Contents

Part A: Introduction and background

• About this paper and the consultation process  
• The subject of the consultation  
• Scientific background and potential benefits  
• Scope of the consultation

Part B: Ethical, legal and social issues

• Moral and ethical status  
• Developmental potential and scientific uncertainty  
• Human biological material, consent and provenance  
• Research design, culture duration and stopping points  
• Legal classification and the existing Singapore framework  
• Oversight, accountability and enforcement  
• Data, privacy, intellectual property and commercialisation  
• Public confidence, terminology and engagement  
• Justice, inclusion and distribution of benefits  
• International collaboration and cross-border issues

Part C: Governance options and questions for consultation

• Principles for consideration  
• Possible governance approaches  
• Questions for consultation  
• Conclusion and submission of views

PART A: INTRODUCTION AND BACKGROUND

1. About this paper and the consultation process

1.1 The Bioethics Advisory Committee (BAC) was established to examine and report on the ethical, legal and social issues arising from advances in biomedical science and technology. In carrying out this role, the BAC has used public consultation to obtain views from researchers, healthcare professionals, institutions, policymakers, industry, community organisations and members of the public. The consultation papers supplied for this draft show a consistent practice of setting out the scientific context, identifying the relevant ethical and legal questions, and inviting considered responses before final recommendations are formulated. [1-3]

1.2 This consultation paper seeks views on research involving human stem cell-based embryo models, referred to in this paper as SCBEMs. It does not seek to approve, prohibit or otherwise determine the status of any individual research project. It is intended to support discussion about whether Singapore’s existing arrangements are adequate and whether additional guidance, institutional processes or legislation may be required.

1.3 The BAC would welcome views from research and healthcare institutions, researchers, Institutional Review Boards (IRBs), research funders, professional bodies, patients and fertility-service users, donors of human biological material, industry, lawyers, ethicists, social scientists, religious and community organisations, and members of the public.

1.4 The consultation would be conducted over eight weeks. In an actual BAC publication, the consultation notice would specify the closing date, methods for submitting views, and any public meetings or focus-group discussions. Written responses could be submitted by individuals or organisations. Respondents would be encouraged to distinguish between empirical claims, legal interpretations, ethical positions and policy preferences.

1.5 Feedback would be considered in the development of any subsequent BAC report, advisory guidance or recommendations. Publication of a response would not imply that the BAC accepts any particular submission. The BAC would also consider whether further evidence is required, including Singapore-specific research on public understanding, stakeholder views, institutional capacity and the operation of existing laws.

2. The subject of the consultation

2.1 Researchers have developed three-dimensional structures from human pluripotent stem cells that reproduce, model or approximate selected aspects of early human embryonic development. These structures have been described using different terms, including embryoids, synthetic embryos, blastoids, gastruloids, embryonic organoids and stem cell-based embryo models. The terms are not interchangeable in all contexts and may carry different scientific, ethical and social implications. [4-6]

2.2 For the purposes of this consultation, SCBEM is used as an umbrella term for a three-dimensional structure created through the assembly, differentiation, aggregation or re-association of human stem cells, including embryonic stem cells or induced pluripotent stem cells, where the structure is intended to model one or more aspects of early human embryonic development. The term does not determine whether a particular model is, or is not, a human embryo in law or ethics. [4, 7]

2.3 SCBEMs differ in their cellular composition, spatial organisation, developmental trajectory, degree of resemblance to an embryo, and possible developmental potential. Some models are intended to reproduce a limited tissue, lineage or developmental process. Others include embryonic and extra-embryonic cell types and seek to model a more integrated conceptus. Some models are produced in large batches, while others are generated under conditions designed to produce a particular developmental stage or structure. [4-6]

2.4 A distinction between “integrated” and “non-integrated” models has been useful in some scientific and governance discussions. However, the literature indicates that this distinction is not a complete ethical classification. Extra-embryonic tissues may not be a reliable proxy for developmental potential, and a model that lacks one lineage may nevertheless exhibit complex organisation. Conversely, not every model with several cell types has a credible capacity for integrated development. [4, 8]

2.5 The BAC therefore invites views on whether Singapore should adopt a definition based on the method of creation, the characteristics of the resulting structure, its developmental potential, its intended use, or a combination of these considerations.

