Stem Cell-Based Embryo Models (SCBEMs), also known as synthetic embryos or stembryos, are laboratory-cultured entities resembling embryos that are created entirely from stem cells in vitro, eliminating the need for sperm or eggs. In rapid succession, two separate research teams from the Weizmann Institute of Science (Israel) and Cambridge University (United Kingdom) independently achieved the formation of SCBEMs by employing human embryonic stem cells (hESCs). Although such SCBEMs cannot be considered as true human embryos, these studies were nevertheless limited to an in vitro culture period of 14 days, based on international ethical standards for human embryo research that aim to avoid primitive streak formation at the onset of gastrulation.

     There is a possibility that SCBEMs might be applied to human clinical assisted reproduction. Among the diverse potential reproductive applications of SCBEMs are the treatment of primary infertility, age-related female infertility, posthumous reproduction, transgender and intersex parenthood, same-sex and solo parenthood. Nevertheless, under Singapore law, only legally married heterosexual couples can have access to clinical assisted reproduction services, while the state does not recognize same-sex marriages and de facto marriages with a live-in partner.

     The utilization of SCBEMs in human clinical assisted reproduction is anticipated to be problematic in Singapore, as it could potentially disrupt familial relationships and kinship ties. Because the resulting offspring would be a genetically identical replicate of just one partner in a conventional heterosexual marriage, while being unrelated to the other partner, thus contradicting the primacy of "genetic affinity" under Singapore's family law. Moreover, under Singapore's "Human Cloning and Other Prohibited Practices Act (2004)", the application of SCBEMs in human clinical assisted reproduction is effectively banned, because such entities are considered to be clones, genetically identical replicates of the human individual from which they were derived.

     Recent landmark court cases in Singapore have established the primacy of genetic affinity and blood ties between children and parents, as well as prioritizing child welfare above public policy based on sociocultural norms. It must be noted that Singapore is a common law jurisdiction modeled on the British judicial system, where legal precedents significantly influence the outcome of future court cases. For instance,  the high court decision regarding the IVF sperm mix-up incident at Thomson Fertility Centre articulated that "The ordinary human experience is that parents and children are bound by ties of blood, and this fact of biological experience — heredity — carries deep sociocultural significance". In another significant legal ruling, the Singapore High Court approved a gay man's request to adopt his biological son, who was born through a foreign surrogate mother. The Chief Justice of Singapore declared that promoting child welfare should outweigh public policy against the formation of same-sex family units.

     Although the problem of "genetic affinity" may be overcome through the creation of chimeric SCBEMs that contain stem cells from both partners in a conventional heterosexual marriage, this is not recommended. Blending male and female stem cells to create sex-discordant "chimeric" SCBEMs that include cells of both sexes would greatly increase the risks of intersex conditions arising from disorders of sex development, leading to ambiguous genitalia in the resultant offspring.

     Same-sex couples also have the option of blending their stem cells to create "chimeric" SCBEMs. If both partners are genetically the same sex (either XX or XY), the chances of developing intersex conditions due to disorders of sex development are low. However, chimeric embryos and offspring are present in nature and often have a higher likelihood of developing cancer and autoimmune disorders. Given these health risks, deliberately producing chimeric SCBEMs solely to satisfy the reproductive needs of same-sex couples raises ethical and moral concerns. In any case, de facto same sex couples are barred from accessing clinical assisted reproduction services in Singapore.

     Additionally, SCBEMs can also be utilized in solo reproduction by generating a genetically identical clone. This approach could appeal to individuals intent on single parenthood by deliberate choice, as it allows for single parenthood without involving any genetic input from another individual, but would face significant legal and ethical hurdles in Singapore. This is because solo parenthood with SCBEMs would run afoul of strict laws banning human reproductive cloning in Singapore, as well as contravene the Singapore government's official policy of encouraging traditional family formation via conventional heterosexual marriages, and would therefore likely be banned in the country.

