Add one fatal flaw to Jiankui He's litany of mistakes in CRISPR baby debacle
Scientists the world over have found plenty of reasons to condemn their Chinese colleague Jiankui He’s experiment with the world’s first CRISPR babies late 2018: The alleged medical need to confer HIV immunity was unfounded, the consent process seemed dubious, the actual gene editing appeared spotty, just to name a few. But a new research paper may have uncovered the most staggering of them all.
Two researchers at UC Berkeley has found that the genetic mutation He attempted to mimic in twins Lulu and Nana — known as CCR5-∆32 — is associated with a higher risk of premature death.
It’s been widely reported that the mutation, which in effect knocked out the CCR5 gene, had already been shown to render people more susceptible to the West Nile virus and more likely to suffer serious complications, including death, from influenza. But the overall effect on mortality has yet to be established.
By combing through genotype and death register details of 410,000 individuals UK Biobank, Berkeley professor Rasmus Nielsen and his postdoc Xinzhu Wei found a 21% increase in all-cause mortality rate among people with two copies of the ∆32 mutation, in which 32 base pairs are omitted from the gene.
Wei and Nielsen are quick to warn against overinterpreting their findings, not least because they only analyzed genomes of UK volunteers, and they don’t necessarily translate to East Asians as “the effect of the mutation depends on the genetic background and the environments,” Wei wrote to National Geographic.
That said, a similar point was also made with regards to the studies that He cited to justify introducing the mutation in the babies in the first place. Signs that CCR5-∆32 had protective effects against HIV, naturally observed in European populations, spurred him to engineer their trait into the embryos that eventually grew into twin baby girls.
Notably, He didn’t exactly recreate the ∆32 mutation in either embryo. Based on the slides he presented at a conference in Hong Kong, Both infants appeared to still carry normal copies of the CCR5 gene, and where the gene editing did work it resulted in very different mutations whose effects have never been studied.
Nonetheless, these new findings once again lay bare the knowledge gap on the consequences — good and bad — of gene variations and, thus, the dangers of applying gene editing tools on human cells, especially when the alterations can be passed onto future generations as in the case of an embryo.
He himself expressed second thoughts about his experiment in an email exchange with Stanford University bioethicist William Hurlbut, STAT’s Sharon Begley reported.
“I have been thinking,” He wrote, “I recognize I pushed too quickly into a first-of-kind clinical study without the necessary open dialog with regulators, the scientific community, and the public.”
As governments and experts rush to propose new regulations on the boundaries of gene editing, with new studies such as this, the world is finally having the conversation that He — now completely sidelined and closely monitored by Chinese authorities — didn’t have.
Image: Jiankui He in November 2018. KIN CHEUNG for AP PHOTO