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Lab-grown embryo models are getting more realistic. Scientists are getting more concerned
Lab-grown embryo models are getting more realistic. Scientists are getting more concerned

CTV News

time03-08-2025

  • Science
  • CTV News

Lab-grown embryo models are getting more realistic. Scientists are getting more concerned

A human embryo model generated from reprogrammed stem cells by the lab of Magdalena Zernicka-Geotz, the Bren professor of biology and biological engineering at Caltech. The structure shows the different cell types present during the very earliest stages of human development. (Zhaodi Liao/Zernicka-Goetz Laboratory via CNN Newsource) Scientists are exploring ways to mimic the origins of human life without two fundamental components: sperm and egg. They are coaxing clusters of stem cells – programmable cells that can transform into many different specialized cell types – to form laboratory-grown structures that resemble human embryos. These embryo models are far from perfect replicas. But as labs compete to grow the best likeness, the structures are becoming increasingly complex, looking and behaving in some way as embryos would. The structures could further the study of human development and the causes infertility. However, the dizzying pace of the research, which started little more than a decade ago, is posing ethical, legal and regulatory challenges for the field of developmental biology. 'We could have never anticipated the science would have just progressed like this. It's incredible, it's been transformative how quickly the field has moved, said Amander Clark, a professor of molecular cell and developmental biology at the University of California, Los Angeles, and the founding director of the UCLA Center for Reproductive Science, Health and Education. 'However, as these models advance, it is crucial that they are studied in a framework that balances scientific progress with ethical, legal and social considerations.' Clark is co-chair of the International Society of Stem Cell Research (ISSCR) Embryo Models Working Group, which is now trying to update such a framework on a global scale. At issue is the question of how far researchers could go with these stem cells, given time and the right conditions. Could scientists eventually replicate an actual embryo that has a heartbeat and experiences pain, or one that could grow into a fully developed human model? Embryo models: How realistic are they? As current research stands, no model mimics the development of a human embryo in its entirety — nor is any model suspected of having the potential to form a fetus, the next stage in human development equivalent to week 8 or day 56 in a human pregnancy. Creating embryo models has also been a hit-and-miss process for most research groups, with only a small percentage of stem cells going on to self-organize into embryo-like structures. However, the models do exhibit several internal features and cell types that an embryo needs to develop, such as the amnion, yolk sac and primitive streak, and that could, 'with future improvements, eventually progress toward later embryo structures including heart, brain, and other organ rudiments,' according to a June paper coauthored by Clark and published in the journal Stem Cell Reports. Similar models made with mouse cells have reached the point where the brain begins to develop and a heart forms. Critically, the goal isn't to develop these models into viable fetuses, ultimately capable of human sentience, but to develop a useful research tool that unlocks the mysteries of how a human cell divides and reproduces to become a human body. The models also make way for experiments that can't be performed on donated embryos in a lab. However, it's possible as research advances that the distinction between a lab-grown model and a living human embryo could become blurred. And because the models lie at the intersection of historically controversial fields — stem cell biology and embryology — the work merits closer oversight than other forms of scientific research, Clark said. Clark and the ISSCR's Embryo Models Working Group in June recommended enhanced oversight of research involving the models. The society's guidelines, which first included guidance on embryo models in 2021, are being revised to incorporate the recommendations of the group and will be released in a few weeks. The current ISSCR guidelines make a distinction between 'integrated embryo models' that replicate the entire embryo, and 'non-integrated models' that replicate just one part of an embryo, requiring stricter oversight of the former. The updated guidelines will instead recommend that all research involving both types of embryo models should undergo 'appropriate ethical and scientific review.' The proposed update will also set out two red lines: The current guidance already prohibits the transfer of human embryo models into a human or animal uterus. The updated version will also advise scientists not use human embryo models to pursue ectogenesis: the development of an embryo outside the human body via the use of artificial wombs — essentially creating life from scratch. According to Clark, the stem cell-based embryo models she and other research teams work on should be considered distinct from research on actual human embryos, usually surplus IVF embryos donated to science. Such research is tightly regulated in many countries, and banned in others, including Germany, Austria and Italy. It makes sense, at least for now, to treat models and real embryos differently, said Emma Cave, a professor of healthcare law at Durham University in the UK who works on embryo models. She uses diamonds as an analogy: Natural diamonds and their commercially lab-grown equivalents are made from the same chemical components, but society assigns them different values. She cautioned there shouldn't be a rush to regulate embryo models too quickly in case it shuts down promising research. 'We are at an early stage in their development, where it could be that in 5, 10, 15, 20 years, that they could look very like a human embryo, or it might be they never get to that stage,' she said. Embryo Scientists Scientists look at a model of an early-stage human embryo created by Israeli scientists at the Weizmann Institute of Science in Rehovot, Israel, September 7, 2023. (Amir Cohen/Reuters via CNN Newsource) A 'Turing test' for embryo models As the scientific research unfolds, oversight of embryo models is taking different shapes in different jurisdictions. Australia has taken the strictest approach. It includes embryo models within the regulatory framework that governs the use of human embryos, requiring a special permit for research. The Netherlands in 2023 similarly proposed treating 'non-conventional embryos' the same as human embryos in the eyes of the law. The proposal is still under discussion, according to the Health Council of the Netherlands. Researchers in the United Kingdom released a voluntary code of conduct in 2024, and Japan has also issued new guidelines governing research in the field. In the United States, embryo models aren't covered by any specific legal framework, and research proposals are considered by individual