SUMMARY
- Human brain organoids are three-dimensional neural tissues grown from human pluripotent stem cells. They reproduce selected cellular, molecular and organisational features of the developing human brain. They do not constitute miniature human brains, whole human organisms, or persons. Current organoids are immature, incomplete and highly variable. They lack the integrated sensory, vascular, immune, endocrine and bodily systems of a living human being.
- Brain organoids can assist research into human brain development, neurological and psychiatric disorders, infection, cancer, drug safety and precision medicine. They may reduce dependence on animal models and permit research that cannot readily be conducted in living persons. Their use may also involve transplantation into animals, complex assemblies of different neural tissues, prolonged culture, and connections to recording or computational systems.
- These developments raise ethical, legal and social issues. The issues include the procurement and use of human biological materials; consent for research whose future applications cannot be completely specified; the privacy of genetic, clinical and organoid-derived data; ownership and commercialisation; research involving transplantation into animals; public understanding; and the possibility that future organoids could develop capacities that warrant special moral consideration.
- The BAC does not consider that current human brain organoids should be regarded as human persons. Neural activity, including electrical oscillations, does not by itself establish consciousness, sentience, pain, memory, self-awareness or legal personhood. Nevertheless, because the purpose of some research is to produce more mature and functionally complex neural models, the possibility of morally significant capacities should be monitored. The appropriate response is neither to assume that all organoids are conscious nor to disregard the possibility of welfare concerns if relevant scientific indicators emerge.
- Existing requirements concerning human biomedical research, human biological material, personal information, animal research and institutional ethics review provide an important foundation for governance. The BAC considers that further guidance may be needed to apply those requirements coherently to human brain organoid research, especially where research involves advanced maturation, attempts to model consciousness or pain, transplantation into animal nervous systems, or computational coupling.
- This Paper sets out background information, identifies particular issues and advances preliminary views where these may reasonably be made. The BAC invites public feedback, especially on the proposed approach to consent, review, monitoring, transparency and public engagement. The preliminary views in this Paper are intended to facilitate discussion and do not necessarily represent the final recommendations which the BAC may make to the Government.
1. Introduction
About this Paper and the consultation process
1.1. This Consultation Paper on Human Brain Organoid Research (the “Paper”) is issued by the Bioethics Advisory Committee, Singapore (BAC) as part of its efforts to obtain professional and public feedback on the issues outlined in this Paper. The feedback and suggestions received by the BAC will help inform and shape the recommendations that the BAC may make to the Government.
1.2. Human brain organoid research is a broad and rapidly developing field. This Paper is not intended as an exhaustive survey of all scientific, ethical or legal questions that could arise. It focuses on issues that require consideration as a matter of priority because they concern the proper acquisition and use of human biological material, the responsible conduct of research, the welfare of animals, public confidence, and the possibility of future moral uncertainty.
1.3. The Paper does not address stem-cell-based embryo models as a subject of regulation. It also does not seek to regulate all organoid research. Its subject is human brain organoid research, including related neural assembloids, transplantation of human brain organoids or organoid-derived neural tissue into animals, and the use of such organoids in recording or computational systems where those uses raise distinctive ethical questions.
1.4. The BAC has advanced preliminary views on issues where it considers that a principled approach can reasonably be stated. The BAC invites views, comments, suggestions and other feedback on these preliminary views, as well as on other matters identified in this Paper.
1.5. The preliminary views in this Paper are intended primarily as a springboard for professional and public discussion. They do not necessarily represent the final recommendations which the BAC may make to the Government.
2. Definitions
2.1. In this Paper, “human brain organoid” means a three-dimensional cellular system generated from human pluripotent stem cells and intended to model selected features of developing human neural tissue. The term includes cerebral organoids and patterned neural organoids. It may include an “assembloid”, where two or more organoids or neural tissues are combined in order to model interactions between brain regions or other neural tissues.