3. Scientific background and potential benefits

3.1 Early human development is difficult to study. Natural human embryos are scarce, access is limited, and research is constrained by ethical, legal and practical considerations. Animal models do not reproduce every aspect of human development. SCBEMs may provide experimentally accessible systems for investigating selected developmental processes without relying exclusively on donated embryos.

3.2 Current research uses SCBEMs to study cell-fate decisions, lineage specification, implantation-related processes, gastrulation, early patterning, organogenesis and the formation of primordial-germ-cell-like cells. The models may also support research into infertility, implantation failure, miscarriage, congenital conditions, developmental disorders, environmental exposures, drug toxicity and therapeutic interventions. [5, 6]

3.3 The potential benefits should not be overstated. Current SCBEMs often diverge from natural embryos in morphology, cellular composition, gene expression, timing, metabolism and interactions with extra-embryonic or maternal tissues. Many models have incomplete or abnormal lineages, variable formation efficiency, limited reproducibility and uncertain functional equivalence. Similarity in morphology or transcriptomic markers does not establish that a model has the same developmental potential as a natural embryo. [5- 9]

3.4 SCBEM research may reduce reliance on donated embryos for some questions, but it is unlikely to eliminate the need for research on natural embryos. Model findings require careful validation. A model may be useful for one scientific purpose without being a faithful model of the whole developmental process. [5-9]

3.5 Scientific progress may change the ethical assessment. A model that currently lacks a credible pathway to later development may acquire new features through changes in cell state, culture conditions, genetic manipulation, co-culture, tissue engineering or the assembly of separately developed components. Governance should therefore consider not only what a researcher intends to create, but also what the protocol could generate under the proposed conditions. [8-10, 11]

4. Scope of the consultation

4.1 This consultation would cover research involving the derivation, generation, culture, characterisation, genetic or epigenetic modification, storage, sharing, transfer, publication, destruction and disposal of human SCBEMs.

4.2 It would include research using SCBEMs derived from embryonic stem-cell lines, induced pluripotent stem-cell lines, reprogrammed adult cells, gametes, embryos or other human biological material. It would also cover research involving extra-embryonic or supporting tissues, endometrial or maternal-tissue models, artificial culture systems, animal hosts, and combinations of SCBEMs with other biological models where those activities may affect developmental potential.

4.3 The consultation would distinguish among three broad contexts:

(a) basic research, including the study of early development and cell biology;

(b) translational or applied research, including disease modelling, drug testing, implantation research and reproductive-health research; and

(c) clinical or reproductive use, including implantation, gestational transfer, artificial gestation or the creation of a human individual.

4.4 The third category raises questions of a different order from laboratory research. The literature reviewed for this paper consistently supports a clear prohibition on transferring human SCBEMs to a human or animal uterus or using them for reproductive purposes. [4, 7, 12-15] This draft does not treat that position as a substitute for analysis of Singapore law. It invites views on whether the prohibition should be stated expressly and how it should apply to artificial gestation or other supportive environments.

4.5 The consultation would also consider whether existing arrangements are sufficient, whether an interim code of practice is needed, whether a statutory amendment would be appropriate, and how Singapore should respond if scientific developments outpace domestic guidance.

PART B: ETHICAL, LEGAL AND SOCIAL ISSUES

5. Moral and ethical status

5.1 The central ethical question is whether, and to what extent, SCBEMs should receive special protection because they resemble or model early human development. Views differ. Some approaches attach significance primarily to the origin of an entity, such as fertilisation. Other approaches focus on developmental potential, biological organisation, the possibility of morally relevant capacities, or the social and symbolic meaning of the entity.