institutions and funding bodies, Clark noted. The National Institutes of Health said in 2021 that it would consider applications for public funding of research into embryo models on a case-by-case basis and monitor developments to understand the capabilities of these models. Few other countries, however, appear poised to adopt specific legislation on embryo models, making the guidelines issued by the ISSCR a 'highly influential' reference for researchers around the world, according to the Nuffield Council on Bioethics, a London-based organization that advises on ethical issues in biomedicine. The council said in a November 2024 report that international guidelines were key to avoid 'research being carried out that does not meet high ethical and scientific standards; this in turn could impact on the national public perception of risk, leading to a more risk-averse approach that hinders responsible scientific development.' Clark said the ISSCR's updated voluntary guidelines would help scientific funding bodies around the world better evaluate applications and publishers of research understand whether work was performed in an ethically responsible way, particularly in places where the law or other guidelines don't take embryo models into account. The future challenge for regulators is to understand when and whether an embryo model would be functionally the same as a human embryo and therefore potentially afforded the same or similar protection as those surrounding human embryos, said Naomi Moris, group leader at The Francis Crick Institute's developmental models laboratory. The only definitive test would be to transfer the model into the uterus of a surrogate, a move that's forbidden by current bioethical standards. However, Moris is among a group of researchers that has proposed to two tipping points or 'Turing tests' — inspired by computer scientist Alan Turing's way of determining whether machines can think like humans — to evaluate when distinctions between a lab-gown model and a human embryo would disappear. 'These things are not embryos at the moment, they clearly don't have the same capacity as an embryo does. But how would we know ahead of time that we were approaching that?' Moris said. 'That was the logic behind it. What metrics would we use as a kind of proxy for the potential of an embryo model that might then suggest that it was at least approaching the same sorts of equivalency as an embryo.' The first test would measure whether the models can be consistently produced and faithfully develop over a given period as normal embryos would. The second test would assess when animal stem cell embryo models — particularly animals closest to humans such as monkeys — show the potential to form living and fertile animals when transferred into surrogate animal wombs, thus suggesting that the same outcome would in theory be possible for human embryo models. That hasn't happened yet, but Chinese researchers in 2023 created embryo models from the stem cells of macaque monkeys that when implanted in a surrogate monkey triggered signs of early pregnancy. Embryo ethics: A delicate dance Proponents of the technology say the models offer an equally, and possibly more, useful, ethical alternative to research on scarce and precious human embryos. The models have the potential to be produced at scale in a lab to screen drugs for embryo toxicology, a impactful application given that pregnant women have often been excluded from drug trials because of safety concerns. Lab based embryo models A 3D-printed replica of a human embryo model on display as part of an exhibit by The Francis Crick Institute at the Royal Society's Summer Science Exhibition in London earlier this month. The replica is about 500 times bigger than the actual embryo model, which was 0.3 millimeters. (Stephen Potvin via CNN Newsource) Yet, the potential for these models to be used in the creation of life has been cause for worry among bioethicists. 'There are commercial and other groups raising the possibility of building an embryo in vitro and combining different bioengineering approaches to bring such an entity to viability,' according to the June paper coauthored by Clark and other members of the ISSCR's embryo model working group. 'Currently the practice of bringing an SCBEM (stem cell-based embryo model) to viability is considered unsafe and unethical and should not be pursued,' the study noted. Cave said ectogenesis may sound like the realm of science fiction, but it isn't impossible. As embryo models continue to be developed, and separate research is advancing into artificial wombs, the two technologies could meet, Cave said. The challenge, she added, is recognizing the value of these research paths but at the same time preventing misuse. Jun Wu, an associate professor at the Department of Molecular Biology at the University of Texas Southwestern is one of a number of stem cell biologists involved in the field. He agreed that ectogenesis should be off the table but explained that researchers developing embryo models must engage in a delicate dance: To the unlock the mysteries of the human embryo, models have to resemble embryos closely enough to offer real insight but they must not resemble them so closely that they risk being viewed as viable. 'The big black box' — and a breakthrough Magdalena Zernicka-Goetz, the Bren professor of biology and biological engineering at Caltech, said she welcomed the new guidelines. She announced in 2023 that her team had succeeded in a world first: growing embryo-like models to a stage resembling 14-day-old embryos. Later the same year, Jacob Hanna, a professor of stem cell biology and embryology at the Weizmann Institute of Science in Israel, said his team had gone a step further with a model derived from skin cells that showed all the cell types that are essential for an embryo's development — including the precursor of the placenta. Together the work represented a breakthrough for the models' potential use in research on pregnancy loss: At 14 days the human embryo has begun to attach to the lining of the uterus, a process known as implantation. Many miscarriages occur around this stage, Zernicka-Geotz said. Lab research on human embryos beyond 14 days, including those donated from IVF treatments, is prohibited in most jurisdictions. And while some scientists do study tissue obtained from abortions, such tissue is limited because few procedures take place between week 2 and week 4 of an embryo's development. The ability to grow an embryo model outside of a womb at this developmental stage paves the way for studies that are not possible in living human embryos. 'Far more pregnancies fail than succeed during the critical window just before, during and immediately after implantation. This is why we created in my lab the embryo-like structures from stem cells as a way to really understand this critical and so highly fragile stage of development,' Zernicka-Goetz said. Clark agreed that embryo models could potentially be used to address infertility problems: 'Implantation. It's the big black box. Once the embryo implants in the uterus, we understand very little about the development,' Clark added. 'And if we can't study it, we don't know what we're missing.' By Katie Hunt, CNN

Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned
Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned

CNN

time30-07-2025

  • Health
  • CNN

Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned

Scientists are exploring ways to mimic the origins of human life without two fundamental components: sperm and egg. They are coaxing clusters of stem cells – programmable cells that can transform into many different specialized cell types – to form laboratory-grown structures that resemble human embryos. These embryo models are far from perfect replicas. But as labs compete to grow the best likeness, the structures are becoming increasingly complex, looking and behaving in some way as embryos would. The structures could further the study of human development and the causes infertility. However, the dizzying pace of the research, which started little more than a decade ago, is posing ethical, legal and regulatory challenges for the field of developmental biology. 'We could have never anticipated the science would have just progressed like this. It's incredible, it's been transformative how quickly the field has moved, said Amander Clark, a professor of molecular cell and developmental biology at the University of California, Los Angeles, and the founding director of the UCLA Center for Reproductive Science, Health and Education. 'However, as these models advance, it is crucial that they are studied in a framework that balances scientific progress with ethical, legal and social considerations.' Clark is co-chair of the International Society of Stem Cell Research (ISSCR) Embryo Models Working Group, which is now trying to update such a framework on a global scale. At issue is the question of how far researchers could go with these stem cells, given time and the right conditions. Could scientists eventually replicate an actual embryo that has a heartbeat and experiences pain, or one that could grow into a fully developed human model? As current research stands, no model mimics the development of a human embryo in its entirety — nor is any model suspected of having the potential to form a fetus, the next stage in human development equivalent to week 8 or day 56 in a human pregnancy. Creating embryo models has also been a hit-and-miss process for most research groups, with only a small percentage of stem cells going on to self-organize into embryo-like structures. However, the models do exhibit several internal features and cell types that an embryo needs to develop, such as the amnion, yolk sac and primitive streak, and that could, 'with future improvements, eventually progress toward later embryo structures including heart, brain, and other organ rudiments,' according to a June paper coauthored by Clark and published in the journal Stem Cell Reports. Similar models made with mouse cells have reached the point where the brain begins to develop and a heart forms. Nobel laureate Jennifer Doudna tells Fareed about her path to becoming a leading scientist and explains how her discovery of CRISPR can help cure diseases and improve crops. Critically, the goal isn't to develop these models into viable fetuses, ultimately capable of human sentience, but to develop a useful research tool that unlocks the mysteries of how a human cell divides and reproduces to become a human body. The models also make way for experiments that can't be performed on donated embryos in a lab. However, it's possible as research advances that the distinction between a lab-grown model and a living human embryo could become blurred. And because the models lie at the intersection of historically controversial fields — stem cell biology and embryology — the work merits closer oversight than other forms of scientific research, Clark said. Clark and the ISSCR's Embryo Models Working Group in June recommended enhanced oversight of research involving the models. The society's guidelines, which first included guidance on embryo models in 2021, are being revised to incorporate the recommendations of the group and will be released in a few weeks. The current ISSCR guidelines make a distinction between 'integrated embryo models' that replicate the entire embryo, and 'non-integrated models' that replicate just one part of an embryo, requiring stricter oversight of the former. The updated guidelines will instead recommend that all research involving both types of embryo models should undergo 'appropriate ethical and scientific review.' The proposed update will also set out two red lines: The current guidance already prohibits the transfer of human embryo models into a human or animal uterus. The updated version will also advise scientists not use human embryo models to pursue ectogenesis: the development of an embryo outside the human body via the use of artificial wombs — essentially creating life from scratch. According to Clark, the stem cell-based embryo models she and other research teams work on should be considered distinct from research on actual human embryos, usually surplus IVF embryos donated to science. Such research is tightly regulated in many countries, and banned in others, including Germany, Austria and Italy. It makes sense, at least for now, to treat models and real embryos differently, said Emma Cave, a professor of healthcare law at Durham University in the UK who works on embryo models. She uses diamonds as an analogy: Natural diamonds and their commercially lab-grown equivalents are made from the same chemical components, but society assigns them different values. She cautioned there shouldn't be a rush to regulate embryo models too quickly in case it shuts down promising research. 'We are at an early stage in their development, where it could be that in 5, 10, 15, 20 years, that they could look very like a human embryo, or it might be they never get to that stage,' she said. As the scientific research unfolds, oversight of embryo models is taking different shapes in different jurisdictions. Australia has taken the strictest approach. It includes embryo models within the regulatory framework that governs the use of human embryos, requiring a special permit for research. The Netherlands in 2023 similarly proposed treating 'non-conventional embryos' the same as human embryos in the eyes of the law. The proposal is still under discussion, according to the Health Council of the Netherlands. Researchers in the United Kingdom released a voluntary code of conduct in 2024, and Japan has also issued new guidelines governing research in the field. In the United States, embryo models aren't covered by any specific legal framework, and research proposals are considered by individual institutions and funding bodies, Clark noted. The National Institutes of Health said in 2021 