2.2. “Human biological material” includes cells, tissues and cell lines from which a human brain organoid is generated, including embryonic stem cells and induced pluripotent stem cells.
2.3. “Organoid intelligence” is used in this Paper to describe exploratory research in which organoids are coupled to electrodes, sensors, robotic devices, software or other computational systems in order to investigate information processing, learning-like responses or biocomputing. The use of this term does not imply that an organoid is intelligent or conscious in a human sense.
2.4. “Consciousness” is used in different ways in scientific and philosophical discussion. For the purposes of this Paper, it refers broadly to subjective experience. “Sentience” refers to a capacity for experiences with positive or negative valence, including pain or distress. Neither term should be inferred merely from the presence of neural activity.
3. Formulating principles
3.1. Biomedical research involving human brain organoids holds the prospect of important benefits. It may improve understanding of disease and support the development of treatments for serious disorders. At the same time, it requires society to consider how human-derived neural tissue should be acquired, used, governed and described.
3.2. The ethical principles applicable to human biomedical research remain relevant. These include respect for persons, the protection of privacy and confidentiality, justice, scientific integrity, proportionality, transparency, accountability and the promotion of social benefit. These principles must be applied in a manner that recognises the distinctive features of human brain organoids without presuming that they are equivalent to human beings.
3.3. The BAC considers that governance should be proportionate to the nature of the proposed research. Research with well-characterised, immature organoids for ordinary disease modelling may not require the same safeguards as research that seeks to prolong maturation, increase complex integration, induce potentially aversive states, transplant neural tissue into an animal nervous system, or connect organoids to systems designed to train learning-like behaviour.
3.4. In rapidly developing fields, scientific uncertainty should not be used either as a reason for blanket prohibition or as a reason for ethical inaction. Measures should be capable of revision as knowledge improves. Clear ethical guidance may enable responsible research by providing researchers, institutions, donors and the public with a common framework for decision-making.
4. HUMAN BRAIN ORGANOID RESEARCH
The role and promise of human brain organoid research
4.1. Human brain organoids are generated by guiding human pluripotent stem cells to differentiate into neural cell types and to organise into three-dimensional structures. Depending on the method used, an organoid may reproduce selected features of a particular brain region or may contain a mixture of neural tissues. They can contain neurons and supporting cells and may show forms of electrical activity [1-3].
4.2. Human brain organoids provide models of developmental processes that are difficult to study directly in human beings. They have been used to investigate neurodevelopmental disorders, neurodegenerative conditions, epilepsy, brain tumours, infectious disease and the effects of genetic variants. They may enable screening of medicines and the study of individual disease mechanisms using patient-derived cells [1,4].
4.3. The scientific value of organoids is linked to their limitations. Current organoids do not reproduce a complete brain. They are generally developmentally immature and lack many of the anatomical and physiological features of a brain in a living body. There remain important challenges in reproducibility, vascularisation, cell diversity, maturation, connectivity and interpretation of activity recordings [1,3].
4.4. For these reasons, a brain organoid should not be described as a “mini-brain” in a manner that implies it possesses the full functions, experiences or moral status of a human brain. Public communications should explain both the value and the limitations of the model.
5. Human brain organoid research in Singapore
5.1. Singapore has a strong biomedical research ecosystem and a long-standing interest in research on neurological, psychiatric and developmental disorders. Human brain organoid research may be conducted in universities, research institutes, healthcare institutions and private research organisations. It may involve domestic and international collaboration, sharing of cell lines and data, and partnerships with industry.
5.2. Research involving human biological material or identifiable personal information is subject to Singapore’s framework for human biomedical research. Research involving animals is also subject to institutional and national requirements concerning animal welfare and ethics. These frameworks provide a foundation for the governance of human brain organoid research [5-7].
5.3. The emergence of brain organoids does not necessarily require an entirely separate regulatory regime. However, there may be uncertainty about how existing requirements apply to some research activities, particularly where the ethical concern is connected to the possible capacities of the organoid rather than directly to the risk borne by a living human participant.