5.2 The fact that a structure is made from stem cells rather than through fertilisation does not by itself settle its ethical status. [4, 12, 16, 17] Conversely, resemblance to an embryo does not establish that every SCBEM should be regulated in the same way as a fertilisation-derived embryo. A proportionate framework may need to distinguish among models according to their characteristics, potential, intended use and possible consequences.

5.3 Potentiality is itself contested. A model may be capable of developing further only under particular culture conditions or after external intervention. It may possess a possibility of development without a substantial probability of achieving that development. It may be predisposed to form particular structures without having a continuous developmental trajectory. The concepts of possibility, probability and predisposition should not be treated as interchangeable. [9, 17]

5.4 The literature identifies possible morally relevant features, including developmental stage, integration of organ systems, fetal potential, formation of neural circuits, and the possibility of sentience, pain perception or consciousness. Scientific knowledge about the neural prerequisites and timing of those capacities remains incomplete. No current source supplied for this consultation establishes that any human SCBEM possesses consciousness, pain perception or viability. [5-10]

5.5 Some features may have social significance even if they do not themselves establish moral status. The formation of a beating cardiac region, an appendage, a facial rudiment or other recognisable human anatomical feature may affect public understanding and concern. These reactions should not automatically determine permissibility, but they may be relevant to public trust, responsible communication and the level of review required. [4, 10, 12]

5.6 The BAC invites views on whether the ethical status of an SCBEM should be assessed by reference to:

(a) its origin or method of creation;

(b) its cellular composition and spatial organisation;

(c) its intrinsic or experimentally enabled developmental potential;

(d) the scientific purpose and intended use of the research;

(e) the possible emergence of morally relevant capacities; or

(f) a combination of these considerations.

6. Developmental potential and scientific uncertainty

6.1 Researchers may not be able to determine in advance whether a model can form particular tissues, reach a defined developmental stage, interact with extra-embryonic tissues or continue development under a different culture environment. The absence of evidence of a capacity should not automatically be treated as evidence that the capacity is absent.

6.2 Directly testing the developmental potential of a human SCBEM by transfer to a uterus would be ethically unacceptable. Researchers must therefore rely on indirect evidence. Possible evidence includes morphology, lineage markers, single-cell transcriptomics, epigenetic profiles, metabolic characteristics, time-lapse imaging, attachment or continued culture assays, and comparison with human embryo reference data. Each measure has limitations. [9]

6.3 Human embryo reference data are incomplete, particularly after implantation and gastrulation. IVF embryo grading is an imperfect predictor of live birth. Animal models may provide useful information but cannot establish human developmental potential with certainty. Morphological or molecular similarity does not necessarily establish functional equivalence.

6.4 The literature proposes different governance responses. Some approaches retain a distinction between integrated and non-integrated models. Others favour case-by-case oversight based on developmental stage, organ-system integration, neural capacity, fetal potential and features of public concern. A further approach would create a separate category of “regulated embryo model” with criteria distinct from both ordinary stem-cell work and natural-embryo research. [4, 12, 15]

6.5 A Singapore framework could require a protocol to state, before the work begins:

(a) the model’s intended characteristics and developmental window;

(b) the evidence supporting its expected developmental potential;

(c) the features that will be monitored;

(d) the maximum duration and endpoint of culture;

(e) the criteria for stopping the experiment;

(f) the conditions that would trigger notification or renewed review; and

(g) the steps to be taken if the model develops features beyond those anticipated.

6.6 If an unexpected feature associated with greater integration or developmental potential appears, the researcher could be required to stop the relevant procedure, preserve records, notify the oversight body, and obtain approval before proceeding. The BAC invites views on whether this should be a universal requirement and how it could be implemented without discouraging responsible reporting.

7. Human biological material, consent and provenance

7.1 SCBEMs may be derived from embryonic stem-cell lines, induced pluripotent stem-cell lines, blood, skin, other adult tissue, gametes, embryos or existing cell banks. Donors may not have anticipated that their material could be used to create structures resembling embryos or to study early developmental processes.

