We Should Resist Making “Synthetic Embryos” Too Realistic
Ethics needs context. So does science – specifically, science that aims to create bioengineered models of early human embryo development in a dish (hereafter synthetic embryos). Even the term "synthetic embryos" begs for an explanation. What are these? And why would anyone want to create them?
"This knowledge may help scientists understand how certain birth defects are formed and why miscarriages often occur."
First the research context. Synthetic embryos are stem cell-derived simulations of human post-implantation embryos that are designed to mimic a stage of early development called gastrulation. That's the stage—around 14-15 days after fertilization – when embryos begin to form a very primitive body plan (basic dorsal-ventral and anterior-posterior axes, and distinct cell lineages). Researchers are starting to create synthetic embryos in the lab – albeit imperfect and incomplete versions – to learn how gastrulation might unfold in real human embryos embedded unseen in the womb. This knowledge may help scientists understand how certain birth defects are formed and why miscarriages often occur soon after implantation. As such, synthetic embryos are meant to be models of human embryo development, not themselves actually embryos. But will synthetic embryos ever get to the point where they are practically the same thing as "natural" human embryos? That is my concern and why I think researchers should avoid creating synthetic embryos capable of doing everything natural embryos can do.
It may not be too difficult to prevent this slide from synthetic to real. Synthetic embryos must be created using sophisticated 3D culture systems that mimic the complex architecture of human embryos. These complex culture systems also have to incorporate precise microinjection systems to chemically trigger the symmetry-breaking events involved in early body plan formation. In short, synthetic embryos need a heavy dose of engineering to get their biological processes going and to help keep them going. And like most engineered entities, designs can be built into the system early to serve well-considered goals – in our case, the goal of not wanting to create synthetic embryos that are too realistic.
"If one wants to study how car engines work, one can model an engine without also modeling the wheels, transmission, and every other car part together."
A good example of this point is found a report published in Nature Communications where scientists created a human stem cell-based 3D model that faithfully recapitulates the biological events around post-implantation amniotic sac development. Importantly, however, the embryo model they developed lacked several key structures and therefore – despite its partial resemblance to an early human embryo – did not have complete human form and potential. While fulfilling their model's aim of revealing a previously inaccessible early developmental event, the team intentionally did not recreate the entire post-implantation human embryo because they did not want to provoke any ethical concerns, as the lead author told me personally. Besides, creating a complete synthetic embryo was not necessary or scientifically justified for the research question they were pursuing. This example goes to show that researchers can create a synthetic embryo to model specific developmental events they want to study without modeling every aspect of a developing embryo. Likewise – to use a somewhat imprecise but instructive analogy – if one wants to study how car engines work, one can model an engine without also modeling the wheels, transmission, and every other car part together.
A representative "synthetic embryo," which in some ways resembles a post-implantation embryo around 14 days after fertilization.
(Courtesy of Yue Shao)
But why should researchers resist creating complete synthetic embryos? To answer this, we need some policy context. Currently there is an embryo research rule in place – a law in many nations, in others a culturally accepted agreement – that intact human embryos must not be grown for research in the lab for longer than 14 consecutive days after fertilization or the formation of the primitive streak (a faint embryonic band that signals the start of gastrulation). This is commonly referred to as the 14-day rule. It was established in the UK decades ago to carve out a space for meritorious human embryo research while simultaneously assuring the public that researchers won't go too far in cultivating embryos to later developmental stages before destroying them at the end of their studies. Many citizens accepting of pre-implantation stage human embryo research would not have tolerated post-implantation stage embryo use. The 14-day rule was a line in the sand, drawn to protect the advancement of embryo research, which otherwise might have been stifled without this clear stopping point. To date, the 14-day rule has not been revoked anywhere in the world, although new research in extended natural embryo cultivation is starting to put some pressure on it.
"Perhaps the day will come when scientists don't have to apply for research funding under such a dark cloud of anti-science sentiment."
Why does this policy context matter? The creation of complete synthetic embryos could raise serious questions (some of them legal) about whether the 14-day rule applies to these lab entities. Although they can be constructed in far fewer than 14 days, they would, at least in theory, be capable of recapitulating all of a natural embryo's developmental events at the gastrulation stage, thus possibly violating the spirit of the 14-day rule. Embryo research laws and policies worldwide are not ready yet to tackle this issue. Furthermore, professional guidelines issued by the International Society for Stem Cell Research prohibit the culture of any "organized embryo-like cellular structures with human organismal potential" to be cultured past the formation of the primitive streak. Thus, researchers should wait until there is greater clarity on this point, or until the 14-day rule is revised through proper policy-making channels to explicitly exclude complete synthetic embryos from its reach.
I should be clear that I am not basing my recommendations on any anti-embryo-research position per se, or on any metaphysical position regarding the positive moral status of synthetic embryos. Rather, I am concerned about the potential backlash that research on complete synthetic embryos might bring to embryo research in general. I began this essay by saying that ethics needs context. The ethics of synthetic embryo research needs to be considered within the context of today's fraught political environment. Perhaps the day will come when scientists don't have to apply for research funding under such a dark cloud of anti-science sentiment. Until then, however, it is my hope that scientists can fulfill their research aims by working on an array of different but each purposefully incomplete synthetic embryo models to generate, in the aggregate of their published work, a unified portrait of human development such that biologically complete synthetic embryo models will not be necessary.
Editor's Note: Read a different viewpoint here written by a leading New York fertility doctor/researcher.
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
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.”