6. Current scientific developments
6.1. Several developments may increase the scientific utility and ethical significance of brain organoids. These include the culture of organoids for longer periods, the combination of region-specific organoids into assembloids, the addition of vascular or immune-cell components, transplantation into animals, and coupling to electrodes or computational systems [3,8].
6.2. The observation of organised electrical activity has led to questions about consciousness. Such activity may be useful for studying neural development and disease. It does not, however, demonstrate that an organoid has subjective experience. Current organoids lack the mature, integrated and embodied systems commonly considered relevant to human consciousness. Scientific and philosophical disagreement remains about which conditions would be necessary or sufficient for consciousness in any system [2,9].
6.3. Research involving transplantation of human neural tissue into animals may assist maturation and permit the study of neural integration. It also requires careful attention to the welfare of the host animal and to possible changes in its capacities or behaviour. Research that connects organoids to computational systems may raise questions about the nature of stimulation, data generated, possible aversive exposure, accuracy of claims, and governance of resulting intellectual property [3,8].
7. LAW, ETHICS AND SOCIAL CONSIDERATIONS
Consent for the donation and use of human biological material
7.1. Full, free and informed consent is a cornerstone of the ethical legitimacy of the donation of human biological material for research. Consent should be obtained in accordance with applicable law and established requirements for human biomedical research [5,6].
7.2. A person donating cells or tissue for the creation of brain organoids should receive a fair explanation of the proposed research and the principal foreseeable uses of the donated material. This should include, where applicable, reprogramming of cells, long-term storage, genetic analysis, sharing with collaborators, use in commercial research, generation of organoids, transplantation into animals, and the possibility that future research uses cannot be fully specified at the time of donation.
7.3. Donors should not be led to believe that an organoid will reproduce their memories, personality, intentions or mental life. Brain organoids generated from reprogrammed cells do not reproduce the donor’s neural circuits. Nevertheless, donors may attach symbolic significance to human-derived neural tissue. Consent processes should use clear and respectful language and should allow sufficient opportunity for questions [10].
7.4. The conditions and limitations of withdrawal should be explained. Withdrawal may not be possible after material has been anonymised, shared, incorporated into cell lines or organoids, or used in completed research. The consent process should also state whether the donor will be contacted about incidental findings, whether any feedback of individual research results is contemplated, and whether the material may be used in research with commercial partners.
7.5. Preliminary view. The BAC considers that consent for human biological material used to create brain organoids should describe the material uses that can reasonably be foreseen, including any proposed transplantation into animals or coupling to computational systems. Where a proposed use falls materially outside the scope of the consent or raises substantially different ethical considerations, the matter should be reviewed by an appropriately constituted institutional review board (IRB), which should determine whether re-consent or other safeguards are required.
8. Privacy, confidentiality and data governance
8.1. Brain organoid research may involve genomic, clinical, imaging, electrophysiological and other data. Such information may identify, or contribute to the identification of, a donor. It may also reveal information about disease risk or familial relationships. Researchers and institutions have an obligation to protect the confidentiality and privacy of donors and other individuals whose personal information is entrusted to them [5,10].
8.2. The use of the term “neuroprivacy” should not obscure the character of the risk. A brain organoid cannot reveal the donor’s memories or private thoughts because it is generated anew and does not recreate the donor’s neural circuitry. However, it may model disease-associated features derived from a donor’s genetic background. The information should be safeguarded as sensitive biomedical information, particularly where the underlying condition may be stigmatising [10].
8.3. Institutions should establish clear systems for access control, de-identification, security, cross-border transfer, data retention and sharing. Data sharing arrangements should be consistent with the donor’s consent and with applicable legal and institutional requirements. Particular care is needed where data or cell lines are made available through biobanks or international collaborations.
