Members of the British public recently gave their backing to a controversial proposal to alter the 14-day limit on human embryo research. If successful, the revised law will enable researchers to grow and study cultured human embryos for longer periods of time.
Some people are against this on moral and ethical grounds, but researchers argue the change will afford them unprecedented insights into human development, with improvements in fertility and health.
What is the 14-day rule?
The 14-day rule is a UK law which forbids research on laboratory-grown human embryos beyond 14 days of development. This includes ‘spare’ IVF embryos that have been donated to research, and also embryos created for research with donated sperm and eggs. It means that any experiment using a cultured human embryo must be stopped at 14 days after fertilisation.
Similar rules exist in other countries, such as the USA, Japan and China. Some of these rules are legally binding, whilst others are just guidelines. Some countries, such as Germany and Russia, do not currently permit any human embryonic research at all.
Why is the current embryo research limit set at 14 days?
The limit was chosen for scientific and practical reasons. At 14 days, the human embryo is a small, simple structure, made of two layers of cells. There is no head or heart, brain or spinal cord, nor recognisable organs of any kind. The embryo is made of stem cells, which have the potential to form specialised cell types, such as neurons and muscle cells, but this is yet to happen.
Unequivocally, the embryo cannot think, feel pain or experience consciousness, so the 14-day cutoff time helped to assuage those who use moral arguments to challenge human embryo experiments.
“It was always an arbitrary limit that enabled some research to go ahead in the face of what was strong opposition at the time,” says Robin Lovell-Badge, head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute, and co-chair of the group that oversaw the public engagement exercise.
When the current law was established back in 1990, researchers were also just starting to learn how to culture human embryos. They could grow them for up to a week, but after that, the embryos all failed. The 14-day limit seemed unachievable, and so the time limit was deemed a safe bet.
Why do some researchers want to change the rule now?
To many, the science has moved on. In 2016, scientists from the UK and the US managed to grow human embryos in the lab for 13 days – the longest time period ever recorded. The embryos probably could have been grown for longer, but the researchers obeyed the law and stopped the experiments. This means that the formerly unachievable 14-day limit is no longer unachievable.
Scientists are also able to make ‘synthetic embryos,’ also called ‘embryo models.’ These are embryo-like structures that are made from stem cells. There is no involvement of egg and sperm, and so there is no fertilisation. Synthetic embryos are not embryos, but they are a lot like them.
Scientists are using them to learn more about human development, fertility, health and disease. The structures aren’t mentioned in the 14-day legislation because they hadn’t been invented when the law was passed. It’s unclear, therefore, how the regulation applies to them.
A few months ago, scientists in Israel managed to grow these synthetic human embryos for 14 days. Now UK scientists have done the same thing.
“They could have taken them further,” says Lovell-Badge, but the researchers terminated the experiments because they knew they were headed for ethically, scientifically and legally unchartered territory.
This, some scientists argue, is another reason to review the 14-day limit and add appropriate regulation for synthetic human embryos.
What do they want to change the embryo research limit to?
Scientists are keen to learn more about the so-called ‘black box’ of embryonic development, which is the time period that occurs between two and five weeks after fertilisation.
During this time, the embryo becomes a multi-layered structure containing specialised cells. It gains a rough body plan in the form of a top and a bottom, a front and a back, and a left and a right. Rudimentary organs, such as the heart, kidneys and gut, begin to form.
Researchers know very little about this process, known as gastrulation, because they have never had access to human embryos of this age. They have studied embryos donated by women having terminations, but these embryos are almost always older than six weeks, and gastrulation is well and truly finished by then.
The new limit has not yet been decided, and scientists are keen to have the public involved in this process. One option is to go for three weeks, but then the law may need to change again as it becomes possible to grow embryos beyond this point.
Another option is to go for five weeks or more, or no limit at all, depending on the nature of the experiment, but this is likely to leave people feeling uneasy.
For many, four weeks is a good compromise. At this point, the embryo still doesn’t have a functioning nervous system, but gastrulation has occurred and is completed with a neatly observable endpoint: the neural tube, which is the structure that goes on to form the brain and spinal cord, finishes forming.
“I think this is the most practical outcome,” says Lovell-Badge.
Do all scientists want the extension?
“Within the field, I think the majority of scientists would like to see the 14-day rule extended,” says Lovell-Badge, who also chairs the International Society for Stem Cell Research Guidelines Update Task Force and works closely with scientists in the field.
For researchers who argue against the extension, a key concern is that the proposal could backfire, and lead to restrictions that make embryo research more, rather than less, difficult.
Although the first 14 days of human embryonic development are well studied, there is still more to learn, so scientists don’t want this to be jeopardised.
Other groups outside of academia, such as Right To Life UK, oppose any experimentation on human embryos.
What could scientists learn from extending the 14-day limit?
Spina bifida is a birth defect that occurs when the neural tube starts developing but doesn’t finish forming correctly. Its origins lie somewhere in the ‘black box’ of embryonic development, so if scientists can study this event in cultured human embryos, they may be able to devise new ways to prevent or treat the condition.
The same goes for other congenital abnormalities, which have their roots in the same time period. We know that when pregnant women take folic acid, it reduces the risk of spina bifida. There could be other dietary supplements that reduce the risk of congenital disorders of the heart and other organs. Extending the 14-day limit will help scientists to work this out, by testing various molecules on cultured embryos.
An extension to the 14-day limit could also help those with fertility problems. The success rate for IVF is just one in three, with many embryos failing around the time of gastrulation. Similarly, many miscarriages occur about the same time.
If scientists are able to study gastrulation directly, then they can begin to understand why the process sometimes goes wrong, and devise ways to prevent this.
It could also help them to improve other fertility techniques, such as mitochondrial donation. This is when healthy energy-generating structures called mitochondria are used to correct faulty versions in eggs or early embryos.
Synthetic human embryos can help with all of this too, but at the moment there is nothing to validate them against. Scientists know they are similar to regular human embryos, but because no one know has been able to study the ‘black box’ of normal embryonic development, it’s impossible to say if the synthetic embryos mimic this part well or not.
If they do, then scientists could end up using fewer normal human embryos and more synthetic ones. Synthetic human embryos are more readily available, so this could speed up the research process.
About our expert
Prof Robin Lovell-Badge is the head of the Laboratory of Stem Cell Biology and Developmental Genetics at the Francis Crick Institute. His research has been published in the journals Science Advances, Cellular and Molecular Life Sciences, and Nature Communications.
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