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.
How sharing, hearing, and remembering positive stories can help shape our brains for the better
Across cultures and through millennia, human beings have always told stories. Whether it’s a group of boy scouts around a campfire sharing ghost stories or the paleolithic Cro-Magnons etching pictures of bison on cave walls, researchers believe that storytelling has been universal to human beings since the development of language.
But storytelling was more than just a way for our ancestors to pass the time. Researchers believe that storytelling served an important evolutionary purpose, helping humans learn empathy, share important information (such as where predators were or what berries were safe to eat), as well as strengthen social bonds. Quite literally, storytelling has made it possible for the human race to survive.
Today, neuroscientists are discovering that storytelling is just as important now as it was millions of years ago. Particularly in sharing positive stories, humans can more easily form relational bonds, develop a more flexible perspective, and actually grow new brain circuitry that helps us survive. Here’s how.
How sharing stories positively impacts the brain
When human beings share stories, it increases the levels of certain neurochemicals in the brain, neuroscientists have found. In a 2021 study published in Proceedings of the National Academy of Sciences (PNAS), Swedish researchers found that simply hearing a story could make hospitalized children feel better, compared to other hospitalized children who played a riddle game for the same amount of time. In their research, children in the intensive care unit who heard stories for just 30 minutes had higher levels of oxytocin, a hormone that promotes positive feelings and is linked to relaxation, trust, social connectedness, and overall psychological stability. Furthermore, the same children showed lower levels of cortisol, a hormone associated with stress. Afterward, the group of children who heard stories tended to describe their hospital experiences more positively, and even reported lower levels of pain.
Annie Brewster, MD, knows the positive effect of storytelling from personal experience. An assistant professor at Harvard Medical School and the author of The Healing Power of Storytelling: Using Personal Narrative to Navigate Illness, Trauma, and Loss, Brewster started sharing her personal experience with chronic illness after being diagnosed with multiple sclerosis in 2001. In doing so, Brewster says it has enabled her to accept her diagnosis and integrate it into her identity. Brewster believes so much in the power of hearing and sharing stories that in 2013 she founded Health Story Collaborative, a forum for others to share their mental and physical health challenges.“I wanted to hear stories of people who had found ways to move forward in positive ways, in spite of health challenges,” Brewster said. In doing so, Brewster believes people with chronic conditions can “move closer to self-acceptance and self-love.”
While hearing and sharing positive stories has been shown to increase oxytocin and other “feel good” chemicals, simply remembering a positive story has an effect on our brains as well. Mark Hoelterhoff, PhD, a lecturer in clinical psychology at the University of Edinburgh, recalling and “savoring” a positive story, thought, or feedback “begins to create new brain circuitry—a new neural network that’s geared toward looking for the positive,” he says. Over time, other research shows, savoring positive stories or thoughts can literally change the shape of your brain, hard-wiring someone to see things in a more positive light.How stories can change your behavior
In 2009, Paul Zak, PhD, a neuroscientist and professor at Claremont Graduate University, set out to measure how storytelling can actually change human behavior for the better. In his study, Zak wanted to measure the behavioral effects of oxytocin, and did this by showing test subjects two short video clips designed to elicit an emotional response.
In the first video they showed the study participants, a father spoke to the camera about his two-year-old son, Ben, who had been diagnosed with terminal brain cancer. The father told the audience that he struggled to connect with and enjoy Ben, as Ben had only a few months left to live. In the end, the father finds the strength to stay emotionally connected to his son until he dies.
The second video clip, however, was much less emotional. In that clip, the same father and son are shown spending the day at the zoo. Ben is only suggested to have cancer (he is bald from chemotherapy and referred to as a ‘miracle’, but the cancer isn’t mentioned directly). The second story lacked the dramatic narrative arc of the first video.
Zak’s team took blood before and after the participants watched one of the two videos and found that the first story increased the viewers’ cortisol and oxytocin, suggesting that they felt distress over the boy’s diagnosis and empathy toward the boy and his father. The second narrative, however, didn’t increase oxytocin or cortisol at all.
But Zak took the experiment a step further. After the movie clips, his team gave the study participants a chance to share money with a stranger in the lab. The participants who had an increase in cortisol and oxytocin were more likely to donate money generously. The participants who had increased cortisol and oxytocin were also more likely to donate money to a charity that works with children who are ill. Zak also found that the amount of oxytocin that was released was correlated with how much money people felt comfortable giving—in other words, the more oxytocin that was released, the more generous they felt, and the more money they donated.
How storytelling strengthens our bond with others
Sharing, hearing, and remembering stories can be a powerful tool for social change–not only in the way it changes our brain and our behavior, but also because it can positively affect our relationships with other people
Emotional stimulation from telling stories, writes Zak, is the foundation for empathy, and empathy strengthens our relationships with other people. “By knowing someone’s story—where they come from, what they do, and who you might know in common—relationships with strangers are formed.”
But why are these relationships important for humanity? Because human beings can use storytelling to build empathy and form relationships, it enables them to “engage in the kinds of large-scale cooperation that builds massive bridges and sends humans into space,” says Zak.
Storytelling, Zak found, and the oxytocin release that follows, also makes people more sensitive to social cues. This sensitivity not only motivates us to form relationships, but also to engage with other people and offer help, particularly if the other person seems to need help.
But as Zak found in his experiments, the type of storytelling matters when it comes to affecting relationships. Where Zak found that storytelling with a dramatic arc helps release oxytocin and cortisol, enabling people to feel more empathic and generous, other researchers have found that sharing happy stories allows for greater closeness between individuals and speakers. A group of Chinese researchers found that, compared to emotionally-neutral stories, happy stories were more “emotionally contagious.” Test subjects who heard happy stories had greater activation in certain areas of their brains, experienced more significant, positive changes in their mood, and felt a greater sense of closeness between themselves and the speaker.
“This finding suggests that when individuals are happy, they become less self-focused and then feel more intimate with others,” the authors of the study wrote. “Therefore, sharing happiness could strengthen interpersonal bonding.” The researchers went on to say that this could lead to developing better social networks, receiving more social support, and leading more successful social lives.
Since the start of the COVID pandemic, social isolation, loneliness, and resulting mental health issues have only gotten worse. In light of this, it’s safe to say that hearing, sharing, and remembering stories isn’t just something we can do for entertainment. Storytelling has always been central to the human experience, and now more than ever it’s become something crucial for our survival.
Want to know how you can reap the benefits of hearing happy stories? Keep an eye out for Upworthy’s first book, GOOD PEOPLE: Stories from the Best of Humanity, published by National Geographic/Disney, available on September 3, 2024. GOOD PEOPLE is a much-needed trove of life-affirming stories told straight from the heart. Handpicked from Upworthy’s community, these 101 stories speak to the breadth, depth, and beauty of the human experience, reminding us we have a lot more in common than we realize.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
MRI scans after a new kind of immunotherapy for brain cancer show remarkable progress in one patient just days after the first treatment.
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”