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International Gene Editing Summit Kicks Off With Wide-Ranging Discussions

WASHINGTON, DC (GenomeWeb) – On the first day of the International Summit on Human Gene Editing, held at the National Academy of Sciences, experts from around the world jumped headlong into discussing the thicket of technical, ethical, legal, and social implications of recent technological advances in genome editing.

In sessions that broadly mapped the intellectual territory to be covered, not only in the next two days, but also in the next several years, selected speakers and attendees began by commenting on the issues of the current state of the art in genome editing technology, the historical and legal context for the current discussion, societal implications for the new technologies, and even the thorny issue of human germline genome editing.

Several strong — though varied — themes emerged, such as the inherent differences between somatic cell and germline modification and the weightiness of their implications for the broader world, the need to standardize how scientists measure on- and off-target effects of genome editing, and questions about the justifications for how the technology might be applied.

The scene was somewhat unprecedented in scientific history. It is notable that the US's NAS, the National Academy of Medicine, the Chinese Academy of Sciences, and the UK's Royal Society are all co-hosting the event, Daniel Kevles, a historian of science at New York University told GenomeWeb. References to the 1975 Asilomar Conference on recombinant DNA technology popped up throughout the day, but Summit Committee Chair David Baltimore, of the California Institute of Technology, said they were fundamentally about different topics.

"Asilomar was about biosafety," he said. "This [summit] is about safety issues to the patient and the continuing human population that, if we do make changes, finds itself with those changes in the individuals around the world. In a sense, it's less technical."

Still, technology was an important consideration for a session featuring many of the top researchers in the genome editing field, including Jennifer Doudna of the University of California, Berkeley; Emmanuelle Charpentier of the Max Planck Institute for Infection Biology; Feng Zhang of the Massachusetts Institute of Technology; Keith Joung of Massachusetts General Hospital and Harvard University; and Maria Jasin of Memorial Sloan-Kettering Cancer Center. Zhang and Joung both echoed Doudna's call for standardized methods to measure efficacy and specificity of genome editing.

"We, as a field, still have a lot of work to do," Joung said. In his presentation he discussed the handful of methods used to detect off-target activity, including his own GUIDE-seq method. Someone, he said, "needs to do the hard work of actually comparing all these different methods to figure out which, if one or two or more of them in combination, will give us the best ability to find out where these off-target effects are occurring."

The small and technical issue of creating standards for finding off-target effects of genome editing in clinical trials at times seemed dwarfed by the enormity of the other challenges presented by other speakers. Not least of those issues were the need to confront the dark history of the Eugenics movement and parse the various levels and styles of regulation available to a scientific community practically begging for it. Kevles, the historian of science, and Alta Charo, of the University of Wisconsin-Madison, spoke to these issues, respectively, in a session designed to provide context for the summit's ensuing talks.

The context informed the basic questions at the heart of this meeting: Do we want to do this? If so, how do we do it right? If not, how do we ensure that?

At times, it seemed easier to discredit arguments against human gene editing, as philosopher John Harris of the University of Manchester did, than to make the case for germline editing, in particular. While few objections arose to the idea of somatic cell editing, the thought of germline editing elicited a stronger reaction.

Hille Haker, a theologist at Loyola University Chicago, argued for a strict ban on germline editing, suggesting that such a ban could be enforced through the United Nations and other international binding agreements. But other presentations, in aggregate, suggested that the application of germline genome editing might naturally be limited.

While some disorders, such as genetic male infertility, might be necessarily treated by germline editing, others, notably rare Mendelian diseases, would not. Several commenters referred to, but did not thoroughly make the argument that pre-implantation genetic diagnosis could preclude the use of germline genome editing, especially when it comes to preventing painful conditions such as cystic fibrosis and Huntington's disease.

Peter Braude, Emeritus Professor of Obstetrics and Gynaecology at King's College London added that about a third of single gene disorders are individualized and would be difficult to edit. "I'm not a molecular biologist, but It seems to be a monumental task to develop a new set of primers, a new set of everything you need, for every patient that comes to see you," he said.

For common diseases, such as heart disease or Alzheimer's, the reward for editing even the most strongly associated genetic variants could be disappointingly small. As Eric Lander, president of the Broad Institute, discussed in his closing presentation, carrying a single genetic variant correlated with developing such diseases may only increase risk by a few percent.

Throughout the day, several speakers asked whether a line could be drawn between medically justifiable changes to the germline and nice-to-have enhancements. How to answer that and how to enforce such a decision often went unanswered, perhaps with the hope that the assembly of experts might consider it over the course of the meeting and beyond.

But unquestionably, the opening sessions reinforced the idea, as the Francis Crick Institute's Robin Lovell-Badge put it, that "the decision whether to go ahead with any application is not one to be made by scientists alone."

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