Scientists in China recently reported that they have edited the genetic code of human embryos. The work relied on new technology that has been heralded as one of the most exciting developments in genetics in decades. But for some researchers, these experiments stepped over an ethical line. Before they had even published their work, rumors of the Chinese scientists’ research had prompted outcry urging a moratorium on such work. A letter last month in the journal Nature stated:
In our view, genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable. Such research could be exploited for non-therapeutic modifications. We are concerned that a public outcry about such an ethical breach could hinder a promising area of therapeutic development, namely making genetic changes that cannot be inherited.
At this early stage, scientists should agree not to modify the DNA of human reproductive cells. Should a truly compelling case ever arise for the therapeutic benefit of germline modification, we encourage an open discussion around the appropriate course of action.
The research team, led by researcher Junjiu Huang, at Sun Yat-sen University in Guangzhou, used a technique called CRISPER/Cas9 to try and edit the gene that causes a potentially fatal blood disorder in human embryos, reports David Cyranoski and Sara Reardon, who broke the story at Nature News. The CRISPR system works like cut and paste at the DNA level. Using the system, scientists can snip out targeted spots of genetic code and insert new sequences. The tool can turn disease-causing genes off or repair mutations with working copies of genes, as the Chinese team attempted to do. Already the tool has been used to engineer lab animals, such as monkeys, with specific gene changes and tweak adult human cells.
The Chinese researchers targeted the gene responsible for a blood disorder called beta-thalassemia. National Geographic’s Phenomena blog, Carl Zimmer reports that the researchers tried this technique on 86 embryos. Most of them, 71, survived long enough for observations. The CRISPR system cleaved and spliced genes in 28 embryos. One of the big concerns for gene editing is the possibility that the wrong genes will be cut, and indeed only a small fraction of those 28 were successfully spliced. The others were either partially repaired by the cells gene preservation mechanisms or cleaved in the wrong place entirely. Misplaced mutations can cause other diseases such as cancer. Even the four spliced embryos weren’t a success: Only some of the cells in the embryos were edited, creating genetic mosaics.
The researchers published their results in the journal Protein & Cell. They write: "Because the edited embryos are genetically mosaic, it would be impossible to predict gene editing outcomes," using genetic techniques to diagnose IVF embryos before they are implanted in the womb. They add, "our study underscores the challenges facing clinical applications of CRISPR/Cas9."
Reardon and Cyranoski of Nature News also report that Huang and his colleagues plant to continue the work, looking for ways to reduce the number of those off-target gene edits, but use adult human cells or animals. However, the reporters write that at least four other groups in China are also working on editing human embryos.
The Guangzhou team tried to allay some of the concerns about the ethics of their work by only using embryos from fertility clinics that had an extra set of chromosomes, after an egg was fertilized by two sperm. Live births would never have come from those embryos, though the zygotes do go through the first stages of development. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” Huang told Cyranoski and Reardon.
But still, the response in the research community has been immediate.
"No researcher should have the moral warrant to flout the globally widespread policy agreement against modifying the human germline," wrote Marcy Darnovsky of the Center for Genetics and Society, a watchdog group, in an email to Rob Stein writing for NPR’s "Shots" blog. "This paper demonstrates the enormous safety risks that any such attempt would entail, and underlines the urgency of working to forestall other such efforts. The social dangers of creating genetically modified human beings cannot be overstated."
Whether further work proceeds or is halted, the study will likely be recognized as pivotal in the history of medicine. Zimmer provides some historical context of changing the genes of humans in his blog post and writes:
Just because this experiment came out poorly doesn’t mean that future experiments will. There’s nothing in this study that’s a conceptual deal-breaker for CRISPR. It’s worth recalling the early days of cloning research. Cloned embryos often failed to develop, and animals that were born successfully often ended up with serious health problems. Cloning is much better now, and it’s even getting to be a business in the world of livestock and pets. We still don’t clone people, though–not because we can’t, but because we choose not to. We may need to make the same choice about editing embryos before too long.
George Daley, a stem cell researcher at Harvard Medical School, told Cyranoski and Reardon at Nature News that the study was "a landmark, as well as a cautionary tale. Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes."
At NPR, Daley added, "We should brace for a wave of these papers, and I worry that if one is published with a more positive spin, it might prompt some IVF clinics to start practicing it, which in my opinion would be grossly premature and dangerous."