I feel an obligation to be balanced Noted biologist comes to defense

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Click to view the privacy policy. Required fields are indicated by an asterisk (*)center_img © Ken Richardson By Jon CohenNov. 28, 2018 , 2:50 PM When a researcher in China startled the world earlier this week with the revelation that he had created the first gene-edited babies, only one prominent scientist quickly spoke out in his defense: geneticist George Church, whose Harvard University lab played a pioneering role in developing CRISPR, the genome editor used to engineer embryonic cells in the hugely controversial experiment. Church has reservations about the actions of He Jiankui, the scientist in Shenzhen, China, who led the work.The fiercely debated experiment, described by He at a meeting in Hong Kong, China, today, used CRISPR to try to make the babies resistant to HIV by crippling a receptor, CCR5, that the virus uses to infect white blood cells. But Church also thinks there’s a frenzy of criticism surrounding He that exaggerates the severity of what one critic gingerly called his “missteps” but another called “monstrous.”ScienceInsider spoke with Church shortly before He’s lecture in Hong Kong, but Church had seen the data earlier. This interview has been edited for clarity and brevity. Q: What do you think of the criticism being heaped on He?A: I’d just as well not hang myself out to dry with someone I barely know, but I feel an obligation to be balanced about it. I’m sitting in the middle and everyone else is so extreme that it makes me look like his buddy. He’s just an acquaintance. But it seems like a bullying situation to me. The most serious thing I’ve heard is that he didn’t do the paperwork right. He wouldn’t be the first person who got the paperwork wrong. It’s just that the stakes are higher. If it had gone south and someone had been damaged, maybe there would be some point. Like what happened with Jesse Gelsinger [who died in a 1999 gene therapy experiment]. But is this a Jesse Gelsinger or a Louise Brown [the first baby born through in vitro fertilization] event? That’s probably what it boils down to.Q: Do you think the experiment is unethical?A: People have said there’s a moratorium on germline editing and I contributed to reports that called for that, but a moratorium is not a permanent ban forever. It’s a checklist of what you have to do. It really seems like he was checking off the published list [see p. 132] by the National Academy of Sciences and added a few things of his own. At some point, we have to say we’ve done hundreds of animal studies and we’ve done quite a few human embryo studies. It may be after the dust settles there’s mosaicism and off targets that affect medical outcomes. It may never be zero. We don’t wait for radiation to be zero before we do [positron emission tomography] scans or x-rays.Q: When did you learn about it and what was your reaction?A: About a week ago, and I was hoping he did everything right. You don’t have that many shots on goal. He’s not doing it the way I’d do it, but I’m hoping it doesn’t work out badly. As long as these are normal, healthy kids it’s going to be fine for the field and the family.Q: What do you think of his decision to cripple a gene to prevent HIV infection?A: It struck me as bold choice to do CCR5. In some ways it doesn’t make sense, but in another way it makes more sense than β-thalassemia or sickle cell, both of which you can prevent with preimplantation genetic diagnosis. [These genetic diseases are two prime targets of many CRISPR researchers.] The real issue is what’s the best first case.Q: But there’s a relatively low rate of HIV infection in Chinese women. This isn’t like in, say, KwaZulu Natal in South Africa, where the medical need to protect young women from the virus is great.A: This was a stretch, there’s no doubt about it. There could be a bunch of small risks. Quite clearly the major motivator was testing CRISPR.Q: What do you think of the criticism the experiment doesn’t address an “unmet medical need”?A: The unmet medical need is there is no cure or vaccine for HIV. And in that sense, there’s more of a medical need than there is for β-thalassemia, for which there is an alternative, unless both parents are homozygous. [If both parents have two copies of the mutant gene, all of their offspring will develop the disease.]Q: What about concerns that CRISPR will make unintended edits in the genome, so-called off-target effects?A: I’m not saying they’ll never be an off-target problem. But let’s be quantitative before we start being accusatory. It might be detectable but not clinical. There’s no evidence of off-target causing problems in animals or cells. We have pigs that have dozens of CRISPR mutations and a mouse strain that has 40 CRISPR sites going off constantly and there are off-target effects in these animals, but we have no evidence of negative consequences.Q: Would you have been part of this experiment?A: Probably not. But I probably wouldn’t have put the sequence of the 1918 flu virus or smallpox virus in the public domain. This is a slightly lower risk than putting potent pathogenic sequences in the public domain.Q: There’s some worry that the backlash to He’s experiment will harm the field.A: In the early days of gene therapies when there were far fewer preliminary studies, there were three deaths that set back the field. It may have just made us more cautious. And gene therapy is certainly back in force. And I don’t think these kids [the babies whose genomes He edited] are going to die.Q: What about the argument that He wasn’t transparent enough and should have published preliminary work and done more to make his intentions clear to the scientific community before implanting the embryos?A: Those are valid critiques, and he probably will pay some price. I’m a little extreme on the transparency end of the spectrum [Church’s website lists more than 100 affiliations he has with funders, companies, and nonprofits], and it’s nice to have company on that. But at some point, we should start focusing on the health of the babies.last_img

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