CRISPR Baby Mutation Linked to Higher Risk of Early Death

Geneticist He Jiankui at the Human Genome Editing Conference in Hong Kong, November 28, 2018.
Image: AP

New research shows that the genetic tweak employed by disgraced Chinese scientist He Jiankui to make babies immune to HIV carries an associated risk of early death.

People with two copies of a mutation that protects against the HIV virus, known as CCR5-delta 32, are more likely to die before age 76 than individuals without the mutation, according to new research published today in Nature Medicine.

Advertisement

The finding is further evidence that geneticist He Jiankui, who used the CRISPR-Cas9 gene editing tool to engineer this mutation in twin babies last year, acted irresponsibly and without a sufficient understanding of how the modification might affect the future health of his unwitting test subjects. The new finding also shows how difficult it will be to devise safe human gene therapies; sometimes, even seemingly good mutations—such as one that confers an immunity to HIV—can produce bad consequences.

Around 11 percent of northern Europeans have the CCR5-delta 32 mutation, but it’s very rare in Asian populations. Previous studies have shown that the mutation, while conferring resistance to the HIV virus, appears to put people at greater risk from other infectious diseases. The mutation, for example, makes people four times more likely to die from the flu.

As prior research and the new study shows, the absence of a fully functional CCR5 gene has a pronounced effect on the overall health of an individual. This gene, which codes for a protein found in immune cells, is exploited by the HIV virus as a gateway into cells. But CCR5 is involved in other important bodily processes as well.

“Here is a functional protein that we know has an effect in the organism, and it is [found and preserved] among many different species, so it is likely that a mutation that destroys the protein is, on average, not good for you,” Rasmus Nielsen, a co-author of the study and a researcher from the University of California, Berkeley, said in a Berkeley release. “Otherwise, evolutionary mechanisms would have destroyed that protein a long time ago.”

Advertisement

That said, the mutation was once selected for in northern European populations, so it must have had some kind of benefit at one point (this would’ve been long before the HIV/AIDS epidemic). This benefit is not known, but the CCR5-delta 32 mutation is known to confer protection against smallpox and flaviviruses like dengue, Zika, and West Nile.

For the new study, Nielsen, along with co-author Xinzhu Wei, also from UC Berkeley, looked at a British database known as the UK Biobank. This database contains genetic information linked to the medical records of over 400,000 people. The researchers were trying to see if a link existed between CCR5-delta 32 and life expectancy. The answer was a big yes.

Advertisement

Specifically, their analysis showed that individuals who have two copies of the mutation—i.e., they’re homozygous carriers—are 21 percent less likely to reach age 76 compared to people who have only one or no copies of the mutation. Revealingly, there were fewer homozygous people with this mutation included in the UK biobank than would be statistically expected. That’s because they’re dead, or as Nielsen put it in the press release, “There is simply a deficiency of individuals with two copies” of the mutation.

Advertisement

He Jiankui has claimed that one of the twin girls produced by his CRISPR experiment is a homozygous carrier, while the other twin has one of the two gene copies edited.

“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,” said 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.”

Advertisement

The new study, while revealing, remains incomplete. It was limited to a very specific population, namely individuals living in Britain. Future research should look to see if these results can be replicated in other parts of the world. Also, studies of the CCR5-delta 32 mutation have been limited to European populations, and its role in the health of Asian individuals is still poorly understood. Finally, while a correlation was found to exist between the mutation and human life expectancy, the exact reason for the increased mortality rate is not known. Obviously, that would be good to know, and a subject worthy of further research.

As a final note, the new study is yet another reminder that human gene editing will be exceptionally tricky work. For each genetic action there will be a vast number of genetic reactions. For scientists, the key will be to identify these unwanted side effects prior to making modifications, and find ways to mitigate negative outcomes. This will be difficult and time consuming, but not impossible. Human gene-editing is in our future, with future being the key word.

Advertisement

We’re still a ways off from viable human trait selection. Sadly, He’s irresponsible experiment will have to serve as a potent reminder of this reality.

Share This Story

About the author

George Dvorsky

George is a senior staff reporter at Gizmodo.