7.2 Consent raises several questions. Should existing broad consent cover SCBEM creation? Should donors be asked specifically about embryo-model research? Should consent address genetic and epigenetic analysis, data linkage, commercial use, international transfer, long-term storage, future uses and publication? Should donors have a right to withdraw, and if so, at what point would withdrawal no longer be practicable?

7.3 Consent cannot resolve every question. A donor’s consent does not by itself make a scientifically invalid or prohibited experiment acceptable. Nor can consent from a donor determine the moral status of an entity created from the donor’s cells. Consent is nevertheless important because it respects donor autonomy, supports trust and clarifies the permitted uses of biological material and associated data.

7.4 Particular care may be required where cells were collected for a different purpose, where a cell line is widely distributed, where donors cannot reasonably be recontacted, or where samples are linked to identifiable genomic information. Institutions should document the provenance of materials and the scope and limitations of the consent on which use is based.

7.5 The BAC invites views on whether Singapore should require:

(a) specific consent for creating SCBEMs;

(b) re-consent or a dynamic-consent process for specified future uses;

(c) disclosure of commercial and international uses;

(d) special safeguards for gametes, embryos and reproductive tissues;

(e) requirements concerning donor withdrawal and destruction; and

(f) public registration of cell-line provenance and consent limitations, subject to privacy and security protections.

8. Research design, culture duration and stopping points

8.1 The traditional 14-day rule is linked to the time elapsed after fertilisation and to the appearance of the primitive streak. It is valued for its clarity and its role as a publicly intelligible boundary in natural-embryo research. Its application to SCBEMs is contested because SCBEMs are not created through fertilisation and may not have a clear developmental day zero.

8.2 Some international guidance recommends that SCBEMs be cultured only for the minimum time necessary to achieve the scientific objective. Other approaches retain a fixed time or developmental limit. Still others would combine a default limit with an exceptional-extension process based on scientific necessity and specialist review.

8.3 A purely elapsed-time limit may be difficult to apply where models develop at different rates, skip stages or represent only a partial developmental process. A purely feature-based limit may be difficult to apply consistently because evidence about the significance of a feature may be incomplete. A proportionate approach may therefore require both a maximum approved duration and a model-specific developmental endpoint.

8.4 The following safeguards could be considered:

(a) the least complex model reasonably capable of answering the research question should be used;

(b) the culture period should be limited to the period scientifically necessary;

(c) protocols should identify stopping points before the work begins;

(d) extensions should require a documented scientific justification and additional review;

(e) open-ended culture should not be permitted; and

(f) transfer to a human or animal uterus, or to an artificial system intended to support development toward viability, should be prohibited.

8.5 The BAC invites views on whether a Singapore framework should retain the 14-day rule for all SCBEMs, apply it only to specified classes, replace it with developmental or feature-based limits, or adopt a combination of these approaches. Respondents are also invited to explain how any alternative could remain clear, enforceable and publicly legitimate.

9. Legal classification and the existing Singapore framework

9.1 Singapore’s existing legal and policy framework includes instruments relevant to human biomedical research, human embryos, reproductive technology, cloning, personal data, human tissue and research ethics. The uploaded BAC materials show that the Committee has previously examined human stem-cell research, human tissue, human-animal combinations, mitochondrial genome replacement technology, genetic research and the governance of human research. [1, 2, 18, 19]

9.2 The Human Biomedical Research Act 2015 and the Human Biomedical Research (Restricted Research) Regulations 2017 are relevant to the governance of human biomedical research and restricted research. [20, 21] The Human Cloning and Other Prohibited Practices Act 2004 is relevant to questions concerning human embryo clones, prohibited embryos and development outside the body of a woman. [22] The Personal Data Protection Act 2012 may be relevant to identifiable donor information and genomic data. [23] The precise application of these instruments to a particular SCBEM protocol requires authoritative legal analysis.

