Several of the world’s leading CRISPR scientists and bioethicists are calling for a global moratorium on editing human genes that can be passed on from parents to children.
In a new Nature commentary, published Wednesday, Feng Zhang and Emmanuelle Charpentier — two discoverers of the revolutionary CRISPR-Cas9 gene editing system — along with MIT biologist Eric Lander and 15 other researchers from around the world, outlined the urgent need to put a pause on the editing of sperm, eggs, and embryos — known as the human germline — to create genetically modified babies until countries agree on the best way forward.
The scientists were inspired to write the sharply worded article, Lander told Vox, after China’s He Jiankui revealed in November that he defied international norms and edited the DNA of three children, ostensibly to make them resistant to HIV.
“By ‘global moratorium’, we do not mean a permanent ban,” the authors wrote. “Rather, we call for the establishment of an international framework in which nations, while retaining the right to make their own decisions, voluntarily commit to not approve any use of clinical germline editing unless certain conditions are met.”
And in the meantime, other CRISPR research would continue, including germline editing for research that doesn’t lead to modified babies, and editing nonheritable (somatic) cells to stamp out disease.
The hope is to move the conversation beyond a focus on individual rogue actors, like He. “The real questions going forward are what decisions will countries make over the years and decades about which applications, if any, should be allowed,” Lander said. “We want a framework in place so that our children are proud of the decisions that get made, rather than thinking society moved forward thoughtlessly.”
Scientists have traditionally avoided the word “moratorium” when talking about CRISPR
Right now, 30 countries, including the United States, have laws that either directly or indirectly prohibit germline editing, according to the Nature paper.
But as CRISPR-Cas9 technology has made gene editing more accessible in recent years — allowing scientists to edit, cut out, and replace genes in any living thing more quickly, cheaply, and efficiently than previous gene editing tools — scientists have been grappling with how best to proceed.
While there’s the potential to eliminate certain heritable genetic diseases in the future, there’s also broad acceptance that it’s simply too early to experiment with germline editing that would lead to genetically modified children. That’s why He Jiankui’s announcement caused such a stir, as did the fact that many scientists knew what he was up to.
Most notably, in December 2015, the organizing committee of the first International Summit on Human Gene Editing at the National Academy of Sciences came out with a consensus statement on human gene editing. The document reflected the excitement and wonder of this new technology, but also the researchers drew the line at clinical research that involves human germline editing.
“It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved... and (ii) there is broad societal consensus about the appropriateness of the proposed application,” they wrote.
But the statement authors stopped short of using the word “moratorium,” a word the Nature authors now embrace.
“This time we’re saying: we have a moratorium, we shouldn’t be afraid to call it a moratorium,” Lander said. The authors also acknowledge, however, that a moratorium will eventually end — and what’s important is figuring out what the world on the other side should look like.
Countries need to get on the same page about questions that “ultimately affect the entire species”
Gene editing has the potential to do incredible things, like delete horrible diseases right out of the human genome, edit crops to make them more nutritious, or alter entire species.
There’s also the distant but looming potential of “designer babies,” or using CRISPR to enhance certain human traits. “The idea that parents could feel peer pressure to genome edit their kids some day is not out of the question,” Lander said. “There will be powerful marketing forces and peer pressure forces that’ll say, ‘how come you didn’t give your kids the latest, greatest, genome edit.’”
In the paper, Lander and his co-authors outline other potential nightmare scenarios on how hasty gene editing could backfire:
Individuals with genetic differences or disabilities can experience stigmatization and discrimination. Parents could be put under powerful peer and marketing pressure to enhance their children. ... Many religious groups and others are likely to find the idea of redesigning the fundamental biology of humans morally troubling. Unequal access to the technology could increase inequality. Genetic enhancement could even divide humans into subspecies.
Even before these nightmare scenarios materialize, we know the gene editing tools on offer are far from perfect, and potentially dangerous. Scientists have learned, for example, that the CRISPR-Cas9 system can inadvertently wipe out and rearrange large swaths of DNA in ways that may imperil human health, so called “off-target edits.” They’ve also shown that CRISPR-edited cells can inadvertently trigger cancer.
But Lander said it’s a mistake to dwell too much on the technical challenges posed by CRISPR and other gene editing technologies.
Instead, nations need to work together to draw boundaries and proceed transparently, first voluntarily pledging not to proceed with germline editing to create babies for a fixed period — perhaps five years, he said. After that, they would agree not to proceed unless certain conditions are met — like alerting the public about the experiment and engaging in an international consultation about its pros and cons.
“Nations might well choose different paths,” the authors wrote, “but they would agree to proceed openly and with due respect to the opinions of humankind on an issue that will ultimately affect the entire species.”
A veiled message to China
To do that, one option might be setting up a coordinating body — potentially organized by the World Health Organization — to support the global framework, the authors suggested. And under that body, they recommend two sub-panels: one comprised of medical and scientific voices and another that takes into account a diversity of perspectives, including “people with disabilities, patients and their families, economically disadvantaged communities, historically marginalized groups, religious groups and civil society at large.”
“Certainly, the framework we are calling for will place major speed bumps in front of the most adventurous plans to reengineer the human species,” they wrote. “But the risks of the alternative — which include harming patients and eroding public trust — are much worse.”
Bioethicists and research organizations embraced the call to action. In a letter accompanying the Nature commentary, representatives at the US National Academy of Medicine, US National Academy of Sciences, and the Royal Society in London called for “broad societal consensus before making any decisions, given the global implications of heritable genome editing.”
(Another CRISPR-Cas9 co-discoverer, Jennifer Doudna, was noticeably absent from the author list. In a statement, she told Vox she opted not to sign on, instead supporting the National Academies recommendation of “strict regulation that precludes use until scientific and technical questions are addressed and until ethical and societal matters are resolved.”)
“The comment is trying to promote something that is more thoughtful,” University of Minnesota bioethicist Leigh Turner, who did not contribute to the paper, told Vox, “public debate, public conversation and serious deliberation of all the ethical, legal, and scientific issues related to heritable genome editing,”
The framework is deliberately open and voluntary, so countries can make decisions “informed by their history, culture, values and political systems,” the authors wrote. “Still, the common principle would be all nations agreeing to proceed deliberately and with due respect to the opinions of humankind.”
It also contained a veiled message to China. While the Chinese government publicly condemned He Jiankui’s actions, there have been questions over whether the government might have been more involved in his work that it let on. The commentary authors repeatedly called for countries to be open about their research agenda and where it’s heading.
“The idea is that countries should come together and be transparent,” said Lander, “if they’re thinking about a potential application. ... They should be straight forward about it, give notice and engage in consultation about it.”
At the same time, there’s only so much even the best-intentioned scientists and international agreements can do to stop rogue gene editors, Turner said.
“It’s easy to see how unwanted activity could occur despite calls for a moratorium,” he said, “how [gene editing] could unfold in a setting where there aren’t effective regulators or sufficient resources to go beyond a moratorium existing on the books but not in reality.” And that’s what makes CRISPR so powerful — and so scary.