British scientists are limited to research on embryos under 14 days old – until recently no one was able keep an embryo alive that long. But now an ethical struggle looms

Later this week some of the world’s leading scientists will gather at University College London to debate a simple but highly controversial notion: that it is time to scrap the 14-day limit on embryo research.

Thanks to recent scientific breakthroughs, researchers have reached a point where they can begin to think of experimenting on embryos up to 28 days in age. The benefits for medical science would be considerable.

As a result, many are pressing for the 14-day rule – which has been enshrined in British law for more than 25 years – to be replaced with one allowing research to be carried out on embryos that have lived for double that period.

But the idea of scrapping a key tenet of Britain’s fertilisation laws dismays many. Among them is Mary Warnock, the eminent British philosopher whose committee first proposed the 14-day limit, a rule that has since been adopted in countries around the world as the ideal upper age for conducting research on embryos in the laboratory. Warnock warns that opponents of embryo research will seize on attempts to extend the limit as an opportunity to place the whole practice in jeopardy. “I suggest that researchers should now take more time to fully utilise the extra days right up to the 14-day limit before arguing for the legal limit to be extended,” she told the Observer last week.

The call to extend the rule will reignite the bitter debate that has surrounded the use of human embryos – created through in vitro fertilisation (IVF) – and will again bring religious figures, scientists, ethicists and politicians into conflict. Some warn that failure to extend the 14-day rule will block new medical treatments from being developed, while others say that any attempt to extend the limit could cause a backlash that could see all embryo research being blocked in the UK – arguments that will dominate the Progress Educational Trust meeting on embryo research that will be held in London on Wednesday.

Embryo research was propelled on to newspaper front pages in 1978 by the birth of Louise Brown, the world’s first IVF baby. Many worried about how the technique might be used. “It was said that mad scientists would set up their laboratories, create embryos using IVF and keep them going for their experiments and not destroy them until they were great big, curled-up foetuses in test tubes,” Warnock recalls. “Researchers might even allow these embryos to develop in the laboratory until they became babies.”

In 1982 the British government decided to set up a committee to investigate and asked Warnock to be its chair. “We were set up to advise ministers on whether or not IVF should happen. And if it was acceptable, how should it be regulated?” she says.

Facebook Twitter Pinterest Mary Warnock, whose committee first proposed the 14-day limit. Photograph: Sophia Evans/The Observer

On one side, scientists were pressing to be allowed to carry out research on early embryos to improve IVF success rates; there had been only a handful of successful births using the technique – and hundreds of failures. On the other, there were widespread public concerns about the uncontrolled creation and use of human embryos, and these fears needed allaying.

“It took us very little time to decide IVF should be allowed to continue,” says Warnock. The question was: what limits should be imposed on its use? To what stages should research on embryos be restricted?

At first the commission considered a cut-off period for banning in vitro research that would depend on the stage of development an embryo had reached, not on how old it was. In other words, once an embryo had reached a particular stage in its growth it could no longer be used in experiments and would be destroyed.

Warnock vetoed the idea. “I would not have that,” she says. “That was my specific contribution to our final report. We were talking about the law, about advising ministers to legalise – and by inference criminalise – the issue. We needed certainty above all. So we decided we had to have a specific number of days, a specific inviable age for an embryo, as a limit for its use in research.”

After some discussion, the commission settled on 14 days. “Before 14 days, it is absolutely certain – beyond any doubt whatsoever – that there are no beginnings of a spinal cord in an embryo,” says Warnock. “That means that whatever is done to the embryo during that period it cannot be feeling anything. And yes, it was a pragmatic decision. Everyone can count up to 14, after all.

“After this stage, however, development of the embryo becomes very rapid and it develops quickly towards becoming a foetus with a spinal cord and a central nervous system. So that is why we came up with that limit.”

Many opponents of Warnock’s proposals picked on this specificity because the 14-day rule looked arbitrary. “It was arbitrary,” admits Warnock. “It could have been a different number, but not a very different number: 12 or 16 perhaps.”

