An advisory panel to the National Academy of Sciences and the National Academy of Medicine on Tuesday issued a report that gave cautious support for clinical trials that involve editing genomes in sperm, eggs, and early-stage embryos—under limited circumstances.
A controversial practice
Genetically altering eggs, sperm, or an embryo in a way that would allow those altered genes to be passed on to future generations is known as human "germline" editing. The practice, the New York Times reports, "has long been seen as an ethical minefield" because of the potential for people to use it for cosmetic enhancements or to genetically alter the human species over time.
About a year ago, an international panel of scientists said it would be "irresponsible to proceed" with making heritable changes to the human genome until risks could be better evaluated and there was "broad societal consensus about the appropriateness" of any suggested change, according to the Times. Further, a 2016 law bars U.S. regulators from reviewing proposals for clinical trials that involve human germline editing.
But the recent advent of a genome-editing tool known as CRISPR-Cas9 has renewed conversations around germline editing. The tool allows researchers to snip, insert, and remove genetic material with growing precision, according to the Times. So far, it has been used to make genetic alterations to identify experimental treatments for conditions that are not inherited, such as cancer and blindness.
And after more than a year of deliberation, the 22-member panel—which includes some of the world's leading bioethicists, geneticists, physicians, and legal experts—has given cautious support for moving toward genome editing related to inherited conditions.
Report details
Although human germline editing is currently restricted in the United States, the report authors note that some countries allow the practice and that advances in technology and will make germline editing nearly "impossible to control completely."
Therefore, the panel recommended that "germline genome-editing research trials might be permitted, but only after much more research to meet appropriate risk/benefit standards for authorizing clinical trials." The panel wrote that such trials must be cautiously approached, "but that caution does not mean" they need to be prohibited.
The report recommended germline editing experiments be limited to modifications that aim to prevent offspring from acquiring genes that are known to cause "serious diseases and disability," and only in cases when there is "no reasonable alternative." The report also stated germline editing should be conducted only if it results in a version of a gene already known, as opposed to one never seen in nature.
The report authors said they do not support genetic alternations that resemble "enhancement," such as editing to give individuals traits "beyond levels considered typical of adequate health." For instance, a genetic technique to strengthen muscles in patients with Duchenne muscular dystrophy could not be used to boost strength in healthy people.
Richard Hynes, a biologist at the Massachusetts Institute of Technology and a lead author for the report, said, "We say proceed with all due caution, but we don't prohibit germline, after considerable discussion and debate. We're talking only about fixing diseases."
Debate
Eric Lander, president of the Broad Institute at MIT and Harvard, called the report's stance "a very careful, conservative position that's just a little bit beyond an absolute bar." He added that he thinks "that's the right place to go for now."
Noting the introduction of new technology—like CRISPR-Cas9—Hynes said, "Things that were not feasible became feasible." He added, "Now we can see a path whereby we might be able to [conduct germline editing] so we have to think about how to make sure it's used only for the right things and not for the wrong things."
However, according to the Times, "it is not clear who would draw those lines."
George Church, a geneticist at Harvard University, said the report does not clearly prohibit against certain enhancements. "If these fixes for severe diseases are shown to be safe and effective, why would small or large enhancements accompanying the fixes be unacceptable?" he asked.
In addition, some opponents have concerns that initiating germline editing will eventually lead to engineering for certain traits. Marcy Darnovsky, executive director of the Center for Genetics and Society, said, "This opens the door to advertisements from fertility clinics of giving your child the best start in life with a gene-editing packet," adding that advantages "would accrue disproportionately to people who are already advantaged."
In addition, according to the Times, while CRISPR is generally precise, there are also considerations regarding "off-target" effects—meaning when DNA is cut at an unintended point.
Still, George Annas a bioethicists at Boston University who reviewed the report prior to publication, said, "The benefits seem to [be] taken as more likely than the risks," provided there is regulatory oversight (Harmon, New York Times, 2/14; Achenbach, "Speaking of Science," Washington Post, 2/14; Dockser-Marcus, Wall Street Journal, 2/14; Begley, "In the Lab," STAT News, 2/14).
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