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Ethicists advise caution in applying CRISPR gene editing to humans

An artist's rendering of the powerful genome editing tool, CRISPR-Cas9. (Stephen Dixon)

Ethicists have been working overtime to figure out how to handle CRISPR, the revolutionary gene-editing technique that could potentially prevent congenital diseases but could also be used for cosmetic enhancements and lead to permanent, heritable changes in the human species.

The latest iteration of this ongoing CRISPR debate is a report published Tuesday by the National Academy of Sciences and the National Academy of Medicine. The report, a series of guidelines written by 22 experts from multiple countries and a variety of academic specialties, presents a kind of flashing red light for CRISPR.

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The report did not recommend an absolute prohibition of gene editing on the human “germline” if such interventions can be proved safe. This would involve genetic changes to eggs, sperm or embryos that would persist in an adult and could be inherited by future generations.

For some ethicists, that represents a slippery slope. At the conclusion of a gene-editing summit in Washington at the National Academy of Sciences in December 2015, scientists said that although some basic research could proceed, it would be irresponsible to use genetically modified germline cells for the purpose of establishing a pregnancy.

But the new report takes a slightly more permissive, forward-thinking position, saying that, if and when such interventions are proved safe — which could be in the near future — and if numerous criteria are met to ensure that such gene editing is regulated and limited, it could potentially be used to treat rare, serious diseases.

“We say proceed with all due caution, but we don’t prohibit germline, after considerable discussion and debate,” said Richard Hynes, an MIT biologist and one of the leaders of the new study. “We’re talking only about fixing diseases.”

The list of criteria for going down that road is a long one, said Alta Charo, a professor of law and bioethics at the University of Wisconsin, speaking at a news conference Tuesday in Washington. For example: The intervention would have to replace the defective, disease-causing gene with a gene already common in the human species. There would also have to be no simpler alternative for parents wishing to have a healthy child. And first and foremost, there needs to be more research to show that such modifications are safe and target well-understood genes, she said.

“We are not even close to the amount of research that we need before you can move forward,” Charo said.

What is less controversial, and already happening, is gene therapy that targets “somatic” cells, in which the changes are not heritable. Such interventions can help an individual patient but would not affect his or her offspring. However, some therapies that can be used to treat a disease could potentially be used for purely cosmetic or competitive purposes.

For example, gene therapy developed as a treatment for muscular dystrophy could potentially be exploited to make a healthy person more muscular. The committee came out strongly against any use of CRISPR for cosmetic enhancements. And the report argues that gene editing in humans should come only after broad public discussion.

This animation depicts the CRISPR-Cas9 method for genome editing – a powerful new technology with many applications in biomedical research, including the potential to treat human genetic disease or provide cosmetic enhancements. (Video: Feng Zhang/McGovern Institute for Brain Research/MIT)

Josephine Johnston, director of research at the Hastings Center, an independent bioethics research institute, said the only thing potentially controversial in this new report is the “openness to germline modification.” Some bioethicists believe that's a bright line that should not be crossed, she said.

Eric Lander, president of the Broad Institute of MIT and Harvard, said of the report, “It’s a very careful, conservative position that’s just a little bit beyond an absolute bar. And I think that’s the right place to go for now. … They say you cannot do this unless you put double-stick tape on the slippery slope so that nothing can slip. That’s a pretty strong set of restrictions.”

Neither Johnston nor Lander were part of the National Academy of Sciences committee that issued the report.

The report drew immediate criticism from a California-based non-profit organization called the Center for Genetics and Society.

“This report is a dramatic departure from the widespread global agreement that human germline modification should remain off limits,” said Marcy Darnovsky, executive director of the center. “It acknowledges many of the widely recognized risks, including stigmatizing people with disabilities, exacerbating existing inequalities, and introducing new eugenic abuses. Strangely, there’s no apparent connection between those dire risks and the recommendation to move ahead.”

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. CRISPR-Cas9, as it is more precisely called, is a natural system developed by bacteria over the course of their long evolutionary history. The bacteria use their own gene-editing system to identify foreign genetic material that has been inserted into the bacterial genome by viruses. These invasive genetic passages are snipped away, and the genome repaired.

Early in this decade, a series of scientific papers described how this system could be exploited in the laboratory for genetic engineering. CRISPR quickly became the go-to method for gene editing, because it's easier and cheaper than previous methods. It can be used to modify the genomes of plants, animals and potentially humans, though experiments with human embryos have been limited so far because of ethical concerns and, in the United States, legal prohibitions.

This story has been updated.

Further Reading:

Scientists debate an unnerving gene-editing technique

Pondering “what it means to be human” on the frontier of gene editing

New gene-editing trick discovered just in time for J-Lo's “CRISPR” TV series