“Synthetic Embryos”: The Wrong Term For Important New Research

This fluorescent image shows a representative post-implantation amniotic sac embroid.
As a subject of research, an unusual degree of consensus appears to exist among scientists, politicians and the public about human embryos being deserving of special considerations. But what those special considerations should be is less clear. And this is where the subject becomes contentious and opinions diverge because, somewhat surprisingly, what really represents a human embryo has so far not been resolved.
"Prior to implantation, embryos must be given a different level of reverence than after implantation."
In 2002, Howard W. Jones Jr., widely considered the "father" of in vitro fertilization (IVF) in the U.S., argued in a widely acclaimed article titled "What is an embryo?" that a precondition for the definition of a human embryo was successful implantation. Only once implantation established a biological unit between embryo and mother, could a relatively small number of human cells be considered a human embryo.
Because he felt strongly that human embryos, indeed, deserve special considerations, and should receive those during IVF, he pointed out that, even inside a woman's body, most human embryos (in contrast to other species) never implant and, therefore, are never given a chance at human life. Consequently, he reasoned that prior to implantation, embryos must be given a different level of reverence than after implantation.
"One cannot help but wonder about the fog of misconceptions and misrepresentations that still surrounds what an embryo is."
This difference, he felt, should also be reflected in scientific language, proposing that embryos prior to implantation in daily IVF practice be called "pre-embryos," with the term "embryo" reserved for post-implantation-stage embryos. Then still unknown to Jones, recent research findings support this viewpoint, since genetic profiles of pre- and post-implantation stage embryos greatly differ.
In an analogy to nature, which in humans allows implantation of only a small minority of naturally generated pre-embryos, IVF centers around the world routinely discard large numbers of pre-embryos, judged inadequate for producing normal pregnancies. Jones' suggestion that only post-implantation embryos should be considered embryos deserving of special considerations, therefore, not only appears prescient and considerate of current IVF practices, but grounded in scientific reality. One, therefore, cannot help but wonder about the fog of misconceptions and misrepresentations that still surrounds what an embryo is.
"Much of the regulatory environment surrounding research on human embryos is guided by emotions rather than science and logical thinking."
In 1984, a British ethics committee issued the Warnock Report, which still today prohibits scientists worldwide from studying human embryos in a lab beyond 14 days from fertilization or past formation of the so-called primitive streak, whichever comes first. Well-meaning in its day, its intent was to apply special considerations to human pre-embryos by protecting them from the potential of "feeling pain," once the primitive streak arose on day-15 of development. Formation of the primitive streak signifies a process known as gastrulation, when a subset of cells from the inner cell mass of the pre-embryo are transformed into the three germ layers that comprise all tissues of the developing embryo: The ectoderm, which gives rise to the nervous system; the mesoderm, which gives rise to the circulatory system, muscle, and kidneys; and the endoderm which gives rise to the interior lining of the digestive and respiratory tracts, among other tissues.
That pre-embryos may feel pain at that stage of development was far-fetched in 1984; in view of what we have learned about early human embryology in the 33 years since, it remains untenable today. And, yet, scientists all over the world remain bound by the ethical constraints imposed by the Warnock Report.
A similar ethical paradox exists today for guidelines affecting huge numbers of so-called "abandoned" cryopreserved embryos, often stored ad infinitum in IVF centers all over the world. These are pre-embryos, whose "parents" are no longer responsive to queries from their IVF centers. Current U.S. guidelines allow the disposal of such pre-embryos but prohibit their use in research that may benefit mankind. One, however, wonders whether disposal of huge numbers of abandoned embryos is really more ethical than their use in potentially life-saving human research?