8.4. Preliminary view. The BAC considers that the existing principles of privacy, confidentiality and data stewardship should apply fully to brain organoid research. Additional protections should be considered where a proposed project combines organoid-derived data with highly sensitive clinical, genomic or behavioural data, or where the risks of re-identification are increased by data linkage.
9. Consciousness, sentience and moral status
9.1. The question whether a brain organoid could be conscious has generated considerable ethical concern. Consciousness is not a single, simple property. It may refer to subjective sensory experience, awareness, self-awareness, memory, planning or other capacities. The moral relevance of these capacities may also differ. An ability to experience pain or distress may require ethical attention even if an entity is not capable of human-like self-awareness [2,9].
9.2. Current brain organoids are not generally regarded by scientists as capable of consciousness or sentience. They are immature models without the integrated sensory, motor, bodily and environmental systems of a living human being. Electrical activity, including oscillations, is not sufficient evidence that an organoid has subjective experience [2,3].
9.3. The BAC does not consider that current brain organoids should be treated as human persons or as entities having the same moral or legal status as human beings. The biological origin of the organoid, or its similarity to some features of human neural tissue, does not by itself establish personhood [11].
9.4. It does not follow that there can never be a need for special ethical attention. If future work produces converging evidence of capacities associated with sentience or other morally significant experience, researchers and institutions should assess whether the research protocol remains acceptable and whether additional safeguards are needed.
9.5. Preliminary view. The BAC considers that research proposals should not infer consciousness or sentience from a single indicator of neural activity. Where the purpose or foreseeable outcome of a project is to develop substantially more mature, integrated or responsive neural models, the IRB should require an explanation of the relevant scientific indicators, the possible welfare implications, and proposed monitoring and stopping arrangements.
10. Welfare, research conduct and humane endpoints
10.1. The central ethical obligation in the use of brain organoids is to conduct scientifically sound research in a manner that is proportionate to the possible benefits and harms. Unnecessary stimulation, injury, deprivation, pharmacological exposure or prolonged culture should not be undertaken merely because it is technically possible.
10.2. Research that intentionally seeks to model states analogous to pain, distress, fear or other aversive experiences requires particular care. The scientific objective, the basis for believing that the organoid could have a relevant experience, and the availability of less ethically concerning alternatives should be addressed in the research protocol.
10.3. Preliminary view. The BAC considers that institutions should develop written procedures for the review of research involving advanced neural maturation, complex assembloids, prolonged culture, potential aversive stimulation, or other activities that could plausibly raise welfare concerns. Procedures should include a requirement to pause or modify research if unexpected evidence raises a serious concern that the organoid may have acquired morally significant capacities.
11. Transplantation into animals and human-animal neural combinations
11.1. Human brain organoids or organoid-derived neural tissue may be transplanted into animals to study maturation, integration, disease or potential therapies. Such research may be valuable, but it may also affect the welfare, behaviour or capacities of the host animal [3,12].
11.2. The ethical assessment should include the species and developmental stage of the animal, the location and extent of the transplant, the expected degree of integration, the methods for monitoring welfare and behaviour, and the arrangements for humane endpoints. The presence of human cells does not automatically make an animal human or confer human legal status upon it. However, a substantial and unexpected alteration of the animal’s capacities should be investigated and reported.
11.3. Preliminary view. The BAC considers that research involving the transplantation of human brain organoids or organoid-derived neural tissue into animal nervous systems should receive specialist ethical review in addition to the ordinary requirements for animal research. The review should include relevant expertise in neuroscience, stem-cell biology, animal welfare and research ethics.
12. Legal status, ownership and commercialisation
12.1. Brain organoids are human-derived research materials. Current brain organoids are not human beings and should not be regarded as legal persons. Legal personhood has consequences for rights, duties, representation and liability that are not established by the present state of science [11,13].
12.2. The absence of legal personhood does not remove the ethical obligations owed to donors, research animals or the public. Institutions should clarify the custody and control of material, cell lines, organoids and data; the conditions for sharing; intellectual-property arrangements; and the responsibility for governance of future uses.