Setting this limit proved to be a successful ploy. Many opponents had claimed that the 14-day limit would soon be disregarded and that society would, over the years, descend down a slippery moral slope in which limits on embryo research were insidiously slackened until it proceeded without any control. However, the 14-day rule – fastidiously policed by the Human Fertilisation and Embryology Authority – has survived in the UK for the past 25 years. Indeed, the limit has become the model for legislation in many other European countries.

However, observers have also pointed to another factor for the survival of the 14-day rule: no scientist had actually come close to developing a technique for keeping an embryo alive for that time. The average age of an embryo’s survival in the laboratory has been around three to five days. There has therefore been little pressure to extend the 14-day limit, because it has remained an unreachable goal. Thus the scientific status quo has been preserved and the slippery slope avoided.

“At the time it was thought to be a very safe limit, because there was no way you would ever be able to keep an embryo alive much beyond seven days,” says Robin Lovell-Badge, of the Francis Crick Institute in London. “So if you set a 14-day limit, that gave a great deal of leeway. It seemed very, very safe.”

But that situation changed dramatically this year when a group led by Magdalena Zernicka-Goetz, at Cambridge University, published a paper in Nature in which they described how they had succeeded in keeping human embryos alive, in special oxygenated environments in their laboratory, for 13 days.

Facebook Twitter Pinterest Magdalena Zernicka-Goetz, from Cambridge University, whose team published research on the viability of keeping embryos alive for 13 days.

“When we reached the 13th day, we stopped the experiment because we were so near the legal limit,” says Zernicka-Goetz. “We could have gone to the limit, but I don’t know how much longer the embryo would have survived. I suspect it may be possible to reach the limit this way or perhaps we will have to make further improvements in our techniques.”

The crucial point is that scientists have, for the first time, developed a technique that could actually allow embryos to grow – outside a mother’s body – for up to 14 days. And that is enormously important, says Zernicka-Goetz. “We really do not know how human embryos develop in the period between the seventh day and 14th day of conception. Now we have the chance to do that – with enormous benefits for medicine.”

For example, by studying embryos at this later stage it should be possible to pinpoint the best markers or biological signals that could help doctors improve IVF implantation rates. These biomarkers could be tracked through an embryo’s early development, making it possible to pick those embryos that are the best candidates for surviving implantation in mothers-to-be. “We might be able to predict which embryos will do well and those that will not, and so improve IVF pregnancy rates,” says Zernicka-Goetz.

However, the creation of embryos that survive in the laboratory for almost 14 days raises a more controversial issue. Can scientists go further, and if they could, is there now a case for changing the 14-day rule to one that will allow them to grow embryos in the laboratory for a greater period of time? Are there likely to be tangible benefits? Lovell-Badge believes there are strong reasons for such a change, and is now suggesting that the 14-day rule be scrapped and a new, higher limit – of 28 days – be imposed on embryo research.

“There is a time known as the black box and it covers the period from around seven days to 28 days after conception. This is a time when all sorts of critically important stages in the development of a human take place.

“In particular there is the process known as gastrulation, when the body plan is laid down and the three main tissue layers – the ectoderm, mesoderm and endoderm – are formed as the biological foundations for the specialised tissues of the nervous system, muscle and blood, and lungs and intestines.

“We know very little about that time in human development. Indeed, we know far more about that stage in other animals. However, by extending the time we can keep human embryos in the laboratory we have a chance to tackle this critically important early stage in human development.”

To emphasise this point, Lovell-Badge quotes the remark of the distinguished embryologist Lewis Wolpert, who once argued that “it is not birth, marriage or death, but gastrulation that is truly the most important time in your life”. By extending the 14-day rule to 28 days, scientists would for the first time be able to study this stage of development – when all sorts of congenital problems can arise to blight later lives – in proper detail.

