This article has been updated to include comment from Wei Xinzhu, the paper’s lead author.

A study of over 400,000 individuals has found that a genetic mutation conferring resistance to HIV could also mean a shorter life span — a sober warning to scientists hoping to enhance humans through gene editing.

Scientists from the University of California, Berkeley examined the genetic data of 409,693 people of British ancestry and found that the mortality rate in individuals with 32 missing base pairs on each of their CCR5 genes — a mutation called Delta 32 that has been linked to HIV resistance — increased by 21%, according to a study published Monday in the journal Nature Medicine. The subjects for the study had voluntarily submitted their DNA to the UK Biobank, a database for public health research.

Most people have two CCR5 genes, and a Delta 32 mutation to one or both can raise resistance to HIV. These findings have shed light on a possible cure for a virus that was once considered a death sentence. But previous research found that people with the mutation are at higher risk of death from influenza, suggesting that genetically modifying CCR5 could have unpredictable effects on human health. The authors of Monday’s study called the Delta 32 mutation “deleterious.”

Rasmus Nielsen, a professor of integrative biology at UC Berkeley and the paper’s second author, said in an article for Berkeley News that an average person would be “worse off” with a Delta 32 mutation. “Beyond the many ethical issues involved with the CRISPR babies, the fact is that, right now, with current knowledge, it is still very dangerous to try to introduce mutations without knowing the full effect of what those mutations do,” Nielsen said.

The effects of other mutations on the CCR5 gene are still being explored. One study published in February suggested that variations in CCR5 could enhance a baby’s ability to learn and memorize information.

The UC Berkeley scientists’ research is especially alarming in the aftermath of a gene-editing scandal that sent shockwaves through the international scientific community late last year.

In November 2018, Chinese geneticist He Jiankui announced that his team had successfully produced twins, Lulu and Nana, with mutations on CCR5 that would make them resistant to HIV. However, data He later revealed at a genetics summit in Hong Kong show that, instead of Delta 32 mutations on both of the twins’ two CCR5 genes, Lulu had a single 15-base-pair deletion, while Nana had four base pairs added to one CCR5 gene and one base pair deleted from the other. How these seemingly haphazard genetic modifications will affect the two girls over the course of their lives remains to be seen.

He’s study sparked intense controversy in China and around the globe. A provincial investigation concluded that his research “seriously violated morality and scientific integrity” by fabricating ethics review documents. It also prompted investigations at foreign universities like Stanford, where He completed a postdoctoral fellowship, to ascertain whether other scientists had participated in his research in any capacity.

Wei Xinzhu, the paper’s lead author, told Sixth Tone that the study was primarily aimed at finding out whether the Delta 32 mutation had experienced recent positive selection in Europe — and that He’s research had “added some urgency” to her own.

“It is important to examine all possible consequences in gene therapy,” Wei said. “A mutation could have multiple effects, and the effects could also depend on the environment.”

In addition to Lulu and Nana, Chinese authorities disclosed in January that a second pregnancy linked with He’s research is underway.

Editor: David Paulk.

(Header image: Chinese scientist He Jiankui attends a panel discussion at the Second International Summit on Human Genome Editing in Hong Kong, Nov. 28, 2018. Anthony Kwan/Bloomberg via Getty Images/VCG)