Is the CRISPR baby controversy the start of a terrifying new chapter in gene editing?

A Chinese scientist shocked the world this week when he reported — through a well-coordinated media campaign that involved an AP exclusive and YouTube videos — that he’d created the world’s first babies genetically edited with CRISPR: a set of twin girls, with a third potential CRISPR baby on the way.

Nearly a week later, He Jiankui’s experiment still hasn’t been fully vetted. But it represents the realization of the fears of many scientists who believe CRISPR isn’t yet safe and precise enough to be used in human embryos.

He says he’s “proud” of his work — and that it has more to do with public health than “designer babies,” since his aim was to eliminate the risk of HIV infection in the babies.

But if a rogue scientist tinkering quietly in a lab can smash through norms and meddle with the human genome to feed his own ego or scientific curiosity, the worry is that many more dangerous applications of CRISPR could be in store. What if others are experimenting with CRISPR in ways that threaten human life? What if they’re using CRISPR to enhance human traits, ushering in a new era of genetic inequality?

Still, while some are calling He reckless, others are calling this a timely and necessary next chapter in the CRISPR story. Let’s unpack the controversy.

We still don’t know if these CRISPR babies really exist

The past several years in science have unleashed the CRISPR revolution. CRISPR/Cas9 — or CRISPR, as it’s known — is a tool that allows researchers to attempt to control which genes get expressed in plants, animals, and even humans; to delete undesirable traits and, potentially, add desirable traits; and to do all this more quickly, and with more precision, than ever before. (You can read about how CRISPR works here.)

He, a Stanford-trained associate professor at the Southern University of Science and Technology in Shenzhen, China, was not well known in the field of CRISPR editing. But he’s claiming a major first: to have used the gene editing technology CRISPR to tweak the DNA of human embryos during in vitro fertilization.

If He’s experiment is confirmed, he would be the first scientist known to use CRISPR to edit human embryos resulting in a live birth, defying the unofficial international moratorium on editing human embryos intended for a pregnancy. (Chinese scientists were also the first to edit nonviable human embryos, which cannot lead to a birth.)

He’s experiment, first reported by the MIT Technology Review and the AP on Sunday, has still not been published in a scientific journal and his data has not been officially peer-reviewed. He says it was self-funded and that he had the consent of parents.

But he would not reveal the identities of the babies and parents involved, and only shared some data in an Excel spreadsheet ahead of a brief presentation at the Second International Summit on Human Genome Editing in Hong Kong.

Researchers who have vetted the information he has made publicly available have determined it’s too sparse to understand what He’s team actually did, whether the editing worked, and whether it was safe.

He says he has submitted his study to a journal for peer review, though he hasn’t yet disclosed which one. If and once he shares his full set of data results, how his experiment went — and that the experiment indeed happened — should be easier to verify.

The reasoning behind the experiment

For now, here’s how He defends his work. The stated objective of his experiment was to disable a gene called CCR5 so the girls might be resistant to potential infection with HIV/AIDS. And He’s justified his experiment two ways: First, he made a human case in the talk at the Hong Kong meeting, saying the father of the girls had HIV and wanted to ensure his children would never suffer like he has.

Second, he made a scientific case: In a YouTube video, he’s said CCR5 is a well-studied genetic mutation, and there’s “real-world medical value” to figuring out how CRISPR can be used to cripple it and prevent HIV/AIDS. In other words, he felt the use of CRISPR technology was medically appropriate.

“Please remember that while there may be vocal critics, there are many silent families who have seen a child suffer from genetic disease and should not have to suffer that pain again,” he pleaded in one of the YouTube videos. “They may not be the director of an ethics center quoted by the New York Times, but they are no less authorities on what is right and wrong — because it’s their life on the line.”

Critics of the CRISPR babies include the technology’s co-founders — and the university where He was affiliated

Many people in the science community in China, as well as scientists involved with gene editing technologies elsewhere, don’t agree with that reasoning. And there are now investigations into his work and conduct.

Southern University of Science and Technology — where He has been on unpaid leave since February — said it wasn’t aware of the research, which seems to have occurred off campus. It has opened an investigation into He for potentially breaking the university’s ethical rules.

“He’s conduct in utilizing CRISPR/Cas9 to edit human embryos has seriously violated academic ethics and codes of conduct,” the university said in a statement. “The University will call for international experts to form an independent committee to investigate this incident, and to release the results to the public.”