     In contrast to the utilization of SCBEMs in human reproduction, the non-reproductive applications of SCBEMs will likely be permitted in Singapore. These include: 

• Developmental Biology

SCBEMs may facilitate a better understanding how tissues and organs form, in particular how stem cells differentiate into various cell types, providing insights into lineage specification during development. Additionally, SCBEMs can also help to identify critical differences in embryo development between different species (e.g., mice and humans) by observing how these differences influence the in vitro formation of SCBEMs.

• Regenerative Medicine

SCBEMs can be directly utilized to generate replacement tissues and organs. Alternatively, SCBEMs can also lead to the development of new therapies for tissue and organ regeneration by facilitating a better understanding of tissue differentiation and organ formation.

• Disease Modeling  

SCBEMs can be used to model various developmental disorders, such as genetic diseases and birth defects, by mimicking their early stages in a controlled setting.  This enables the identification of disease mechanisms, potential therapeutic targets, and the development of novel therapeutic strategies. 

• Drug Discovery and Testing of Biomedical Devices

SCBEMs can provide testing and screening platforms for evaluating newly developed pharmaceutical drugs and biomedical devices.

• Assisted Reproductive Technologies

SCBEMs can provide insights into early embryo development and implantation, which may lead to improved in vitro fertilization (IVF) success rates. These can also be used to study the causes of miscarriage and develop strategies to prevent pregnancy loss. 

• Personalized and Precision Medicine

In the future, SCBEMs may contribute to personalized medicine approaches, tailoring treatments based on an individual's genetic makeup and developmental profile. 

     The key advantages of utilizing SCBEMs in research are as follows:

• Studying Inaccessible Stages of Development

SCBEMs allow researchers to examine early stages of human development, such as pre-implantation and gastrulation, which are difficult or impossible to study in vivo. These stages are crucial for understanding the origins of many developmental disorders and reproductive problems. 

• Reduced Reliance on Animal Models

SCBEMs can reduce the need for animal models, like mice and rats, which may not perfectly replicate human development. 

• Avoid Utilizing Human Embryos in Biomedical Research

SCBEMs provide a valuable platform to study human development without directly using human embryos, thereby circumventing highly controversial ethical issues. This is because SCBEMs are created from stem cells, which can be derived from embryos or reprogrammed from other human tissues (i.e., induced pluripotent stem cells). 

     These potential non-reproductive applications of human SCBEMs thus align with the Singapore government’s objective of building Singapore into an international biomedical hub of excellence. Nevertheless, despite the potential benefits, research on human SCBEMs raises some serious ethical questions, particularly regarding their moral status in relation to human embryos and their potentiality of developing consciousness and sentience, as well as generating human life. While SCBEMs are widely perceived as distinct from human embryos, researchers are mindful of the ethical implications of their increasing similarity to embryos and the need for appropriate oversight.

     Currently, Singapore has a robust framework for ethical review of research involving human biological materials, including stem cell research. The aim is to build public trust by ensuring transparency and openness in biomedical research through clear guidelines and oversight processes.  Such an approach would emphasize the importance of appropriate review, clear scientific rationale, and limited timelines for research involving SCBEMs. In any case, Singapore's Ministry of Health (MOH) would certainly ensure that research on human SCBEMs is conducted responsibly and ethically. While human SCBEMs do raise some ethical considerations, they are generally seen as a more ethical alternative to using human embryos for research. The development of clear guidelines and regulations, like the SCBEM Code of Practice in the UK, is crucial for ensuring responsible research practices. 

     In an elected democracy such as Singapore, government policymakers are obliged to consider public opinion, as well as carefully deliberate the broad impacts that new biomedical technology platforms such as SCBEMs might have on the entire nation in relation to its cultural values, sociopolitical dynamics and relevant laws. This is why the Singapore government has specifically set up the Bioethics Advisory Committee (BAC) to regularly carry out public consultation and dialogue with the public to solicit feedback on new biomedical technologies. Other countries should learn from Singapore’s example and follow suit.