12.3. Commercial research may contribute to scientific and therapeutic advances. Its involvement should be disclosed in consent processes and should not reduce the requirements for valid consent, scientific integrity, ethics review, privacy protection or transparency.
12.4. Preliminary view. The BAC considers that brain organoids should not presently be assigned legal personhood. The law and institutional arrangements should instead focus on protecting donors, ensuring responsible research conduct, safeguarding animals, managing sensitive data, and responding proportionately if future scientific developments raise new concerns.
13. Governance, transparency and public engagement
13.1. Existing institutional arrangements provide a foundation for ethical review. However, brain organoid research may require access to specialist expertise where it involves advanced neural modelling, transplantation into animals, extensive genetic modification, computational coupling or other novel procedures.
13.2. IRBs should be able to obtain specialist advice or refer projects for enhanced review. The appropriate review should remain proportionate. Ordinary disease-modelling studies using established methods should not be subjected to unnecessary burden. More ethically sensitive work should include a clear statement of scientific purpose, consent conditions, data governance, monitoring, adverse-event reporting and final disposition of organoids.
13.3. Transparency is important for public confidence. Researchers should use accurate language when describing organoids and should avoid claims that exaggerate human-like capacities. Institutions should maintain appropriate records of provenance, consent conditions, culture methods, genetic modifications, use in animals, sharing and final disposition.
13.4. Public views may not be identical to professional bioethical views. Some persons may be particularly concerned about the significance of brain tissue, the relationship between the donor and the organoid, the mixing of human and animal material, or the prospect of creating systems that appear to think. These perspectives should be taken seriously in public engagement, even where they do not determine scientific facts [14].
13.5. Preliminary view. The BAC considers that Singapore should adopt an adaptive and proportionate governance approach. Institutions should apply existing human biomedical research, data-governance and animal-research requirements, supplemented by guidance for higher-sensitivity brain organoid research. A national advisory mechanism may be considered if developments show that common standards, specialist advice or periodic review cannot be achieved adequately through existing arrangements [15].
14. POSSIBLE GOVERNANCE APPROACHES
Approaches to governance
14.1. Human brain organoid research combines matters that are already governed in Singapore—human biological material, consent, personal information, animal research, institutional ethics review and research integrity—with matters that may become more significant as the science develops. The BAC does not consider that the existence of brain organoids, by itself, requires an entirely separate legal regime. The question is whether existing arrangements, supplemented where necessary, can provide adequate ethical direction, accountability and public confidence.
14.2. The BAC considers that governance should be sensitive to the nature and degree of ethical concern. A single, uniform approach is unlikely to be appropriate. Routine research using established and immature organoid models may be adequately governed through existing requirements for human biomedical research and institutional review. Research that substantially increases the complexity, maturation or functional integration of organoids, or that involves transplantation into animals or computational coupling, may require additional safeguards.
Institutional governance and professional standards
14.3. One approach is to rely on existing statutory requirements, institutional policies and IRB review, supported by national interpretive guidance. Under this approach, institutions conducting brain organoid research would develop written policies, standard operating procedures and consent materials that address the particular features of such research. IRBs would assess research proposals according to their scientific merit, consent conditions, data governance, animal-welfare implications, commercial interests and social concerns.
14.4. The BAC considers that this approach has the advantage of building upon familiar and established responsibilities. It also enables guidance to be updated as scientific knowledge develops. However, its effectiveness would depend on institutions having access to appropriate expertise and on comparable standards being applied across institutions.
Enhanced review of higher-sensitivity research
14.5. A second approach is to supplement ordinary ethics review with enhanced or specialist review for specified categories of research. These categories might include research intended to generate substantially more mature or integrated neural systems; research involving potential aversive stimulation; transplantation into an animal nervous system; research directed at consciousness or sentience; and coupling to computational systems for learning-like or biocomputing purposes.
