Should the 14-day limit on embryo research be extended?

In 1984, a committee appointed by the British government to draw up guidelines for in vitro fertilisation (IVF) in the wake of the birth of Louise Brown, the first “test-tube” baby, recommended that scientific research on human embryos should be permitted up to a maximum of 14 days after conception.

The recommendations of this report, led by moral philosopher Mary (now Baroness) Warnock, didn’t become law until the Human Fertilisation and Embryology Act was passed by parliament six years later. Among other things, the act set up the Human Fertilisation and Embryology Authority (HFEA) to license and regulate all in vitro embryo creation and manipulation, whether for IVF or for scientific research. Violations of the 14-day limit became a criminal offence.

That limit has remained in place ever since. But now some scientists believe it should be extended to 28 days. These proposals were discussed on 7th December at a meeting in London organised by charity the Progress Educational Trust. It marked the beginning of what seems likely to be a broad and extended discussion among scientists, bioethicists, fertility specialists, religious leaders and others who have a stake in the moral, legal and scientific status of the human embryo.

The meeting was a rather unique gathering of high-level specialists, which included Sally Cheshire, chair of the HFEA, the former Archbishop of Canterbury George Carey, Ian Wilmut, the lead scientist of the team at the Roslin Institute in Scotland that cloned Dolly the Sheep, geneticist Kathy Niakan of the Crick Institute who has been granted the sole license so far from the HFEA to genetically modify human embryos, and Warnock herself.

Until now there would have been little point in debating extensions to the time limit for embryo research, because no one had been able to keep a human embryo alive reliably and systematically for more than about a week. But this has changed very recently. Earlier this year a group at Cambridge University led by Magdalena Zernicka-Goetz (who also spoke at the meeting) reported that they have developed a method for culturing live human embryos for 13 days. They stopped the experiment at that point to comply with the law.

Up until day 14, human embryos are still rather simple entities. A key developmental state happens around day 5, when the ball of cells turns into a so-called blastocyst, the structure that is ready for implanting into the wall of the uterus. By this point, what began as a cluster of identical cells has “differentiated” into cells of different tissue types. Some have become the cells that will go on to become the body of the fetus: they’ll keep differentiating into the cells of the central nervous system, liver, heart, brain and so on. Others form the yolk sac, and others become the placenta.

So the 14-day embryo has begun the process that leads to the laying down of the human body plan—but only just. A key stage, called gastrulation, begins around day 16: this is when the embryo acquires a three-layered structure, the precursor to the appearance of different body-tissue types. So the time between day 14 and day 28 sees the embryo progress through some crucial stages of development, and understanding the details of what goes on, such as the genetic changes involved, should provide a wealth of information that might offer insights into human health, disease and malformation. Much of what we know about these stages at present comes from studies of mice—but as several of the speakers acknowledged, there are some important differences between mice and men.

This is why it looks so enticing for cell biologists and geneticists to investigate the post-14-day embryo. But should that be allowed by a change in the law?

Warnock herself advised against rushing into it. She explained that the 14-day limit, while in some respects arbitrary, was in other respects carefully thought through. As the secretary of the Warnock Report Jenny Croft has said, “there really isn’t a point at which the embryo becomes special.” But you can only legislate by creating such a point, however artificial and arbitrary it might be.

The 14-day cutoff wasn’t by any means totally arbitrary, however. It was partly selected because, shortly after that, the onset of gastrulation is marked by the appearance of a furrow called the primitive streak—the axis of the body’s mirror symmetry. Once that happens, the embryo can no longer divide into identical twins. So the primitive streak could be seen (albeit without real biological justification) as a marker of “individuality.” Fourteen days is also well before the beginnings of what will become the central nervous system, and so there is no hint that the embryo could have anything like sensation, let alone pain. (That point hasn’t, however, been reached at 28 days either.)

All the same, Warnock made no apology for the lack of any firm intellectual or scientific rationale for the 14-day limit. It was, as Sarah Franklin of the Reproductive Sociology Research Group at Cambridge put it, a distinctively English form of pragmatism: a compromise born of overlapping and to some extent conflicting logics.

Forging a consensus in the face of those conflicts was a major, indeed somewhat extraordinary, achievement of the Warnock Report. To destabilise it, said Warnock, would be to risk exposing the entire structure of embryo research to the substantial opposition that still exists, especially from some religious groups, who could easily use it to support accusations of a slippery slope.

