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Advancements in in vitro human embryo research prompt a reconsideration of the 14-day rule, highlighting the integration of global religious perspectives, particularly Islam. Through analyzing classical Muslim scholars' perspectives and modern interdisciplinary Islamic bioethical discussions, we advocate extending the 14-day limit to at least 40 days, with specified conditions., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Many writers in bioethics, science, and medicine contend that embryo selection is a morally better way of avoiding genetic disorders then gene editing, as the latter has risks that the former does not. We argue that one reason to use gene editing is that in many cases it would be better for the person who would develop from the edited embryo, so that not to have done it would have been worse for that person. By contrast, embryo selection is never better for the person who develops from the selected embryo. This reason to use gene editing has, however, been challenged on two grounds: first, that it makes no difference, morally, whether a bad effect is worse for someone, or a good effect better for someone; and, second, that beneficent gene editing would not be unequivocally better for the person who would develop from the edited embryo. We argue that both of these objections can be satisfactorily answered and thus that there is indeed a significant moral reason, at least in some cases, to use gene editing rather than embryo selection.

In vivo studies offer a detailed understanding of organism functioning, surpassing the insights provided by in vitro studies. These experiments are crucial for comprehending disease emergence, progression, and associated mechanisms in humans, as well as for developing treatments. When choosing experimental models, factors such as genomic similarity, physiological relevance, ethical appropriateness, and economic feasibility must be considered. Standardized protocols enhance the reliability, and reproducibility of scientific methods, promoting the assessment of research in the scientific literature. Researchers conducting embryo studies should establish and document standardized protocols for increased data comparability. Standardization is vital for scientific validity, reproducibility, and comparability in both in vivo and in vitro studies, ensuring the accuracy and reliability of experimental results and advancing scientific knowledge., (© 2024 The Author(s). Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

In the rapidly moving field of stem cell and embryo research, research questions often sit at the intersection of scientific inquiry and ethical considerations. The International Society for Stem Cell Research (ISSCR) produces guidelines to help navigate decisions in this area. For Cell's 50th Anniversary Focus on Developmental Biology, scientific editor Sarah Geisler discussed the importance of the ISSCR guidelines on stem cell and embryo research for both the stem cell community and the broader public with Amander Clark, Robin Lovell-Badge, and Janet Rossant, who have been involved in the ongoing evolution of the guidelines. A lightly edited transcript of their conversation is shared here., Competing Interests: Declaration of interests Amander T. Clark is President of the International Society for Stem Cell Research (ISSCR) and a past member of the Taskforce Steering Committee to update the ISSCR Guidelines for Stem Cell Research and Translation (2021). She is currently co-Chair of the ISSCR Taskforce to update the 2021 ISSCR Guidelines for Stem Cell Research and Translation regarding research and oversight using stem-cell-based embryo models. Janet Rossant serves on the editorial boards of Cell Stem Cell, Developmental Cell, and Stem Cell Reports. Robin Lovell-Badge serves as President of the Institute of Animal Technology; a co-opted member of the Scientific and Clinical Advances Advisory Committee of the Human Fertilisation and Embryology Authority (HFEA); a member of the Board of Trustees for Sense About Science; a member of the ISSCR Policy Committee (October 2015); Chair of “Genetic Technologies Program” for the Royal Society; Chair of the Board of Trustees for Progress Educational Trust; a member of the External Advisory Board, “Cambridge Reproduction Strategic Research Initiative,” University of Cambridge, UK; a member of “mitoHOPE” Independent Advisory Committee (for Mitochondrial Replacement project centered at Monash University, Australia); and a member of the HDBR Project on “Stem-Cell-Based Embryo Models” Review Panel. He also chaired the Taskforce for the 2021 version of the ISSCR’s Guidelines., (Copyright © 2024. Published by Elsevier Inc.)