That much of the regulatory environment surrounding research on human embryos is, indeed, guided by emotions rather than science and logical thinking, is also demonstrated by recently expressed concern about so-called "artificial" or "synthetic" embryos. Though both of these terms suggest impending ability to create human embryos from synthetic building blocks, this is not what these terms are meant to describe (such abilities also are not on the horizon). They also do not describe abilities to create gametes (i.e., eggs and sperm) from somatic cells by reprogramming adult peripheral cells, which has already been successfully done in mice by Japanese investigators, leading to the creation of healthy embryos and births and three generations of healthy pubs. Such an approach is at least conceivable as an upcoming infertility treatment.
"A team of biologists and engineers at the University of Michigan recently received media attention after creating organoids from embryonic stem cells that resembled human embryos."
What all of this noise is really about is the discovery that, as several Rockefeller University investigators recently noted, "Cells have an intrinsic ability to self-assemble and self-organize into complex and functional tissues and organs." Investigators have taken advantage of this ability by creating in the lab so-called "organoids" from accumulations of individual embryonic stem cells. They are defined by three characteristics: (i) they contain a variety of cell types and tissue layers, all typical for a given organ; (ii) these cells are organized similarly to their organization in a specific organ; and (iii) the organoid mimics functions of the organ.
Several other biologists from the Cincinnati Children Hospital Medical Center recently noted that in the last five years, quite a variety of human stem cell-derived organoids, including all three germ layers, have been generated by different research groups around the world, thereby establishing new human model systems that can be used outside the body, in a dish, to investigate otherwise difficult-to-approach organs. Interestingly, they can also be used to investigate early stages of human embryological development.
A team of biologists and engineers at the University of Michigan recently received media attention after creating organoids from embryonic stem cells that resembled human embryos and, therefore, were given the name "embroids." Though clearly not embryos (the only thing they had in common with human embryos were cell types), they were nevertheless awarded in at least one article the identity of "artificial embryos," which "no one knows how to handle." As Howard Jones so correctly noted, with the word embryo often comes undeserved reverence.
"Any association with the term "embryo" should be avoided; it is not only misleading and irresponsible but scientifically incorrect."
Artificial embryos, therefore, do not exist. Organoids that resemble embryos (i.e., "embroids"), while potentially very useful research objects in studies of early human embryonic cell organization and lineage development, are not embryos--not even pre-embryos. Special considerations for "artificial" or "synthetic" embryos, as recently advocated by some scientists, therefore, appear ethically undeserved. How misdirected and forced some of these efforts are is probably best demonstrated by a recent publication in which a group of Harvard University investigators proposed the term "synthetic human entities with embryo-like features" or SHEEFS" in place of "organoids." Preferably, however, in describing these laboratory-created entities, any association with the term "embryo" should be avoided. It is not only misleading and irresponsible but scientifically incorrect.
Clinical reproductive medicine and reproductive biology, for valid ethical reasons, but also because of myths, misperceptions and, sometimes, outright misrepresentations of facts for political reasons, are under more public scrutiny than most other science areas. Yet, at least in the realm of biomedical research, nothing appears more important than better understanding the first few days of human embryo development. A recent study involving genetic editing of human embryos, reported by British investigators in Nature, once again confirmed what biologist have known for some time: No animal model faithfully recapitulates most of human developmental origins. The most important secrets nature still has to tell us, will not be revealed through mouse or other animal studies. We will discover them only through the study of early-stage human embryos – and we, therefore, should not limit the use of lab-grown organoids to help further that research.
Understanding early human development "will not only greatly enhance the biological understanding of our species; but also will open groundbreaking new therapeutic options in all areas of medicine."
As Howard Jones intuitively noticed, words matter. Appropriate and uniformly accepted definitions and terms are not only essential for scientific communications but, within the context of human reproduction, often elicit strong emotional reactions, and are easily misappropriated by those opposed to most interventions into human reproduction.
Who does not recall the early days of IVF in the late 1970s, when even reputable news outlets raised the specter of Frankenstein monsters created through the IVF process? Millions of IVF births later, a Nobel Prize in Medicine and Physiology was in 2010 finally awarded to the biologist Robert Edwards who, together with the gynecologist Patrick Steptoe, reported the first live birth through IVF on July 25, 1978. Many more awards are still waiting for recipients who through the study of early human embryo development will discover how cell fate is determined and cells acquire highly specific functions; how rapid cell proliferation takes place and, when required, stops; why chromosomal abnormalities are so common in early stage embryos and what their function may be.
