Regulation and the law are often slow to keep pace with breakthrough technologies. This is a conundrum that is particularly acute given how CRISPR has accelerated the pace and increased the volume of research into gene editing.
“The rapid advances made in gene editing technology over the last three to five years, particularly in the context of human therapeutics and experiments involving embryos, have highlighted areas in which active discussion and debate is sorely needed.”
So says Dr Samuel Sternberg, describing the immense challenge of reaching decisions that safely control the rapid advances in gene editing created by technologies like CRISPR.
And with the spread of CRISPR research across the world, this is a global issue requiring global answers. “Ideally the international community would decide how we are going to proceed and would do so together - but that’s not very realistic.”
Sam is very well placed to take a view on the issue. A key researcher involved in the CRISPR-Cas9 breakthrough at the University of California, Berkeley, he went on in 2016 to co-author “A Crack in Creation” with his former PhD advisor, Jennifer Doudna, a book detailing their research and calling for an urgent debate on the ethical and social issues it raised.
He then became Group Leader of Technology Development at Caribou Biosciences, Inc., one of the spin-off companies set up to develop CRISPR technologies, and next year will head back into the academic research world as an Assistant Professor with his own lab at Columbia University.
Here is a scientist who has seen the gene editing field from more angles than most.
And the picture he sees is one of extraordinary complexity and uncertainty, illustrated well by the current state of U.S. regulation.
In February 2017 a committee representing the U.S. National Academy of Sciences and National Academy of Medicine issued a report on human germline editing, in which changes made to germ cells such as eggs, sperm, and embryonic stem cells would be heritable and passed on to future generations.
It followed two landmark debates held in 2015 called to take urgent stock of where gene-editing technology was going, particularly on the issue of germline gene editing in humans. The first meeting in Napa Valley, California, included only some two dozen individuals comprising mostly scientists, but the second meeting in December saw the U.S. Academies convene a diverse range of stakeholders, including international scientists (their UK and Chinese counterparts were there, too), policymakers, bioethicists and patient advocates. Following that meeting, a committee spent a year of detailed deliberation, including public consultation, to reach a carefully worded conclusion:
“In light of the technical and social concerns involved, the committee concluded that germline genome-editing research trials might be permitted, but only following much more research aimed at meeting existing risk/benefit standards for authorizing clinical trials and even then, only for compelling reasons and under strict oversight.”
“I think it’s become clear,” says Sam, who was present at both the Napa Valley and Washington, DC meetings, “that germline gene editing is probably going to happen at some point, and that we need to be ready, from a regulatory point of view, on how to proceed.”
But that’s difficult at a time when the U.S. Food and Drug Administration, the main regulator in the area, is subject to a rider in the 2016 Congressional Appropriations Act that forbids the agency from reviewing any drug applications that involve genetic modification of embryos.
“We have a kind of stalemate, with an advisory committee prescribing editing in certain scenarios while the regulatory body is prevented from even considering it.”
In another example, UK regulators have given the green light for mitochondrial replacement therapy or ‘three-parent babies,’ another assisted reproductive technology that alters the genetic material in embryos contained within structures called organelles. “The U.S. National Academy has said this should be allowable, but it falls into the same category where the FDA would not currently be allowed to review any application proposing to use it clinically.”
Those inconsistencies in regulation threaten to encourage the sort of “health tourism” that has been seen in the field of stem cell medicine. Indeed, Sam points to a recent case where a New York doctor carried out a procedure on an embryo called mitochondrial replacement therapy and then, to evade U.S. law, flew to Mexico where the embryo was implanted in the mother.
“There are some clear concerns that if the U.S. and other countries don’t take a clear and consistent stance on some of these budding technologies, medical tourism will become more common, with people going to jurisdictions that are more lax.”
The issue has been on the political radar in the U.S., but action is proving slow. White House pledges to update regulation in this area appear to have stalled in the current political environment, and Sam notes that the new President has yet to appoint his key scientific advisor, the director of the Office of Science and Technology Policy.
So, as the technology has advanced, how has the public discourse evolved since that crucial National Academy meeting two years ago?
Here Sam has some concerns. “How that public outreach feeds back into policy is one of the big challenges,” he says.
“No-one wants a feeling that decisions on these complex issues have been made by scientists pushing the envelope, and that other stakeholders have been denied a voice. We all want to avoid that. But sometimes it’s hard to know what the best mechanism is to make sure all those voices are included.”
Sam expresses passion for doing his part by educating the public about some of the emerging issues surrounding gene editing, as well as the growing excitement in developing gene editing technology to treat and prevent disease.
“It’s critical that scientists take an active role in public outreach, and in ensuring that non-specialists are aware of the enormous strides being made in gene editing research. Discussions about how to grapple with the accompanying challenges must happen out in the open, rather than behind closed doors.”