Embryo-like structures (ELS) are intended for the study of embryonic development without the use of human supernumerary embryos. Scientists working in countries that do not allow research on embryos hope that these structures will replace natural embryos. The interest in ELS is largely based on two misconceptions: the belief that there is a shortage of research embryos and the belief that research on ELS will make research on natural embryos redundant. This paper argues that research efforts should be refocused on natural embryos., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A human embryo's legal definition and its entitlement to protection vary greatly worldwide. Recently, human pluripotent stem cells have been used to form in vitro models of early embryos that have challenged legal definitions and raised questions regarding their usage. In this light, we propose a refined legal definition of an embryo, suggest "tipping points" for when human embryo models could eventually be afforded similar protection to that of embryos, and then revisit basic ethical principles that might help to draft a roadmap for the gradual, justified usage of embryo models in a manner that aims to maximize benefits to society., Competing Interests: Declaration of interests N.C.R. is an inventor on the patents “Blastoid, cell line based artificial blastocyst” (EP2986711) and “Blastocyst-like cell aggregate and methods” (EP21151455.9) that are both licensed to dawn-bio, a company he co-founded. A.M.A. and N.M. are inventors on the patents "Polarised three-dimensional cellular aggregates” (PCT/GB2019/052668) and “human polarised three-dimensional cellular” (PCT/GB2019/052670), maintained by Cambridge Enterprise., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

The article aims to elaborate the progress made in partial ectogenesis research on sheep as well as human embryos. Since the ban on embryos experimentation after the 14-day window is a major roadblock in terms of partial ectogenesis research, the authors have weighed the possibility that such a ban could be reconsidered. In favor of easing such a restriction, it may be argued that: (a) unlike the Catholic approach, prevalent ethics precepts hold that the embryo's interest ought to be balanced against the interests of the other parties involved; (b) an extension of the 14-day deadline would no longer make ethically untenable practices acceptable; hence, the "slippery slope" argument, although generally worthy, would not conclusively apply to partial ectogenesis; (c) in mainstream embryo research efforts, there is a conflict between the lives of embryos and the health of individuals already born; as for partial ectogenesis, however, such a conflict would be between the lives of embryos and the lives of fetuses which would not survive otherwise. Still, in light of the embryo's status as a human being, the authors conclude that such research practices should only be allowed on supernumerary embryos.

Abstract: The paper addresses the issue of the legality and ethical admissi-bility of invasive experiments on embryos and the correlated one of the degree of legal protection and dignity to be recognized for human embryos, particularly in light of the growing importance that scientific research on embryonic stem cells has been gaining from the clinical and biomedical standpoints in the therapeutic treatments of diseases so far considered incurable, in the interest of public health. Furthermore, the issue of experimentation on cryopreserved supernumerary human embryos is still extremely polarizing, which makes it harder to arrive at shared solutions. The author hopes for a broad-ranging debate at the international level, for the ultimate purpose of achieving shared regulatory frameworks.

Programs should create and enforce written policies addressing the designation, retention, and disposal of unclaimed embryos. In the absence of program-specific policies, it is ethically permissible for a program or facility to consider embryos to have been unclaimed if a reasonable period of time has passed since contact with an individual or couple; efforts as outlined in the consent form have been made to contact the individual or couple; and no written instructions from the individual or couple with dispositional control exist concerning disposition. In such cases, programs or facilities may dispose of unclaimed embryos by removing them from storage and thawing without transfer. In the absence of specific written instructions, unclaimed embryos may not be donated to others for reproductive use or be used in research. This statement replaces the American Society for Reproductive Medicine Ethics Committee document "Disposition of Abandoned Embryos" published in 2013., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

