Ethics in gene editing: U.K. taking deeper look at practical applications

LONDON – A U.K. enquiry into the moral and ethical issues raised by genome editing has concluded existing regulations provide sufficient oversight for the majority of applications but that its potential uses in treating inherited diseases by altering the germline in humans, and to increase production in livestock, requires urgent scrutiny.

Following on from the initial investigation by the Nuffield Council on Bioethics, the findings of which were published Friday, a working party on genome editing in human reproduction for the prevention of inherited diseases has been set up to look at the ethical and practical considerations. The group will hold its first meeting shortly and report early in 2017.

“We’ve seen CRISPR/Cas9 genome editing take off across biosciences,” said Hugh Whittall, director of the Nuffield Council. “It has been quite transformational in the context of basic research. The question for us was how it will land when it comes down to practical applications,” he told BioWorld Today.

The review heard evidence from a wide range of individuals, industry and patient groups, clinicians, academics and ethicists. A key conclusion is that genome editing should not be regulated as a technology, but in the light of specific applications.

“We are not looking into genome editing in human reproduction because anyone is about to do anything, but because it has generated a lot of attention. It is time to get a handle on the issues before it becomes a practical proposition,” Whittall said.

In contrast to that human application, where there has been much talk but little activity, there is a surprising amount of progress in research aimed at increasing food production in farmed animals, the review found.

“There is actually quite a lot of work going on, but it is not so much talked about,” said Whittall. A second working group has been set up to investigate that area.

The Nuffield Council review points out that genome editing has quite a long history, dating back to the discovery of zinc finger nucleases in 1985. What changed with the arrival of CRISPR/Cas9 in 2012 was the ease of making precisely targeted alterations to DNA sequences.

The versatility, ease of use and low cost led to widespread uptake. Successful genome editing by CRISPR/Cas9 “requires skills that can readily be acquired by those with standard degree level skills in molecular biology,” the review notes.

“When you look at CRISPR/Cas9 itself, in some ways it’s a tweak. The ethical challenge is more about the speed and ease of uptake,” said Whittall. “You can’t look at it as a technology and say what it means in an ethical context; the better way is to look at the areas of application.”

So in the case of treating inherited diseases, manipulation of somatic cells is covered by existing regulations relating to gene therapy, Whittall said. “There may still be some questions, for example, the possibility of off-target effects. These are serious issues but they are manageable in the framework of the regulation as it exists now. However, germline alteration goes beyond [any existing regulation].”

A long path to legislative change will have to be followed before editing the germline could become a treatment option, said Karen Yeong, director of the Center for Technology, Ethics & Law at King’s College London, who will chair the working group. But, she said, “it is only right that we acknowledge where this new science may lead and explore the possible paths ahead.”

While germline editing is prohibited in many countries, the U.K. does permits its use in research in germ cells, including human embryos up to 14 days old, where that is supported by scientific and ethical review. The regulator, the Human Embryology and Fertilization Authority, has granted approval to a research project using the technology to systematically edit genes, in order to understand which genes human embryos need to develop successfully.

The findings could have potential applications in improving success rates in in vitro fertilization, lead to better treatments for infertility and provide insights into the molecular mechanisms that regulate embryonic stem cell pluripotency. (See BioWorld Today, Sept. 21, 2015.)

The Nuffield Council is in touch with the international forum on genome editing that was set up following the summit on the issue convened in Washington by the national academies of China, the U.K. and the U.S. at the end of last year. (See BioWorld Today, Dec. 8, 2015.)

The forum’s brief is to establish norms concerning acceptable uses of human germline editing, discuss potential clinical uses, help inform decisions by national policymakers and promote coordination among nations.

“There is now a good international network amongst groups with an interest in the field and we are very much involved in that,” Whittall said.

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