Our scientific understanding of early human embryogenesis is the product of costly trade-offs. Despite the illuminating insights human embryo research could yield for the understanding of human congenital diseases and infertility problems, the field remains hindered by many technical, legal and ethical challenges. Instead of human embryos, researchers are often forced to use animal models for research, which do not necessarily have results that are transferable to humans. Although transferability issues are mitigated in places where human embryo research is legally allowed, limits presented by the 14-day rule and a requirement to use surplus human embryos still pose some challenges. Moreover, jurisdictions that, like the United Kingdom, conditionally permit the creation of human embryos for research, also face research limitations due to the small number of oocytes available.
It is against this background that researchers have started to redirect their efforts towards so-called human 'embryo-like models'. Unlike human embryos created from fertilisation, these models are created from clusters of different types of human stem cells that when clustered together start to self-organise in ways that simulate particular stages or aspects in early human embryogenesis. Even though these models are currently incapable of progressing throughout the distinct embryonic stages, their increasing likeness to human embryos means that researchers can use them to bypass the limitations posed by human embryo research.
That an increasing likeness to human embryos may make these models ethically contentious to some, did not go unnoticed by the International Society for Stem Cell Research (ISSCR), who publish guidelines on responsible stem cell research. In its revised guidelines issued in May 2021 (see BioNews 1097), the first formal set of recommendations for research with embryo-like structures is strongly linked to the degree to which these models behave like human embryos. Research with models (such as 'blastoids' (see BioNews 1088)) that could one day possess a developmental potential akin to human embryos (called 'integrated models' by the ISSCR) is advised to require review by scientific and ethics oversight bodies in the guidelines. Research with models (such as ‘gastruloids' (see BioNews 970)) which lack important cell types and, therefore, cannot undergo continuous human development (referred to as 'non-integrated models' in the guidelines), are not deemed to require the same level of evaluation. There are also challenges in the field associated with 'benchmarking' human embryo-like models as there is a lack of human embryo studies to which these models can be compared.
Incidentally, these guidelines were issued at about the same time we concluded a pioneering focus group study on non-scientists' perspectives towards the creation and research use of human embryo-like models. This study is part of an ongoing research project aimed at exploring the ethical ramifications of research with human embryo-like models and at providing policy recommendations for its governance in the Netherlands. In our study, which included focus group interviews with a cross-section of the Dutch public as well as health ethics and health law professionals, we found that participants would have confidence in research with human embryo-like models as long as it was regulated. We believe the ISSCR's recommendations mark an important step towards meeting this requirement.
In the focus groups, calls for regulation were most prominent when considering the so far hypothetical scenario where human embryo-like models acquire a capacity for continuous human development. For some, models that had this ability were considered too valuable to be reduced to mere research material. For others, this capacity was only taken to mean a small change in moral and legal status. But rarely was it taken lightly by participants. These results reflect the ISSCR's more stringent recommendations for research with integrated embryo-like models, as these could potentially, one day, acquire this capacity.
The focus group participants' answers to the question of how far embryo-like models should be allowed to develop were generally related to the emergence of certain organs and systems, particularly the human heart and central nervous system. The emergence of these features was considered significant even if the embryo-like models they appeared in could not develop further. For ethicists, the question that rises is: on what basis? The central nervous system is traditionally regarded as morally relevant insofar as it provides the basis for sentience, and thus for feeling pain, which would matter independently of an entity's developmental potential. This was also part of the reasoning behind the 14-day rule even though any real capacity to feel pain can only emerge at much later stages in fetal development.
The moral relevance our focus group participants attributed to a beating human heart is not reflected as such in the ethical literature on the moral status of the human embryo, however. As it seems, this feature can only derive – at most, symbolic – moral value from the 'human being in the making' it presumably denotes. For embryo-like models that are incapable of developing into fully-grown humans, this should not be relevant.
We assume that, in order to view beating human hearts as bearing moral value in models that clearly cannot give rise to human beings, participants in our focus groups must have relied on a reversal of the reasoning mentioned above. Instead of the feature (in this case: a beating human heart) deriving its value from the organism it symbolises (in the traditional debate: the human embryo), the organism in question here (namely: the embryo-like model) is regarded as being morally considerable because of it having this feature. While it would be easy to dismiss this view as both unscientific and ethically problematic, we feel it is important for those involved in the development of guidelines for research with human embryo-like models to be aware of these public perceptions in an effort to further explore and connect with them.
Ana Pereira Daoud will be discussing ethical and policy implications of stem-cell-based embryo models at the Progress Educational Trust's online conference 'Reproducing Regulation: Who Regulates Fertility and How?', on Wednesday 1 December 2021.
Find out more and register here.