The experimental production of complex structures resembling mammalian embryos (e.g., blastoids, gastruloids) from pluripotent stem cells in vitro has become a booming research field. Since some of these embryoid models appear to reach a degree of complexity that may come close to viability, a broad discussion has set in with the aim to arrive at a consensus on the ethical implications with regard to acceptability of the use of this technology with human cells. The present text focuses on aspects of the gain of organismic wholeness of such stem cell-derived constructs, and of autonomy of self-organization, raised by recent reports on blastocyst-like cysts spontaneously budding in mouse stem cell cultures, and by previous reports on likewise spontaneous formation of gastrulating embryonic disc-like structures in primate models. Mechanisms of pattern (axis) formation in early embryogenesis are discussed in the context of self-organization of stem cell clusters. It is concluded that ethical aspects of development of organismic wholeness in the formation of embryoids need to receive more attention in the present discussions about new legal regulations in this field.

The newly revised 2021 ISSCR Guidelines for Stem Cell Research and Clinical Translation includes scientific and ethical guidance for the transfer of human pluripotent stem cells and their direct derivatives into animal models. In this white paper, the ISSCR subcommittee that drafted these guidelines for research involving the use of nonhuman embryos and postnatal animals explains and summarizes their recommendations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The ISSCR Guidelines for Stem Cell Research and Clinical Translation were last revised in 2016. Since then, rapid progress has been made in research areas related to in vitro culture of human embryos, creation of stem cell-based embryo models, and in vitro gametogenesis. Therefore, a working group of international experts was convened to review the oversight process and provide an update to the guidelines. This report captures the discussion and summarizes the major recommendations made by this working group, with a specific emphasis on updating the categories of review and engagement with the specialized scientific and ethical oversight process., Competing Interests: Conflicts of interest Amander T. Clark is a board member of the ISSCR and a Scientific Advisory Board member of the Tepper Foundation. Ali Brivanlou is a co-founder or OvaNova Inc., as well as a co-founder of Rumi Scientific Inc. Debra Mathews is a member of the Maryland Stem Cell Research Commission and a paid Academic Collaborator of the National Academy of Medicine's Committee on Emerging Science, Technology, and Innovation in Health and Medicine. Nicolas Rivron is an inventor on two patents describing the blastoid technology (EP2986711 and EP21151455.9). He has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Program ERC-Co grant agreement no. 101002317. Mitinori Saitou is an inventor on patent applications relating to the induction of germ cells from PSCs filed by Kyoto University. Janet Rossant is a member of the Board of Directors of Notch Therapeutics; a member of the editorial board of Stem Cell Reports; and a member of the editorial board of Cell Stem Cell., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

In this article, we discuss the ethics of human embryoids, i.e., embryo-like structures made from pluripotent stem cells for modeling natural embryos. We argue that defining our social priorities is critical to design a consistent ethical guideline for research on those new entities. The absence of clear regulations on these emerging technologies stems from an unresolved debate surrounding natural human embryo research and one common opinion that one needs to solve the question of the moral status of the human embryo before regulating their surrogate. The recent NIH funding restrictions for research on human embryoids have made scientists even more unlikely to raise their voices. As a result, the scientific community has maintained a low profile while longing for a more favorable socio-political climate for their research. This article is a call for consistency among biomedical research on human materials, trying to position human embryoids within a spectrum of existing practice from stem cell research or IVF to research involving human subjects. We specifically note that the current practices in infertility clinics of freezing human embryos or disposing of them without any consideration for their potential benefits contradicts the assumption of special consideration for human material. Conversely, creating human embryoids for research purposes could ensure that no human material be used in vain, always serving humankind. We argue here that it is time to reconsider the full ban on embryo research (human embryos and embryoids) beyond the 14-day rule and that research on those entities should obey a sliding scale combining the completeness of the model (e.g., complete vs. partial) and the developmental stage: with more advanced completeness and developmental stage of the considered entity, being associated with more rigorous evaluation of societal benefits, statements of intention, and necessity of such research.

Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the "gastruloid," which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos. But fitting an ambiguous object into an existing category with well-worn pathways in research ethics, like the embryo, is only a temporary fix. The bigger problem is that we no longer know what an embryo is. We haven't had a non-absurd definition of 'embryo' for several decades and without a well-defined comparison class, asking whether gastruloids belong to the morally relevant class of things we call embryos is to ask a question without an answer. What's the alternative? A better approach needs to avoid what I'll refer to as "the potentiality trap" and, instead, rely on the emergence of morally salient facts about gastruloids and other synthetic embryos.

Recent scientific advances have indicated that it may be technically feasible to sustain human embryos in vitro beyond 14 days. Research beyond this stage is currently restricted by a guideline known as the 14-day rule. Since the advances in embryo culturing there have been calls to extend the current limit. Much of the current debate concerning an extension has regarded the 14-day rule as a political compromise and has, therefore, focused on policy concerns rather than assessing the philosophical foundations of the limit. While there are relevant political considerations, I maintain that the success of extension arguments will ultimately depend on the strength of the justifications supporting the current 14-day limit. I argue that the strongest and most prevalent justifications for the 14-day rule-an appeal to individuation and neural development-do not provide adequate support for the limit of 14 days. I instead suggest that an alternative justification based on sentience would constitute a more defensible basis for embryo protection and that a consideration of such grounds appears to support an amendment to the current limit, rather than the retention of it. While these conclusions do not establish conclusively that the current limit should be extended; they do suggest that an extension may be warranted and permissible. As such, this paper offers grounds on which a reassessment of the 14-day rule may be justified.

Many controversies in bioethics turn on questions of moral status. Some moral status issues have received extensive bioethical attention, including those raised by abortion, embryo experimentation, and animal research. Beyond these established debates lie a less familiar set of moral status issues, many of which are tied to recent scientific breakthroughs. This review article surveys some key developments that raise moral status issues, including the development of in vitro brains, part-human animals, "synthetic" embryos, and artificial womb technologies. It introduces the papers in this Special Issue, contextualises their contributions to the moral status literature, and highlights some enduring challenges of determining the moral status of novel types of beings.

Background: Studying the human peri-implantation period remains hindered by the limited accessibility of the in vivo environment and scarcity of research material. As such, continuing efforts have been directed towards developing embryo-like structures (ELS) from pluripotent stem cells (PSCs) that recapitulate aspects of embryogenesis in vitro. While the creation of such models offers immense potential for studying fundamental processes in both pre- and early post-implantation development, it also proves ethically contentious due to wide-ranging views on the moral and legal reverence due to human embryos. Lack of clarity on how to qualify and regulate research with ELS thus presents a challenge in that it may either limit this new field of research without valid grounds or allow it to develop without policies that reflect justified ethical concerns., Objective and Rationale: The aim of this article is to provide a comprehensive overview of the existing scientific approaches to generate ELS from mouse and human PSCs, as well as discuss future strategies towards innovation in the context of human development. Concurrently, we aim to set the agenda for the ethical and policy issues surrounding research on human ELS., Search Methods: The PubMed database was used to search peer-reviewed articles and reviews using the following terms: 'stem cells', 'pluripotency', 'implantation', 'preimplantation', 'post-implantation', 'blastocyst', 'embryoid bodies', 'synthetic embryos', 'embryo models', 'self-assembly', 'human embryo-like structures', 'artificial embryos' in combination with other keywords related to the subject area. The PubMed and Web of Science databases were also used to systematically search publications on the ethics of ELS and human embryo research by using the aforementioned keywords in combination with 'ethics', 'law', 'regulation' and equivalent terms. All relevant publications until December 2019 were critically evaluated and discussed., Outcomes: In vitro systems provide a promising way forward for uncovering early human development. Current platforms utilize PSCs in both two- and three-dimensional settings to mimic various early developmental stages, including epiblast, trophoblast and amniotic cavity formation, in addition to axis development and gastrulation. Nevertheless, much hinges on the term 'embryo-like'. Extension of traditional embryo frameworks to research with ELS reveals that (i) current embryo definitions require reconsideration, (ii) cellular convertibility challenges the attribution of moral standing on the basis of 'active potentiality' and (iii) meaningful application of embryo protective directives will require rethinking of the 14-day culture limit and moral weight attributed to (non-)viability. Many conceptual and normative (dis)similarities between ELS and embryos thus remain to be thoroughly elucidated., Wider Implications: Modelling embryogenesis holds vast potential for both human developmental biology and understanding various etiologies associated with infertility. To date, ELS have been shown to recapitulate several aspects of peri-implantation development, but critically, cannot develop into a fetus. Yet, concurrent to scientific innovation, considering the extent to which the use of ELS may raise moral concerns typical of human embryo research remains paramount. This will be crucial for harnessing the potential of ELS as a valuable research tool, whilst remaining within a robust moral and legal framework of professionally acceptable practices., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Research using human embryos and embryoids has expanded in recent years due to technological advances. Surveying laws and guidelines among the top research and development (R&D) investing nations highlights existing barriers to expanding this area of research. Of the 22 nations surveyed, we found 12 countries with a 14-day limit, one with a seven-day limit, five with prohibitions and four without national laws or guidelines that limit or prohibit human embryo research. Sixteen national laws or guidelines define an embryo or related entities, with five nations limiting human embryoid research. Other laws are ambiguous in relation to embryoid research, leave unanswered questions regarding what research is permitted or restricted and need additional clarity for researchers.