14.6. Enhanced review could be conducted by an IRB with co-opted specialist expertise or by a designated institutional committee. The review should be proportionate and should not delay ordinary disease-modelling studies unnecessarily. Its purpose would be to ensure that higher-sensitivity proposals include a clear scientific justification, suitable monitoring, defined intervention or stopping arrangements, and accurate public communication.
National advisory coordination
14.7. A third approach is the establishment of a national-level advisory or consultative mechanism. Such a body could comprise scientific, clinical, legal, ethical, animal-welfare, data-governance and public representatives. It could develop common guidance, advise on unusual or novel proposals, promote shared standards among institutions, review emerging scientific developments and facilitate continuing public engagement.
14.8. A national advisory mechanism need not replace institutional responsibility or ordinary ethics review. It could instead provide a forum for coordination and expert advice in cases where institutional practice alone may not produce consistent standards. It could also assist Singapore in engaging with international developments and avoiding the transfer of ethically sensitive research to settings with weaker oversight [13,15].
Targeted statutory intervention
14.9. A fourth approach is to introduce specific statutory requirements for defined activities. Such intervention may provide clarity where voluntary standards, professional guidance and institutional review are unable to secure adequate protection or accountability. It may be appropriate if an activity presents substantial and persistent risks that cannot be managed through less formal measures.
14.10. The BAC notes, however, that highly specific legislation may become obsolete as techniques change. It may also create unnecessary barriers to low-risk research. Legislative intervention should therefore be carefully targeted, based on clear evidence of need, and capable of being supplemented by adaptable professional and ethical guidance.
14.11. The BAC invites views on the appropriate balance among these approaches. In particular, the BAC invites comment on whether Singapore should rely primarily on existing requirements with supplementary guidance, establish a national advisory mechanism, define categories for enhanced review, or introduce targeted statutory controls for specified activities.
15. INTERIM RECOMMENDATIONS
Interim recommendations
15.1. In this section, the BAC sets out preliminary recommendations arising from the matters discussed above. These are interim recommendations. Human brain organoid research is rapidly evolving, and further scientific, ethical, legal and social questions may arise. Some questions cannot yet be resolved conclusively. They will require continuing professional and public discussion, together with improved scientific understanding.
15.2. THE BAC RECOMMENDS THAT:
Recommended ethical principles
15.2.1. Human brain organoid research should be directed to scientifically sound objectives that may advance knowledge, improve health or contribute to other substantial public benefits. The likely value of the research should be proportionate to the burdens and ethical concerns it creates.
15.2.2. The welfare, safety, autonomy, privacy and other legitimate interests of donors should be protected. The research use of human biological material should not compromise the medical care of the donor or be made dependent on a decision to donate material for research.
15.2.3. The generation and use of brain organoids should be conducted with respect for the human biological material from which they are derived and with sensitivity to relevant social, cultural and religious perspectives.
Consent and stewardship
15.2.4. Consent for the donation of human biological material for brain organoid research should be full, free and informed. It should provide a fair account of the principal foreseeable research uses, including long-term culture, genetic analysis, sharing, commercial research, transplantation into animals and computational coupling where these uses are envisaged.
15.2.5. Institutions should maintain systems that record the provenance of human biological material and the conditions of consent. They should have clear policies governing withdrawal, re-contact, incidental findings, sharing, commercialisation and final disposition.
15.2.6. Researchers and institutions should protect the confidentiality and privacy of donors. They should treat organoid-derived genetic, clinical and phenotypic information as sensitive biomedical information and should apply appropriate safeguards to access, storage, sharing and cross-border transfer.
Ethical review and oversight
15.2.7. All research using human biological material to create or use brain organoids should undergo ethics review in accordance with applicable requirements. The review should consider the scientific value of the project, consent, data governance, commercial interests, sharing arrangements and relevant social concerns.
