February 22, 2024

Singapore should ban reproductive applications of synthetic human embryos

In recent years, Singapore has invested heavily in developing its biomedical industry. Of particular interest for policymakers are new assisted reproductive technology (ART) platforms and the related field of human developmental biology to overcome the country’s ultra-low fertility rates.

Scientists are intrigued by the generation of synthetic human embryos entirely from stem cells (also known as human embryo models, embryo-like structures, or stembryos). This which bypasses the need for sperm or eggs. An Israeli research team at the Weizmann Institute of Science achieved this feat with mouse and human stem cells in quick succession in 2022 and 2023.

These synthetic embryos were reported to display brains, beating hearts, as well as foundational structures of all other organs within the body, in addition to also possessing rudimentary placenta, yolk sac, and other external tissues that could potentially ensure their continued growth and development upon transfer into a womb.

Upon its debut, non-reproductive biomedical applications of synthetic embryos were widely touted. For example, synthetic human embryos can serve as experimental models for studying human birth defects, be a source of transplantable tissues and organs, and a screening and testing platform for newly developed pharmaceutical drugs.

This is incredibly controversial. To date, no animal or human-derived synthetic embryos have yet generated live offspring, but given the rapid pace of scientific advancements in recent years, it is highly plausible that this hurdle might be overcome soon.

Consequently, the potential utilization of synthetic embryos in human reproduction would undoubtedly provoke an even higher degree of moral outrage and ethical controversy as compared to its non-reproductive biomedical applications. Hence, it is imperative to critically examine whether reproductive applications of synthetic human embryos are aligned with Singapore’s ethical values and Government policy stances as follows:

Other avenues

At the moment, other alternatives for overcoming age-related female infertility include egg freezing and ovarian tissue freezing (which also has the advantage of mitigating menopausal symptoms).

Then there is in vitro gametogenesis (IVG). This refers to the generation of artificial lab-grown sperm and eggs from other cell types within the body such as skin cells. Utilizing advanced molecular biology techniques, skin cells can be reprogrammed into an embryonic stem cell-like state, which can then be induced into functional sperm or eggs by various chemicals and growth factors within a laboratory dish.

Several research groups in Japan and China have already demonstrated the birth of live healthy offspring from IVG-generated sperm and eggs derived from the skin cells of mice and rats, which could in turn reproduce normally and give rise to the next generation of healthy offspring. It is highly plausible that these would soon be replicated in humans within the near future.

Given the availability of such alternative technology platforms for overcoming infertility, it is difficult to justify the reproductive applications of synthetic human embryos.

The Government’s enthusiastic sponsorship of ART to boost the country’s dismal birth rates is based on the promotion of traditional family formation via heterosexual marriage. This emphasizes genetic affinity and blood ties, in line with the predominantly Confucian ethos of Singaporean society. Indeed, genetic affinity and blood ties have been used as the basis of some family court case verdicts in Singapore. Legal precedents in Singapore, stress that an individual’s desire to have a child that carry their genes is a basic human impulse, and that in the “ordinary human experience”, parents and children are related by blood and share physical traits.

This may be contravened by the utilization of synthetic human embryos in reproduction. Like human cloning, the hypothetical offspring produced from synthetic embryos would be a genetically identical replicate of only one of the parents who provided stem cells for its formation, while being completely unrelated to the other parent in a conventional heterosexual marriage. Under Singapore law, only legally married heterosexual couples are allowed to use ART.

It must be noted that for infertility treatment, it is not advisable to mix and combine male and female stem cells from a man and a woman to produce a sex-discordant “chimeric” synthetic embryo containing cells of two sexes, due to the strong likelihood of hermaphroditism in the resultant offspring.

Some religious groups in Singapore, especially Christians and Muslims, would most likely consider the use of synthetic embryos in human reproduction to be a violation of the sanctity of marriage, similar to the case of human cloning. This is because this technique bypasses sexual intercourse. It would disrupt familial and kinship ties because the offspring would be a genetically identical replicate of just one partner.

More controversies

In the case of bereaved parents and spouses, the use of synthetic human embryos may offer the possibility of recreating a genetically identical replicate of their deceased loved one, similar to human cloning. Needless to say, this would be highly controversial, especially if there was no informed consent from the deceased. Additionally, there are also ethical concerns about the rights, welfare, and psychological impact on posthumous children.

Same-sex and transgender couples have the option of mixing and combining the stem cells of both partners to generate a “chimeric” synthetic human embryo. Provided that both partners are of the same genetic sex (XX or XY), there are minimal risks of hermaphroditism. Nevertheless, chimeric human and animal embryos and offspring do occur in nature, and often exhibit increased risks of cancer and autoimmune diseases. Given the increased health risk faced by such chimeric individuals, the deliberate creation of chimeric synthetic human embryos just to fulfill the reproductive desires of same-sex and transgender couples is therefore ethically and morally questionable.

Because the utilization of synthetic embryos in human reproduction offers the opportunity to create a genetically identical replicate of an individual, this may be perfectly suited for those intent on single parenthood by deliberate choice. Compared to the use of donor sperm and eggs, there is no genetic contribution from a second party. This would contravene official Singapore Government policy on promoting traditional family formation via conventional heterosexual marriages.

The creation of synthetic human embryos by some egotistical, rich, and powerful individuals intent on perpetuating genetically identical replicates of themselves would certainly spark much controversy. Equally controversial would be misguided attempts by some organizations to create genetically identical replicates of highly-talented individuals (i.e. Nobel prize-winning scientists), with or without their consent, to “benefit” all of mankind.

A technical bottleneck for the controversial issue of human enhancement through human germline genome editing is that there are a limited number of embryos available. Screening of millions of human stem cells to eliminate gene-editing errors, before using these to create synthetic embryos, would thus make germline genome editing much safer and more precise. But does Singaporean society really want to commercialise socially desirable traits such as high IQ, athletic prowess, and beauty?

Conclusion

In an era of falling birth rates, it is tempting for Singapore (and other countries) to experiment with radical new ART techniques to boost the number of babies. But the technical hurdles are formidable and the moral objections are probably insurmountable. Singapore should ban reproductive applications of synthetic human embryos, as these are not aligned with its sociocultural values and relevant Government policy objectives.

Alexis Heng