What’s more, the ability to explore embryo development right up to the current limit is so new that there remains plenty still to be learnt from it. Why, then, rush (as one attendee said) to change the law the moment it becomes possible to break it? Although the six-year hiatus between the recommendations of the 1984 report and the passing of the HFE Act was largely due to the nervousness of governments to address this contentious issue at all, Warnock explained that the delay was useful for researchers—it gave them time to explain the benefits that could come from such research.

Such efforts have proved essential in other controversial areas of science for swaying what might be an initially hostile public reception. IVF itself was greeted with a great deal of suspicion and even disgust until it was explained that the purpose was to enable the creation of loving families. Warnock’s point is made not only from a position of unparalleled experience but with immense wisdom, and it seems worth heeding. The 14-day limit doesn’t necessarily have to remain fixed forever—but changing it needs a social mandate and public confidence, and the scientific case for benefits has not yet been properly made.

The meeting also included a session on the moral status of the embryo, but it would have been unrealistic to expect that this immensely contentious philosophical question could be resolved, or even much advanced. There simply is no “correct” answer.

Still, no one at any rate—not even Carey—mentioned the soul, which perhaps shows that the tenor of the debate has moved on somewhat from the 1980s. One person who is not averse to doing so in principle is David Albert Jones, director of the Anscombe Bioethics Centre in Oxford, who argued the moral case for a complete ban on human embryo research in his 2004 book The Soul of the Embryo. He recapitulated that case at the meeting, but he evidently feels his view is a minority one, marginalised and even dismissed as preposterous.

It isn’t that—but it does look increasingly hard to sustain, relying as it does on a kind of essentialism that the biological facts can’t support. Jones encapsulated the position neatly when he argued that, as the embryo is a developmental stage just like “fetus,” “baby” and “adolescent,” we keep the moral issues best in sight not by talking about the “human embryo”—as if it is some species of its own—but the “embryonic human.” It is a human at the embryonic stage.

That view depends, however, on a forward projection that isn’t universally or even usually valid. Most embryos never become human babies: Niakan pointed out that only around 12 per cent of eggs fertilised in the body develop beyond three months. Most either fail to clear some contingent hurdle of development or lack from the outset the necessary genetic endowment to develop to full term. Jones’ argument is somewhat like saying that, because all Olympic champions began as children, all children—regardless of innate endowment or even disabilities—must be considered “Olympic champions in waiting.”

The basic problem with arguments like Jones’ is that they attempt to project categories of living, breathing people onto biological tissues. This is inevitable, and shouldn’t be condemned—it is, as Alison Murdoch, professor of reproductive medicine at Newcastle University, explained, a common aspect of how people undergoing IVF regard the embryos they produce.

But it won’t work if we are trying to resolve moral questions of what is and is not permissible. And it’s only taking that position to its logical extreme when we witness such bizarre situations as the actress Sofia Vergara being in effect sued by her frozen embryos for denying them the possibility of being born, after her split from the man with whom they were conceived. This is possible in Louisiana, where the case is being contested, because this “pro-life” state recognises an embryo as a “juridical person.”

Biomedical advances make the incompatibility even more plain. It will soon be possible to turn mature adult cells—of skin, say—into gametes: eggs and sperm. Both gametes can be produced from the cells of either sex. Not only does this muddy the waters of what the real “potential” of our cells is—and make embryos seem a little less unique in this regard—but it raises complicated issues of responsibilities, rights and ownership.

Veteran stem-cell researcher Stephen Minger, in the audience, explained that it should be possible in principle for him one day to make embryos purely from his own cells, for research purposes. Do these then have the same moral status as embryos from IVF? Or should they even be regarded as Minger’s personal property, just like any other of his tissues? It isn’t obvious.

Even raising such prospects risks conjuring up visions of perverse, Frankenstein-style experiments. But no responsible scientist would engage in such experiments idly, and in the UK they are and will continue to be tightly regulated by the HFEA. And as Niakan has attested, the very existence of such a regulatory body, with clear, firm and well enforced rules, is not constraining but, rather, empowering for research. It is what has allowed British embryo and stem-cell research to be world-leading, and is what has attracted leading scientists like the American Niakan herself to come here to work. That too is part of the enormous legacy of the Warnock Report.