On Tuesday, CNN reported that China’s National Health Commission is launching an investigation into the claims. The hospital where the babies were allegedly born, Shenzhen Harmonicare Women’s and Children’s Hospital, is also now distancing itself from He, and the Chinese government says it intervened and halted the research.

Side note: There are wrinkles in the hospital’s and university’s versions of events. As the Washington Post reported, a hospital executive appeared in an AP video applauding He’s work. And the informed consent form He used states his university helped fund of the experiment. So it’s possible He wasn’t quite the rogue operator he’s painted himself to be.

But some of He’s peers in science, who work on gene editing and ethics, also aren’t happy with the experiment. He broke a scientific taboo to edit out a disease that’s now highly treatable — using a potentially dangerous and unproven technique. Hank Greely, a Stanford law and ethics professor, called the experiment “reckless [because] of a terrible benefit/risk ratio for the baby.” Others have called the experiment “monstrous,” “unconscionable” and “premature,” and 122 Chinese scientists wrote a joint statement denouncing the work.

Most notably, the CRISPR co-inventors are also disturbed by He’s move. Feng Zhang, a member of the Broad Institute of MIT and Harvard and the co-inventor of CRISPR/Cas9, called for a moratorium on gene-edited babies.

Jennifer Doudna, a CRISPR co-inventor from the University of California Berkeley, said in a statement that “this work reinforces the urgent need to confine the use of gene editing in human embryos to settings where a clear unmet medical need exists, and where no other medical approach is a viable option, as recommended by the National Academy of Sciences.”

Nobel laureate David Baltimore said the experiment showed “there has been a failure of self-regulation in the scientific community.” And this is the scary truth He’s experiment resurfaced: that the scientific community can’t necessarily protect the public from rogue scientists using CRISPR for potentially dangerous applications, including driving human evolution, enhancing humans by selecting certain traits, or using CRISPR to increase inequality.

A few prominent scientists are less alarmed and even supportive of He’s work

But there are at least a couple of prominent researchers who have sided with He — including Harvard University’s George Church, another CRISPR pioneer.

In a lengthy interview with Science magazine, Church explained that if the kids in the experiment are normal and healthy, then maybe the babies will be viewed more like Louise Brown (the first baby born through in vitro fertilization) than Jesse Gelsinger (who died in an early gene therapy experiment).

“At some point, we have to say we’ve done hundreds of animal studies and we’ve done quite a few human embryo studies,” Church told Science. “It may be after the dust settles there’s mosaicism and off targets that affect medical outcomes. It may never be zero. We don’t wait for radiation to be zero before we do [positron emission tomography] scans or x-rays.”

Similarly, Dr. George Daley, dean of Harvard Medical School, said at the Hong Kong gene editing meeting that, “It is time to move forward from [debates about] ethical permissibility to outline the path to clinical translation … in order to bring this technology forward.”

Daley continued: “The fact that the first instance of human germline editing came forward as a misstep should not let us stick our neck in the sand. … I don’t think a single practitioner who goes against the norms of the field represents a failure of scientific self-regulation.” And Harvard researchers are indeed beginning to use CRISPR to tinker with the DNA of sperm, though only in embryos not intended for pregnancy.

Researchers are still calling for a “take it slow” approach on CRISPR in humans

For now, the scientific consensus still holds: Most experts think CRISPR isn’t ready for tinkering in humans.

A 2017 National Academies of Sciences report on gene editing stated that clinical trials could be green lit in the future “for serious conditions under stringent oversight.” But that “genome editing for enhancement should not be allowed at this time.”

That’s because there are real limits to what CRISPR can do, at least right now. Scientists have recently learned that the approach to gene editing can inadvertently wipe out and rearrange large swaths of DNA in ways that may imperil human health. That follows recent studies showing that CRISPR-edited cells can inadvertently trigger cancer.

According to Stat, He visited Feng Zhang’s lab in August asking about how to reduce some of these risks. “It was clear to me that he was having the same challenges as other researchers around lack of efficiency and lack of precision,” Zhang said. “I told him that the technology is neither efficient nor precise enough for real-world application in embryos, including in human IVF applications.”

That’s why scientists have generally advocated for a slow, cautious approach to gene-editing human embryos — which makes the news from China all the more shocking.

“I feel a strong responsibility that it’s not just to make a first, but also make it an example,” He said. Whether others follow his lead, he added: “Society will decide what to do next.” Or before society agrees on anything, He and other scientists may continue forging ahead.

Sourse: vox.com

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