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The 14-day rule: calling time on embryo research

9 January 2017
By Dr Valerie Shaikly
Consultant embryologist
Appeared in BioNews 883

The second session of the Progress Educational Trust's annual conference 'Rethinking the Ethics of Embryo Research: Genome Editing, 14 Days and Beyond', looked at new embryo images that have potential to challenge the 14-day rule and discussed the potential benefits of extending the rule beyond the existing time limit.

The session was chaired by Sally Cheshire of the Human Fertilisation and Embryology Authority (HFEA), and followed the buzz of Baroness Mary Warnock's keynote address on the rule that she and colleagues established in 1984. It has only just become possible to culture embryos in the lab up to 13 days, and Baroness Warnock had admitted to being surprised at how long it had taken to challenge the rule.

Professor Sarah Franklin, director of the Reproductive Sociology Research Group at the University of Cambridge, characterised the development of the 14-day rule as a 'certain kind of English pragmatism'. She described the rapid normalisation and global spread of clinical IVF over the last three decades, and argued that IVF is more than simply a biological process but also a social process of translating biological facts. The Warnock Report, said Professor Franklin, was a social contract that was achieved against the odds, and any new limits 'would have to be based on what was alright to enough people to enable successful legislation'. Although the rule has stood the test of time, she said it was uncertain whether a revised rule would achieve the same alignment of reasoning and consensus.

The second speaker, Magdalena Zernicka-Goetz, professor of mammalian development and stem cell biology at the University of Cambridge, opened up the 'black box' of embryo development. In May of this year, she successfully cultured human embryos to 13 days – a stage of development that had previously been hidden within maternal tissues (see BioNews 850). Using fluorescent markers for five tissues that differentiate during days five to 13, she showed us amazing 3D microscopy images of embryo development. The self-organising capacity of cells without maternal input was evident.

Professor Zernicka-Goetz explained that a basic understanding of how these structures form in the early embryo could lead to the identification of causes of early embryo loss in pregnancy. Her research team had also noted differences in development between mouse and human embryos with regard to cell types and organisation, supporting the need to work with human embryos to understand human development. Such understanding, she claimed, could improve IVF efficacy by identifying markers of successful development. In addition, studies of early embryonic stem cell types could be used to discover the mechanism of some diseases and ultimately to develop cell replacement therapies. Although the embryos she cultured were destroyed (as per the rule) at 13 days, she had her doubts about whether they would grow beyond 14 days in her system. But she argued that extending the rule beyond 14 days would be a 'giant leap for science in the long term'.

This was taken up by the final speaker, Dr Simon Fishel, founder and president of CARE Fertility and the Rachel Foundation. He acknowledged the potential difficulties in extending the rule, recounting his experience in 1984, when he published his own research investigating the secretion of the pregnancy hormone human chorionic gonadotropin (HCG) by human embryos after seven days in culture. After the news of his research was publicised, he received a writ for murder!

However, he pointed out that more often than not human embryos don't lead to a pregnancy and live birth – it's estimated that 70 percent of fertilised eggs do not result in a baby being born. This is because genetic errors and chromosome abnormalities can occur in any of the 23 human chromosomes, and many of these are not compatible with life. Yet our understanding of human embryos is far less than our understanding of the fruit fly embryo, said Dr Fishel.

'A mouse is a mouse; a human is a human', he went on. Given the structural and molecular differences identified between species, he argued, further human embryo research is essential. Over a century ago, Fuss and Felix first investigated the formation of germ cells (1, 2), said Dr Fishel. We have had more than 100 years of questioning, and it is now time to use the molecular tools available to us to provide answers for the next generation, he argued.

The discussion that followed highlighted that there is still much to learn about embryos in the first 14 days of development. If the rule were extended, it was asked, would we expect to correct embryos with genetic or chromosomal abnormalities? It was pointed out that the 14-day rule was a cut-off associated with sentience and the ability to feel harm – but is there new evidence to challenge this? And was the association legitimate to begin with, given that the primitive streak represents only the earliest beginnings of the nervous system, long before there is any possibility of sensation or sentience? Professor Zernicka-Goetz said that she herself had not observed initiation of the primitive streak – the first cells that form the central nervous system – at day 13–14. As one audience member responded: 'Without information from research after 14 days, how do we know what questions to ask?'

PET would like to thank the sponsor of this session, the Anne McLaren Memorial Trust Fund, and the other sponsors of its conference - Merck, the Anne McLaren Memorial Trust Fund, Ferring Pharmaceuticals, the London Women's Clinic, the Medical Research Council and Caribou Biosciences.

