Skip to story Colored scanning electron micrograph (SEM) of a human embryo at the eight cell stage. Yorgos Nikas/Science Photo Library/Corbis
In an international first, researchers in China have reported doing experiments that involve editing the genome of a human embryo. Ever since scientists developed the ability to cut and splice DNA, they have worried over the safety and ethical implications of applying those techniques to the human genome. Now, though the reported work was preliminary and not completely successful, researchers will have to contend with a challenging set of questions about this newly-opened genetic frontier.
In the research, published a week ago in the journal Protein and Cell, the scientists used a powerful new DNA-editing method called CRISPR/Cas9 to replace the genes that cause a potentially deadly blood disorder. If the edit had been successful, the new genes would have manifested in every new cell as the embryo developed. (The embryos used in the study would never have reached term, because they had been fertilized with two sperm each.) Because only a small number of the 86 cells in the trial survived and carried on the material, the experiment was abandoned. The study’s lead author, Junjiu Huang of Sun Yat-sen University in Guangzhou, told Nature News, “If you want to do it in normal embryos, you need to be close to 100%. That’s why we stopped, we still think it’s too immature.”
The technique Huang and his co-investigators used, CRISPR/Cas9, allows researchers to snip out and insert specific segments of genetic code. Discovered in 2012, the technique is the subject of a lot of excitement and trepidation in the cell sciences (and its inventors are already being suggested as candidates for a Nobel Prize). Relative to other gene editing techniques, CRISPR/Cas9 is easy to use, and it seems to work in just about every living organism. That means it could, among other possibilities, hold the key to personalized medical therapies, new drugs, and (as the Chinese scientists attempted) human genetic modification.
But—and this is a big but—using the technique without proper guidance could result in unforeseen consequences. The Chinese researchers, for example, found mutations in many of the embryos in genes other than the ones they’d targeted with CRISPR/Cas9. They assumed this was due to errors in the method, but also mentioned that the mutations could have been because the eggs were double-fertilized.
Within the past few months, several groups of scientists around the world have called for a moratorium on just this type of research—calling for no more human embryo modification. They’re worried about all the science-fiction problems you’d imagine: The technology has the potential to erase genetic diseases, but it could also be used to make designer humans. And this kind of genome editing is on what’s called the “germ line,” which is to say, the edits get passed along to subsequent generations.
WIRED spoke to many of the people who called for moratoriums in two of world’s top scientific journals, to see what they thought about this Chinese research, and what it means for the prioritizing the national discussion on the ethics of germline editing.
These quotes have been edited and condensed for clarity.
This paper completely validates the technical and scientific concerns that we raised in the Nature article, especially in terms of the “off target” gene modifications, and the inefficiencies in modifying the target gene. I think this exacerbates or highlights the need for the kind of broad-based discussion that we called for, and for a renewed sense of urgency.
Also, there is an important distinction between modifications to the germ line—which is passing things on from generation to generation—and somatic cell modification, which is already being used to treat disease, and we’re having great successes there.
George Q. Daley, co-author of Science moratorium; stem cell biologist—Boston Children’s Hospital
We need to start having this conversation now, immediately if not sooner. Because I think this paper indicates that researchers are actively pursuing the area of embryonic DNA editing.
There are two issues: One is trying to understand at a deeper scientific level whether such an approach can be made safely. The second would be the broader and deeper ethical considerations of editing our heredity. I feel very significant concerns about using a new technology to do something as bold as changing someone’s germ line—not just for that individual, but all of the offspring.
This article really reported the remarkable inefficiency and highlighted a lot of challenges in getting this procedure to work in a human embryo. It’s a cautionary tale, and it should make any practitioner take pause before moving forward.
R. Alta Charo, co-author of Science moratorium; professor of medical history and bioethics—University of Wisconsin-Madison
The number of unintended effects is precisely why this technique is not appropriate for use in clinical applications. Regulatory agencies look for a reasonable balance between possible benefit and risks. I was among the authors on the paper in Science calling for a temporary moratorium on clinical efforts to use CRISPR for germ line gene editing of nuclear DNA. The call for a moratorium while public discussion and safety research proceeds is especially pertinent, therefore, in places where regulation is weak or absent.
G. Steven Martin, co-author of Science moratorium; cell and molecular biologist—University of California, Berkeley
It was precisely this sort of possibility that just reinforces our conclusion that there should be some temporary moratorium on this sort of research until we figure out what’s safe and what’s ethical. It’s clear from the results they describe that there are lots of problems with the application of the technology.
If we have an open and vigorous discussion in the US, then the Chinese authorities and Chinese Academy of Science will take notice and try to make sure that research is conducted more responsibly in China. That’s really all we can do. We hope to conduct those debates in a very public way, and the sooner we can conduct them the better.
Jennifer Doudna, co-author of Science moratorium; cell biologist; co-discoverer of CRISPR/Cas9—University of California, Berkeley
Although it has attracted a lot of attention, the study simply underscores the point that the technology is not ready for clinical application in the human germline. And that application of the technology needs to be on hold pending a broader societal discussion of the scientific and ethical issues surrounding such use.
Hank Greely, co-author of Science moratorium—Stanford Law School
I don’t think there’s anything wrong with their research. The fact that they used triponuclear zygotes, and their work could not in any respect ever become a baby, is an important ethical safeguard. As far as we can tell, they met legal requirements in China. What they did would be illegal in some US states, and they certainly couldn’t apply for federal funding. But I don’t think they have anything to be ashamed of.
I thought it was useful research, but if anything this makes it more real, and makes it look like it may happen more. And even just beyond the fact of how poorly it worked, it did work in a human embryo. This makes it even more urgent to have a societal conversation about how far to go. My own view of the Science paper is that it didn’t call for a moratorium on all research, it called for a moratorium on making babies this way.
Mike Botchan, co-author of Science moratorium; cell biologist—University of California, Berkeley
I think this is an important point: This is not something that scientists can have an opinion on that’s any better than yours. These are ethical, political, economic issues. It behooves scientists to be transparent about what’s possible and what isn’t, and get ahead of any potential hysteria that might come from misinformation of what we can and can’t with genome editing do on a technical level. We can have opinions, but our opinions are part of the process.