15.2.8. Research involving one or more of the following should receive enhanced or specialist review: substantial enhancement of neural complexity or maturation; deliberate research on consciousness, sentience or aversive experience; prolonged culture with novel functional aims; transplantation into an animal nervous system; coupling to computational systems designed to train learning-like behaviour; or other novel procedures whose ethical significance is uncertain.
15.2.9. Institutions conducting higher-sensitivity brain organoid research should establish proportionate monitoring and reporting arrangements. These should include procedures to pause, modify or terminate research if unexpected evidence raises a serious ethical concern.
Human-animal neural combinations
15.2.10. Research involving transplantation of human brain organoids or organoid-derived neural tissue into animals should comply with applicable animal-research requirements and should receive specialist ethical review. The welfare and behaviour of the host animal should be monitored. Protocols should state the criteria for intervention and humane endpoints.
Transparency, public engagement and review
15.2.11. Researchers and institutions should communicate accurately about the capacities and limitations of brain organoids. They should not describe an organoid as conscious, sentient or human-like without an adequate scientific basis.
15.2.12. The BAC recommends continuing public and professional engagement on human brain organoid research. This Paper is issued as part of that process. Engagement should include patient and donor communities, researchers, healthcare professionals, ethicists, lawyers, animal-welfare specialists, industry, religious and community organisations, and members of the public.
15.2.13. The BAC recommends that the relevant authorities and research institutions periodically review the adequacy of governance arrangements in light of scientific developments, international standards and public feedback. Legislative intervention should be considered only if ethical guidance, professional standards and institutional review are unable to provide adequate protection or accountability.
16. INVITATION TO COMMENT
Before making final recommendations on human brain organoid research and its implications, the BAC would like to seek public feedback on the subject. The BAC values views from both individuals and organisations. Interested parties may specifically address the following questions, or give their comments on any of the issues presented in this Consultation Paper or relating to human brain organoid research.
- What information should be provided to persons who donate cells or tissue for the creation of human brain organoids? In particular, should consent expressly address long-term culture, genetic analysis, commercial research, transplantation into animals and coupling to computational systems?
- Should broad consent ordinarily be sufficient for future research uses of donated material to create human brain organoids? If not, what uses should require re-consent or enhanced ethics review?
- What safeguards should apply where a proposed research project may substantially increase neural maturation, integration, responsiveness or functional complexity? What scientific indicators, if any, should trigger additional monitoring or a pause in research?
- Should research that intentionally models pain, distress or other potentially aversive states in human brain organoids be permitted? If so, under what conditions and with what humane endpoints?
- What additional safeguards should apply to the transplantation of human brain organoids or organoid-derived neural tissue into animals? How should the welfare and possible behavioural or cognitive changes of host animals be assessed?
- Are Singapore’s current arrangements for human biomedical research, data governance, animal research and institutional ethics review sufficient for human brain organoid research? If not, what additional guidance, specialist review or national oversight is required?
- How should the privacy, confidentiality and stewardship of genomic, clinical and organoid-derived data be managed, particularly in research involving biobanks, international collaboration or commercial partners?
- What forms of public engagement would assist Singapore in developing an ethically sound and socially acceptable approach to human brain organoid research? How should cultural, religious and community perspectives be taken into account?
Responses should be submitted through the BAC’s official consultation channels, together with any relevant organisational affiliation. Respondents may comment on the preliminary views and recommendations in this Paper, on the questions above, or on any other issue concerning human brain organoid research.
