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

George Church has a more nuanced view than many scientists on the recently disclosed release of human baby genes.

© Ken Richardson

By Jon Cohen

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 his stand: the geneticist George Church, whose University lab Harvard played a pioneering role in development. CRISPR, the genome editor used to design embryonic cells as part of an extremely controversial experiment. Church has reservations about the actions of He Jiankiu, the scientist in Shenzhen, China, who led the work.

The experience was the subject of a heated debate, described by HE at a meeting in Hong Kong, China, today, with CRISPR to make babies resistant to HIV by neutralizing a receptor, CCR5, used by the virus 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".

ScienceInsider spoke with Church shortly before his conference in Hong Kong, but Church had already seen the data. This interview has been modified for clarity and brevity.

Q: What do you think of the criticism made to Him?

A: I would like as well not to let myself go to dry with someone I hardly know, but I feel compelled to be balanced about it. 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 it Jesse Gelsinger or Louise Brown? [the first baby born through in vitro fertilization] Event? That's probably what it means.

Q: Do you think that the experience is unethical?

A: People said there was a moratorium on germline modification and I contributed to the reports that called for it, but a moratorium is not a permanent ban. This is a checklist of what you need to do. It really seems that it checks the published list [see p. 132] by the National Academy of Sciences and added a few things of his own. 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. It can never be zero. We do not expect the radiation to be zero before doing so [positron emission tomography] scans or X-rays.

Q: When did you hear about this and what was your reaction?

A: 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 for the family.

Q: What do you think of his decision to paralyze a gene to prevent HIV infection?

A: It has appeared to me as a bold choice to make CCR5. In some ways, that makes no sense, but in another way, it makes more sense than β-thalassemia 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 knowing which is the best first case.

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

A: It was exaggerated, there is no doubt. There could be a lot of small risks. Obviously, the main motivator was testing CRISPR.

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

A: The unmet medical need is that there is no HIV treatment or vaccine. And in this sense, the medical need is more important than 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 changes in the genome, called non-targeted effects?

A: I'm 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 non-targeted effects in these animals, but we have no evidence of negative consequences.

Q: Would you have participated 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. It is a slightly lower risk than putting powerful pathogenic sequences in the public domain.

Q: It is to be feared that feedback from He's experience will harm 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 kids [the babies whose genomes He edited] going to die.

Q: What about the argument that it was not transparent enough and should have published some preliminary work and done more to clarify its intentions to the scientific community before it started? implant the embryos?

A: These are valid critics, and he will probably pay a price. I'm a bit extreme on the spectrum transparency side [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.

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