World Health Organization advisers urge global effort to regulate genome editing

On Monday, a World Health Organization advisory committee called on the world’s largest public health authority to stand by the 2019 statement of its director-general urging a halt to any experiments that might lead to the births of more gene-edited humans.

The committee — established in December 2018, weeks after news broke of the birth of twin girls whose genomes were edited by Chinese scientist He Jiankui — said in a pair of long-awaited reports that the germline editing technology that led to the “CRISPR babies” scandal is still too scientifically and ethically fraught for use. But for other, less controversial forms of gene-editing, the reports offer a path to how governments might establish the technology as a tool for improving public health.

“The framework recognizes that policies governing the technology will likely vary from country to country,” committee co-chair and former U.S. Food and Drug Administration commissioner Margaret Hamburg said at a virtual press conference Monday. “Nonetheless the framework calls on all countries to incorporate key values and principles into their policies, such as inclusiveness, equal moral worth, social justice, responsible stewardship of science, solidarity, and global health justice.”

In the backlash that followed the scandal, the 18-member committee coalesced around a mission to examine the scientific, ethical, social, and legal issues surrounding both germline editing, which alters eggs, sperm, or embryos, and somatic editing, which changes DNA in non-reproductive cells. Part of its charge was to make recommendations on governance and oversight mechanisms of each technology.

The newly released reports are intended to complement an effort by the International Commission on the Clinical Use of Human Germline Genome Editing, which last year developed scientific and technical standards critical to deciding when the technology is ready for prime time. The first of the WHO advisory committee’s reports focused on issues of governance. But while many expected it to dictate a list of do’s and do-not’s, the report instead broke down genome editing into five different areas: making changes to somatic (adult cells) after someone is born; making changes to somatic cells in-utero; making changes to germline cells (eggs, sperm, embryos); making changes not to the DNA code itself, but to how it is expressed; and making changes not to treat disease but to enhance a person’s genetic lot.

Within each area, the committee outlined hypothetical scenarios and developed questions about how potential oversight mechanisms might work for each of them, including how they might take into account the values, ethical dilemmas, and financial realities of various societies.

“It’s not prescriptive, but rather is a well-thought-out and accessible document with a lot of cognizance toward the differences between different countries,” said Bartha Maria Knoppers, who directs the Centre for Genomics and Policy at McGill University and served as a member on the International Commission. “I’m very impressed, it’s an excellent policy toolkit.”

The approach may have been, at least in part, a decision of convenience. It’s a lot easier to get 18 people to agree on what the right questions are to ask than to achieve consensus on policy mandates. But the flexibility of the end-result is a welcome one for many scientists in the field.

“There is no one-size-fits-all approach to regulating genome editing on the global scale, and I’m glad to see that the report recognized that there are many different applications of genome editing, each with its own set of benefits and challenges,” CRISPR pioneer and Nobel laureate Jennifer Doudna of the University of California, Berkeley, told STAT via email. Doudna was not a member of the commission nor the advisory committee. “This new WHO report strikes me as more practical than any prior pieces and an important step to providing a workable practical framework,” she continued.

The second report spells out a list of suggestions for the WHO to take up directly, including facilitating meetings to explore the use of patent pools and other ethical licensing mechanisms, establishing a whistleblowing system for researchers to report unsafe or unethical gene editing research, and putting out a policy statement restricting human genome editing research and commercial enterprises to operating in countries where the technology is regulated.

But the true threat of an offshore CRISPR tourism market is still murky. According to a 2020 survey conducted by the Center for Genetics and Society, only 11 countries allow lab experiments to genetically modify human embryos, while 75 countries prohibit using genetically altered — including with gene editing — embryos to initiate a pregnancy. No country explicitly permits it.

The committee also advised improving and expanding an international registry to track and monitor any genome editing clinical trials or preclinical experiments, an idea it first proposed in 2019.

Doudna told STAT such a registry would be useful for keeping tabs on research, but only to a point. “It may be challenging to get transparency from for-profit companies or to be comprehensive with early-stage research,” she wrote. A registration requirement on scientists not funded by reputable agencies nor swayed by publishing penalties would also be difficult to enforce.

The first of the committee’s nine recommendations says that the WHO should assume a position of moral and scientific leadership with regards to genome editing. That includes developing an ethics statement aimed at addressing equitable access to the technology and outlining the consequences of proceeding without doing so, At a minimum, they wrote, this statement should reiterate the 2019 statement of WHO Director-General Tedros Adhanom Ghebreysus that “it would be irresponsible at this time for anyone to proceed with clinical applications of human germline genome editing.”

But some outside experts expressed concern that the WHO’s handling of the Covid-19 pandemic may have undermined its effectiveness at serving in that role.

“I’m not sure WHO has the reputation, or the political and bureaucratic flexibility and power to exercise the scientific and moral leadership this report calls on it to take,” said Hank Greely, director of the Stanford Center for Law and Biosciences, who has followed the evolution of CRISPR technology closely. On the other hand, he said, a more suitable alternative may not exist.

That leaves the ball now squarely in the courts of national governments, regional groups, and professional societies, said Greely. “They need to take up the task of deciding how to regulate gene editing in its many forms, and these reports should help them to some extent.”

But on Monday, the WHO announced it will also be pressing forward with some immediate new efforts, including establishing a small expert committee to determine next steps for the registry and convening a more expansive group of stakeholders to develop a more concrete mechanism for whistleblowers to report concerns about possibly illegal, unethical, or unsafe genome editing research. The committee advised that within three years, the WHO’s science division should begin reviewing how well the public health authority is following through on its recommendations. At the press conference, WHO officials did not immediately commit to this timeline, but described it as a “very reasonable suggestion.”

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