The regulation of human blastoid research: A bioethical discussion of the limits of regulation.

The creation of human blastoids holds great potential for research on early human development but also raises considerations about the ethics of such research and its regulation.

Stem cell-derived embryo models: moral advance or moral obfuscation?

Stem cell-derived embryo models (SCEMs) are model embryos used in scientific research to gain a better understanding of early embryonic development. The way humans develop from a single-cell zygote to a complex multicellular organism remains poorly understood. However, research looking at embryo development is difficult because of restrictions on the use of human embryos in research. Stem cell embryo models could reduce the need for human embryos, allowing us to both understand early development and improve assisted reproductive technologies. There have been several rapid advances in creating SCEMs in recent years. These advances potentially provide a new avenue to study early human development. The benefits of SCEMs are predicated on the claim that they are different from embryos and should, therefore, be exempt from existing regulations that apply to embryos (such as the 14-day rule). SCEMs are proposed as offering a model that can capture the inner workings of the embryo but lack its moral sensitivities. However, the ethical basis for making this distinction has not been clearly explained. In this current controversy, we focus on the ethical justification for treating SCEMs differently to embryos, based on considerations of moral status.

The Donation of Human Biological Material for Brain Organoid Research: The Problems of Consciousness and Consent.

Human brain organoids are three-dimensional masses of tissues derived from human stem cells that partially recapitulate the characteristics of the human brain. They have promising applications in many fields, from basic research to applied medicine. However, ethical concerns have been raised regarding the use of human brain organoids. These concerns primarily relate to the possibility that brain organoids may become conscious in the future. This possibility is associated with uncertainties about whether and in what sense brain organoids could have consciousness and what the moral significance of that would be. These uncertainties raise further concerns regarding consent from stem cell donors who may not be sufficiently informed to provide valid consent to the use of their donated cells in human brain organoid research. Furthermore, the possibility of harm to the brain organoids raises question about the scope of the donor's autonomy in consenting to research involving these entities. Donor consent does not establish the reasonableness of the risk and harms to the organoids, which ethical oversight must ensure by establishing some measures to mitigate them. To address these concerns, we provide three proposals for the consent procedure for human brain organoid research. First, it is vital to obtain project-specific consent rather than broad consent. Second, donors should be assured that appropriate measures will be taken to protect human brain organoids during research. Lastly, these assurances should be fulfilled through the implementation of precautionary measures. These proposals aim to enhance the ethical framework surrounding human brain organoid research.

Promises and rules: The implications of rethinking the 14-day rule for research on human embryos.

Removing the 14-day limit for research on human embryos without public deliberation could jeopardize public trust in and support of research on human development.

Animus: human-embodied animals.

We review recent research to introduce human brain organoids into the brains of infant rats. This research shows these organoids integrate and function to affect behaviour in rats. We argue that this raises issues of moral status that will imminently arise and must be addressed through functional studies of these new life forms. We situate this research in the broader context of the biological revolution, arguing we already have the technological power to create fully human embodied animals. This raises profound, so far unaddressed ethical issues which call for urgent attention.

The moral status of human embryo-like structures: potentiality matters?: The moral status of human synthetic embryos.

New techniques to generate and culture embryo-like structures from stem cells require a more fine-grained distinction of potential to define the moral status of these structures.

The moral value of induced pluripotent stem cells: a Japanese bioethics perspective on human embryo research.

In contemporary Japan, at least in the field of regenerative medicine, human induced pluripotent stem cells (hiPSCs) are given no moral status and are treated in a purely instrumental way. However, some authors have mentioned the potentiality of hiPSCs in that 'tetraploid complementation' would make it possible to create humans directly from human embryonic stem cells (hESCs) and hiPSCs. A blastocyst consists of inner cell mass (ICM) cells and a trophoblast. The tetraploid complementation technique demonstrates that hESCs and hiPSCs both have the same capacity as ICM cells. If ICM cells, hESCs and hiPSCs were all provided with a trophoblast or a substitute with the same function, which would work as a placenta, they would have the same potential to develop into embryos, fetuses and adult human beings. Thus hiPSCs could be regarded as potential humans. However, no authority or guideline in Japan has specifically considered the status and use of hiPSCs. In this paper, I will address the extent to which the existing recommendations apply to hiPSCs and develop a novel Japanese bioethical perspective on the status of hiPSCs and its implications for hiPSC research, based on the reasoning in the report, 'The fundamental way of thinking in treating the human embryo' presented by the Bioethics Committee of the Council for Science and Technology Policy in 2004, and broader consideration of Japanese culture.

