Genetics Health News

The Curious case of CRISPR Edited Babies

Written by Editorial

The quest for a ‘designer’ baby has finally come true as recently a Chinese scientist He Jiankui along with colleagues edited baby twins so that they cannot become HIV positive. It has been claimed by the scientist that the twins’ father was HIV positive but both the daughters weren’t. Still some mutations, of unknown nature, were added to the CCR5 receptor where the Human Immunodeficiency virus attaches.

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.

4. There were problems with informed consent.

It’s not clear if the participants in He’s trial were actually aware of what they were signing up for. He relied on an aids association to reach out to the patients and falsely described his work as an “aids-vaccine development project.” He told delegates at the Hong Kong summit that he personally took the volunteers through the informed-consent process, along with another professor. But taking consent is a specific skill that requires training; He had none.

The consent document that he used describes crispr and gene editing, but it does so in heavily technical language. He has said that his patients were “very well educated” and already knowledgeable about gene-editing technology. But according to a news report from the Chinese magazine Sanlian Life Week (which has since been removed, but not before a digital copy was saved and translated), one of the people who dropped out of the experiment had only a high-school understanding of biology, and only heard the term “gene editing” when news stories about He’s experiment broke. The man claimed that he was not informed about the risks of off-target effects, or about the fact that gene editing was a prohibited and ethically controversial technology.

Also, the consent form “is not a consent form,” says Kelly Hills, a bioethicist at Rogue Bioethics. “It’s a business form, of the kind that a company might use when subcontracting.” For example, the section about possible risks says nothing about any negative consequences of deactivating CCR5, and is instead more focused on absolving He’s team of legal responsibility for problems arising from the procedure. The form also gives He’s team rights to use photos of the babies in magazines, calendars, billboards, propaganda, product packaging, and posters in cars and elevators. Can you imagine the atrocity of this?



About the author