9.3 The legal difficulty is that statutes may use terms such as “human embryo,” “human embryo clone” or “development” that were drafted before the emergence of current SCBEM technologies. A definition may turn on fertilisation, nuclear transfer, the appearance of pronuclei, initiation by other means, developmental potential, or another criterion. It may be unclear whether a particular SCBEM falls within the statutory term, whether a 14-day limit can be calculated, and which authority has responsibility for review.

9.4 The literature does not support a single international answer. Some jurisdictions have expressly addressed SCBEMs through guidelines or codes. Others rely on existing embryo or stem-cell rules. Several have regulatory gaps or uncertainty. International professional guidance may inform Singapore’s policy but does not automatically become Singapore law or a substitute for domestic decisions.

9.5 This consultation therefore seeks views on whether Singapore should:

(a) clarify existing statutory definitions;

(b) create a separate statutory category for SCBEMs;

(c) apply existing embryo-research provisions to specified SCBEMs;

(d) regulate according to developmental potential or functional characteristics;

(e) establish an interim code of practice while legislative options are considered; or

(f) use a combination of legal and non-statutory measures.

9.6 Any clarification should also address privately conducted research, commercially available cell lines, research conducted under international collaboration, the transfer of models or materials overseas, and publication or disclosure of work undertaken outside a formal institutional setting.

10. Oversight, accountability and enforcement

10.1 All research involving human SCBEMs should be subject to review before the model is generated or acquired, rather than only before publication or clinical translation. Review should consider scientific validity, the necessity of the model, the proposed duration, developmental potential, consent, data, cell-line provenance, storage, disposal, publication and downstream use.

10.2 Existing IRBs may have relevant expertise, but the literature raises questions about whether every committee has sufficient specialist knowledge in developmental biology, reproductive medicine, stem-cell science, ethics and law. A specialised committee, a designated national panel, or an IRB with demonstrated expertise could be required for higher-risk projects.

10.3 A tiered framework could distinguish among:

(a) lower-risk work with disorganised aggregates, two-dimensional cultures or models without a credible route to integrated embryonic development;

(b) work involving organised three-dimensional models that reproduce specified developmental features and require specialised review; and

(c) prohibited activities, including implantation, reproductive use, or development intended to produce a human individual.

10.4 Tiering should not depend solely on labels. A project initially classified as lower risk may require escalation if the model, culture conditions, genetic modifications or supporting tissues change. The framework should specify who may make that determination and how disagreements are resolved.

10.5 Institutions could be required to maintain records of the creation, provenance, culture, storage, transfer, use and disposal of SCBEMs. Records should be sufficiently detailed to permit audit, scientific reproducibility and investigation of unexpected events. Batch production creates a practical challenge: requirements designed for individually tracked embryos may need adaptation without losing accountability.

10.6 Compliance could be supported through institutional conditions, research-funding requirements, publication standards, registration, inspection, sanctions and referral to the relevant authorities. Enforcement should be proportionate. The BAC invites views on whether existing sanctions are suitable for SCBEM research or whether separate measures are required.

11. Data, privacy, intellectual property and commercialisation

11.1 SCBEM research may involve genomic, epigenomic, imaging and other data that can reveal information about donors or their relatives. Long-term storage and artificial-intelligence analysis may increase the risk of re-identification. [21, 24] Data governance should therefore address access, linkage, retention, security, cross-border transfer and responsible publication.

11.2 Commercial development may support research and translation, but commercial incentives may also create pressure to overstate model fidelity, minimise limitations, or pursue applications before safety and ethical questions are resolved. Commercial research should not be exempt from the ethical and scientific standards that apply to academic research.

11.3 Questions may arise concerning ownership or control of cell lines, models, data, inventions and downstream products. A donor’s consent to research does not necessarily answer whether the donor should share in commercial benefits. Nor should commercialisation undermine the principle that the human body and its parts should not be treated merely as commodities.

11.4 Public registers, conflict-of-interest declarations, publication of negative or inconclusive results, and transparent statements about model limitations could support accountability. The BAC invites views on whether registration should be mandatory and whether requirements should apply equally to public, private and collaborative projects.