1) Felix W, Die Entwicklung der Harn- und Geschlechtsorgane
Keibel-Mall Handbuch der Entwicklungageschichte des Menshen, Hirzel-Leipzig  2: 732-95 |  1911
2) Fuss A, Uber extraregionare Geschlechtszellen bei einem menschlichen Embryo von 4 Wochen
Anat Am. 39: 407-409 |  1911
9 March 2020 - by Julian Hitchcock 
The Dance of Life: Symmetry, Cells and How We Become Human is the autobiography of the developmental biologist Professor Magdalena Zernicka-Goetz, written with the unobtrusive but unerring support of a master science writer, Dr Roger Highfield...
18 December 2017 - by Dr Avi Lerner 
The Progress Educational Trust (PET)'s Annual Conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction' discussed some of the most important ethical and scientific questions facing human reproduction. The first session, chaired by Sarah Norcross, the Director of PET, tackled the very fundamentals. What is a sperm? What is an egg? And what is an embryo?...
6 February 2017 - by Dr Ciara Staunton 
Some have suggested that, after Brexit, British influence on rules about embryo research will be diluted. But this is far from true...
30 January 2017 - by Sarah Gregory 
Matthew Hill covers the 30-year history of the 14-day rule on human embryo research, bringing the topic right up to the present day and the current debate on extending the rule...
23 January 2017 - by Rachel Siden 
In this podcast, Professor Magdalena Zernicka-Goetz and Sarah Norcross discuss the current UK ban on researching human embryos in the lab for longer than 14 days...
9 January 2017 - by Baroness Mary Warnock 
As the Progress Educational Trust's Patron, Baroness Mary Warnock, is made a Companion of Honour in the New Year Honours List 2017, she offers her thoughts on whether the 14-day limit on human embryo research (which she originally proposed in 1984) should be extended...
19 December 2016 - by Giulia Cavaliere 
It's not enough to just talk about the benefits of extending the 14-day rule, we must also consider the views of those who believe that human embyros are persons...
19 December 2016 - by Dr Cathy Herbrand 
Baroness Mary Warnock was the first speaker at this year's Progress Educational Trust Annual Conference. She is best known for The Warnock report, which was written more than 30 years ago and has shaped legislation in the UK and around the world...
5 December 2016 - by Annabel Slater 
An extension to the 14-day human embryo research rule will be proposed at the annual Progress Educational Trust conference on 7 December...
24 October 2016 - by Anneesa Amjad 
In this podcast, Radiolab presenter Molly Webster explores the origins of the 14-day rule – the internationally agreed two-week time constraint on growing embryos in a lab...
Spineless criticism ( - 13/01/2017)
With respect, the final paragraph of Dr Valerie Shaikly's report appears likely to mislead some readers.  I'm sure that this was not intended and that Dr Shaikly merely meant to record questions raised on the floor at the PET conference.  Nevertheless, by blurring indirect speech with what appear to be statements of fact by the author, the report inadvertently gives credence to a common (and very harmful) misconception.  The error is so significant to any consideration of the 14 day rule that it is vital to record it here so that visitors to this site are not misled and so that they are able to correct the same mistake when they come upon it elsewhere.

Dr Shaikly is undoubtedly correct to suggest that the 14-day cut-off is associated with the embryo's "sentience and the ability to feel harm”.  It is also reasonable of her to link these capacities to the development of the nervous system.  However, she fails to record that the association is entirely misconceived.  The criteria of awareness and suffering were not adopted by the Warnock Committee as a basis for the 14-day limit.  Nor is it, as Dr Shaikly states, “given that the primitive streak represents only the earliest beginnings of the nervous system” or that its components are "the first cells that form the central nervous system”.  Cells that are neither phenotypically neuronal nor share any neurological function cannot be said to belong to even a primordial "nervous system”, let alone a “central” one.

Whilst it would be perfectly legitimate to have regard to the “sentience and the ability to feel harm” that a later stage embryo might have, the myth of the 14-day nervous system is so widely held, even among intelligent, well-informed people that there can be no sensible discussion about research limits without far better public understanding of human embryology.  Indeed, the primitive streak spinal cord is but one of a number of folkloric beliefs in embryology that persistently contaminate discourse on this important subject.

The prevalence of these ideas is a reflection of just how dark and deep is the black box of development that Professor Zernica-Goetz has prised open for us.  As the box's lid is raised and the light pours in, our understanding of these matters will inevitably provide new insights into how we become human; insights that will make us better equipped to make decisions on any extension of the current research limit.

Julian Hitchcock
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