The World Health Organization (WHO) is moving swiftly to address the complex ethical issues raised by scientists’ ability to make heritable changes to the human genome using CRISPR and other techniques. On August 29, the WHO launched a global registry to track research on human genome editing — the first concrete recommendation of an advisory committee charged with determining what an effective oversight and governance framework should look like in the CRISPR era.
Consultations to develop the registry are ongoing, but the initial phase will require researchers around the world to report clinical trials that involve making changes to the human genome, using an existing, publicly accessible clinical trials platform. The registry will cover both genetic modifications to reproductive (germ) cells that can be passed to future generations, as well as modifications to somatic (non-reproductive cells), which are non-heritable.
“People need to be able to register that data so that we can understand what's going on in the world,” said philosopher Françoise Baylis of Dalhousie University, who is a member of the WHO’s committee, in an interview with RE$EARCH MONEY. “Not only is the registry designed to promote transparency, but it could also be part of a governance framework. And we've been tasked with thinking about new and creative ways to govern.”
When announcing the registry, WHO's Director-General Dr. Tedros Adhanom Ghebreyesus reiterated that countries should prohibit clinical uses of germline editing until the ethical and technical implications have been thoroughly assessed. Clinical trials of CRISPR therapies targeting somatic cells are already underway for some cancers, blood disorders and eye disease.
A separate international group of experts has been convened by the U.S. National Academies (NAS) and the U.K. Royal Society to examine the scientific, clinical and regulatory issues that could arise if human germline genome editing ever moves to the clinic. The first meeting of the International Commission on the Clinical Applications of Human Germline Genome Editing took place in mid August.
Bartha Knoppers, Director of the Centre of Genomics and Policy at McGill University, is a member of the new commission. In an interview with RE$EARCH MONEY, she said there is a need for crosstalk between the two initiatives: "There isn't a fine line of separation between the ethical governance issues and the scientific issues."
"This kind of policy direction goes beyond local or national politics, laws or cultures. It affects all humans. It affects where we go in terms of the treatment, avoidance or even elimination of serious hereditable genetic conditions," she said.
Setting a Global Standard
Chinese researcher He Jiankui stunned the world in November 2018 when he announced the birth of twins Nana and Lulu, the first so-called "CRISPR babies." In the months that followed, Russian scientist Denis Rebrikov declared his intent to implant genetically modified embryos in women.
Most countries, including Canada, have rules and regulations banning implantation of genetically modified embryos, though in some cases, the laws are ambiguous or have not kept pace with new technologies. But Jiankui and Rebrikov's recent announcements, and the real potential of using CRISPR to treat genetic diseases, are forcing the global scientific community to take a hard look at risks and benefits of germline genome editing.
At the international level, several policy documents on the ethics, science and governance of human genome editing were published between 2015 and 2017. But Baylis said the global discourse has been largely informed by the knowledge and interests of high-income countries: “What's critically important and different about this [WHO] committee is we're looking at global standards that could work anywhere in the world, not just in places like Canada, the U.S. and Europe.”
Furthermore, she said the committee’s work is designed to serve as a blueprint for future WHO initiatives related to science and technology. “If you think about emerging technologies, whether you’re looking at artificial intelligence or genome editing, we’re really seeing transformation. [The WHO has] a director-general with foresight, wanting to say, ‘How do we position ourselves to have global impact in these new arenas?’”
While the WHO can use moral suasion to influence issues of global importance, it has no legal or regulatory force. To encourage global adoption of the registry, for example, WHO plans to ask funding agencies around the world to require registration as a condition of funding and scientific journals to require a registration number prior to publishing the results of a trial.
Knoppers said the registry is “highly desirable,” but also questioned whether the WHO has the jurisdiction to ensure it succeeds. “What kind of power does the WHO have? What is the jurisdiction of the WHO to have such a registry? They would have to look at some jurisdictional issues to make sure that such a registry, which is welcome, is also workable.” And while the WHO can work with funders, those would mainly be public funders. “What do you do when the funding comes from other sources that are not public?” she asked.
Reconsidering Canada's stance
In Canada, the Assisted Human Reproduction Act (AHRA), passed in 2004, prohibits germline genome editing for research or clinical purposes. Somatic gene editing is permitted, provided the research follows the Tri-Council Policy Statement (TCPS) on ethical conduct for research involving human participants.
In recent years, a group of stakeholders has urged Health Canada to review the AHRA. In a series of publications, members of the Stem Cell Network and the Centre of Genomics and Policy, which Knoppers directs, have argued that Canada's criminal ban is too blunt a policy instrument, and have urged the government to permit basic and pre-clinical research on human germ cells and early embryos. At this time, however, Health Canada has not initiated a review of the AHRA, according to Baylis.
Should federal law eventually change, a group of experts in Quebec — Commission de l’éthique en science et en technologie — released a set of recommendations (pdf) on the ethics of human germline genome editing in March.
There is also a new project to assess the legal/regulatory, ethical, social and policy challenges related to the clinical use of somatic genome editing in Canada. It was launched in mid-August by the Council of Canadian Academies (CCA) at the request of the National Research Council. The CCA is in the process of appointing a multidisciplinary expert panel and expects to issue a report in 2020.
Both Baylis and Knoppers said there is a need to reexamine the governance of genome editing in somatic cells. "The world is focused on germline genome editing because of its implications to make heritable modifications. But I think we actually need more robust standards for somatic genome editing," said Baylis, whose new book, Altered Inheritance: CRISPR and the Ethics of Human Genome Editing (Harvard University Press), was published this week.
"Everyone seems to take somatic genome editing as a given, but it also has issues associated with it," said Knoppers. She also suggested that Canada should set up a working group to do some horizon scanning related to germline genome editing. "If and when it comes, Canadians who wish to avail themselves of it will be looking to find out where they can take part."