Those who will discover these and many other important answers, will not only greatly enhance the biological understanding of our species; but also will open groundbreaking new therapeutic options in all areas of medicine. Learning how to control cell proliferation, for example, will likely revolutionize cancer therapy; I started my research career in biology with a study published in 1980 of "common denominators of pregnancy and malignancy." If regulatory prohibitions are not allowed to interfere in rapidly progressing research opportunities involving organoids and pre-embryos, we will, finally, see the circle closing, with the most rewarding benefits for mankind ever achieved through biological research.
Editor's Note: Read a different viewpoint here written by one of the world's top experts on the ethics of stem cell research.
Is there a robot nanny in your child's future?
Some researchers argue that active, playful engagement with a "robot nanny" for a few hours a day is better than several hours in front of a TV or with an iPad.
From ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. Copyright © 2024 by the author and reprinted by permission of St. Martin’s Publishing Group.
Could the use of robots take some of the workload off teachers, add engagement among students, and ultimately invigorate learning by taking it to a new level that is more consonant with the everyday experiences of young people? Do robots have the potential to become full-fledged educators and further push human teachers out of the profession? The preponderance of opinion on this subject is that, just as AI and medical technology are not going to eliminate doctors, robot teachers will never replace human teachers. Rather, they will change the job of teaching.
A 2017 study led by Google executive James Manyika suggested that skills like creativity, emotional intelligence, and communication will always be needed in the classroom and that robots aren’t likely to provide them at the same level that humans naturally do. But robot teachers do bring advantages, such as a depth of subject knowledge that teachers can’t match, and they’re great for student engagement.
The teacher and robot can complement each other in new ways, with the teacher facilitating interactions between robots and students. So far, this is the case with teaching “assistants” being adopted now in China, Japan, the U.S., and Europe. In this scenario, the robot (usually the SoftBank child-size robot NAO) is a tool for teaching mainly science, technology, engineering, and math (the STEM subjects), but the teacher is very involved in planning, overseeing, and evaluating progress. The students get an entertaining and enriched learning experience, and some of the teaching load is taken off the teacher. At least, that’s what researchers have been able to observe so far.
To be sure, there are some powerful arguments for having robots in the classroom. A not-to-be-underestimated one is that robots “speak the language” of today’s children, who have been steeped in technology since birth. These children are adept at navigating a media-rich environment that is highly visual and interactive. They are plugged into the Internet 24-7. They consume music, games, and huge numbers of videos on a weekly basis. They expect to be dazzled because they are used to being dazzled by more and more spectacular displays of digital artistry. Education has to compete with social media and the entertainment vehicles of students’ everyday lives.
Another compelling argument for teaching robots is that they help prepare students for the technological realities they will encounter in the real world when robots will be ubiquitous. From childhood on, they will be interacting and collaborating with robots in every sphere of their lives from the jobs they do to dealing with retail robots and helper robots in the home. Including robots in the classroom is one way of making sure that children of all socioeconomic backgrounds will be better prepared for a highly automated age, when successfully using robots will be as essential as reading and writing. We’ve already crossed this threshold with computers and smartphones.
Students need multimedia entertainment with their teaching. This is something robots can provide through their ability to connect to the Internet and act as a centralized host to videos, music, and games. Children also need interaction, something robots can deliver up to a point, but which humans can surpass. The education of a child is not just intended to make them technologically functional in a wired world, it’s to help them grow in intellectual, creative, social, and emotional ways. When considered through this perspective, it opens the door to questions concerning just how far robots should go. Robots don’t just teach and engage children; they’re designed to tug at their heartstrings.
