"I feel obligated to be balanced." A recognized biologist comes to defend the genetics of genetic publishing | Science

When a researcher in China surprised the world earlier this week by revealing that he had created the first genetically modified babies, only one leading scientist quickly took up his defense: the geneticist George Church. , whose Harvard University lab played a pioneering role in the development of CRISPR, the genome editor used to design embryonic cells as part of a highly controversial experiment. The church has reservations about the actions of He Jiankui, the scientist in Shenzhen, China, who led the work.

The extremely controversial experience described by HE at a meeting in Hong Kong, China, today used CRISPR to try to achieve HIV-resistant babies by disabling a receptor, CCR5, which the virus uses to infect white blood cells. But Church also thinks that there is a frenzy of criticism around Him that exaggerates the severity of what one critic has cautiously termed "missteps" but another called "monstrous".

Science An initiate spoke to Church shortly before his reading in Hong Kong, but Church had seen the data earlier. This interview has been modified for clarity and brevity.

Q: What do you think of the criticism that is made to him?

A: I would like just as well not to hang myself dry with someone I hardly know, but I feel an obligation to be balanced at this subject. I sit in the middle and everyone is so extreme that it makes me look like his boyfriend. He is just an acquaintance. But that seems to me to be a situation of intimidation. The most serious thing I've heard is that he did not complete the paperwork properly. He would not be the first person to go wrong. It's just that the stakes are more important. If he had gone to the south and someone had been damaged, he might be worth it. Like what happened with Jesse Gelsinger [who died in a 1999 gene therapy experiment]. But is there an event by Jesse Gelsinger or Louise Brown [the first baby born through in vitro fertilization]?

Q: Do you think that the experience is unethical?

A: People said that there was a moratorium on germline modification and I contributed to the reports that called for this, but a moratorium is not a permanent ban forever. This is a checklist of what you need to do. It really seems that he checks the published list [see p. 132] of the National Academy of Sciences and adds a few things to it. At one point, we must say that we have done hundreds of animal studies and several studies on the human embryo. It may be once the dust settles, as the mosaicism and targets that affect the medical outcome. This can never be zero. We do not expect the radiation to be zero before [positron emission tomography] scans or X-rays.

Q: When did you first learn about the existence of this radiation and what was your reaction?

. ] R: About a week ago, and I hoped that he had done everything right. You do not have as many shots on goal. It does not do it as I would, but I hope it will not work badly. As long as they are normal and healthy children, everything will be fine for the field and the family.

Q: What do you think of his decision to paralyze a gene in order to prevent HIV infection? [19659005] R: It even seemed like a bold choice to do it CCR5 . In some ways, that makes no sense, but in another way, it makes more sense than β-thalbademia or sickle cell disease, which you can prevent with pre-implantation genetic diagnosis. [These genetic diseases are two prime targets of many CRISPR researchers.] The real problem is what is the best first case.

Q: But the rate of HIV infection among Chinese women is relatively low. This is not like in, for example, KwaZulu Natal in South Africa, where the medical need to protect young women from the virus is great.

A: This was a stretch, there is no doubt about it. There could be a lot of small risks. It is clear that the main motivator was testing CRISPR.

Q: What do you think of the criticism that the experiment does not respond to an "unmet medical need"?

R: The unmet medical need is that there is no treatment or vaccine against HIV. And in this sense, the medical need is more important than for β-thalbademia, 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 fears that CRISPR is making involuntary changes in the genome, supposedly off-target effects?

A: I am not saying that they will never be a problem off target. But let's be quantitative before starting to be accusers. This could be detectable but not clinical. There is no evidence that off-target problems can cause problems in animals or cells. We have pigs that have dozens of CRISPR mutations and a strain of mice on which 40 CRISPR sites are constantly stopping and there are non-targeted effects in these animals, but we have no evidence of negative consequences.

Q: Did you participate in this experiment?

A: Probably not. But I probably would not have put the sequence of the 1918 influenza virus or the smallpox virus in the public domain. This is a slightly lower risk than placing strong pathogenic sequences in the public domain.

Q: It is to be feared that the negative reaction of the experience that he has suffered damages the field.

A: At the beginning of gene therapies, while there were many fewer preliminary studies, three deaths delayed the field. It may just make us more cautious. And gene therapy is definitely back in force. And I do not think these children [the babies whose genomes He edited] will die.

Q: What about the argument that it was not transparent enough and should have published preliminary work and done more to make its intentions clear? ? The scientific community before implanting embryos? I'm a little extreme about transparency [Church’s website lists more than 100 affiliations he has with funders, companies, and nonprofits] and it's good to have company on this. But at some point, we should start focusing on the health of babies.