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CRISPR-baby scientist fails to satisfy critics



He Jiankui will be on a podium at his presentation on November 28th.

He Jiankui spoke at the Second International Summit on Human Genome Publishing in Hong Kong.Credit: Alex Hofford / EPA-EFE / Shutterstock

He Jiankui, the Chinese scientist who claims to have helped produce the first people born with a modified genome – binoculars – appeared today at a summit on gene editing in Hong Kong to explain his experience. He delivered his speech in the midst of threats of legal action and growing issues from the scientific community and beyond regarding the ethics of his work and the way he published the results.

He had never presented his work publicly apart from a handful of videos that he had posted on YouTube. Scientists have welcomed the fact that it has appeared – but his speech has left many people lacking answers and are still not absolutely certain that he has achieved what he claims.

"There is no reason not to believe it," says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. "I'm just not completely convinced."

The conversation encompasses He works in animals and explains in detail how he genetically modified embryos and implanted them in women. He explained how he had checked the gene modifications – and revealed that another woman was pregnant with a gene-modified embryo.

Lovell-Badge, like others at the conference, said an independent body should confirm the results of the test by making a thorough comparison of the genes of parents and children.

Many scientists criticize him for lack of transparency and the seemingly cavalier nature in which he embarked on a project of such magnitude and potentially risky.

"I'm glad he came, but I was really horrified and stunned when he described the process that he used," says Jennifer Doudna, a biochemist at the University of Toronto. University of California at Berkeley and pioneer of the CRISPR / Cas-9 gene modification technique. that he used. "It was so inappropriate at so many levels."

Alta Charo, a bioethicist from the University of Wisconsin-Madison and a member of the summit's organizing committee, is also critical. "After listening to Dr. He, I can only conclude that this was wrong, premature, useless and largely useless," she says.

He answers questions during his presentation on November 28th.

The scientists sprinkled questions at He Jiankui after clarifying his claim that he helped create the first babies to be published on the genome.Credit: Kin Cheung / AP / Shutterstock

Nervous speech

He seemed fragile when approaching the scene and nervous during the conversation. "I think he was scared," said Matthew Porteus, who is doing research on genome modification at Stanford University in California and co-moderated a question-and-answer session with He after his presentation. Porteus attributes this to either the legal pressures he is facing or the growing criticism of the scientists and media he was about to face.

He began by apologizing for the tumult that he caused after the first publication of his work on November 26th. He then spent 20 minutes looking at his presentation entitled "CCR5 gene modification in mouse, monkey and human embryos with CRISPR / Cas9" – before asking 40 minutes of questions.

The CCR5 gene, which he published, is used by some strains of HIV to infect immune cells. Many scientists have criticized this choice, in part because there are other ways to prevent people from contracting HIV, for example by using caesarean section to deliver babies from infected mothers. by the virus. Critics also say that other diseases are more obvious targets to eliminate by modifying the genome of embryos.

In the keynote presentation of the day, George Daley, Dean of Harvard Medical School in Boston, Massachusetts, cited Huntington's disease or Tay Sachs as examples of diseases that, under certain circumstances, could only be avoided by genetic engineering.

HIV-resistant twin

At the summit, he revealed that one of the genetically modified twins will be resistant to HIV because the gene modification removed both copies of the CCR5 gene. The other would still be susceptible to infection because the gene editing process inadvertently left a copy of CCR5 intact, he said.

His decision to implant the second embryo prompted sharp criticism. "Why choose this embryo? Scientifically, that makes no sense, "said Jin Soo Kim, a geneticist at the Seoul National University. During his interview, he explained that he had explained the situation to the parents and that they had decided to do so.

And as he clearly stated during the question-and-answer session, his goal is to prepare the technique for global use. "Do you see your friends or family who could have an illness? They need help, "he said. "For millions of families with an inherited or infectious disease, if we have this technology, we can help them."