It’s no coincidence that many toy makers and manufacturers are designing cute robots that look and behave like real children or animals, says Turkle. “When they make eye contact and gesture toward us, they predispose us to view them as thinking and caring,” she has written in The Washington Post. “They are designed to be cute, to provide a nurturing response” from the child. As mentioned previously, this nurturing experience is a powerful vehicle for drawing children in and promoting strong attachment. But should children really love their robots?
ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold (January 9, 2024).
St. Martin’s Publishing Group
The problem, once again, is that a child can be lulled into thinking that she’s in an actual relationship, when a robot can’t possibly love her back. If adults have these vulnerabilities, what might such asymmetrical relationships do to the emotional development of a small child? Turkle notes that while we tend to ascribe a mind and emotions to a socially interactive robot, “simulated thinking may be thinking, but simulated feeling is never feeling, and simulated love is never love.”
Always a consideration is the fact that in the first few years of life, a child’s brain is undergoing rapid growth and development that will form the foundation of their lifelong emotional health. These formative experiences are literally shaping the child’s brain, their expectations, and their view of the world and their place in it. In Alone Together, Turkle asks: What are we saying to children about their importance to us when we’re willing to outsource their care to a robot? A child might be superficially entertained by the robot while his self-esteem is systematically undermined.
Research has emerged showing that there are clear downsides to child-robot relationships.
Still, in the case of robot nannies in the home, is active, playful engagement with a robot for a few hours a day any more harmful than several hours in front of a TV or with an iPad? Some, like Xiong, regard interacting with a robot as better than mere passive entertainment. iPal’s manufacturers say that their robot can’t replace parents or teachers and is best used by three- to eight-year-olds after school, while they wait for their parents to get off work. But as robots become ever-more sophisticated, they’re expected to perform more of the tasks of day-to-day care and to be much more emotionally advanced. There is no question children will form deep attachments to some of them. And research has emerged showing that there are clear downsides to child-robot relationships.
Some studies, performed by Turkle and fellow MIT colleague Cynthia Breazeal, have revealed a darker side to the child-robot bond. Turkle has reported extensively on these studies in The Washington Post and in her book Alone Together. Most children love robots, but some act out their inner bully on the hapless machines, hitting and kicking them and otherwise trying to hurt them. The trouble is that the robot can’t fight back, teaching children that they can bully and abuse without consequences. As in any other robot relationship, such harmful behavior could carry over into the child’s human relationships.
And, ironically, it turns out that communicative machines don’t actually teach kids good communication skills. It’s well known that parent-child communication in the first three years of life sets the stage for a very young child’s intellectual and academic success. Verbal back-and-forth with parents and care-givers is like fuel for a child’s growing brain. One article that examined several types of play and their effect on children’s communication skills, published in JAMA Pediatrics in 2015, showed that babies who played with electronic toys—like the popular robot dog Aibo—show a decrease in both the quantity and quality of their language skills.
Anna V. Sosa of the Child Speech and Language Lab at Northern Arizona University studied twenty-six ten- to sixteen- month-old infants to compare the growth of their language skills after they played with three types of toys: electronic toys like a baby laptop and talking farm; traditional toys like wooden puzzles and building blocks; and books read aloud by their parents. The play that produced the most growth in verbal ability was having books read to them by a caregiver, followed by play with traditional toys. Language gains after playing with electronic toys came dead last. This form of play involved the least use of adult words, the least conversational turntaking, and the least verbalizations from the children. While the study sample was small, it’s not hard to extrapolate that no electronic toy or even more abled robot could supply the intimate responsiveness of a parent reading stories to a child, explaining new words, answering the child’s questions, and modeling the kind of back- and-forth interaction that promotes empathy and reciprocity in relationships.
***
Most experts acknowledge that robots can be valuable educational tools. But they can’t make a child feel truly loved, validated, and valued. That’s the job of parents, and when parents abdicate this responsibility, it’s not only the child who misses out on one of life’s most profound experiences.
