EXPERT REACTION: Potential synthetic human embryos created

Besides what my colleagues have already discussed, to be honest, I do not think that this should be so rushed. Based on what was presented, it is not clear how the model that they created is different to all the human blastocyst-like structures that we and others reported in 2021. I would also want to put a note of caution, as far as I know and as explained in "The Guardian" press article, this work has not been published in a peer reviewed journal. Furthermore, it is very difficult to make any informed comment based on what was presented at ISSCR as it was mostly related to previous mouse work and only a few slides on the "new model". Thus, we should be cautious with what was reported by "the Guardian", and wait for the outcome of a rigorous scientific peer review process, as is the standard in scientific research.

It is noted in the Guardian article that synthetic human embryos would fall outside current legislation in the UK. However, because of the different way that human embryos are defined in the Australian legislation it is more likely that these synthetic embryos would fall within current legislation, but this would need to be determined. If it is the case, then the research would need to be licensed and monitored by the Embryo Research Licensing Committee in Australia, and would need to be compliant with the 14 day rule.  

The ability to recapitulate early events of human development using stem cells in a dish is a remarkable breakthrough in cellular and reproductive technologies. The potential benefits are huge, and range from better understanding how the early tissues self-organise during stages that are otherwise unfeasible to study with current approaches, to elucidating the genetic and cellular requirements involved in early human development in health and disease. It is important to note that this approach cannot be used to generate full-grown babies, so any potential applications in human reproduction are still far from feasible. However, these new assays in vitro will pave the way for future studies that aim to unravel the mechanisms of human development, as well as the effects of environmental and genetic anomalies. As with most emerging technologies, society will need to balance the evidence about the risks and benefits of this approach, and update the current legislation accordingly.

It is extremely important to develop a much deeper understanding of the earliest stages of human development, particularly as these are essential for developing better clinical responses to infertility, miscarriage, and developmental errors. However it is very likely that this research will lead to further debates about the so-called 14-day rule, which is the current legal limit for using embryos or embryo-like structures for research purposes. We need to engage various publics about their understandings of and expectations from this sort of research, and more generally about their views on early human development, as these biological processes are deeply tied to our values and what we think counts as human life. Furthermore, researchers need to consider whether these sorts of 'models' are in fact fundamentally different from human embryos: although they originate from different sources and processes, they have similar characteristics to human embryos, which makes the issue about how we view and treat them much more complex. Most importantly, it is critical that researchers be transparent about this type of research and what is known and unknown, in order to ensure that our regulatory processes address the necessary issues and that the public is assured that there are adequate oversight mechanisms and safeguards.

The successful creation of human embryo-like models holds promise for research into genetic disorders and overcomes one of the major obstacles in early life studies: the 14-day limit for cultivating embryos ex vivo. However, it also highlights the need for ethical guidance when dealing with entities that have not previously existed and are not covered by existing ethico-legal systems.

While it is not clear yet how these synthetic embryos might develop or be used in research, if it is determined they are not equivalent to human embryos, or it is possible to restrict their development such that they do not acquire certain characteristics associated with legal and ethical personhood, they could potentially be useful in research currently considered too risky to use human embryos.

For example, artificial womb technology research is currently hampered by the 14-day rule and the fact there is no data regarding how a fetus might develop in an artificial environment between this stage of development and that of the youngest known premature infants to survive via existing neonatal incubation systems. A synthetic alternative to human embryo experimentation might help advance this, and many other, reproductive technologies.

Novel beings such as synthetic embryos [developed by University of Cambridge and the California Institute of Technology] raise fundamental challenges for regulatory frameworks. Some of these lifeforms are prohibited under Australian legislation, but the scope and justifications for the application of such prohibitions is unclear. They also raise difficult questions about how we ought to treat novel beings. But current Australian regulations are not clear on this treatment and a 2022 decision on a similar being is controversial.
In 2022, Australia’s regulator [the National Health and Medical Research Council (NHMRC)] licensed Monash University scientists’ development of a similar novel being called "iBlastoids". These lacked the ability to implant into a uterus and develop full-term. The regulator ultimately determined that iBlastoids met the definition of a human embryo and were therefore subject to existing laws on embryo research. However, this decision was controversial.

The creation of synthetic human embryos is a breakthrough, which has a vital role in fundamental biology and understanding how living organisms develop and perhaps function. This is a key piece in the puzzle to studying all developmental processes including disease or biological impairments.

The use of synthetic embryos may help understanding not only the pathological/disease process but also answer some questions about longevity and ageing. It is likely that this work will allow us to develop new strategies to treat different developmental dysfunctions, and perhaps even extend lifespan. This work on the one hand mitigates any ethical concerns related to fundamental biology research on embryos, but on the other hand, raises substantial concerns about whether such embryos will not be misused to generate some ‘super forms’ of life. Similarly, to the use of AI, the regulatory, ethical and integrity aspects are important to consider.

However, fundamental knowledge that can be obtained from the use of synthetic embryos in laboratory settings could be game-changing in preventing, and treating physiological dysfunctions – it is perhaps another step towards bionic humans.

The development of a human-like embryo from human embryonic stem cells raises many ethical questions in addition to any questions regarding their status under the law.
 
If human embryonic stem cells are needed to create these human-like embryos for research, then synthetic embryos may not avoid having to use human embryos for research. This is an ongoing moral issue around respect for human life.
 
Further, there is a moral issue involved in creating something for research that may or may not have the potential to live as its own full entity. If they could live as their own full entities, then we must ask whether it is morally permissible to create living beings purely for research purposes. 
 
Right now, animal models suggest that these synthetic embryos would not be able to grow into a human baby. This raises two further questions: One, if they are not the sort of thing that can really grow into a human baby, then how useful are they really for scientific knowledge into human reproduction and development? And two, will researchers decide that ‘fixing the problem’ of these embryos not being able to grow into human babies is something worth pursuing, for questionable ends?

Ironically, Australia’s pioneer of synthetic embryo technology, Professor Jose Polo from the University of Adelaide, faces challenges in further pursuing his research due to legislation lag. As a result, I fear Australia will once again be left behind the rest of the world and we will lose visionaries like Prof. Polo to overseas institutions.