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Genome editing: CRISPR at the cutting edge

23 January 2017
Appeared in BioNews 885

The fourth session of the Progress Educational Trust conference 'Rethinking the Ethics of Embryo Research: Genome Editing, 14 Days and Beyond' delved into CRISPR genome editing techniques – in particular, CRISPR/Cas9 – and what these mean for embryo research. Two speakers, Professor Bruce Whitelaw and Dr Kathy Niakan, spoke of how new scientific tools are challenging boundaries and the role that society has to play in judging the use of these tools.

First to speak was Professor Whitelaw, deputy director at the University of Edinburgh's Roslin Institute. For around 50 years, it has been possible to 'read' the human genome, he said. 'Now, we can rewrite the genome. Any sequence, in any genome. That is quite an unbelievable power to have.'

Genome editing has long since been technically possible, and Professor Whitelaw outlined previous techniques before explaining that they have been vastly superseded by easier, faster, and more precise CRISPR techniques. How these should be used is for society to decide, he argued, working from the basis that some of the ideas offered by science will be taken forward by society while others will be rejected. In order to make sound judgements, the public need to know how scientists might potentially use this technology in human embryo research.

Professor Whitelaw outlined work being carried out at the Roslin Institute, where he and his colleagues are using CRISPR/Cas9 to introduce useful genetic variation into livestock. They are also interested in manipulating elements of reproduction, potentially making it possible to produce animal offspring of just one gender. Other teams have used CRISPR/Cas9 to introduce cells from one species to another – for example introducing rat pancreatic cells into mouse embryos. This work could lead to placing human cells into animal embryos, for research into potential medical treatments.

Yet there was only one person in the room who was actually permitted to edit human embryos in the UK, and that was Dr Kathy Niakan of the Francis Crick Institute in London. Her team received the first (and to date, only) UK licence to use CRISPR/Cas9 on human embryos (see BioNews 837). Dr Niakan's team is primarily focused on the first seven days of human embryo development. Specifically, they are interested in the window between an egg being fertilised and its development into an embryo. At some point, the cells of the fertilised egg begin to differentiate into a specialised cells, and Dr Niakan's team want to identify which genes are responsible for this process. They plan to use CRISPR/Cas9 to remove one of the most likely genes, and observe the effect on developing human embryos.

Dr Niakan's team have not yet edited any human embryos. The areas of DNA they are investigating are incredibly variable and difficult to target. As a result, the team have so far been refining the technique in mouse embryos. Dr Niakan emphasised how useful genome editing is, and how essential it is to carry out experiments in human embryos. There are a vast range of genes that could be involved in early development. Using computational models to investigate genes is still extremely inaccurate, and genome editing allows scientists to move beyond hypotheses to actual experiments.

There is also a vast amount to learn about early embryo development. More is known about how mouse embryos develop than human embryos, and Dr Niakan gave a number of examples of the large differences between mouse and human embryo development. For instance, mouse embryos begin actively transcribing their own genes at the stage of one to two cells, whereas this occurs at four to eight cells in humans. Just 50 percent of fertilised human eggs successfully reach the blastocyst stage – and only 50 percent of these go on to implant as embryos. The HFEA decided to permit editing of human embryos in order to learn more about human development, which could ultimately reduce this wastage of embryos in research and in IVF, and could lead to better stem cell experiments.

Professor Whitelaw reflected on the impact of CRISPR compared with Dolly the sheep, which had been thoroughly discussed in the previous session (see BioNews 881). 'The explosion of media surrounding Dolly was quite unbelievable. But it's nothing compared to the scope of how CRISPR has gone into our lexicon.' Because the technology is so easy to use, it has taken months to be adopted, not years. And it is still a very new technology, which is just beginning to produce results. Scientific advances such as genome editing, and culturing human embryos up to (and beyond?) 14 days, open up new possibilities to investigate existing challenges, he said. However, both scientists and society need to agree on use of these scientific approaches. The challenge at the moment, said Professor Whitelaw, is balancing an environment in which scientists are regulated with freedom to experiment and innovate.

Professor Whitelaw argued that public engagement on this topic is 'absolutely essential'. He reflected that there is no single group known as 'the public', but rather the public consists of many different groups within society. Consequently, he thinks it is important for scientists to engage with all aspects of media and public events, in order to reach as many people as possible. Professor Whitelaw concluded that such events are essential not only to improve public understanding and involve the public in debate, but also allow individual scientists to develop and improve their own understanding too.

PET would like to thank the 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.

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