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Gene-editing summit touts sickle cell success, while questions on embryo editing linger

After decades of living with often excruciating pain, Victoria Gray had to get used to a new sensation in recent years: waking up without it. “It may sound crazy, but I had to pinch myself to see was I still able to feel pain,” she says.

Gray, a 37-year-old mother of four from Forest, Mississippi, who was born with sickle cell disease, arguably became the star of last week’s International Summit on Human Genome Editing in London when she spoke about her transformation. In 2019, she was the first person to undergo an experimental therapy in which blood stem cells were taken from her, altered with the gene editor CRISPR to compensate for the sickle cell mutation, and returned to her body.

She now produces few of the abnormally rigid, sickle-shaped red blood cells that can block blood flow, causing intense pain. “At one point in my life, I stopped planning for the future because I felt I didn’t have one,” Gray told a rapt audience at the summit. “Now, I can dream again without limitation.”

Gray’s appearance was designed to underscore the rapid clinical advances in somatic cell gene editing—making noninheritable changes to a person’s DNA—and redirect attention away from the controversial prospect of heritable changes. “The Organising Committee had a clear intent … to shift the focus away from heritable to somatic,” says bioethicist Françoise Baylis, now retired from Dalhousie University, who was part of that committee. That is a stark contrast to the 2018 summit in Hong Kong that became dominated by news a few days earlier that Chinese researcher He Jiankui had used CRISPR to modify the genomes of human embryos and implanted some of them in a woman. The twin girls she gave birth to likely carry the genetic changes in their eggs and could pass them on to subsequent generations; the announcement led to outrage, and He’s imprisonment.

Since then, there has been no known attempt to produce gene-edited babies, but somatic gene-editing therapies using CRISPR or related methods have surged. Clinical trials are underway for blood disorders, cancers, diabetes, blindness, and more. The CRISPR method used to treat Gray has already been tested in more than 75 people and could be approved in the United States this year.

The progress has raised a new ethical issue: how to ensure these new therapies reach those who most need them. “We’re already seeing significant challenges with access to [existing] gene therapies,” says Claire Booth, a gene therapy researcher at University College London. “With so much growth in this area of therapeutic gene editing the problem of delivering therapies to patients is only going to grow.”

The two companies developing Gray’s therapy, Vertex Pharmaceuticals and CRISPR Therapeutics, haven’t set a price on it. But the procedure is complex, requiring each patient to undergo costly and somewhat risky chemotherapy to wipe out their current blood stem cells in the bone marrow to make room for cells altered outside the body. The price tag could be more than $1 million per person.

Yet over half of the more than 300,000 people born annually with sickle cell disease live in three countries where few would be able to afford that: Nigeria, the Democratic Republic of the Congo, and India. It’s unclear how even the U.S. health care system can manage such costs. “It’s heartbreaking because I do still have family members who suffer from sickle cell disease,” says Gray, who was treated for free as part of a clinical trial. “How is it fair that something lifesaving comes with a price tag that high?”

There are other barriers. High-income countries have hundreds of bone marrow transplant centers, where stem cells can be wiped out and replaced, but sub-Saharan Africa has just three. Few countries in the region even screen for the disease and give affected newborns penicillin as prophylaxis against the infections to which their condition predisposes them, says Ambroise Wonkam, a geneticist at Johns Hopkins University. “If even the simple newborn screening plus penicillin is not implemented in Africa, why should we be talking about genome editing?” Wonkam asks. “But I do think one does not exclude the other.”

Genetically editing cells in the body rather than outside it could cut costs. The Bill & Melinda Gates Foundation and the National Institutes of Health have put $200 million toward developing such “in vivo” genetic editing, and clinical trials are beginning. The components of CRISPR, for example, could be loaded in delivery vehicles such as harmless viruses or lipid nanoparticles like those used to ferry in RNA for certain COVID-19 vaccines.

New ways to commercialize or pay for these therapies may be needed, too. “I’m afraid that we’re not ready,” Steve Pearson, who heads the Institute for Clinical and Economic Review, told the summit. “I don’t know how we’re going to be able to create the pricing, the payment, and the intellectual property innovation at the speed that the science is bringing these treatments forward.”

Bringing African scientists into the research is also an essential part of equity, says Jantina de Vries, a bioethicist at the University of Cape Town. The Gates in vivo–editing push largely funds U.S. researchers, she notes. “What happens then is that Africa is cast merely as a recipient of innovation, not a driver.”

Despite the focus on somatic gene editing, the summit, the last in a series of three, could not avoid the shadow of He’s experiment. Safety concerns around altering the DNA of embryos have only grown in the past few years, says Dagan Wells, a gene-editing researcher at the University of Oxford. Standard CRISPR works by breaking DNA’s double-stranded helix and exploiting a cell’s DNA repair machinery to insert a replacement genetic sequence. But studies have shown DNA repair is deficient in early embryos. In human embryos gene edited at fertilization, Wells found that in 40% of the altered cells, they had not repaired the double-strand breaks introduced by CRISPR. If the embryos had developed, they might have suffered from severe genetic diseases.

In vitro–fertilized eggs are appealing targets for embryo gene editing because the researchers have to target just one easily accessible cell. “But it also seems that that may be exactly the wrong time to do it,” Wells says. “I think everything we’ve learned in the last few years has really cemented those kinds of concerns that were expressed back in 2018.”

Newer methods such as base editing and prime editing that avoid double-break strands may be safer. “Perhaps, it’ll be possible to revisit the application of genome editing to embryos with those methods,” Wells says. But he cautions that their safety is unknown. “Hopefully, people will learn the lessons of the past, and they won’t hurry too fast.”

Some meeting attendees felt there was not enough opportunity to discuss the ethical implications of this. “My suspicion is that this summit was designed to be uncontroversial, to even at points almost be boring,” says Ben Hurlbut, a bioethicist at Arizona State University, Tempe. That way no progress is made around the real challenges in the field, he says. “And if we’re not here to make progress on those things, what are we here for?”

In a closing statement, organizers of the London summit seemed to solidify the status quo, concluding “heritable human genome editing remains unacceptable at this time.” If anything, questions about a way forward appear less resolved now than 5 years ago. Back then, the organizers of the second summit concluded that “it is time to define a rigorous, responsible translational pathway” toward clinical trials of germline editing. This year, organizers wrote that further consideration was needed to resolve “whether this technology should be used.” Baylis says that is an important shift. “It’s a bit of a pulling back to acknowledge that those debates and discussions have not been concluded.”

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