that it would consider applications for public funding of research into embryo models on a case-by-case basis and monitor developments to understand the capabilities of these models. Few other countries, however, appear poised to adopt specific legislation on embryo models, making the guidelines issued by the ISSCR a 'highly influential' reference for researchers around the world, according to the Nuffield Council on Bioethics, a London-based organization that advises on ethical issues in biomedicine. The council said in a November 2024 report that international guidelines were key to avoid 'research being carried out that does not meet high ethical and scientific standards; this in turn could impact on the national public perception of risk, leading to a more risk-averse approach that hinders responsible scientific development.' Clark said the ISSCR's updated voluntary guidelines would help scientific funding bodies around the world better evaluate applications and publishers of research understand whether work was performed in an ethically responsible way, particularly in places where the law or other guidelines don't take embryo models into account. The future challenge for regulators is to understand when and whether an embryo model would be functionally the same as a human embryo and therefore potentially afforded the same or similar protection as those surrounding human embryos, said Naomi Moris, group leader at The Francis Crick Institute's developmental models laboratory. The only definitive test would be to transfer the model into the uterus of a surrogate, a move that's forbidden by current bioethical standards. However, Moris is among a group of researchers that has proposed to two tipping points or 'Turing tests' — inspired by computer scientist Alan Turing's way of determining whether machines can think like humans — to evaluate when distinctions between a lab-gown model and a human embryo would disappear. 'These things are not embryos at the moment, they clearly don't have the same capacity as an embryo does. But how would we know ahead of time that we were approaching that?' Moris said. 'That was the logic behind it. What metrics would we use as a kind of proxy for the potential of an embryo model that might then suggest that it was at least approaching the same sorts of equivalency as an embryo.' The first test would measure whether the models can be consistently produced and faithfully develop over a given period as normal embryos would. The second test would assess when animal stem cell embryo models — particularly animals closest to humans such as monkeys — show the potential to form living and fertile animals when transferred into surrogate animal wombs, thus suggesting that the same outcome would in theory be possible for human embryo models. That hasn't happened yet, but Chinese researchers in 2023 created embryo models from the stem cells of macaque monkeys that when implanted in a surrogate monkey triggered signs of early pregnancy. Proponents of the technology say the models offer an equally, and possibly more, useful, ethical alternative to research on scarce and precious human embryos. The models have the potential to be produced at scale in a lab to screen drugs for embryo toxicology, a impactful application given that pregnant women have often been excluded from drug trials because of safety concerns. Yet, the potential for these models to be used in the creation of life has been cause for worry among bioethicists. 'There are commercial and other groups raising the possibility of building an embryo in vitro and combining different bioengineering approaches to bring such an entity to viability,' according to the June paper coauthored by Clark and other members of the ISSCR's embryo model working group. 'Currently the practice of bringing an SCBEM (stem cell-based embryo model) to viability is considered unsafe and unethical and should not be pursued,' the study noted. Cave said ectogenesis may sound like the realm of science fiction, but it isn't impossible. As embryo models continue to be developed, and separate research is advancing into artificial wombs, the two technologies could meet, Cave said. The challenge, she added, is recognizing the value of these research paths but at the same time preventing misuse. Jun Wu, an associate professor at the Department of Molecular Biology at the University of Texas Southwestern is one of a number of stem cell biologists involved in the field. He agreed that ectogenesis should be off the table but explained that researchers developing embryo models must engage in a delicate dance: To the unlock the mysteries of the human embryo, models have to resemble embryos closely enough to offer real insight but they must not resemble them so closely that they risk being viewed as viable. Magdalena Zernicka-Geotz, the Bren professor of biology and biological engineering at Caltech, said she welcomed the new guidelines. She announced in 2023 that her team had succeeded in a world first: growing embryo-like models to a stage resembling 14-day-old embryos. Later the same year, Jacob Hanna, a professor of stem cell biology and embryology at the Weizmann Institute of Science in Israel, said his team had gone a step further with a model derived from skin cells that showed all the cell types that are essential for an embryo's development — including the precursor of the placenta. Together the work represented a breakthrough for the models' potential use in research on pregnancy loss: At 14 days the human embryo has begun to attach to the lining of the uterus, a process known as implantation. Many miscarriages occur around this stage, Zernicka-Geotz said. Lab research on human embryos beyond 14 days, including those donated from IVF treatments, is prohibited in most jurisdictions. And while some scientists do study tissue obtained from abortions, such tissue is limited because few procedures take place between week 2 and week 4 of an embryo's development. The ability to grow an embryo model outside of a womb at this developmental stage paves the way for studies that are not possible in living human embryos. 'Far more pregnancies fail than succeed during the critical window just before, during and immediately after implantation. This is why we created in my lab the embryo-like structures from stem cells as a way to really understand this critical and so highly fragile stage of development,' Zernicka-Goetz said. Clark agreed that embryo models could potentially be used to address infertility problems: 'Implantation. It's the big black box. Once the embryo implants in the uterus, we understand very little about the development,' Clark added. 'And if we can't study it, we don't know what we're missing.'

Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned
Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned

CNN

time30-07-2025

  • Health
  • CNN

Could stem cells be used to create life without sperm or egg? Not yet, but here's why scientists are concerned

Scientists are exploring ways to mimic the origins of human life without two fundamental components: sperm and egg. They are coaxing clusters of stem cells – programmable cells that can transform into many different specialized cell types – to form laboratory-grown structures that resemble human embryos. These embryo models are far from perfect replicas. But as labs compete to grow the best likeness, the structures are becoming increasingly complex, looking and behaving in some way as embryos would. The structures could further the study of human development and the causes infertility. However, the dizzying pace of the research, which started little more than a decade ago, is posing ethical, legal and regulatory challenges for the field of developmental biology. 'We could have never anticipated the science would have just progressed like this. It's incredible, it's been transformative how quickly the field has moved, said Amander Clark, a professor of molecular cell and developmental biology at the University of California, Los Angeles, and the founding director of the UCLA Center for Reproductive Science, Health and Education. 'However, as these models advance, it is crucial that they are studied in a framework that balances scientific progress with ethical, legal and social considerations.' Clark is co-chair of the International Society of Stem Cell Research (ISSCR) Embryo Models Working Group, which is now trying to update such a framework on a global scale. At issue is the question of how far researchers could go with these stem cells, given time and the right conditions. Could scientists eventually replicate an actual embryo that has a heartbeat and experiences pain, or one that could grow into a fully developed human model? As current research stands, no model mimics the development of a human embryo in its entirety — nor is any model suspected of having the potential to form a fetus, the next stage in human development equivalent to week 8 or day 56 in a human pregnancy. Creating embryo models has also been a hit-and-miss process for most research groups, with only a small percentage of stem cells going on to self-organize into embryo-like structures. However, the models do exhibit several internal features and cell types that an embryo needs to develop, such as the amnion, yolk sac and primitive streak, and that could, 'with future improvements, eventually progress toward later embryo structures including heart, brain, and other organ rudiments,' according to a June paper coauthored by Clark and published in the journal Stem Cell Reports. Similar models made with mouse cells have reached the point where the brain begins to develop and a heart forms. Nobel laureate Jennifer Doudna tells Fareed about her path to becoming a leading scientist and explains how her discovery of CRISPR can help cure diseases and improve crops. Critically, the goal isn't to develop these models into viable fetuses, ultimately capable of human sentience, but to develop a useful research tool that unlocks the mysteries of how a human cell divides and reproduces to become a human body. The models also make way for experiments that can't be performed on donated embryos in a lab. However, it's possible as research advances that the distinction between a lab-grown model and a living human embryo could become blurred. And because the models lie at the intersection of historically controversial fields — stem cell biology and embryology — the work merits closer oversight than other forms of scientific research, Clark said. Clark and the ISSCR's Embryo Models Working Group in June recommended enhanced oversight of research involving the models. The society's guidelines, which first included guidance on embryo models in 2021, are being revised to incorporate the recommendations of the group and will be released in a few weeks. The current ISSCR guidelines make a distinction between 'integrated embryo models' that replicate the entire embryo, and 'non-integrated models' that replicate just one part of an embryo, requiring stricter oversight of the former. The updated guidelines will instead recommend that all research involving both types of embryo models should undergo 'appropriate ethical and scientific review.' The proposed update will also set out two red lines: The current guidance already prohibits the transfer of human embryo models into a human or animal uterus. The updated version will also advise scientists not use human embryo models to pursue ectogenesis: the development of an embryo outside the human body via the use of artificial wombs — essentially creating life from scratch. According to Clark, the stem cell-based embryo models she and other research teams work on should be considered distinct from research on actual human embryos, usually surplus IVF embryos donated to science. Such research is tightly regulated in many countries, and banned in others, including Germany, Austria and Italy. It makes sense, at least for now, to treat models and real embryos differently, said Emma Cave, a professor of healthcare law at Durham University in the UK who works on embryo models. She uses diamonds as an analogy: Natural diamonds and their commercially lab-grown equivalents are made from the same chemical components, but society assigns them different values. She cautioned there shouldn't be a rush to regulate embryo models too quickly in case it shuts down promising research. 'We are at an early stage in their development, where it could be that in 5, 10, 15, 20 years, that they could look very like a human embryo, or it might be they never get to that stage,' she said. As the scientific research unfolds, oversight of embryo models is taking different shapes in different jurisdictions. Australia has taken the strictest approach. It includes embryo models within the regulatory framework that governs the use of human embryos, requiring a special permit for research. The Netherlands in 2023 similarly proposed treating 'non-conventional embryos' the same as human embryos in the eyes of the law. The proposal is still under discussion, according to the Health Council of the Netherlands. Researchers in the United Kingdom released a voluntary code of conduct in 2024, and Japan has also issued new guidelines governing research in the field. In the United States, embryo models aren't covered by any specific legal framework, and research proposals are considered by individual institutions and funding bodies, Clark noted. The National Institutes