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.”
The current gene editing debacle is the legacy of human embryonic stem cell (hESC) research, which stripped human embryos of their humanity to achieve all sorts of promised utilitarian gains. Without a sound scientific or ethical basis, in many countries embryos have been excluded from the legal and ethical protections given to more mature human research subjects; and deprived of their intrinsic right to life and equal protection under the law. It should not be surprising that some scientists, who in the past promoted hESC research, now find it difficult to condemn Dr. He’s actions. After all, the only essential difference between the past claims of human cloning and the present claims of the live birth of gene-edited embryos is that presently the latter seems to basically work. If in the past it had been possible to make viable cloned human embryos, implantation, gestation, and live birth of cloned babies would have been right around the corner.
So, the answer to Knoepfler’s question (“Why the researchers running these meetings seem increasingly attached to the idea of future germline human gene editing?”) is simple. Because, like him, they do not care about the humanity of all human beings, including embryos. The moral and ethical irony of Knoepfler’s proposed temporary moratorium is that hundreds or more human embryos have already died in germline editing research and many more would be destroyed during a moratorium with sanctions only against implantation. The better solution is to give human embryos their humanity back and start treating them like we do human beings who are at later stages of development. Ban experimentation with human embryos altogether, unless as with older humans, a clear benefit of the research can be assigned to the research subject and not someone else.
Thank you for this thoughtful piece. In contrast to Dr. Natio, I understand Paul’s reference to feelings instead of facts. We do not have facts. This is not peer review of a proposal or a manuscript, so we can’t judge the science. We can only assume that He was aware that genomic rearrangements that can be induced by double strand breaks in DNA, but he chose not to look for them. Because of the amplification of genotypes that occurs during embryonic development, scientists should be have the opportunity to fully sequence DNA from all three germ layers. The simplest cell collection could be obtained from the placenta- amnion for ectoderm, mesenchyme for mesoderm, and yolk sac for endoderm. One would hope that those tissues were saved.
As a scientist I’m deeply disappointed that this piece offered not one bit of science for why we should kick the can down the road another 3 years. It’s Entirely “I think, I believe, I feel”. Great. So why should we think, believe, and feel, in agreement with you? What exactly should be the criteria? This reminds me of the arguments I read against GMO foods “Something bad could happen.” Sure, something bad could happen when a new plane is released into a fleet, but very extensive testing, design review, etc. goes into that so something bad doesn’t happen. Alpha, beta testing, simulation, etc. Not one bit of that “process” was discussed in this think piece…though I really shouldn’t even call it think since almost none of that is required when reading it.
You’re really comparing girls genetically altered by a rogue scientist to testing out a new plane? Also, Dr He it seems did not design things carefully nor do proper testing I’d say prior to the human experiment. He sought advice from experts and then ignored it. He seems to have kept some of this a secret, may have mislead team members, and may not have had the proper approvals.
The gene editing, which probably shouldn’t even be called that in this case, didn’t work properly. Random chunks of the CCR5 gene were deleted in some cells but not others, leaving the girls mosaics. There may be off-target mutations as well. We just don’t know. Perhaps I could have restate this stuff in the article, but it has been widely discussed already.
Speaking of new planes and bad things happening, the Boeing 737 Max is a hot topic as of this reply.
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