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The CRISPR Baby Scandal Gets Worse by the Day

Published: December 5, 2018
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Source: The Atlantic

Before last week, few people had heard the name He Jiankui. But on November 25, the young Chinese researcher became the center of a global firestorm when it emerged that he had allegedly made the first crispr-edited babies, twin girls named Lulu and Nana. Antonio Regalado broke the story for MIT Technology Review, and He himself described the experiment at an international gene-editing summit in Hong Kong. After his talk, He revealed that another early pregnancy is under way.

It is still unclear if He did what he claims to have done. Nonetheless, the reaction was swift and negative. The crispr pioneer Jennifer Doudna says she was “horrified,” NIH Director Francis Collins said the experiment was “profoundly disturbing,” and even Julian Savulescu, an ethicist who has described gene-editing research as “a moral necessity,” described He’s work as “monstrous.”

Such a strong reaction is understandable, given the many puzzling and worrying details about the experiment. Even without any speculation about designer babies and Gattaca-like futures that may or may not come to pass, the details about what has already transpired are galling enough. If you wanted to create the worst possible scenario for introducing the first gene-edited babies into the world, it is difficult to imagine how you could improve on this 15-part farce.

1. He didn’t address an unmet medical need.He focused on a gene called CCR5, which the HIV virus uses as a doorway for infiltrating human cells. To lock the virus out, several scientists have tried extracting the immune cells of HIV patients and deactivating CCR5 using gene-editing techniques before injecting the cells back into the body. Although Nana and Lulu’s father is HIV-positive, neither of the infants actually had HIV. As I’ve written before, He’s team deactivated a perfectly normal gene in an attempt to reduce the risk of a disease that neither child had—and one that can be controlled through safe-sex education or antiviral drugs. Even if you wanted to block CCR5 specifically, there are drugs out there that could do the job, many of which have been repeatedly tested in clinical trials. The rationale for using a method as extreme and untested as gene editing doesn’t hold up.

Deactivating CCR5 doesn’t confer complete immunity to HIV, either, since some strains of the virus can enter cells via a different protein. And although people with natural deficiencies in the gene appear healthy, they might be more susceptible to West Nile virus, and more likely to die when they catch influenza. Essentially, He gave Nana and Lulu resistance to a virus that they could have avoided in myriad other ways, and may have opened them up to other dangers.

2. The actual editing wasn’t executed well.

He’s data haven’t been published or peer reviewed, so many of the details of his experiment are unclear. But based on the slides that he presented at the Hong Kong summit, other scientists have denounced the work for being amateurish.

For example, it appears that He only managed to edit half of Lulu’s CCR5 genes; the rest are normal. That could either be because every cell in her body has one normal copy of CCR5 and one edited one (she’s heterozygous) or because half of her cells carry two edited genes and half carry two normal ones (she’s mosaic). If it’s the former, she would not be resistant to HIV. If it’s the latter, it depends on whether her immune cells specifically carry the edits. The same might apply to Nana, who, based on the slides, seems to also have normal copies of CCR5 somewhere.

What’s more, the edited cells don’t seem to have been edited in the right way. He planned to delete a small section of the CCR5 gene, mimicking a naturally occurring mutation called delta 32 that’s found in about 10 percent of Europeans. But according to Sean Ryder, a biochemist from the University of Massachusetts Medical School, He’s slides show no sign of delta 32 in either girl. Instead, Lulu has an entirely different CCR5 mutation, and Nana has two. These mutations are in roughly the same part of the gene as delta 32, but “it’s a fairly outrageous assumption that any change to this region would lead to some benefit,” Ryder says. “He made new mutations, and there’s no reason to think that they’d be protective—or even that they’d be safe.”

3. It’s not clear what those new mutations will do.At least two of the three mutations that He introduced into Nana and Lulu’s genomes are substantial changes that could alter how CCR5 works. Typically, scientists would introduce the same mutations into mice or other lab animals to see what would happen. If they felt reassured enough to move into human patients, they could recruit patients with HIV, take out some immune cells, introduce the new CCR5 mutations, transplant the cells back, and monitor the volunteers to see if they’re healthy. “That could take months or years, but to do anything less would be cutting corners,” Ryder says.

But He appears to have leapfrogged over all of those basic checks and implanted the edited embryos into a woman. “The children are test subjects for variants that haven’t been vetted in animals,” Ryder says. What’s shocking about this “is the blatant disregard of all the rules and conventions we have in place for how one should approach any proposed intervention,” said Leonid Kruglyak, a geneticist at the University of California at Los Angeles, on Twitter.

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