Zernicka-Goetz agrees. “Extending the rule would have benefits for our understanding of our own development, in explaining why it goes wrong and in finding ways to put those errors right. However, I don’t think that we should make any change without there being a consensus among the public, ethicists and scientists. We need to set limits within which most of us are comfortable.”

This view is also backed by IVF expert Simon Fishel, head of the CARE Fertility Group. “I think if we could extend the limit for embryo research to around 28 days, the benefits for medical research would be enormous,” he says. “It would give us 20 years of research that would transform our understanding of ourselves. There is only so much we can learn from animal experiments, from other species, after all. Certain tumours, developmental abnormalities, miscarriage: there is a whole raft of issues in medical science that we could start to understand.”



The debate will be fraught and passionate, however. Not everyone is so enthusiastic about the proposed extension of the 14-day rule, or for that matter the legislation that enacted Warnock’s ideas. Some believe, many on religious grounds, that 14 days, or indeed one hour, is already too long.

Professor David Jones, director of the Anscombe Bioethics Centre in Oxford – who will speak at this week’s conference – believes the act is a hypocritical one that pretends to give protection to embryos but does not. “In the original act, a lot of things were prohibited – the creation of hybrid embryos, the cloning of embryos and the genetic modification of embryos. These have all been swept away, so I wouldn’t be surprised if they did shift the 14-day limit,” he says. “In any case the 14-day limit is not philosophically defensible. I don’t think there is a difference between a 10-day-old embryo and a 20-day embryo in terms of its moral status.”

Nor does the idea of extending the limit impress Warnock. She believes such a move could have unintended consequences for embryo research. “If we raise the limit, objectors could argue that the 14-day rule has remained intact simply because no researcher had the technique to keep an embryo alive for so long, and that now one has been discovered the rush down the slippery slope will follow. They will say: ‘We always knew that the slippery slope would prove itself.’

“That is why I want the 14-day rule to remain in place. You cannot successfully block a slippery slope except by a fixed and invariable obstacle, which is what the 14-day rule provided.”

For his part, Lovell-Badge denies the existence of Warnock’s slippery slope. “After 28 days, we have other sources of embryonic material – those created during ectopic pregnancies that cannot, of course, go to term, for example. So we could say, quite legitimately, that this would be an inflexible barrier and would not be changed in future. The alternative is to lose a very important source of information that would bring major improvements to our understanding of congenital conditions and other ailments.”

Warnock acknowledges that, if there are overpowering scientific reasons for extending her 14-day rule, then this should be allowed to go ahead. However, she sounded a note of caution. “We should note that every time the law about embryo research has been changed or amended the opposition has rallied its forces, and I think it would do so again if we try to get the 14-day rule extended. The risk is that all the progress we have made since 1990 would be lost.”

Rethinking the Ethics of Embryo Research: Genome Editing, 14 Days and Beyond. Progress Educational Trust. Institute of Child Health, University College London, 7 Dec, 9.30am-5pm.

THE WARNOCK COMMITTEE

At the time that the Warnock committee was sitting, scientists were most concerned with keeping embryos alive so that they could use them to study the causes of infertility. However, a decade later, when the Human Fertilisation and Embryology Act was being put in place, in 1990, there had been a distinct shift in priorities.

Scientists believed that within a few years their studies of early embryos would allow them to pinpoint those that were affected by serious, potentially lethal ailments which could be corrected to allow those embryos to develop into healthy children.

“There was tremendous excitement at this time,” says Warnock. “However, progress has turned out to be amazingly slow. Work on interventions like these is only just beginning.” This work has become possible thanks to the very recent development of gene editing which works like the find-and-replace function on a word processor. It locates a gene to be edited, then it makes the necessary change to it, either by deleting or repairing it or by inserting a new gene from another species. Genetic modification has become a dramatically simpler process as a result.

Yet the technique is still only in its infancy. To date, only one scientist - Kathy Niakan, of the Francis Crick Institute in London - has been given approval in the UK to gene-edit human embryos in vitro, and this work is aimed purely at altering genes that are active in the first few days after fertilisation in order to help in the development of treatments for infertility.