12. Public confidence, terminology and engagement

12.1 The language used to describe SCBEMs affects public understanding. “Synthetic embryo” may imply a degree of equivalence that the scientific evidence does not support. “Mere model” may minimise features that are ethically significant. The term SCBEM is used in this paper because it identifies the technology without determining its moral or legal status.

12.2 Responsible communication should explain the purpose of the research, the model’s known and unknown capabilities, the safeguards in place, the limits of what can be inferred, and any commercial interests. Claims about curing infertility, creating life or solving population decline should not be made without evidence.

12.3 Public engagement should be more than one-way communication. It should provide opportunities for people to ask questions, express concerns, consider competing values and understand how their views will inform governance. Engagement should include people directly affected by infertility, pregnancy loss, developmental disorders and reproductive technologies, as well as communities with different cultural and religious perspectives.

12.4 Public views should be taken seriously but should not be treated as a substitute for scientific evidence or legal analysis. A legitimate governance framework should explain how public concerns are weighed alongside research value, individual autonomy, human dignity, justice, safety and institutional accountability.

13. Justice, inclusion and distribution of benefits

13.1 SCBEM research may produce benefits for conditions that cause substantial suffering. However, research priorities may be influenced by commercial opportunities rather than disease burden. Benefits may also be distributed unequally if resulting therapies are costly or available only through private services or overseas treatment.

13.2 The burdens of research may also be uneven. Donors may contribute biological material without sharing in downstream benefits. Certain groups may face pressure to donate or may be underrepresented in cell banks and reference datasets. Genomic research may expose donors or communities to privacy risks, stigma or discrimination.

13.3 A consultation should include the perspectives of patients, donors, people with disabilities, donor-conceived persons, people experiencing infertility, and communities that may be affected by changes in reproductive technology. No assumption should be made that Singapore has a single social or religious view on when human life begins or how embryo-like entities should be treated.

13.4 The BAC also invites views on whether research funding should prioritise questions of significant public benefit, whether benefit-sharing arrangements are appropriate, and how Singapore can participate in international research without shifting ethical burdens to jurisdictions with weaker protections.

14. International collaboration and cross-border issues

14.1 SCBEM research is likely to involve international cell lines, data, collaborators, funders, journals, biobanks and contract research organisations. Differences among jurisdictions may create uncertainty concerning consent, culture limits, prohibited uses, transfer, publication and enforcement.

14.2 Singapore should consider whether material-transfer agreements and collaboration agreements should prohibit implantation, reproductive use, onward transfer to inadequately protected settings and use outside the scope of consent. Agreements should identify responsibility for ethics review, incident reporting, data protection and disposal.

14.3 International standards can improve consistency, but international alignment should not prevent Singapore from adopting more protective requirements where justified by local law, social values or public interest. [4, 7, 14] Mutual recognition should not become a mechanism for avoiding Singapore requirements.

14.4 The BAC invites views on whether a Singapore framework should include a national register, cross-border reporting arrangements, minimum contractual terms, restrictions on export or import, or a requirement that overseas collaborators meet standards equivalent to those applicable in Singapore.

PART C: GOVERNANCE OPTIONS AND QUESTIONS FOR CONSULTATION

15. Principles for consideration

15.1 The following principles are proposed as a basis for consultation. They are not final recommendations.

Respect for human dignity. Research should respect the significance of human biological material and structures that model early human development. Researchers should use accurate, non-sensational and non-dismissive language.

Scientific and social value. Research should have a clear scientific rationale and should address a question that cannot reasonably be answered by a less ethically sensitive method.

Proportionality. Oversight should be proportionate to the characteristics and developmental potential of the model, the methods used, the duration of culture, the intended purpose and the possible consequences.

Precaution under uncertainty. Where evidence about developmental potential or morally relevant capacities is incomplete, safeguards should be appropriate to the uncertainty. Uncertainty should not automatically be treated as evidence of safety.

