Why has a UK team genetically edited human embryos?
Dr Kathy Niakan/Nature By Michael Le Page Human embryos have been genetically edited in the UK for the first time, using a technique called CRISPR. But why do researchers think this is so important? The UK team, led by Kathy Niakan of the Francis Crick Institute in London, used the CRISPR genome-editing method to disable a gene thought to play a key role in early development. The researchers used around 60 spare embryos donated by couples who’d had IVF, which would otherwise have been discarded. The embryos had been frozen at the one-cell stage, soon after fertilisation. After the embryos were thawed, the team injected CRISPR components that target and cut DNA in a specific place. These were designed to disable the gene that produces a protein called OCT4. The embryos were allowed to develop for a week before their DNA was analysed. In humans, only around 12 per cent of fertilised embryos make it all the way to a live birth, says Niakan. In the long term, she hopes this kind of work will reveal why. “If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure,” she says. “Our study is just the first step.” In fact, the main aim of the study was just to see if CRISPR can be used to disable genes in human embryos – and the results prove it can, says Fredrik Lanner of Karolinska University Hospital in Sweden, who also works on CRISPR. “This has not been possible before,” he says. No, there’s more. As expected, the results confirm that OCT4 plays a key role in early human development, just as it does in mice. In the rodent, however, OCT4 is only needed after the embryo has developed into a blastocyst: the 200-cell stage reached by around seven days. Niakan’s team found that human embryos in which OCT4 was disabled failed to develop to the blastocyst stage. So OCT4 seems to kick in earlier in human development. It also seems to have extra roles not seen in mice. This shows the importance of studying human embryos as well as those of animals, says Lanner. The short answer is that we don’t know yet. But there are several possibilities. For instance, embryos release molecules into the nutrient medium in which they grow, says Niakan. It might be possible to use these to work out which embryos are healthiest before implantation. The nutrient media used in IVF are also based on what works for mice rather than humans. A better understanding of early human development could help us develop better formulas. Several studies involving genome editing of human embryos have been done in China and the US, but their aim was to find out whether CRISPR could be used to repair the genes of our children, rather than to study embryonic development. Only two of these studies used apparently healthy embryos as Niakan did – the others used embryos with abnormalities because the teams involved thought this was more ethical. The results of these earlier studies suggest several hurdles remain before we can think of using CRISPR to edit the genes of our children. Last month, a US team said it had solved some of these problems, but there are serious doubts about the claims. As far as we know, nobody is planning to perform this kind of editing to create so-called “designer babies”. Not directly. Niakan’s team used CRISPR in a way that is very effective at disabling genes, but not for making the precise changes necessary for preventing genetic diseases or creating “designer babies”. “You would not want to use this,” says Niakan. “It’s introducing insertions and deletions randomly.” That varies widely from country to country. In the UK, it is overseen by the Human Fertilisation and Embryology Authority. Niakan had to apply for permission from the HFEA as well as from a separate ethics committee before going ahead. She has approval for two more studies to investigate the role of other genes. Many other countries either ban research on human embryos outright or – like the US and China – don’t have laws specifically preventing it. However, in the US, federal funds cannot be used for such research. Journal reference: Nature, DOI: 10.1038/nature24033 More on these topics: