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5 May 2015

Now we can edit the human genome, the question is: should we?

Some of the diseases that could be cured are far more distressing than mutations in an embyro that was never going to develop anyway.

By Michael Brooks

Editing the genome of a human is now officially a thing – and it’s a thing we need to talk about.

Our capabilities in this field are becoming astonishing. We have identified a set of tools that can be put in contact with a biological cell (or a group of cells) and that will go to work, robot-like, on the DNA within them. In theory, this will allow us to fix disease-causing sections of DNA, like a plumber replacing a faulty valve on a radiator.

And things could get even better than that. If you catch the fault when it is in sperm, or an egg, or even an embryo, it would be like repairing a faulty production-line robot: all the DNA units produced after the fix would be healthy and fully functioning, and so will the organism that subsequently develops.

Chinese researchers have tested this theory. They looked at embryos containing a faulty gene that would lead, in a fully formed human, to a hereditary blood disorder – unless the gene was replaced. Enter the gene editor, a co-operative group of molecules known as CRISPR, which scientists have borrowed from bacteria. The molecules evolved to help bacteria fight off viruses and the design of their weapon system allows you to customise them to chop out a particular sequence of DNA. All you have to do is supply the DNA you want in the gap. If the cell takes it up, you have a perfect repair.

The chief attraction of doing this with an embryo – or even with eggs and sperm containing faulty DNA – is that it’s a long-term fix. The fault is stopped in its tracks and taken out of the hereditary line. The problem is that if the repair induces side effects, those are passed on, too.

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In the Chinese experiment, there were side effects aplenty. The team put CRISPR to work on 86 embryos. CRISPR successfully removed the faulty gene from 28 of them but only a few had taken up the correct form of the gene. Even more disappointingly, the researchers found that CRISPR had been something of a loose cannon. The embryos contained a disturbingly high number of mutations in other parts of their genomes, possibly the result of poorly focused cutting and splicing on CRISPR’s part.

There was no risk of mutant human beings, however. The Chinese work was carried out on embryos identified as “non-viable”: there was no chance of them developing beyond a tiny handful of cells.

This research is certainly far from ready for deployment on anything approaching viable human embryos. Indeed, because it works so poorly, many scientists have called for a halt on all human genome editing research. The two most prestigious journals in the field, Nature and Science, refused to publish the Chinese work on ethical grounds. Ironically, that may be good news: the paper eventually appeared in a journal that is free to access (Science and Nature are not), so all who are interested, whether they are scientists or not, can read about the work and join in the conversation about it.

And we do need to talk about this. The call for a halt is far from universal. Many scientists argue that the Chinese research was well within the boundaries of ethical practice. It is also desirable, supporters say. Some of the diseases that could eventually be cured by this technique are far more dangerous and distressing than genetic mutations in an embryo that was never going to develop anyway. In theory, genetic editing can rid humanity of sickle-cell disease, haemophilia and a host of less well-known diseases.

What’s more, the Chinese team wasn’t using state-of-the-art CRISPR techniques. In many ways, it may have skewed the pitch: we can do better than this publication suggests. The only question is: should we try?

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