Read: The CRISPR baby scandal gets worse by the day
The girls’ CCR5 genes were altered, according to data He presented, but they do not exactly match the 32-letter deletion; it’s unclear whether either of them is actually resistant to HIV. Even if they were unable to get HIV, a body of research already suggested that CCR5-Δ32 made people more vulnerable to the flu and West Nile virus. A “good” mutation in the context of HIV can be “bad” in another context. No one knew, exactly, the net effect of a CCR5-Δ32 mutation.
However, the new study, by Rasmus Nielsen and Xinzhu “April” Wei of UC Berkeley, shows that people with two copies of the mutation are 21 percent more likely to die at the age of 76, with a mortality rate of 16.5 percent, compared with 13.6 percent for those who have only one or zero copies. Only recently, Nielsen told me, have genetic databases even become big enough for these effects on mortality to be apparent.
The effect of CCR5-Δ32 on mortality is ultimately subtle, but it follows from what’s already known about this gene. CCR5 usually codes for a receptor on the surface of white blood cells, and it plays a role in normal immune responses. HIV co-opts CCR5 as a way to get into white blood cells. So to block HIV is, ironically, also to eliminate a small piece of the normal immune system.
“If you think about what these people are with Δ32, they’re like human knockouts for a fairly important gene in immune response,” says Bill Paxton, a microbiologist at the University of Liverpool who helped discover the role of CCR5 in HIV. “It’s not wholly surprising you [would] read a paper like this, and the finding is there.”
After HIV researchers made CCR5-Δ32 famous, scientists in other fields got interested in the mutation, too. Flu researchers who studied it found that it predisposes people to fatal outcomes with flu. West Nile virus researchers found the same with that disease. Neurobiologists have found evidence that CCR5-Δ32 actually enhances recovery from stroke. But this process of understanding the full scope of CCR5 has been piecemeal, essentially limited by what scientists think to look for.
Geneticists have proposed more systematic ways to understand all the effects of a single gene. Instead of picking a disease and looking for associated genes among a large group of people, geneticists can pick a gene of interest and look for associated traits. This is called PheWAS, or phenome-wide association study, where phenome refers to the set of observable traits. The idea is to look for links “that we just never knew to look for before,” says Marylyn Ritchie, a geneticist at the University of Pennsylvania who uses PheWAS in her research. Crucially, PheWAS requires not just DNA from volunteers but rich and detailed health data from those same volunteers—everything that could be conceivably linked to a gene, from height to brain volume to white-blood-cell count. PheWAS studies are necessarily limited by what health data have been collected.