Least ethically sensitive means. Where a less complex model can answer the research question, it should ordinarily be preferred.

Responsibility and accountability. Researchers, institutions, funders, publishers and regulators should have clear responsibilities. Records should permit provenance, use, transfer and disposal to be audited.

Transparency. Research should be registered or reported in a manner that permits meaningful scientific and public scrutiny, subject to privacy, security and intellectual-property protections.

Fairness and inclusion. The distribution of burdens and benefits should be considered. Donor communities and the public should have meaningful opportunities to contribute to research priorities and governance.

Non-commercialisation of the human body. Commercial activity involving human cells, embryos, embryo models or derived data should be subject to safeguards and should not undermine voluntary consent or public trust.

Adaptability. Governance should be capable of revision as scientific evidence, social understanding and legal requirements change.

16. Possible governance approaches

16.1 The BAC invites views on the following approaches, which could be adopted singly or in combination.

Approach A: reliance on existing arrangements. Existing legislation, IRB review, institutional policies and professional guidelines could continue to apply. This would avoid creating new categories but might leave uncertainty about definitions, culture limits and review responsibility.

Approach B: an interim code of practice. A non-statutory code could set out definitions, review expectations, prohibitions, consent requirements, culture limits, record-keeping and incident reporting while longer-term legislative options are considered. The code would not be equivalent to law.

Approach C: specialised review for all organised human SCBEMs. Every project involving a spatially organised three-dimensional human SCBEM could require review by an IRB with relevant expertise or by a specialised committee. The intensity of review could remain proportionate to the model and purpose.

Approach D: a tiered framework. Lower-risk work could proceed under ordinary institutional review. More complex or integrated models could require specialised review, registration, monitoring and national notification. Prohibited activities would include implantation, reproductive use and development intended to produce a human individual.

Approach E: statutory clarification or amendment. Singapore could clarify the application of existing definitions and restrictions or create a distinct category for SCBEMs. Any amendment would need to address the relationship among human biomedical research, reproductive technology, cloning, human tissue, data protection and international collaboration.

16.2 Under any approach, protocols could be required to state the maximum culture duration, developmental endpoint, stopping criteria, monitoring plan, model-characterisation data, donor-consent basis, storage and disposal plan, and response to unexpected findings.

16.3 A framework could also require periodic review by the relevant authority or BAC, public reporting, specialist training for reviewers, conflict-of-interest disclosure and a process for revising classifications when scientific evidence changes.

17. Questions for consultation

The BAC would welcome views on the following questions. Respondents need not answer every question and may raise additional issues.

Definitions and scope

Question 1. Is the proposed umbrella definition of SCBEM sufficiently clear? If not, which features should be included or excluded?

Question 2. Should Singapore distinguish among SCBEMs according to method of creation, cellular composition, spatial organisation, developmental potential, intended use, or a combination of these factors?

Question 3. Should the terms “integrated” and “non-integrated” be retained, supplemented or replaced for governance purposes?

Scientific value and necessity

Question 4. What scientific or social benefits should be required before SCBEM research is approved?

Question 5. Should applicants be required to show why a less complex model, animal model, natural embryo or other method cannot reasonably answer the research question?

Question 6. What minimum standards of model characterisation, reproducibility, validation and reporting should apply?

Developmental potential and culture limits

Question 7. What evidence should be used to assess developmental potential where direct testing by uterine transfer is prohibited?

Question 8. Should the 14-day limit apply to SCBEMs? If not, should it be replaced by a developmental-stage limit, a feature-based limit, a model-specific endpoint, or a combination of these?

Question 9. Should extensions beyond an approved endpoint ever be permitted? If so, what scientific justification and additional review should be required?

Question 10. What features should trigger enhanced review, including developmental stage, organ-system integration, neural capacity, fetal potential, extra-embryonic support or recognisable human anatomy?

Question 11. What procedures should apply if a model develops features or capabilities beyond those anticipated in the approved protocol?