of Health said in 2021 that it would consider applications for public funding of research into embryo models on a case-by-case basis and monitor developments to understand the capabilities of these models. Few other countries, however, appear poised to adopt specific legislation on embryo models, making the guidelines issued by the ISSCR a 'highly influential' reference for researchers around the world, according to the Nuffield Council on Bioethics, a London-based organization that advises on ethical issues in biomedicine. The council said in a November 2024 report that international guidelines were key to avoid 'research being carried out that does not meet high ethical and scientific standards; this in turn could impact on the national public perception of risk, leading to a more risk-averse approach that hinders responsible scientific development.' Clark said the ISSCR's updated voluntary guidelines would help scientific funding bodies around the world better evaluate applications and publishers of research understand whether work was performed in an ethically responsible way, particularly in places where the law or other guidelines don't take embryo models into account. The future challenge for regulators is to understand when and whether an embryo model would be functionally the same as a human embryo and therefore potentially afforded the same or similar protection as those surrounding human embryos, said Naomi Moris, group leader at The Francis Crick Institute's developmental models laboratory. The only definitive test would be to transfer the model into the uterus of a surrogate, a move that's forbidden by current bioethical standards. However, Moris is among a group of researchers that has proposed to two tipping points or 'Turing tests' — inspired by computer scientist Alan Turing's way of determining whether machines can think like humans — to evaluate when distinctions between a lab-gown model and a human embryo would disappear. 'These things are not embryos at the moment, they clearly don't have the same capacity as an embryo does. But how would we know ahead of time that we were approaching that?' Moris said. 'That was the logic behind it. What metrics would we use as a kind of proxy for the potential of an embryo model that might then suggest that it was at least approaching the same sorts of equivalency as an embryo.' The first test would measure whether the models can be consistently produced and faithfully develop over a given period as normal embryos would. The second test would assess when animal stem cell embryo models — particularly animals closest to humans such as monkeys — show the potential to form living and fertile animals when transferred into surrogate animal wombs, thus suggesting that the same outcome would in theory be possible for human embryo models. That hasn't happened yet, but Chinese researchers in 2023 created embryo models from the stem cells of macaque monkeys that when implanted in a surrogate monkey triggered signs of early pregnancy. Proponents of the technology say the models offer an equally, and possibly more, useful, ethical alternative to research on scarce and precious human embryos. The models have the potential to be produced at scale in a lab to screen drugs for embryo toxicology, a impactful application given that pregnant women have often been excluded from drug trials because of safety concerns. Yet, the potential for these models to be used in the creation of life has been cause for worry among bioethicists. 'There are commercial and other groups raising the possibility of building an embryo in vitro and combining different bioengineering approaches to bring such an entity to viability,' according to the June paper coauthored by Clark and other members of the ISSCR's embryo model working group. 'Currently the practice of bringing an SCBEM (stem cell-based embryo model) to viability is considered unsafe and unethical and should not be pursued,' the study noted. Cave said ectogenesis may sound like the realm of science fiction, but it isn't impossible. As embryo models continue to be developed, and separate research is advancing into artificial wombs, the two technologies could meet, Cave said. The challenge, she added, is recognizing the value of these research paths but at the same time preventing misuse. Jun Wu, an associate professor at the Department of Molecular Biology at the University of Texas Southwestern is one of a number of stem cell biologists involved in the field. He agreed that ectogenesis should be off the table but explained that researchers developing embryo models must engage in a delicate dance: To the unlock the mysteries of the human embryo, models have to resemble embryos closely enough to offer real insight but they must not resemble them so closely that they risk being viewed as viable. Magdalena Zernicka-Geotz, the Bren professor of biology and biological engineering at Caltech, said she welcomed the new guidelines. She announced in 2023 that her team had succeeded in a world first: growing embryo-like models to a stage resembling 14-day-old embryos. Later the same year, Jacob Hanna, a professor of stem cell biology and embryology at the Weizmann Institute of Science in Israel, said his team had gone a step further with a model derived from skin cells that showed all the cell types that are essential for an embryo's development — including the precursor of the placenta. Together the work represented a breakthrough for the models' potential use in research on pregnancy loss: At 14 days the human embryo has begun to attach to the lining of the uterus, a process known as implantation. Many miscarriages occur around this stage, Zernicka-Geotz said. Lab research on human embryos beyond 14 days, including those donated from IVF treatments, is prohibited in most jurisdictions. And while some scientists do study tissue obtained from abortions, such tissue is limited because few procedures take place between week 2 and week 4 of an embryo's development. The ability to grow an embryo model outside of a womb at this developmental stage paves the way for studies that are not possible in living human embryos. 'Far more pregnancies fail than succeed during the critical window just before, during and immediately after implantation. This is why we created in my lab the embryo-like structures from stem cells as a way to really understand this critical and so highly fragile stage of development,' Zernicka-Goetz said. Clark agreed that embryo models could potentially be used to address infertility problems: 'Implantation. It's the big black box. Once the embryo implants in the uterus, we understand very little about the development,' Clark added. 'And if we can't study it, we don't know what we're missing.'

