Setting aside the thorniest issues around CRISPR babies, scientists say embryo-editing research should proceed

LONDON — The Francis Crick Institute is a glimmering chameleon of a building, spanning four acres of downtown London, that took 10 years and cost nearly $850 million to build. The curves of its vaulted twin roofs manage to resemble the hull of an alien spacecraft while still echoing the steel and glass forms found at the bustling St. Pancras train station across the street. If trains were the vehicles that carried people into the 19th century’s industrial revolution, buildings like the Crick, as it’s known, seem designed to lift us off into the biological revolution of the 21st. “Discovery without boundaries,” is its motto.

Out front, a Conrad Shawcross sculpture rises out of the sidewalk in English weather-worn steel. The stack of twisting, growing tetrahedra — a nod to nonlinear scientific advancement — looms, 42 feet high, like a sphinx. Its questions emerge out of the brickwork behind it; Would you eradicate disease? Would you enhance your body? Where would you draw the line?

Splashed in bright colors, the questions are part of an art exhibit called “Cut + Paste” housed inside the Crick — the goal of which is to familiarize non-scientists with genome editing. They’re also the sorts of questions for which the Third International Summit on Human Genome Editing promised to provide a prominent theater of engagement; a place for them to be wrestled with by the world’s top scientists, ethicists, and legal scholars. And over the course of three days last week, issues of equity and access to treatments in development for genetic conditions such as sickle cell disease took center stage.

But many of the much thornier issues raised by editing of the germline — changing the DNA of sperm, eggs, or embryos — were often punted, breezed past, or cut short before real discussion got underway. Only one day was devoted to these kinds of modifications, which would be passed on to every subsequent generation, and of that, the entire afternoon was spent showcasing the latest in germline editing science. The sessions devoted to the ethics of germline editing largely took up the issue of how to lay out rules and guidelines for regulating it.

“The agenda real estate seems to be allocated in a way that discouraged engagement with difficult and uncomfortable issues, while at the same time presenting the science as a foregone conclusion,” said Benjamin Hurlbut, a bioethicist at Arizona State University who attended the gathering. “There was no invitation to ask whether this is science that we want or whether it should be done.”

At the summit’s conclusion, organizers urged policymakers and the public to have those difficult discussions, but not at the expense of stopping progress. In a statement issued on March 8, they pulled back from the idea that heritable genome editing required a broad societal consensus to proceed. “We are still keen that the research goes ahead,” said developmental biologist Robin Lovell-Badge, who chaired the organizing committee. “In parallel, there has to be more debate about whether the technique is ever used.”

This doesn’t sit well with Hurlbut, who is one of a growing number of academics from both inside and outside the life sciences concerned with how quickly CRISPR and other genome-editing advances are outpacing serious public dialogues. In recent years, he and others have begun building new organizations to help foster more meaningful, inclusive conversations about the technology’s uses.

Last year, Hurlbut helped launch the Global Observatory for Genome Editing with University of Wisconsin-Madison biomedical engineer Krishanu Saha and Sheila Jasanoff, a professor of science and technology studies at Harvard’s Kennedy School of Government. In London, they held a public meeting on Tuesday night of the summit focused on genome editing and social justice.

“We wanted to see where we would go if we don’t start with the science, but instead invert the directionality of the conversation to start from ideas of equity, global governance, and social justice,” Saha told STAT in an interview.

About 100 people from the summit took them up on it, cramming into a windowless room in the basement of the Wellcome Center just down the road from the Crick. There was no projector here and no stage, only one weak microphone that forced the person wielding it to stand to be heard. And unlike at the summit, a protester wearing a white T-shirt with a red stop sign and emblazoned with the words “Stop Designer Babies, was allowed inside.

While the event featured some of the same faces — Françoise Baylis and Julie Makani, both members of the summit organizing committee, spoke at the Observatory event — the conversations here were more provocative, more willing to reckon with the sources and nature of inequity.

“When we’re talking about genome editing, it’s important to ask, what biologies are assumed? And what worlds are assumed?” said anthropologist Kaushik Sundar Rajan of the University of Chicago. “We have a tendency to imagine the corporatized scientific world as normal, but in fact it is only 40 years old. And the assumption that ethics will emerge in fundamentally democratic structures, that’s no longer true. So we have to ask ourselves, what will de-democratization look like when it comes to the implementation of gene-editing technologies?”

In addition to the Global Observatory, which is based in the U.S., there is the Global Citizens’ Assembly on Genome Editing in Australia and the Association for Responsible Research and Innovation in Genome Editing, based in Europe, helmed by the deputy director of the Spanish National Biotechnology Center, Lluís Montoliu. The issue has also been taken up by SAMA Resource Group for Women and Health, which works on issues of reproductive rights in India. Each has slightly different approaches for reaching people and drawing them into a public discussion, but representatives from each spoke on the last day of the summit about funding being a barrier to doing so.

