On a cold, drizzly night almost three years ago, I stood inside the nearly deserted Lincoln Memorial in Washington, D.C., I was in town to attend the first International Summit on Human Gene Editing organized by the National Academy of Sciences and the National Academy of Medicine. After a day of intense talks at the meeting, I had gone for a long walk and found myself looking up at Big Abe. A big question was on my mind: Would the organizers of the meeting call for a moratorium on using CRISPR to make gene-edited babies, as I hoped they would?
When I learned of that decision, my feeling was that someone would report the creation of the first “CRISPR baby” within the next few years. That might happen even with a moratorium, but the odds had just increased substantially.
Since then, there have been similar meetings around the world about human germline gene editing — editing eggs, sperm, and embryos that are then used to make people — along with official reports from committees. None called for a moratorium on this work, and some like the Nuffield report even suggested that, in the future, it might be okay to make gene-edited babies. There has also been a steady stream of research reports about gene editing human embryos, but none of the embryos had been implanted into a woman’s uterus.
Until last week.
That’s when Chinese researcher He Jiankiu dropped the bomb with his claim that he produced twin CRISPR’d babies. He cited a 2017 National Academies of Sciences, Engineering, and Medicine consensus report as one reason he felt it was alright for him to proceed with his efforts to do this.
I question He’s interpretation of that report, but in my view the experts issuing various reports left the door too open to this kind of work.
He’s announcement was likely timed to coincide with last week’s Second International Summit on Human Genome Editing in Hong Kong, also sponsored by the National Academies.
I watched a livestream of parts of that meeting. I was surprised that He was scheduled to speak at it — twice. One other talk really shook me: Dr. George Daley, dean of Harvard Medical School and one of the summit organizers, made the case in favor of human germline editing in the not too distant future and vaguely characterized He’s effort as just a “misstep.”
Later on, as I watched He’s own talk, it didn’t take long to realize that his project hadn’t gone so well. The data he presented suggested the girls are mosaics, meaning some cells in their bodies contain normal genomes and others contain various CRISPR-modified genomes — though we can’t be sure unless He allows someone to directly sample and independently analyze the girls’ DNA, which I doubt he will allow. The direct sampling is crucial, as DNA that He supplies could come from cells or embryos, rather than from the twins.
Condemnation for He’s work was swift and vociferous, shining a critical light on what he had done. We still don’t know, for instance, if he sought, or was granted, the required ethics approvals. Nor do we know if the project was intentionally kept a secret. He also seems to have disregarded advice from others not to use CRISPR on embryos to create genetically modified babies. There’s also a growing consensus that his choice to target the CCR5 gene was unwise.
As the Hong Kong meeting wrapped up, the organizers released a statement that did not explicitly call for a moratorium on making gene-edited babies. To be fair, they did use stern words to indicate such work should not be done at present, and this statement was stronger than the one from 2015. But the organizers of the 2018 meeting diluted their statement’s impact by making the case for a path toward future human germline gene editing if strict criteria are met. This path, combined with the earlier words of Daley and other speakers at the meeting arguing in favor of moving toward such a goal, yield a mixed message.
I’ve been asked why the researchers running these meetings seem increasingly attached to the idea of future germline human gene editing. I don’t have a good answer. Am I missing something?
The rationales for human germline editing in the near future don’t make much sense to me. They largely consist of invoking incredibly rare or even hypothetical scenarios where CRISPR might serve some purpose that cannot be achieved by already proven and safe embryo screening methods such as pre-implantation genetic diagnosis. I’m also concerned that the 2018 meeting statement didn’t include an earlier call for a societal consensus before proceeding. This controversial omission means that social justice and ethical issues are less likely to be resolved.
Unlike the meeting organizers, I favor a low-risk, temporary, three-year moratorium on implantation of gene-edited human embryos to make genetically modified babies. A moratorium won’t stop the most driven rogue, and one can reasonably ask how it would be enforced. But I believe it would send a strong message that going down this road in the near future won’t be tolerated. Three years is enough time for both the science and societal discussions to advance without being a burden.
I’m not an outlier in my call for a moratorium. Others have made similar statements, including CRISPR pioneer Feng Zhang.
What happens next?
I suspect that we will see more reports of CRISPR-modified babies in the coming years. It’s not legal to do such research in the U.S., much of Europe, and many other countries around the world, but countries like China remain regulatory gray areas. It’s even possible that a cultural sense of “getting used” to the idea of gene-edited babies will emerge. Scientists or companies may eventually start selling services to make genetically modified babies at clinics, possibly fertility clinics adapted to the task, on a for-profit basis.
We’ve seen a similar phenomenon with stem cell clinics in the U.S. About a decade ago, the first for-profit U.S. stem cell clinic popped up, even though there was little hard evidence that stem cell transplants are safe and effective for anything but blood disorders. In part because of a lack of vigilance, the number of stem cell clinics is rocketing upward and there may now be 1,000 of them in the U.S., most of them operating without complying with FDA regulations. While FDA commissioner Scott Gottlieb seems committed to taking action on the worst of the clinics, it may be too late.
The scientific community needs to take a firmer and clearer stance that making genetically modified babies is prohibited for the time being. A temporary moratorium specifically on implantation of gene-edited human embryos would achieve that with minimal risk of over-regulating research and no impact on in vitro research.
Paul Knoepfler, Ph.D., is a professor at the University of California Davis School of Medicine whose research is focused on stem cells and cancer. He writes about ethics, policy, and other matters on his blog The Niche. He is also the author of two books: “GMO Sapiens” on the potential use of CRISPR in humans and “Stem Cells: An Insider’s Guide.”