Shock waves circled the globe in 2018 when Chinese scientist Jiankui He announced that he’d used CRISPR gene editing to manipulate the genetics of two twin babies. The mutation of their CCR5 gene was intended to prevent HIV infection by providing the twins with two copies of the CCR5 gene. Beyond the obvious ethical issues that may be involved, it appears that the intentional mutation is causing a serious problem with increased mortality risk.
Specifically, a University of California Berkeley analysis has shown that individuals with two copies of the CCR5 gene have a 21% increased risk of death between ages 41-78, as compared to individuals who have one or no copies of that specific gene. The college made several statements within the analysis looking at issues from CRISPR gene editing to be faced by these twins in the future.
“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,” mentioned senior author Rasmus Nielsen. “In this case, it is probably not a mutation that most people would want to have. You are actually, on average, worse off having it.”
“Because one gene could affect multiple traits, and because, depending on the environment, the effects of a mutation could be quite different, I think there can be many uncertainties and unknown effects in any germline editing,” added the paper’s first author, Xinzhu Wei.
Specifically, the gene has been linked to a number of issues that can arise. One study showed that those with two copies of the CCR5 gene had a four-fold rise in death rate following an influenza infection. Though this single issue could cause an overall higher rate of mortality, researchers believe there are other possible explanations, given that the CCR5 gene codes a protein that has multiple functions within the body.
Among these functions is its position on the surface of various immune cells. This protein can help some strains of HIV to enter the body’s cells, infecting them. There’s a natural CCR5 mutation that appears in 11% of northern European genetics that disabled the protein, protecting those individuals against HIV. Given the rarity of this mutation in Asian populations, He was focused on creating a viable mutation that could improve resistance to this disease within that population.
However, He was not able to duplicate the mutation as it occurred in nature, but rather introduced an alternative mutation that would still disable the protein. That being said, inactivating proteins that are commonly found in humans and animals will often have negative effects, given the mutation’s survival through evolutionary forces.
“Here is a functional protein that we know has an effect in the organism, and it is well-conserved among many different species, so it is likely that a mutation that destroys the protein is, on average, not good for you,” Nielsen expounded. “Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago.”
Following He’s announcement, Wei and Nielson investigated the impact of mutating the CCR5 gene, discovering the high mortality rate for those who had two mutated genes. Because there were fewer individuals than was expected that had both mutations in the database they used, it suggested that they had died at higher rates than the general populous, with fewer than expected survivors between ages 41-78. This suggests that the benefit of protection from HIV is not worth the risk of early mortality from the mutation.