Why Don’t We Have Artificial Wombs for Premature Infants?
A lamb which was prematurely born at the equivalent of 23 weeks' human gestation, after 28 days of support from an artificial womb.
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.
Catching colds may help protect kids from Covid
A new study shows that the immune system's response to colds can help prepare it to defend against COVID-19 - but only in the very young.
A common cold virus causes the immune system to produce T cells that also provide protection against SARS-CoV-2, according to new research. The study, published last month in PNAS, shows that this effect is most pronounced in young children. The finding may help explain why most young people who have been exposed to the cold-causing coronavirus have not developed serious cases of COVID-19.
One curiosity stood out in the early days of the COVID-19 pandemic – why were so few kids getting sick. Generally young children and the elderly are the most vulnerable to disease outbreaks, particularly viral infections, either because their immune systems are not fully developed or they are starting to fail.
But solid information on the new infection was so scarce that many public health officials acted on the precautionary principle, assumed a worst-case scenario, and applied the broadest, most restrictive policies to all people to try to contain the coronavirus SARS-CoV-2.
One early thought was that lockdowns worked and kids (ages 6 months to 17 years) simply were not being exposed to the virus. So it was a shock when data started to come in showing that well over half of them carried antibodies to the virus, indicating exposure without getting sick. That trend grew over time and the latest tracking data from the CDC shows that 96.3 percent of kids in the U.S. now carry those antibodies.
Antibodies are relatively quick and easy to measure, but some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
But that couldn't be the whole story because antibody protection fades, sometimes as early as a month after exposure and usually within a year. Additionally, SARS-CoV-2 has been spewing out waves of different variants that were more resistant to antibodies generated by their predecessors. The resistance was so significant that over time the FDA withdrew its emergency use authorization for a handful of monoclonal antibodies with earlier approval to treat the infection because they no longer worked.
Antibodies got most of the attention early on because they are part of the first line response of the immune system. Antibodies can bind to viruses and neutralize them, preventing infection. They are relatively quick and easy to measure and even manufacture, but as SARS-CoV-2 showed us, often viruses can quickly evolve to become more resistant to them. Some scientists are exploring whether the reactions of T cells could serve as a more useful measure of immune protection.
Kids, colds and T cells
T cells are part of the immune system that deals with cells once they have become infected. But working with T cells is much more difficult, takes longer, and is more expensive than working with antibodies. So studies often lags behind on this part of the immune system.
A group of researchers led by Annika Karlsson at the Karolinska Institute in Sweden focuses on T cells targeting virus-infected cells and, unsurprisingly, saw that they can play a role in SARS-CoV-2 infection. Other labs have shown that vaccination and natural exposure to the virus generates different patterns of T cell responses.
The Swedes also looked at another member of the coronavirus family, OC43, which circulates widely and is one of several causes of the common cold. The molecular structure of OC43 is similar to its more deadly cousin SARS-CoV-2. Sometimes a T cell response to one virus can produce a cross-reactive response to a similar protein structure in another virus, meaning that T cells will identify and respond to the two viruses in much the same way. Karlsson looked to see if T cells for OC43 from a wide age range of patients were cross-reactive to SARS-CoV-2.
And that is what they found, as reported in the PNAS study last month; there was cross-reactive activity, but it depended on a person’s age. A subset of a certain type of T cells, called mCD4+,, that recognized various protein parts of the cold-causing virus, OC43, expressed on the surface of an infected cell – also recognized those same protein parts from SARS-CoV-2. The T cell response was lower than that generated by natural exposure to SARS-CoV-2, but it was functional and thus could help limit the severity of COVID-19.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco.
“The cross-reactivity peaked at age six when more than half the people tested have a cross-reactive immune response,” says Karlsson, though their sample is too small to say if this finding applies more broadly across the population. The vast majority of children as young as two years had OC43-specific mCD4+ T cell responses. In adulthood, the functionality of both the OC43-specific and the cross-reactive T cells wane significantly, especially with advanced age.
“Considering that the mortality rate in children is the lowest from ages five to nine, and higher in younger children, our results imply that cross-reactive mCD4+ T cells may have a role in the control of SARS-CoV-2 infection in children,” the authors wrote in their paper.
“One of the most politicized aspects of our pandemic response was not accepting that children are so much less at risk for severe disease with COVID-19,” because usually young children are among the most vulnerable to pathogens, says Monica Gandhi, professor of medicine at the University of California San Francisco and author of the book, Endemic: A Post-Pandemic Playbook, to be released by the Mayo Clinic Press this summer. The immune response of kids to SARS-CoV-2 stood our expectations on their head. “We just haven't seen this before, so knowing the mechanism of protection is really important.”
Why the T cell immune response can fade with age is largely unknown. With some viruses such as measles, a single vaccination or infection generates life-long protection. But respiratory tract infections, like SARS-CoV-2, cause a localized infection - specific to certain organs - and that response tends to be shorter lived than systemic infections that affect the entire body. Karlsson suspects the elderly might be exposed to these localized types of viruses less often. Also, frequent continued exposure to a virus that results in reactivation of the memory T cell pool might eventually result in “a kind of immunosenescence or immune exhaustion that is associated with aging,” Karlsson says. https://leaps.org/scientists-just-started-testing-a-new-class-of-drugs-to-slow-and-even-reverse-aging/particle-3 This fading protection is why older people need to be repeatedly vaccinated against SARS-CoV-2.
Policy implications
Following the numbers on COVID-19 infections and severity over the last three years have shown us that healthy young people without risk factors are not likely to develop serious disease. This latest study points to a mechanism that helps explain why. But the inertia of existing policies remains. How should we adjust policy recommendations based on what we know today?
The World Health Organization (WHO) updated their COVID-19 vaccination guidance on March 28. It calls for a focus on vaccinating and boosting those at risk for developing serious disease. The guidance basically shrugged its shoulders when it came to healthy children and young adults receiving vaccinations and boosters against COVID-19. It said the priority should be to administer the “traditional essential vaccines for children,” such as those that protect against measles, rubella, and mumps.
“As an immunologist and a mother, I think that catching a cold or two when you are a kid and otherwise healthy is not that bad for you. Children have a much lower risk of becoming severely ill with SARS-CoV-2,” says Karlsson. She has followed public health guidance in Sweden, which means that her young children have not been vaccinated, but being older, she has received the vaccine and boosters. Gandhi and her children have been vaccinated, but they do not plan on additional boosters.
The WHO got it right in “concentrating on what matters,” which is getting traditional childhood immunizations back on track after their dramatic decline over the last three years, says Gandhi. Nor is there a need for masking in schools, according to a study from the Catalonia region of Spain. It found “no difference in masking and spread in schools,” particularly since tracking data indicate that nearly all young people have been exposed to SARS-CoV-2.
Both researchers lament that public discussion has overemphasized the quickly fading antibody part of the immune response to SARS-CoV-2 compared with the more durable T cell component. They say developing an efficient measure of T cell response for doctors to use in the clinic would help to monitor immunity in people at risk for severe cases of COVID-19 compared with the current method of toting up potential risk factors.
In this week's Friday Five: The eyes are the windows to the soul - and biological aging?
Plus, what bean genes mean for health and the planet, a breathing practice that could lower levels of tau proteins in the brain, AI beats humans at assessing heart health, and the benefits of "nature prescriptions"
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the stories covered this week:
- The eyes are the windows to the soul - and biological aging?
- What bean genes mean for health and the planet
- This breathing practice could lower levels of tau proteins
- AI beats humans at assessing heart health
- Should you get a nature prescription?