麻豆传媒

SAN DIEGO -- In another decade or two, gene-editing may make it possible for two parents with cystic fibrosis (CF) to have a child without the disease even if they have recessive genes for it. But bioethicist and philosopher Mary Devereaux, PhD, doubts whether this kind of genetic engineering in the womb will ever be a good idea.

"Even in cases as dire as cystic fibrosis, germline editing may be something we decide to forestall for ethical and other social reasons," Devereaux told the audience in a Sunday debate at the annual meeting of the Society of Thoracic Surgeons here. For now, she said, "neither the science nor the ethics are ready for prime time."

But her debate opponent, pediatrician Kyle Brothers, MD, PhD, said CF is a "perfect first target" for gene editing aimed at preventing disease at the embryo stage.

Gene-editing of babies has been an especially hot topic over the past 2 months since broke that a Chinese scientist claimed to have altered genes in two human embryos.

At the ATS debate, Brothers and Devereaux considered the hypothetical case of a young husband and wife who want to understand what the future holds for gene-editing in case they have children. The man has a severe form of CF, and the wife has a milder case. They both have two variant copies of the autosomal recessive CF gene.

Brothers, an associate professor of pediatrics at the University of Louisville who's affiliated with the college's Institute for Bioethics, Health Policy, and Law, expects gene-editing of embryos via CRISPR-Cas9 technology will be ready for clinical trials within 10 to 20 years.

"CRISPR technology will eventually be used to prevent serious pediatric conditions," he said. "As a pediatrician, I think that's a good thing, and cystic fibrosis is a great place to start."

That's because CF poses such a high burden. "There's a lot of attention given to the successes of CF, but a lot of children still die of it," he said. Life expectancy remains low, he said, and patients face high risks of malabsorption, diabetes, and male infertility. Treatments, meanwhile, are lifelong, expensive, and burdensome.

Gene therapy after birth in patients with CF is not an ideal solution, he said. Gene-editing, on the other hand, is suited to prevent CF in the womb, he said, unlike de novo variant conditions that are not amenable to it.

Devereaux, assistant director of the University of California at San Diego's Research Ethics Program, warned that the entire fertilization process would be questionable in this hypothetical case. Sperm is blocked in most men with CF, so the husband's sperm would need to be aspirated from his testes, she said, while the wife would need to undergo ovarian stimulation and oocyte extraction.

Alternatives such as adoption or a sperm donation would be feasible alternatives to gene-editing, she said.

It's also important to consider the needs of the offspring, Devereaux said. For one thing, his or her parents face a limited life expectancy. And the gene-editing process could go awry, she noted. "If we make a mistake, we can't quite undo that."

She mentioned that questions crop up in other areas such as accessibility, affordability, safety and consent. And she raised the specter of a slippery slope, suggesting that allowing procedures like this could lead to greater acceptance of unacceptable procedures.

Brothers, the pediatrician, has a much less grim outlook. He said he'd offer a hopeful message to the husband and wife: "There needs to be a couple who agree to do this first, and this could be you."

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