positive results, Flake is pushing ahead to get FDA approval for pre-clinical trials with premature human babies. The need is urgent. According to Emily Partridge, a surgeon scientist and a member of the research team, if results hold up in humans, the biobags would represent "a vast improvement over the latest standard of care." Partridge is from Toronto and trained at U of T; she chose to work in Flake's lab because it's considered one of the best in the world in premature infant research.
Flake estimates clinical trials in extremely premature infants could begin within three-to-five years, pending approval.
The biobags are cheap to make. Early iterations were "a lot of Home Depot and eBay and Amazon stuff," said Marcus Davey, who built the device. This bodes well for access to the technology in developing nations, where resources can be scarce.
Although keeping fetuses alive at the equivalent of 23 weeks is an impressive technical achievement, what about dialling back the clock even further? Why need a womb at all? Simply artificially-inseminate an egg, pop it in a biobag and nine months later, voila.
"At present there is no technology, even on the horizon," said Flake, "to support the embryo to the test-tube stage [when it can be grown in an artificial womb]."
We're limited to our reproductive physiology—in some form or another—for awhile yet to come.
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