We really don’t know how the tech-savvy children of today will ultimately process their attachments to robots and whether they will be excessively predisposed to choosing robot companionship over that of humans. It’s possible their techno literacy will draw for them a bold line between real life and a quasi-imaginary history with a robot. But it will be decades before we see long-term studies culminating in sufficient data to help scientists, and the rest of us, to parse out the effects of a lifetime spent with robots.
This is an excerpt from ROBOTS AND THE PEOPLE WHO LOVE THEM: Holding on to Our Humanity in an Age of Social Robots by Eve Herold. The book will be published on January 9, 2024.
Stem cells from a fetus can travel to the heart and regenerate the muscle, essentially saving a mother’s life.
Story by Big Think
In rare cases, a woman’s heart can start to fail in the months before or after giving birth. The all-important muscle weakens as its chambers enlarge, reducing the amount of blood pumped with each beat. Peripartum cardiomyopathy can threaten the lives of both mother and child. Viral illness, nutritional deficiency, the bodily stress of pregnancy, or an abnormal immune response could all play a role, but the causes aren’t concretely known.
If there is a silver lining to peripartum cardiomyopathy, it’s that it is perhaps the most survivable form of heart failure. A remarkable 50% of women recover spontaneously. And there’s an even more remarkable explanation for that glowing statistic: The fetus‘ stem cells migrate to the heart and regenerate the beleaguered muscle. In essence, the developing or recently born child saves its mother’s life.
Saving mama
While this process has not been observed directly in humans, it has been witnessed in mice. In a 2015 study, researchers tracked stem cells from fetal mice as they traveled to mothers’ damaged cardiac cells and integrated themselves into hearts.
Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Scientists also have spotted cells from the fetus within the hearts of human mothers, as well as countless other places inside the body, including the skin, spleen, liver, brain, lung, kidney, thyroid, lymph nodes, salivary glands, gallbladder, and intestine. These cells essentially get everywhere. While most are eliminated by the immune system during pregnancy, some can persist for an incredibly long time — up to three decades after childbirth.
This integration of the fetus’ cells into the mother’s body has been given a name: fetal microchimerism. The process appears to start between the fourth and sixth week of gestation in humans. Scientists are actively trying to suss out its purpose. Fetal stem cells, which can differentiate into all sorts of specialized cells, appear to target areas of injury. So their role in healing seems apparent. Evolutionarily, this function makes sense: It is in the fetus’ best interest that its mother remains healthy.
Sending cells into the mother’s body may also prime her immune system to grow more tolerant of the developing fetus. Successful pregnancy requires that the immune system not see the fetus as an interloper and thus dispatch cells to attack it.
Fetal microchimerism
But fetal microchimerism might not be entirely beneficial. Greater concentrations of the cells have been associated with various autoimmune diseases such as lupus, Sjogren’s syndrome, and even multiple sclerosis. After all, they are foreign cells living in the mother’s body, so it’s possible that they might trigger subtle, yet constant inflammation. Fetal cells also have been linked to cancer, although it isn’t clear whether they abet or hinder the disease.
A team of Spanish scientists summarized the apparent give and take of fetal microchimerism in a 2022 review article. “On the one hand, fetal microchimerism could be a source of progenitor cells with a beneficial effect on the mother’s health by intervening in tissue repair, angiogenesis, or neurogenesis. On the other hand, fetal microchimerism might have a detrimental function by activating the immune response and contributing to autoimmune diseases,” they wrote.
Regardless of a fetus’ cells net effect, their existence alone is intriguing. In a paper published earlier this year, University of London biologist Francisco Úbeda and University of Western Ontario mathematical biologist Geoff Wild noted that these cells might very well persist within mothers for life.
“Therefore, throughout their reproductive lives, mothers accumulate fetal cells from each of their past pregnancies including those resulting in miscarriages. Furthermore, mothers inherit, from their own mothers, a pool of cells contributed by all fetuses carried by their mothers, often referred to as grandmaternal microchimerism.”
So every mother may carry within her literal pieces of her ancestors.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.