Navigating equity in global access to genome therapy expanding access to potentially transformative therapies and benefiting those in need requires global policy changes.

In December 2023, the US Food and Drug Administration and the UK Medicines and Healthcare Products Regulatory Agency granted the first regulatory approval for genome therapy for sickle cell disease. This approval brings hope to those suffering from this debilitating genetic disease. However, several barriers may hinder global patient access, including high treatment costs, obtaining informed consent for minors, inadequate public health infrastructure, and insufficient regulatory oversight. These barriers reflect the structural inequalities inherent in global health governance, where patient access often depends on social and institutional arrangements. This article addresses concerns around informed consent, treatment costs, and patient access, and proposes corresponding policy reforms. We argue that these discussions should be framed within a broader global context that considers social and institutional structures, global research priorities, and a commitment to health equity.

Evaluating neuroprivacy concerns in human brain organoid research.

Neuroprivacy, or the privacy of neural data, has attracted considerable interest. Here, we explore the implications of neuroprivacy in human brain organoid research, detailing different interpretations of this right. Findings suggest a limited connection between neuroprivacy and brain organoid research, underscoring the importance of further examination of this critical issue.

Human genome editing in clinical applications: Japanese lay and expert attitudes.

Background: The world's first gene-edited babies, reported by the Chinese scientist He Jiankui, prompted an outcry of criticism and concerns worldwide over the use of genome editing for reproductive purposes. Many countries and academic associations opposed to heritable genome editing (HGE) called for public discussion involving various stakeholders. To hold a discussion of this nature and form a consensus concerning HGE, we must understand under what conditions stakeholders consider HGE acceptable and the reasons for which they deem it unacceptable. Methods: Laypeople and researchers were surveyed in May 2019. They were asked about the degree of their acceptance toward somatic genome editing (SGE) and HGE; those who answered "acceptable depending on the purpose" were queried further regarding their acceptance in the contexts of specific clinical purposes. Results: Responses were obtained from 4,424 laypeople and 98 researchers. The percentage of respondents choosing each option in attitudes to HGE was, from largest to smallest: "acceptable depending on purpose" (laypeople 49.3%; researchers 56.1%), "not acceptable for any purpose" (laypeople 45.8%; researchers 40.8%), and "acceptable for any purpose" (laypeople 5.0%; researchers 3.1%). In an additional question for those who answered "acceptable depending on the purpose," laypeople found the following purposes acceptable: infertility treatment (54.5%), treatment of life-threatening diseases (52.2%), and treatment of debilitating diseases (51.4%). Meanwhile, the degree of acceptance for enhancement purposes was 10.7, 7.9, 6.2, and 5.5% for physical, cognitive, health, and personality enhancements, respectively. In contrast, acceptance among the researchers was 94.5% and 92.7% for the treatment of life-threatening and debilitating diseases, respectively, compared with 69.1% for infertility treatment. Researchers' acceptance for enhancement purposes was similar to that of the lay participants, with 12.7, 9.1, 10.9, and 5.5% for physical, cognitive, health, and personality enhancement, respectively. Conclusion: In the past, debates regarding the acceptability of human genome editing in clinical applications tend to focus on HGE in many countries. Society will now need to debate the acceptability of both types of human genome editing, HGE and SGE.

The Ethics of Human Brain Organoid Transplantation in Animals.

In this paper, we outline how one might conduct a comprehensive ethical evaluation of human brain organoid transplantation in animals. Thus far, ethical concerns regarding this type of research have been assumed to be similar to those associated with other transplants of human cells in animals, and have therefore not received significant attention. The focus has been only on the welfare, moral status, or mental capacities of the host animal. However, the transplantation of human brain organoids introduces several new ethical issues. Many of these are related to uncertainty regarding whether or not brain organoids might be conscious. While these concerns might not be immediately relevant, they warrant closer scrutiny. We discuss how various ethical issues are relevant to different stages of human brain organoid transplantation and can guide the ethical evaluation of research. Our examination would broaden the horizons of the debate on the transplantation of brain organoids.

Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications.

Epigenome editing offers ethical advantages with non-inheritable gene expression control. However, concerns arise regarding potential transgenerational effects in humans. Ethical and regulatory evaluation is crucial, considering recent advancements and enhanced understanding of transgenerational epigenetics in both mammals and humans.

Genome editing of human embryos for research purposes: Japanese lay and expert attitudes.

Background: Multiple surveys of the general public and experts on human genome editing have been conducted. However, many focused only on editing in clinical applications, with few regarding its use for basic research. Given that genome editing for research purposes is indispensable for the realization of clinical genome editing, understanding lay attitudes toward genome editing in research, particularly using human embryos, which is likely to provoke ethical concerns, is helpful for future societal discussion. Methods: An online survey was conducted with Japanese laypeople and researchers to ascertain their views regarding human genome editing for research purposes. Participants were queried about their acceptance as a function of the target of genome editing (germ cells, surplus IVF embryos, research embryos, somatic cells); then, those who answered "acceptable depending on the purpose" were asked about their acceptance in the context of specific research purposes of genome editing. Participants were also asked about their expectations and concerns regarding human genome editing. Results: Replies were obtained from 4,424 laypeople and 98 researchers. Approximately 28.2-36.9% of the laypeople exhibited strong resistance to genome editing for research purposes regardless of their applications. In contrast, 25.5% of the researchers demonstrated resistance only to genome editing in research embryos; this percentage was substantially higher than those concerning the other three targets (5.1-9.2%). Approximately 50.4-63.4% of laypeople who answered "acceptable depending on the purpose" approved germline genome editing for disease research; however, only 39.3-42.8% approved genome editing in basic research to obtain biological knowledge. In contrast, the researchers displayed a lower degree of acceptance of germline genome editing for research purposes related to chronic diseases (60.9-66.7%) than for other research purposes (73.6-90.8%). Analysis of responses concerning expectations and concerns indicated that laypeople who would not accept genome editing of human embryos did not necessarily worry about "instrumentalization of the embryo." They also had substantially low expectations for recognized advantages of genome editing, including "advances in science" and "reduction of intractable diseases," compared with other groups of respondents. Conclusion: The assumptions shared among experts in conventional bioethical debates and policy discussions on human genome editing are not self-evident to laypeople.

The legal personhood of human brain organoids.

Research using three-dimensional neural tissues derived from human pluripotent stem cells-known as 'human brain organoids'-has progressed rapidly in recent years. Although related ethical issues have been intensively discussed, legal issues have only been sparsely examined compared with the related ethical issues. In this paper, we explore a fundamental issue concerning the legal status of human brain organoids: whether they can be considered legal persons. We clearly distinguish between two types of legal personhood: 'natural person' as a human legal person and 'juridical person' as a nonhuman legal person. By examining natural and juridical personhood separately, we point out the bias and confusion in the remarks on the legal personhood of human brain organoids and provide a more comprehensive picture of the problem.

The importance of accurate representation of human brain organoid research.

Representations of brain organoids in the media are often negatively or positively exaggerated without appropriate discussion. Here, we examine two topics (the possibility of consciousness and medical applications) and call on scientists, ethicists, and the media to represent brain organoid research and its ethical issues more accurately.

The technology, opportunities, and challenges of Synthetic Biological Intelligence.

Integrating neural cultures developed through synthetic biology methods with digital computing has enabled the early development of Synthetic Biological Intelligence (SBI). Recently, key studies have emphasized the advantages of biological neural systems in some information processing tasks. However, neither the technology behind this early development, nor the potential ethical opportunities or challenges, have been explored in detail yet. Here, we review the key aspects that facilitate the development of SBI and explore potential applications. Considering these foreseeable use cases, various ethical implications are proposed. Ultimately, this work aims to provide a robust framework to structure ethical considerations to ensure that SBI technology can be both researched and applied responsibly.