“You need resources to do this properly and professionally, to draw on all the tools available to reach everyone in society,” Montoliu said during a summit panel on public engagement. He and others said that foundations and other grant-making organizations have so far been interested only in backing projects that quickly get to solutions that keep the science advancing. Projects aimed at really clarifying what people believe and value, which might take many years, even decades, not so much.

It was not the first time the question of urgency arose during the session. Earlier, in what an apologetic Lovell-Badge described as “unfortunate” timing, a fire alarm went off as part of a routine test. It stopped after a second or two, but then it rang out again. And again, and again, 13 times over the next 10 minutes, punctuating the auditorium with a blare that forced the speakers to repeatedly halt their presentations or comments. That individuals who have grave reservations about CRISPR were in a literal sense being silenced by a building that was, at that very moment, turning sunlight into current to power four floors of labs beyond the security checkpoint where 1,500 scientists were going about their daily business of manipulating the DNA of cells, was not lost on the room.

“In a way, this thing is metaphorically right, because the fire alarm thinks that we should behave in accordance with its setting of the agenda and to some degree that is what the scientific community understandably believes,” said Jasanoff. She continued, “I think there’s a kind of hubris in assuming that you can engage the public in,” before the alarm sounded again, this time not for a brief second, but for 18 of them. “Why are we subjected to the machine,” she began again when silence returned. “Why is it hitting this session and not some other session?” This time, she was interrupted not by the peals of the alarm, but by the clapping of hands.

At the end of the session, Lovell-Badge apologized again and assured the audience that the scheduling had not been deliberate. He went on to defend the Crick’s decision to not postpone the test, since that, apparently, was not the way it was supposed to work, “demonstrating that it needed to be tested, “ he said. The flaw, now flagged, had been fixed.

But another specter over the summit was not so easily banished. He Jiankui — the Chinese scientist who created the world’s first gene-edited children in an ethics-breaching experiment in 2018 and was released last April from prison after serving a three-year sentence — was both constantly present and conspicuously absent from the choreography of the event.

It began with a set of sessions featuring scientists like Peng Yaojin of the Chinese Academy of Sciences providing a look at the rules and regulations that China’s government has put into place to prevent an individual from trying to do what He did.

After that, He and the children his research project brought into the world were rarely mentioned by any scientists in the room. There wasn’t any discussion about the role that the highly competitive, lucrative world of biomedical research played in motivating He to do what he did. And then, it was over. The organizing committee came to the front of the room and Lovell-Badge read their consensus statement — their recommendations for a path forward.

“Heritable human genome editing should not be used, unless, at a minimum, it meets reasonable standards for safety and efficacy, is legally sanctioned, and has been developed and tested under a system of rigorous oversight that is subject to responsible governance,” Lovell-Badge said. “At this time, these conditions have not been met.”

That might sound like a hard yellow light. But it actually suggests that the scientific community has shifted, in the wake of the CRISPR baby scandal, away from asking whether they should to asking how they might, said Hurlbut. In 2015, the organizing committee’s consensus statement said the conditions that had to be met for heritable genetic alteration to be done responsibly were twofold; that safety and efficacy had been demonstrated, and that there was “broad societal consensus.” That latter requirement has since been dropped.

In response to the closing remarks, Perry Hackett, a geneticist at the University of Minnesota, questioned the wisdom of moving forward without a more thorough reckoning with the fact that this field has already produced three children born with permanently altered DNA. They’ll turn 5 years old this year, and there is almost no information about their current condition or well-being.

“We heard yesterday that we don’t want human genome editing to blow up on the launchpad right now,” Hackett said. But it did blow up already, he pointed out, at the last summit in 2018, when He revealed the details of his experiment after news of its existence broke on the eve of the event. “We’ve avoided a lot of the issues of actually picking up the pieces of that blow-up and putting them together by talking about a lot of other things.”

After his talk, Yaojin did not answer any of STAT’s questions, saying only “thank you” repeatedly before walking quickly out of the room. He and the other representatives from China also declined to answer questions from other members of the media.

And now, the summits have concluded. The plan, Lovell-Badge said, was always to have three, one in the U.S., one in China, and one in the U.K. It’s unclear who would step up and organize and find funding to bring all the biggest names in genome editing together on a regular basis. Or if any organizations that aren’t the National Academies or Royal Society would even have the clout to pull something like that off.

“If you think there’s a reason for having another one, someone should take the reins and do it,” Lovell-Badge said to the audience, but suggested that maybe it’s time to let it become a series of much smaller, more specialized conferences, more like any other kind of scientific meeting.

“Rather than rising to new heights, it seems to me that we are worse off than when we started,” Hurlbut told STAT. “Because there was more of an appetite, more of an aspiration to face these things head-on eight years ago than there seems to be today.”

The message out of London, it seemed, was that it was time to keep calm and CRISPR on.