This is a significant paper, not only for the reasons stated in the Discussion, but because of its potential (which the authors do not state) to help frame future regulations on the use of human embryos and simbryos (the class of artificially-induced, self-constructing stem cell structures used or proposed as models of early development).

Some readers are likely to be taken aback by the fact that the human embryo used in the research had reached 16 to 19 days of development. Is this legally possible? Isn’t there a strict 14 day limitation? Well, the answer is that, of course there is a 14 day limit, but that the research fell well within the applicable regulatory framework. The legal significance of the paper lies not in the fact that research was undertaken on a post 14 day human embryo, but in the findings of the research itself. These findings may inform the revision of the existing limitations and the decisions of ethical boards.

First, we need to be clear that the regulatory activities took place in England. The embryo concerned was provided via the Human Developmental Biology Resource and fully consented for research for which there was ethical approval (see Methods). Second, the embryo was not “live”. It is this fact, rather than that the embryo was not the product of in vitro fertilisation, which prevents the prohibition under section 3 of the Human Fertilisation & Embryology Act 1990 (HFE Act) applying. Instead, the embryo is regulated under a different UK statute, the Human Tissue Act 2004 (HT Act), which applies to foetuses and to non-foetal products of conception (such as amniotic fluid, umbilical cord, placenta and membranes). In other words, not just the embryo, but anything deriving from the trophectoderm, provided it comes from the mother’s body, falls under the HTA. For all these reasons, the famous 14 day rule does not apply. The research fell well within the regulatory framework.

The material involved, a single, perfectly preserved embryo at Carnegie Stage 7, is very unlikely to become available often, not least because of the prohibition on cloning human embryos. However if, hypothetically, aborted embryos were maintained “live” in a culture dish, a licence from the HFEA would be required, although no research would be possible after appearance of the primitive streak (at 14 days) without a change in the law.

Hopefully, that clears up the regulatory whys and wherefores concerning this sort of research. But it really is an exceptional study, not only because pristine, naturally-occurring human embryos of such an early stage of development are extraordinarily difficult to come upon, nor because of the exquisite techniques applied to identify and map the gene expression of all the embryo’s cells, but because of the significance of the actual discoveries made. It provides a genomic map for human and comparative anatomy, taken shortly after the formation of the structure that will develop into a human body. It will undoubtedly help researchers to triangulate studies involving a range of species and simbryo/xenobot models exposing developmental divergences to further investigation.

Despite having dismissed any legal complications in this research project, I would now like to suggest that the research actually is of legal significance, as a data set for informing any revision of the UK HFE Act. This is because the 14 day limit established by that Act was the creature of a pre-genomic age in which the ethical status of the embryo was largely determined by morphological and religious considerations. Studies such as Tyser, Mahammadov, Nakanoh et al provide an opportunity to appraise the ethical significance of particular genes being activated at particular points in development. The authors note, for example, that “Our characterization reveals that the embryo at [16-19 days] already had [primordial germ cells] and red blood cells, but had not yet initiated neural specification”. [Para 2, Discussion]. Depending on the ethical weight given to such aspects, future legislators may use these data as a reference point in re-considering an advance on current limitations on human embryo research. It will certainly be a touchstone to those ethical bodies in jurisdictions looking to the 2021 guidance of the ISSCR, in relation to both human embryos and simbryos.  Although there are no plans to reform the HFE Act, the Authority may recommend to the Secretary of State that it be taken into consideration in any revision of the Act. Certainly, pressure for change is building up, most recently in relation to the period of consent to the use of gametes, but also in relation to the terms of heritable human genome editing and, as here, the period for which embryos may be cultured.