Research into what could be termed “embryo models” manufactured artificially in laboratories has been conducted for several years by a few teams (United Kingdom, Israel, United States etc.). They have been the subject of recent scientific publications, with some reverberations in the media – between facts, fantasy and illusory promises – for which Alliance VITA proposed a decryption at the end of June. However, currently, in the rare states where such research is conducted, the scientific teams, in the absence of any legislation, refer to the recommendations issued by the Société Internationale de Recherche sur les Cellules Souches (ISSCR – International Society for Stem Cell Research).
In that context, in France, the Steering Council of the Biomedicine Agency (ABM) has decided to define a “framework agreement” for this type of research, which it has just published. The ABM stresses in its press release that this is “the very first document of its type produced by an ethical organisation both nationally and internationally”, which is worth mentioning.
Since the last French bioethics law adopted in 2021 – which considerably relaxed certain regulations governing research on embryos and embryonic stem cells – some research protocols on human embryo stem cells are subject to a declaration to the Biomedicine Agency which systematically consults its Steering Council for guidance. That is the context in which this advice is being published.
According to this advice, although the first publications on research are recent (2014), rapid progress has been made over the last few years, with the publication of the constitution of embryo models, for mice and for the human species. The authors also underline that their thinking is dependent on the current state of scientific knowledge, which by definition, is in perpetual motion.
Concerning terminology, the Biomedicine Agency has chosen to use two terms: ‘embryonic model’, which is the term preferred by the ISSCR, and the term ‘embryoids’, as an equivalent.
An advice based on ISSCR guidance
There is therefore currently no true legislation in the world precisely devoted to these models. The ISSCR guidance is therefore used as a reference, in the absence of any alternative.
In its latest issue, their guidance identifies the different stakes concerning “non-integrated models” and “integrated models”, which are differentiated by the types of cells used.
- The first case is a model which, at the current state of knowledge, is considered unable to form a complete embryo.
- The second case, the “integrated embryo model”, if it were to be implanted, again according to the current state of scientific knowledge, could initiate the early stages of development.
The ISSCR therefore recommends that “research on integrated models must be approved from the ethics committees whereas research on non-integrated models may be simply notified to those same committees”.
The ISSCR maintains the prohibition to implant these models in a human or animal uterus.
On the other hand, the ISSCR has deleted from its recommendations the prohibition for the culture of human embryos beyond 14 days. On the contrary, the authors of the advice consider that if the “setting of a time limit always appears arbitrary”, the limit of the fourteenth day was founded on “embryological events”, among which, the possibility for an embryo to separate to form monozygotic twins.
An intermediate position
In its paragraph on “Which ethical considerations should be considered?”, the advice by the ABM mentions primarily the scientific benefits of research in this field, and underlines that “numerous biomedical applications may be expected”. The advice is presented as a middle of the road position between a restrictive position (controlling research on these models as research on human embryos) and a so-called more permissive position (these models are mere” clusters of cells” requiring no specific control).
The “intermediate position” considers that the embryo models “therefore need specific control which should be more flexible than that for research on embryos, but more strict than that concerning research on conventional cell lineages.”
Status of the models
Although the ABM position is similar to that by the ISSCR on this middle of the road position, the advice also includes a more distinct position on the status of embryo models.
According to the authors, “human embryoids, by essence, cannot be equivalent to embryos”, and they give two reasons.
- First of all, the absence of fertilisation between two gametes as the source of the embryo model,
- Secondly the ‘intention’, which distinguishes the initial “parental project” of an embryo, even if it is subsequently donated for research, and the absence of such a “project” for embryo models.
The advice does not elaborate on the validity of this criterion in the event that a research scientist might intend to create a model to be implanted for a pregnancy.
The authors state that “the parallel constantly being made between embryoids and embryos compels us to consider the status of the human embryo”.
They note that “the development of the zygote at birth, thus constitutes a continuum, whereby any segmentation is artificial in nature” whilst at the same time quoting the position of the CCNE (National Consultative Ethics Committee) which “considers that it is impossible to define a status for the embryo”. A kind of major ethical discrepancy which is bewildering.
On the basis of general principles (proportionality, precaution) the ABM Steering Council provides several concrete recommendations at the end of its advice:
- An unfavourable advice concerning any extension of the 14-day limitfor the culture of human embryos “even if scientific advances would make it possible”
- Authorisation for research on “integrated embryo models”, in particular on the most complete models, up to a development stage equivalent to the 28th day of development of a natural embryo, with a total termination of any experimentation beyond that stage.
- Prohibition of their implantation in vivo.
- The advice also recommends reconsidering the question of consent for donors of embryos or somatic cells intended to generate IPS stem cells.
A partial and biased approach
According to Alliance VITA, the advice has the advantage of providing a framework for recent research whose developments are rapid and fascinating for research scientists.
It is also laudable that their advice does not follow the ISSCR line concerning an extension for the culture of human embryos beyond 14 days.
It is nevertheless undeniable that the use of scientific benefits or subjective principles such as the intention, as a basis to support an ethical vision remains a partial and biased approach stemming from a research agency.
Fundamentally, the possibilities offered by biotechnologies must not be allowed to dictate ethical decisions nor to modify our view and our relationship with the living and life in a more utilitarian direction.