Medical News
He Jiankui told scientists of his attempt to edit the CCR5 gene at a summit in 2019S.C. Leung/SOPA Images/ZUMA Wire/Alamy Live News
By Michael Le PageA genetic variant that makes people resistant to HIV infection may also have detrimental affects. People who have this variant are more likely to die a little early, according to a study of 400,000 people in the UK.
The finding has strong implications for our abilities to enhance future generations using genome editing techniques. Last year, He Jiankui (pictured above) in China controversially used CRISPR to mimic this naturally-occuring gene variant in two babies. But the new study suggests we simply don’t know enough about the full effects of most genetic variants to be sure that giving them to people will be beneficial.
“This is a good example of the great danger of manipulating genes in humans when our understanding of the function of most genes is so rudimentary,” says Alcino Silva of the University of California, Los Angeles.
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The CCR5 gene codes for a protein that sticks out of some of the cells in our immune system and in our brain. HIV infects immune cells by first binding to this protein, and some people are naturally resistant to HIV because they have a mutation called delta 32 in both their copies of the CCR5 gene. This mutation disables the protein.
As well as making people resistant to HIV, this delta 32 mutation has also been found to boost the memories of mice and has been linked to improved stroke recovery in people. But the mutation may also have negative effects, such as making people more vulnerable to some other viruses, including West Nile and, possibly, flu.
Living two years less
To get an idea of the overall effect of the mutation, Rasmus Nielsen of the University of California, Berkeley, and his colleagues analysed data on 400,000 people in the UK Biobank. They found that people who have two copies of the delta 32 variant of the CCR5 gene were 20 per cent more likely die before the age of 76 than those who had one copy or who did not have the mutation at all.
The study suggests that people would live around two years less on average, says Luke Jostins-Dean of Oxford University, who studies genetic variants in the immune system.
Jostins-Dean has previously criticised claims about CCR5 for being based only on small studies. The latest study is not completely robust, he says, but it is enough to show that we should not be engineering this mutation into children.
Geneticist George Church previously included the delta 32 mutation in his list of 10 beneficial gene variants. In 2018, Jiankui attempted to use CRISPR gene editing to induce the delta 32 mutation in IVF embryos from couples where the father was HIV positive.
“The girls are safe and healthy as any other babies,” He claimed in a video announcing the birth of two girls. But his actions were condemned as unethical for many reasons, including the fact that the full consequences of this mutation are not yet understood.
Does the new study suggest the gene-edited girls might die earlier? Perhaps. The mutations reportedly induced in these children are not the same as delta 32, and are not present in all the cells in their bodies either, says Robin Lovell-Badge of the Francis Crick Institute in the UK, so we can’t be sure.
What’s more, the effect of mutations in CCR5 could be different in different populations exposed to different diseases. “The UK Biobank is certainly not representative of the population of China,” says Jostins-Dean.
Journal reference: Nature Medicine, DOI: 10.1038/s41591-019-0459-6
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