Following gene editing milestone, bioethics professor ventures into CRISPR minefield

In the face of a gene editing breakthrough this week, Insoo Hyun, an associate professor in the Department of Bioethics at Case Western Reserve University talked about CRISPR vs. preimplantation genetic diagnosis to help couples select healthy embryos.

Researchers in the U.S. and South Korea have shown that gene editing can correct a genetic disorder in an embryo. Using CRISPR-Cas9, they repaired mutated MYBPC3 genes, which can cause hypertrophic cardiomyopathy (HCM). People with HCM are at greater risk for sudden cardiac death, heart failure and other cardiovascular issues.

On a basic research level, this is a tremendous milestone, but it also frames the ethical and practical dilemmas that accompany germline gene editing. For example, was HCM the right choice?

“I was a little disappointed at the condition they tried to edit out because it’s not a super serious one,” said Insoo Hyun, an associate professor in the Department of Bioethics at Case Western Reserve University in a phone interview. “This one raises your risk, but there are ways to clinically manage it.”

Hyun, who also spoke at the MedCity CONVERGE conference this week, noted that, given the potential for controversy, the researchers might have chosen a graver condition, such as Huntington’s disease.

“As far as proof of principle, it wasn’t an ideal case where someone could say: Yeah, this is a really controversial area, but could be genetically or ethically justified because of the dire circumstances,” said Hyun.

While the study does prove the concept, there are also questions about its practicality in a clinical setting. The scientists introduced CRISPR and fertilized the eggs simultaneously to avoid generating cells with different genotypes. Hyun is concerned that, by correcting the mutation before fertilization, they had no idea which embryos might have carried it. Their process makes the fix regardless of whether the embryo needs fixing.

Hyun questions the practical advantages of using CRISPR to repair these embryos, when an existing technology – preimplantation genetic diagnosis (PGD) – could more easily help couples select healthy embryos. Given that roughly half of the embryos in this scenario would be healthy, PGD could be used to select those for implantation and clinicians could ignore the ones with HCM mutations.

“Whenever you do your edit, at some point you have to do preimplantation genetic diagnosis to see your research results,” said Hyun. “If you’re looking at diseases and can use PGD to see your results, why wouldn’t the couple just use PGD? If this were a disease that every embryo was going to be affected, or one so horrible that even the slight risk PGD could be wrong and you could implant affected embryos is too high, that would be a different case. None of that is true of this condition.”

There are also stringent guidelines regarding embryo creation and destruction. Researchers cannot use federal funds to make embryos for research or implant modified embryos for clinical trials. Given that the paper provides instructions to make these modifications, some might take their work to other countries to escape regulatory oversight.

“We do know from the mitochondrial transfer work that researchers have recruited people in New York City and done the research in Mexico,” said Hyun.

Ultimately, the ability to create additional healthy embryos may not be enough payoff for such a rigorous approach.

“This kind of editing research is very valuable for basic developmental biology and disease research. If you want to understand how genes control development, then this is a good scientific methodology, but not if your overall need is to create a new reproductive technique.”

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