Jennifer Doudna, who jointly discovered a revolutionary new DNA-editing technique, says we ignore the ethical ramifications at our peril.

We need to talk about ‘cut-and-paste’ genome editing, warns pioneer

By Georgina Ferry

In science the greatest discoveries often turn up when least expected. It’s one of the strongest arguments in favour of supporting curiosity-driven research, as Professor Jennifer Doudna can attest.

It was curiosity that led to her and colleague Emmanuelle Charpentier discovering a technique that makes it possible to edit the genomic information in any individual – adding, removing or altering genes – as easily as executing a ‘search and replace’ command with word-processing software.

Less than a year after they announced their discovery in 2012, the technique had revolutionised research in biology, from plant breeding to human development. Here in Oxford new facilities have sprung up, helping researchers to share expertise in the technique — cumbrously named CRISPR/Cas9 — and exploring ways to develop it further. Yet the ethical and legal implications of its potential to treat human disease have yet to be fully explored, warned  Doudna in the prestigious Jenkinson Lecture this month. ‘I think it will be an ongoing discussion… In some cases it might be really desirable.’ In the 360-seat theatre at the Mathematics Institute, it was standing room only.

We need to talk about ‘cut-and-paste’ genome editing, warns pioneerDoudna, of the University of California at Berkeley, began her research ‘out of curiosity about how bacteria fight viruses’. Bacteria have adaptive immune systems that enable them to recognise invading viruses and disable them by cutting their DNA at precise locations. Doudna and Charpentier, who was then at the University of Umeå in Sweden, turned this knowledge into a tool that could quickly, easily and accurately make targeted edits to DNA at any point, in any species. The two scientists have since been garlanded with most of the major international prizes for science, short (so far) of a Nobel.

‘Being able to ask powerful questions in biology often comes down to changing a gene sequence and seeing what happens,’ says William James, Professor of Virology in the Sir William Dunn School of Pathology, who studies disease using induced pluripotent stem cells (another transformative technology). ‘When Jennifer’s work was published it was really exciting for all of us.’ While previous genome-editing methods existed, they were ‘expensive and laborious’, while drugs that blocked the action of genes were inevitably plagued by side effects.

In contrast, says James, the CRISPR technique is so easy he can pretty much guarantee visiting researchers that ‘if they are with us for two months they can knock out three genes’.

So far the technique has mostly been used to help answer research questions about the relationship between genes and disease. James can hunt down such links by correcting a mutation in cells from a sick patient while introducing the same mutation in cells from a healthy person. ‘It’s an immensely powerful way of closing the mechanistic loop,’ he says.

But in her lecture Doudna listed other applications that are already having an impact in agriculture and medicine. Researchers at Penn State College of Agricultural Sciences have edited the genome of a mushroom to prevent it from browning. And last year the US National Institutes of Health approved the first clinical trial to use CRISPR to treat cancer patients with their own immune cells, edited to fight tumours more effectively. Working with mice, Doudna’s team have edited the genomes of cells in the living brain, a technique that could potentially be used in neurodegenerative conditions such as Huntingdon’s and Parkinson’s diseases.

The most controversial potential application is to edit very early human embryos to eliminate faulty genes that cause life-limiting conditions such as muscular dystrophy and cystic fibrosis. Such ‘germline’ treatments are not currently legal in most countries.

One of the first to address the ethical implications of CRISPR is Christopher Gyngell, Marie Sklodowska-Curie Fellow at the Oxford Uehiro Centre for Practical Ethics. ‘CRISPR is the first editing technique to be efficient and precise enough to be used in humans’, he says. He thinks that even for germline editing, the ethical arguments are largely in favour. Pre-implantation genetic diagnosis already allows doctors to select a healthy IVF embryo for implantation where there is a risk of genetic disease. ‘We pick which will come into existence and which will not’, says Gyngell. ‘With editing, it’s more like a cure. You could say that was more ethically desirable.’

Genome editing is certainly here to stay. Before her lecture, Doudna met a group of graduate students from several Oxford departments over lunch. ‘Two years ago, maybe one or two of them might have been using CRISPR/Cas9,’ she told me. ‘Today, every single one of them was.’

Georgina Ferryformer editor of Oxford Today, is a science writer and biographer.

Genetic science image by wichy via Shutterstock. Portrait courtesy of Jennifer Doudna.

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