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Editing genomes in human germline cells—eggs and sperm—that can be passed on to future generations has been considered off-limits to scientists. But advancements in gene editing are catalyzing a change in the zeitgeist. On Feb. 14, a committee of scientists, doctors, lawyers, and ethicists from ten countries agreed that germline genome editing in humans may be permissible in the future, under a set of stringent conditions outlined in a report from the National Academy of Sciences and the National Academy of Medicine.
The 261 page National Academies document gives an expected green light to editing somatic cells—ones that cannot be passed to offspring—to treat disease. It also gives a “yield” signal to both germline editing and somatic edits used for improving the genes of someone who is not ill.
“Being cautious does not mean prohibition,” says R. Alta Charo, co-chair of the committee and professor of law and bioethics at the University of Wisconsin, Madison. At a public meeting presenting the report she emphasized the need for more basic scientific research before proceeding with in-human trials.
Ethical concerns about editing human genes are decades old, but the rapid rise of the cheap and simple CRISPR/Cas9 gene editing technology has spurred debates anew. U.S. restrictions currently block federal funding for human germline editing, but scientists can still obtain funding for such work through other means.
Last year, Chinese researchers were the first to use CRISPR in human cells that were removed from the body, edited, then reinjected to help fight cancer. Similar trials are expected to begin in the U.S. this year, and several companies are planning to deliver CRISPR directly into the body in an attempt to fix genetic mutations in children and adults. Those methods, however, only use CRISPR to edit somatic cells.
The prospect of germline genome editing is both appealing and appalling for the same reason: its permanence. Carriers of genetic conditions such as sickle cell anemia or Huntington’s disease could theoretically use genome editing to fix their offending DNA mutations in their germline, thus sparing their children of the disease. But the edited DNA would remain in the family forever, raising the stakes if something were to go wrong, such as an incorrect edit.
The committee’s report outlines ten criteria that should be met before future groups consider the possibility of germline editing. Those include only editing to prevent “a serious disease” and only in the “absence of reasonable alternatives.” Charo noted that one alternative may simply be using somatic genome editing to fix a disease after a child is born, rather than before.
Marcy Darnovsky, executive director of the Center for Genetics and Society, a progressive nonprofit that advocates for responsible governance of genetic and reproductive technologies, called the committee’s effective green light of germline editing “unsettling and disappointing” in a statement. Darnovsky told C&EN that “in the vast majority of cases, people at risk of transmitting genetic disease can have unaffected children related to both parents in other ways,” such as embryo screening or preimplantation genetic diagnosis.
Others think the international group took the right approach, including Kyle Orwig, a reproductive biologist at the University of Pittsburgh. “I think it is appropriately cautious,” he says. Although embryos and egg cells usually dominate discussions about germline modification, Orwig notes that editing sperm-producing stem cells is “imminently possible.”
“In the past we were talking more science fiction than science, whereas now we really can talk science,” says Orwig, an expert on sperm stem cells.
The report allays fears of human enhancement, arguing that so-called “designer baby” applications of gene-editing, such as changing eye color or enhancing muscle strength, should not be pursued right now. The committee goes as far to say that many of the concerns regarding enhancement, such as boosting intelligence, “are not possible.”
Richard O. Hynes, committee co-chair and cancer researcher at MIT, says that there is no question that “taking somebody and turning them into a body-building muscle man” is enhancement. “But fixing the muscles of someone who has muscular dystrophy, clearly that would be a good thing,” he adds. “Defining where prevention ends and enhancement begins is not easy,” Hynes admits.
The report attempts to take a middle ground, Hynes says. “I don’t think it is jumping in the deep-end. I think it is a cautious step forward, and caution is what is required, not prohibition.”
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