Off the Grid: Sally breaks down USA TODAY's daily crossword puzzle, Double Time
Off the Grid: Sally breaks down USA TODAY's daily crossword puzzle, Double Time

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time08-06-2025

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Off the Grid: Sally breaks down USA TODAY's daily crossword puzzle, Double Time

There are spoilers ahead. You might want to solve today's puzzle before reading further! Double Time Constructor: Joe Rodini Editor: Jared Goudsmit ETON (65A: John Gurdon's alma mater) Sir John Gurdon is a developmental biologist. In 2012, he shared the Nobel Prize for Physiology or Medicine with Shinya Yamanaka for their (separate) research on stem-cells. John Gurdon attended ETON College before heading to Christ Church, Oxford to obtain his graduate degrees. Here's a fascinating thing I learned about John Gurdon: When he was in high school, he ranked last in science in a class of 250 boys, and one of his schoolmasters told him he had no chance of becoming a scientist. Well, I'd say he proved that schoolmaster wrong. EVAN (8A: Actress ___ Rachel Wood) EVAN Rachel Wood's acting credits include the role of Delores Abernathy in the HBO TV series Westworld (2016-2022) and Madonna in the movie Weird: The Al Yankovic Story (2022). HERS (13A: Belonging to that woman) and OURS (2D: Belonging to us) Nice use of parallel structure in these two clues. EST (22A: Guinness World Records suffix) Since 1955, Guinness World Records has kept track of a number of records, such as: the LargEST human mattress dominoes (2,355), the HighEST annual earnings for a musician ever (Taylor Swift), and the GreatEST distance travelled with a pool cue balanced on the chin (10,826 ft 9 in). ASPCA (48A: Pet protection org.) The abbreviation of the word organization in the clue alerts solvers that the answer will be an abbreviation – in this case, ASPCA for the American Society for the Prevention of Cruelty to Animals. ASPCA is a nonprofit organization founded in 1866. Its mission is "to provide effective means for the prevention of cruelty to animals throughout the United States." My cat, Willow, says this is a worthy mission indeed. ASL (56A: Language in Deaf West Theatre shows) Productions at the Deaf West Theatre in Los Angeles, California feature deaf and hearing artists, and combine ASL and spoken English. The Deaf West Theatre was founded in 1991. Their performances are "inspired by deaf culture and the expressive power of sign language." In addition to their stage productions, they have collaborated with artists to produce music videos and performances such as Kelly Clarkson's "I Dare You," and Ingrid Michaelson's "Hell No!" (If you need a bit of joy in your day – and who doesn't? – I highly recommend checking out these videos.) NAOMI (63A: "Birdman" actress Watts) Birdman is a 2014 movie about a former Hollywood actor (portrayed by Michael Keaton) who is best known for playing a superhero named Birdman. NAOMI Watts portrays Broadway newcomer Lesley. TYPO (67A: Mistake in this cclue) I will never get tired of TYPO clues; they make me smile every single time. CLERIC (4D: D&D class skilled in divine magic) In the fantasy role-playing game Dungeons & Dragons (D&D), when players create a character they choose a class for that character. Each class gives a character certain perks and abilities. Characters in the CLERIC class can channel divine magic. CHUM (5D: The ___ Bucket ("SpongeBob" restaurant)) On the animated TV series SpongeBob Square Pants, SpongeBob works as a fry cook at the Krusty Krab, a fast food restaurant owned by Mr. Krabs. The CHUM Bucket is a rival restaurant, owned by a one-eyed crustacean named Plankton and his computer wife, Karen. LEGO SET (21D: The 2,022-brick Taj Mahal kit, for example) I like the inclusion of a specific example in this clue. According to the LEGO website, the 2,022-brick Taj Mahal LEGO SET is a retired product (as is a previous 5,923-brick Taj Mahal LEGO SET). Might I interest you instead in a 4,090-brick River Steamboat LEGO SET (for a mere $329.99)? SEA (28D: Poseidon's domain) In Greek mythology, Poseidon is the god of the SEA, storms, earthquakes, and horses. In some tellings, Poseidon became the ruler of the SEA when the world was divided among the three sons of Cronus. Poseidon was given the SEA, Zeus was given the sky, and Hades was given the underworld. ARG (36D: Buenos Aires' country (Abbr.)) Buenos Aires is the capital and most-populous city of Argentina (ARG). It is located on the Río de la Plata, earning it the nickname "The Queen of El Plata." DOHA (37D: Capital of Qatar) DOHA is the capital of Qatar, and is home to over 80% of the country's population. ANI (39D: "32 Flavors" singer DiFranco) "32 Flavors" is a 1995 song by ANI DiFranco. The song's title is a play on Baskin-Robbins' "31 flavors" slogan. WYATT (44D: Labor leader Addie) Addie WYATT (1924-2012) was a civil rights activist as well as a leader in the United States Labor movement. She was one of 12 women named as Time magazine's Women of the Year in 1975, chosen for "speaking out effectively against sexual and racial discrimination in hiring, promotion and pay." AT LAST (46D: Etta James tune with the lyric "My lonely days are over / And life is like a song") "AT LAST" is the title track of Etta James's debut album, which was released in 1960. It became her signature song, and her version of it was inducted into the Grammy Hall of Fame in 1999. "AT LAST" was originally written for a 1941 musical, Sun Valley Serenade. YEOH (55D: "Everything Everywhere All at Once" star Michelle) Michelle YEOH plays the role of Evelyn Quan Wang in the 2022 movie Everything Everywhere All at Once. She also portrays several alternate universe versions of the character. Michele YEOH won a Best Actress Academy Award for this role. COOP (57D: Chicken's house) and AUTO (58D: Sedan or coupe) It's a small thing, but it was fun to fill in the answer "COOP" and then in the next clue see the word "coupe." A couple of other clues I especially enjoyed: PENS (6D: Pocket protectors may hold them) TSA (31D: Org. that deals with a lot of baggage) FREE LUNCH (16A: No-cost meal in an adage) CLOSING NIGHT (26A: Last chance to catch a musical) HIGH QUALITY (45A: Well-made) ABOUT FACE (61A: Complete reversal) DOUBLE TIME: Each word of the theme answers can be paired with the word TIME to create a new phrase: FREE TIME, LUNCH TIME, CLOSING TIME, NIGHTTIME, HIGH TIME, QUALITY TIME, ABOUT TIME, and FACE TIME. It's ABOUT TIME! The theme is ABOUT TIME, that is. It's always DOUBLE the fun when both parts of the theme answers are directly involved in the theme. Thank you, Joe, for this TIMEly puzzle. USA TODAY's Daily Crossword Puzzles Sudoku & Crossword Puzzle Answers This article originally appeared on USA TODAY: Crossword Blog & Answers for June 8, 2025 by Sally Hoelscher

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