In one of the biggest science stories of 2018, Chinese scientist He Jiankui used CRISPR technology to disable a gene in two unborn children, protecting them (theoretically, at least) against HIV – making the twins the world's first gene-edited babies.
But, according to a report recently published in Nature Medicine, by modifying the gene associated with HIV, He may have unwittingly put the girls at risk of early death.
This is because many genes serve more than one function. As such, tinkering with DNA can lead to a number of unintended consequences. The edited gene (CCR5), for example, has been linked to cognitive activity – hence, suggestions earlier this year that removal of the said gene may boost memory and rev up learning potential – and vulnerability to diseases like the West Nile virus and the flu, as well as immunity to HIV.
"To go ahead and alter the germline based on partial understanding is not responsible," Feng Zhang, a CRISPR expert and biologist at the Massachusetts Institute of Technology, told the MIT Technology Review.
"It's another piece of information that we shouldn't be so careless."
The basis for He's procedure is evidence suggesting that people who inherit two malfunctioning copies of the CCR5 gene are immune to a common strain of HIV, which relies on the receptors produced by working CCR5 genes to "enter" and infect cells. We don't know why this mutation occurs naturally in some people, but scientists believe it first arose in prehistoric northern Europe. Today, an estimated 10 percent of Brits have one broken copy and another 1 percent have two.
But while the mutation may prove handy against HIV (and – some suggest – bubonic plague), it may prove detrimental against other diseases. Previous studies have linked the faulty genes to susceptibility to infections like the West Nile virus. Others have suggested that those with the mutation are more likely to die from the flu. The general implication being that it has an overall negative effect on mortality.
The Nature Medicine study appears to confirm this argument. Professor Rasmus Nielsen, and Xinzhu Wei, both of the University of California, Berkeley, analyzed genetic and mortality data collected for the UK Biobank. In all, they studied the data of more than 400,000 middle-aged adults, findings that those who carried two malfunctioning copies a) appeared less often in the Biobank that would be expected by chance, and b) showed a higher mortality rate.
"This tells us there is a process that removes individuals with two copies, and that process is probably natural selection. People die," said Nielsen.
By comparing the volunteers' data with death records, Nielson and Wei found that the mutation increased the chance of dying before 76 years by 3-46 percent. Taken as an average, people with two malfunctioning copies are some 21 percent less likely to reach 76 than those who did not.
"We don't have enough data to say for certain what is the mechanism for increased mortality but this effect on infectious diseases, particularly influenza, is a good candidate," Nielson told CNN.
The volunteers are not a perfect substitution for the two CRISPR babies – first, they were British (the infants are East Asian) and second, the research looks at naturally occurring mutations (He's surgery was a bit more haphazard, damaging the genes rather than perfectly replicating the mutation). But the research does hint at some of the possible dangers (and unintended consequences) of editing DNA – an already highly contentious subject ethically-speaking.