In the event that human embryo genome editing is considered safe enough for the clinic, researchers will need to consider how to administer consent so that would-be recipients of edited embryos can make an informed decision. Informed consent will require truthfulness, sensitivity, regulatory compliance, and attention to the highest ethical standards., (Copyright © 2020 The Author. Published by Elsevier Inc. All rights reserved.)

Over the past 10 years' significant research developments have taken place on human pluripotent stem cells and human embryonic stem cells to exploit the future potential in gene therapy and other focused treatments. There remains concerns around ethics of research and the fate of the human embryo used in such studies. European Board and College of Obstetrics and Gynaecology urge upon all scientists and the research bodies to adhere to the highest ethical principles of confidentiality and their actions should meet the criteria as set out by the international society for stem cell research., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In July 2018, the Nuffield Council on Bioethics released the report Genome editing and human reproduction: Social and ethical issues, concluding that human germline modification of human embryos for implantation is not 'morally unacceptable in itself' and could be ethically permissible in certain circumstances once the risks of adverse outcomes have been assessed and the procedure appears 'reasonably safe'. The Nuffield Council set forth two main principles governing anticipated uses and envisions applications that may include health enhancements as a public health measure. This essay provides a critique of three aspects in the Nuffield Council's Report: its presumption of therapeutic efficacy, its inflation of parental rights to create a certain type of child, and its reliance on a specially commissioned report that appears to distort key definitions in international law., (© 2020 John Wiley & Sons Ltd.)

Over the past few years, a number of research groups have reported striking progress on the generation of in vitro models from mouse and human stem cells that replicate aspects of early embryonic development. Not only do these models reproduce some key cell fate decisions but, especially in the mouse system, they also mimic the spatiotemporal arrangements of embryonic and extraembryonic tissues that are required for developmental patterning and implantation in the uterus. If such models could be developed for the early human embryo, they would have great potential benefits for understanding early human development, for biomedical science, and for reducing the use of animals and human embryos in research. However, guidelines for the ethical conduct of this line of work are at present not well defined. In this Forum article, we discuss some key aspects of this emerging area of research and provide some recommendations for its ethical oversight., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Scientific research using human embryos advances human health and offspring well-being and provides vital insights into the mechanisms for reproduction and disease. Research involving human embryos is ethically acceptable if it is likely to provide significant new knowledge that may benefit human health, well-being of the offspring, or reproduction., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)