Genetic Mutation in “CRISPR Babies” May Shorten Lifespan

#Genetic_Mutation in “#CRISPR_Babies” May Shorten Lifespan

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When Chinese scientist He Jiankui edited the genes of twin baby girls last year, he said he was doing it to protect them against HIV infection; their father was HIV-positive. The now-disgraced scientist has said he did not want the girls to get the virus, which causes AIDS, because of a severe stigma against it in China.

But a new study suggests that he may have subjected them to a danger separate from the risk of catching HIV. The intended gene mutation appears to shorten people’s lives by nearly two years, according to a study published Monday in Nature Medicine.

“JK was foolish in choosing this gene to mutate, because he may have compromised lifespan in the two girls,” says British stem cell scientist Robin Lovell-Badge of the Francis Crick Institute, referring to He by his nickname. Lovell-Badge was not involved in the new study.  

The so-called delta-32 mutation appears to make people resistant to HIV when it occurs on both copies of the CCR5 gene—one inherited from each parent; while one copy of the mutation provides somewhat weaker protection.

Researchers at the University of California, Berkeley looked for this common CCR5-delta-32 mutation in a database of more than 400,000 middle-aged and older volunteers in the United Kingdom. In the database, people who naturally had two copies of the mutated gene were found to be 20 percent more likely to die by age 76 than those with either one copy or none. In addition, there were fewer volunteers with the double mutation than would be expected by its prevalence in the general British population, suggesting that the missing people had died or were not healthy enough to volunteer, says the study’s lead author, April Wei. People with only one copy of the mutation lived just as long as those with no copies.

Scientists cannot yet explain the connection between the gene mutation and a shortened lifespan, says Wei, an evolutionary geneticist and postdoctoral student at Berkeley. But it may be because the mutation also seems to be associated with an increased vulnerability to viruses like the flu and West Nile.

He’s experiment marked the first time that a human embryo had been gene-edited and then allowed to develop until birth. Gene-edited cells in an adult are not passed down to future generations (unless they are reproductive cells), and medical treatments that target these genes are considered preliminary but promising. Edits to an embryo change the genetic code of most of its cells and are passed down to future generations. Some people consider all edits to an embryo immoral, while others, including Lovell-Badge, can see some benefit to gene edits that prevent an otherwise unavoidable disease. But many say the science is too premature for human use.

The global scientific community reacted with outrage to news of He’s gene edits. Scientists nearly universally condemned the fact that he had edited embryonic genes, as well as the choice of gene and the process he used to inform the families of what he was doing. The World Health Organization, several national academies, and scientific groups have since called for (or considered) a global moratorium on gene editing.