17. REFERENCES
- Lancaster MA, Renner M, Martin C-A, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA. Cerebral organoids model human brain development and microcephaly. Nature. 2013;501(7467):373-379. doi:10.1038/nature12517
- Jeziorski J, Brandt R, Evans JH, Campana W, Kalichman M, Thompson E, Goldstein L, Koch C, Muotri AR. Brain organoids, consciousness, ethics and moral status. Seminars in Cell & Developmental Biology. 2023;144:97-102. doi:10.1016/j.semcdb.2022.03.020
- Hartung T, Morales Pantoja IE, Smirnova L. Brain organoids and organoid intelligence from ethical, legal, and social points of view. Frontiers in Artificial Intelligence. 2024;6:1307613. doi:10.3389/frai.2023.1307613
- Kataoka M, Niikawa T, Nagaishi N, Lee T-L, Erler A, Savulescu J, Sawai T. Beyond consciousness: ethical, legal, and social issues in human brain organoid research and application. European Journal of Cell Biology. 2025;104(1):151470. doi:10.1016/j.ejcb.2024.151470
- Human Biomedical Research Act 2015 (No. 29 of 2015). Singapore Statutes Online. Available from: https://sso.agc.gov.sg/Act/HBRA2015
- Human Biomedical Research Regulations 2017. Singapore Statutes Online. Available from: https://sso.agc.gov.sg/SL/HBRA2015-S621-2017
- Bioethics Advisory Committee, Singapore. Ethics guidelines for human biomedical research. Singapore: Bioethics Advisory Committee; 2012. Available from: https://www.bioethics-singapore.gov.sg/files/publications/reports/ethics-guidelines-for-human-biomedical-research-annex-a.pdf
- Smirnova L, Caffo BS, Gracias DH, Huang Q, Morales Pantoja IE, Tang B, Zack DJ, Berlinicke CA, Boyd JL, Harris TD, Johnson EC, Kagan BJ, Kahn J, Muotri AR, Paulhamus BL, Schwamborn JC, Plotkin J, Szalay AS, Vogelstein JT, Worley PF, Hartung T. Organoid intelligence (OI): the new frontier in biocomputing and intelligence-in-a-dish. Frontiers in Science. 2023;1:1017235. doi:10.3389/fsci.2023.1017235
- Sawai T, Sakaguchi H, Thomas E, Takahashi J, Fujita M. The ethics of cerebral organoid research: being conscious of consciousness. Stem Cell Reports. 2019;13(3):440-447. doi:10.1016/j.stemcr.2019.08.003
- Kataoka M, Ishida S, Kobayashi C, Lee T-L, Sawai T. Evaluating neuroprivacy concerns in human brain organoid research. Trends in Biotechnology. 2025;43(3):491-493. doi:10.1016/j.tibtech.2024.09.001
- Kataoka M, Lee T-L, Sawai T. The legal personhood of human brain organoids. Journal of Law and the Biosciences. 2023;10(1):lsad007. doi:10.1093/jlb/lsad007
- National Academies of Sciences, Engineering, and Medicine. The emerging field of human neural organoids, transplants, and chimeras: science, ethics, and governance. Washington (DC): National Academies Press; 2021. ISBN-13: 978-0-309-30336-1. doi:10.17226/26078. Available from: https://nap.nationalacademies.org/catalog/26078/the-emerging-field-of-human-neural-organoids-transplants-and-chimeras
- Kataoka M, Lee T-L, Sawai T. Human brain organoid research and applications: where and how to meet legal challenges? Journal of Bioethical Inquiry. 2024;21(4):603-610. doi:10.1007/s11673-024-10349-9
- Evans JH. The public’s ethical issues with brain organoid research and application. AJOB Neuroscience. 2022;13(2):101-103. doi:10.1080/21507740.2022.2048727
- Ishida S, Kagan BJ, Kataoka M, Koplin J, Porsdam Mann S, Lewis J, Browning H, Erler A, Feroz F, Fukushi T, Holm S, Kokubo M, Latham S, Lavazza A, Lee I, Lee T-L, Lyreskog D, Menikoff J, Niikawa T, Nagaishi N, Nakazawa E, Ong S, Ota K, Register C, Veit W, Yang JH, Yeo SL, Sawai T, Savulescu J, Earp BD. Ethics and regulation of human brain organoid research: recommendations from the Asia Pacific Neuroethics Working Group. Asian Bioethics Review. 2026;18(3):649-679. doi:10.1007/s41649-025-00398-6