Wednesday, January 1, 2020

CRISPR babies background

[This was  supposed to be posted in 12/18, but became intermingled with another posting.]

Doudna, who co-led a 2012 study showing that a weird bacterial immune system called CRISPR could edit DNA as niftily as Word edits documents, and hundreds of other experts were in Hong Kong for the International Human Genome Editing Summit. He Jiankui, who was scheduled to speak at the summit on Wednesday, had asked to meet privately with Doudna, one of the summit’s organizers. In his presentation, He had planned to talk about the ethics of embryo editing and his experiments on mouse, monkey, and human embryos, with nary a hint that two of those embryos were now living, breathing, baby girls whom He, in an astonishing YouTube birth announcement, called Nana and Lulu. Was that okay?, he asked Doudna as they sat in the lobby.

Um, Doudna replied, you’ve dropped this shocking news on the world, right before our summit, and you’re not planning to mention it? He seemed surprised that she expected him to but agreed to have dinner with her and other members of the summit organizing committee that evening to talk it out.
“His demeanor was an odd combination of hubris and naivete,” she recalled in an interview. “He was very confident in his work, and totally not understanding what an explosion he had caused” — one that, some scientists feared, could derail hopes for using CRISPR to prevent some of the most devastating diseases lurking in the double helix….

He confided in at least two U.S. scientists about his plan, but ignored their arguments that he was making a potentially disastrous mistake. He studied recommended ethical guidelines for embryo editing — but flouted them. He claimed he had been transparent about working toward pregnancies with CRISPR’d embryos — yet never breathed a word about those plans in his talks at science meetings and stalled for months before listing his experiment on an official Chinese registry of clinical trials.

For a driven and fame-seeking scientist who had set his star on changing the world, heeding doubters and sticklers wasn’t part of the plan.

He believed he would be hailed for his scientific first, especially in his homeland, as someone who did for China what the Sputnik engineers did for the old Soviet Union. In conversations with scientists and others, he brought up Dr. Robert Edwards, part of the team who created the world’s first test tube baby, won the 2010 Nobel prize for it, and brought joy to millions of otherwise infertile couples.

No wonder He seemed stunned that Monday, as worldwide condemnation of his work grew and even the stars of the CRISPR firmament weren’t applauding him. Over the hastily arranged Cantonese buffet dinner at Le Méridien, Doudna and three other summit organizers peppered him with technical questions (How many embryos did you try to edit with CRISPR? How many succeeded? How did you decide which embryos to implant? What tests did you run to see if the editing worked as planned?) and challenged the ethics of the experiment (Why did you pick the gene CCR5, which is involved in HIV infection, to edit? Did the parents understand the risks to their potential child? How do you know?).

After just over an hour, He had enough, participants told STAT. He pulled some cash out of his pocket, threw it on the table, and stormed off. Fearful of his safety, he left the Méridien and checked into another hotel. His dinner companions were left wondering if he would even show up for his scheduled talk at the summit on Wednesday…

He had written no important CRISPR papers before his shocking announcement. (He still hasn’t: The CRISPR babies experiment remains unpublished, and a study editing mouse, monkey, and human embryos without starting pregnancies has been rejected.) He was on no one’s radar screen…

Maybe we should invite him, Doudna proposed to Hurlbut. They did. He came. On the workshop’s second day, in a session called “Evolution and Human Development,” He presented work on using CRISPR to edit mouse, monkey, and human embryos (without pregnancies). His talk did not leave much of an impression, “and I don’t think it was received very well,” Doudna said.

That was partly because He was, in a sense, two years late. In 2015, scientists at Sun Yat-sen University in Guangzhou used CRISPR to edit the gene whose abnormality causes the often-fatal blood disease beta thalassemia. Their experiment, which also sent shock waves around the world, used nonviable IVF embryos. He, too, was using nonviable embryos. It didn’t seem like he was moving the science forward.

Worse, another attendee recalled, scientists said He’s “science was sloppy and the application unnecessary.” One biologist challenged He on technical details of his work, especially how he analyzed the edited genomes for the unintended edits called off-target effects, a critical safety concern.

Other scholars who attended were struck by what Harvard’s Sheila Jasanoff called He’s “great smoothness.” Although He did not explicitly discuss his ethical views, Jasanoff said, he “clearly did not have deep misgivings about plugging ahead with gene editing, and I sensed no exposure to the sorts of ethical debates our guys are routinely involved in.”…

But now something new entered the discussions. He told DeWitt he was planning to start pregnancies with CRISPR’d human embryos. DeWitt was aghast, he told STAT, and argued that there was no justification for such an experiment. The technology simply wasn’t ready to use on babies-to-be…

“I knew where he was heading,” Hurlbut said. “I tried to give him a sense of the practical and moral implications,” including ethical objections to research on human embryos. He pushed back; wasn’t it only a fringe group in the U.S. that adamantly opposes that?, he asked; if CRISPR can be used to prevent a dreaded genetic disorder in a baby who would otherwise inherit it, why should we hold a one-cell embryo in the same ethical regard as a suffering child?

“My overall feeling,” Hurlbut said, “was that he’s a well-meaning person who wants his efforts to count for good.”…

In July 2017 He gave an updated version of his Berkeley talk, at a meeting on “Genome Engineering: The CRISPR-Cas Revolution” at Cold Spring Harbor Laboratory on New York’s Long Island. The data from his experiments in mouse, monkey, and human embryos included ways to improve CRISPR’s efficiency and measurements of its accuracy. He had injected CRISPR into the first human embryo, he said, on Nov. 10, 2016, doing two or three each month (though four that December). He reminded his audience of the many ways embryo editing could fail, including off-target edits and mosaicism (when only some of an organism’s cells are edited, creating a genetic patchwork with unknown implications for health).

Viewing He as less than a heavy hitter in the genome-editing world, many skipped his talk. Computational biologist Max Haeussler of UC Santa Cruz, who shared a double room with He and did attend, is struck in retrospect at He’s discussing how dangerous editing human embryos is. “I found this remark already strange back then,” he said. “Everyone in the room knew that it’s out of the question to edit human embryos. Why mention that it’s dangerous?”

[Much more at link]

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