Prohibited or restricted activities

Question 12. Should Singapore expressly prohibit the transfer of a human SCBEM to a human or animal uterus?

Question 13. Should Singapore expressly prohibit reproductive use, artificial gestation intended to achieve viability, reproductive cloning, or any attempt to create a human individual from an SCBEM?

Question 14. Should co-culture with endometrial, maternal, animal or artificial supporting systems require specialised review even where implantation or gestation is not intended?

Consent, provenance and data

Question 15. What form and scope of consent should be required for cells, embryos, gametes, tissues and existing cell lines used to create SCBEMs?

Question 16. Should existing broad consent be sufficient for SCBEM research, or should specific consent, re-consent or dynamic consent be required for defined uses?

Question 17. What safeguards should apply to genomic data, re-identification risks, long-term storage, withdrawal requests, data linkage and international transfer?

Question 18. Should donors be informed about commercial use, patenting, material transfer, publication and possible future applications? Should benefit-sharing be considered?

Oversight and accountability

Question 19. Should all human SCBEM research require specialised ethics review, or should a tiered framework apply?

Question 20. What expertise should be required on an IRB or specialised committee reviewing SCBEM research?

Question 21. Should SCBEM research be registered nationally, and should protocols, review outcomes, culture-limit extensions, deviations and unexpected findings be reported?

Question 22. What sanctions, funding conditions, publication requirements or institutional measures should apply to non-compliance?

Social values, justice and public engagement

Question 23. What ethical, cultural, religious or social values should guide Singapore’s approach to SCBEM research?

Question 24. How should Singapore engage patients, donors, affected communities, religious and community organisations, private-sector researchers and the wider public?

Question 25. How should the burdens and benefits of SCBEM research be distributed, including issues of affordability, representation in cell banks, access to future therapies and benefit-sharing?

International and future governance

Question 26. How should Singapore respond to international guidance such as the ISSCR framework while preserving domestic legal and policy choices?

Question 27. What contractual or regulatory safeguards should apply to international transfers, overseas collaborators, private research and commercial cell banks?

Question 28. How often should Singapore review its SCBEM framework, and what scientific or social developments should trigger an earlier review?

18. Conclusion and submission of views

18.1 SCBEM research may provide significant opportunities to study early human development and conditions that affect reproduction, pregnancy and health. It also challenges categories that have traditionally been based on fertilisation, a defined developmental day zero or a clear distinction between embryos and other biological material.

18.2 The ethical, legal and social issues cannot be resolved by scientific classification alone. A responsible framework should recognise scientific uncertainty, require meaningful scientific justification, protect donors, prohibit reproductive use, provide proportionate oversight, support transparent communication, and remain capable of revision.

18.3 The BAC would consider all submissions carefully. In particular, it would welcome evidence about the scientific capabilities of current SCBEMs, the operation of Singapore’s existing laws and institutions, the views of affected communities, and the practical consequences of different governance options.

18.4 In an actual consultation, responses would be submitted by the closing date stated in the consultation notice. Respondents would be asked to indicate whether their submissions may be published and whether any material should be treated as confidential. The BAC would publish a subsequent report or summary of responses in accordance with its established practice.

19. References

1. Bioethics Advisory Committee, Singapore. Ethical, Legal, and Social Issues in Human Stem Cell Research, Reproductive and Therapeutic Cloning [consultation paper]. Singapore: Bioethics Advisory Committee; 2002. Available at: https://www.bioethics-singapore.gov.sg/bioethics-resource/publications/ethical-legal-and-social-issues-in-human-stem-cell-research-reproductive-and-therapeutic-cloning/
2. Bioethics Advisory Committee, Singapore. Advancing the Framework of Ethics Governance for Human Research [consultation paper]. Singapore: Bioethics Advisory Committee; 2003. Available at: https://isomer-user-content.by.gov.sg/154/b1eec79b-f155-4555-84ea-c299290fefe9/advancing-the-framework-of-ethics-governance-for-human-research.pdf
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