Amid Reports That Chinese Researcher May Have Used CRISPR to Edit Cholesterol Gene, He's Gone Missing
Proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme encoded by the PCSK9 gene in humans.
Last week, He Jiankui, a researcher from the Southern University of Science and Technology of China announced that a set of twins had been born in which he had used CRISPR gene editing to modify the embryos. He made this announcement at the Second International Summit on Human Genome Editing held at the University of Hong Kong. He Jiankui modified the CCR5 gene, which should make the babies less susceptible to HIV infection.
The announcement was met by widespread condemnation worldwide, and investigations are being launched by Southern University, Rice University, where researcher Michael Deem works—Deem reportedly assisted He Jiankui—the China government and the U.S. National Institutes of Health (NIH).
Another announcement He Jiankui made before reportedly leaving the conference to return to China, was that there was another successful pregnancy. There is some question as to He Jiankui’s whereabouts, however. There were rumors that he was being detained by the Chinese government, but a spokeswoman for the Southern University told the South China Morning Post, “Right now nobody’s information is accurate, only the official channels are.”
At least one U.S. researcher who was in touch with He Jiankui and his team speculates that the second pregnancy may involve a baby or babies whose PCSK9 gene was editing using CRISPR. PCSK9 is involved in control of cholesterol.
As reported by STAT, about a year ago Kiran Musunuru, a researcher at the University of Pennsylvania, was contacted by a graduate student at Southern University, Feifei Cheng. In the email, Feifei Cheng described the work performed in the laboratory using CRISPR to disable the PCSK9 gene in human embryos. “Our results have shown that CRISPR/Cas9 technology can reach a high editing efficiency for PCSK9 gene in human and monkey embryos,” the email stated. And concluded, “Do you think it is reasonable and feasible?”
According to STAT, Musunuru “offered little encouragement,” replying, “I’m not sure I have much technical advice to offer.”
He then forgot about it until He Jiankui’s announcement. Then he dug up the emails. The student, Feifei Cheng, worked with He and together they had presented a paper on their work in April in China at a meeting.
Now, reviewing the emails, Musunuru thinks the second pregnancy may be with embryos where the PCSK9 gene was disabled. “It seems clear,” Musunuru tells STAT, “this PCSK9 work in human embryos goes back at least two years. I think it’s possible that He’s group has implanted PCSK9-disrupted embryos, though I have no evidence it went that far. It was clearly in their plans, though.”
He Jiankui had also contacted one of the CRISPR developers, Feng Zhang, of the Broad Institute of MIT and Harvard, in April 2016, requesting a tour of Feng Zhang’s laboratory. That tour never occurred, although He Jiankui did pay a visit this past August, according to Zhang, to talk about making CRISPR more accurate.
Zhang told STAT, “By August, he must have been quite far along in his work in humans, at least according to his most recent claims. He certainly never mentioned this work when I saw him.”
Going through his emails, Musunuru finds several from Cheng requesting reagents for gene editing, and later was asked to review an article by an international scientific journal authored by Cheng and He on editing of PCSK9. Because the peer-review process is supposed to be confidential, Musunuru declined to name the journal.
Broadly speaking, the moral and ethical problems with editing embryos that are then implanted for pregnancy, relate to potential off-target edits and inheritance. First, there have been reports that CRISPR, though relatively precise, accidentally edits other areas of the genome at the same time as the target area, with potential unknown short-term and long-term side effects. Along those same lines, the results from disabling either of these genes, CCR5 or PCSK9, is not completely understood. In fact, there is research suggesting that ultra-low cholesterol modification increases the risk of type 2 diabetes by approximately 30 percent.
And secondly, because the editing was conducted on embryos that were implanted and became live human beings, whatever changes made to their genomes can be passed along to any children they may eventually have, as well as their children’s children, and so on.
This has resulted in the widespread condemnation, calls for global guidelines, and the launch of numerous investigations. A group of more than 100 Chinese scientists co-signed a letter condemning it, calling it “crazy.” Other ethicists have called it “monstrous,” “unconscionable” and “a grave abuse of human rights.”
Francis Collins, director of the NIH, called it “a lesson in the potential for human hubris to take over.”
For his part, Musunuru told STAT, “It makes me sick to my stomach,” to think that his own research “probably motivated him [He] to pursue PCSK9 in human embryos, possibly all the way to pregnancy.”
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