He not only worked with the parents of the twins, he said, but with eight couples, all of whom were HIV-positive fathers and HIV-negative mothers. A couple later gave up.

His team washed men's sperm to make sure HIV was not present. The researchers then injected sperm and CRISPR / Cas-9 enzymes into unfertilized eggs of the male partners. This gave a total of 30 fertilized embryos, of which 19 were viable and looked healthy, he said. Two of the four embryos in a couple contained CCR5 modifications and implanted them in the female, although an embryo also had an intact copy of the CCR5 gene. This pregnancy produced the twins.

It is not known what happened to other embryos, but he says that there is another "early" pregnancy with a gene-modified embryo.

Kim says that he is 90% sure that twins are the first babies born with a modified genome, as he claims. This is partly because of the state-of-the-art sequencing methods that he used before and after implantation to show that there were no unwanted mutations in embryos – a possible drawback of the process. "I was impressed," Kim said.

But, like Lovell-Badge, Kim thinks that work should be independently verified. "There should be an independent inquiry committee. The Chinese authorities should do it. "

Unanswered questions

He speaks leaves a host of other unanswered questions, including whether future parents were properly informed of the risks; why he chose CCR5 when there are other proven ways of preventing HIV; why he chose to experiment with couples in which fathers have HIV, rather than mothers who are more likely to transmit the virus to their children; and if the risks of neutralizing CCR5 – a gene normally present in humans, which could have necessary but still unknown functions – outweighed the benefits in this case.

During the discussion that followed his speech, a scientist asked why he had continued his experiments despite the clear consensus of scientists around the world that such research should not be conducted. He did not answer the question.

David Baltimore, one of the organizers of the summit, described He's experience as irresponsible and criticized his lack of transparency. Baltimore has also accepted the responsibility of the scientific community. "The scientific community has failed in its process of self-regulation," he said.

He tried to justify his actions mainly. Answering questions about why the scientific community had not been informed about the experiences before the first women were impregnated, he cited the presentations he gave last year at meetings at the University of California at Berkeley and Cold Spring Harbor Laboratory in New York. York. But Doudna, who organized the Berkeley meeting, said he had not presented anything that would show he was ready to experiment on people. She called her defense "hypocritical at best".

He also said he had discussed the human experience with anonymous scientists in the United States. But Porteus says this is not enough for such an extraordinary experience: "You do not need the feedback from your two closest friends, but from the entire community." Porteus wants him to publish the data as soon as possible. his experiences with people and monkeys on a website like BioArxiv. as much as possible so that other scientists can verify it.

Mounting pressure

The pressure mounted on He before the presentation. On November 27, the National Health Commission of China ordered the Guangdong Health Commission, in the province where He University is located, to conduct an investigation.

The same day, the Chinese Academy of Sciences issued a statement condemning his work, while the China Society of Genetics and the Chinese Society for Stem Cell Research issued a statement claiming that the "experience" violated the internationally recognized ethical principles governing human experimentation and human rights law ".

The hospital cited in the Chinese clinical trial registry as having ethically approved Il's work issued a press release on November 27 stating that he had given no approval. He questioned the signatures on the approval form and indicated that the hospital's medical ethics committee had never held a meeting related to He's research. The hospital, which is itself being investigated by health authorities in Shenzhen after He's revelations, wrote: "The company does not tolerate the means of the claimed project and has reservations about the accuracy, reliability and veracity of its content and results. "

It has not yet responded to requests for comments on these statements and inquiries, nor on why the hospital was listed in the registry and the allegation of apparent false signatures.

Other governments have also begun to weigh in his experiments. On November 28, the US National Institutes of Health (NIH) declared that they did not support the use of gene editing technologies in human embryos. "This work represents a deeply troubling desire on the part of Dr. He and his team to showcase international ethical standards," NIH Director Francis Collins said in a statement. "The need to develop a binding international consensus on setting limits for this type of research, currently under discussion in Hong Kong, has never been so obvious."

Cooling effect?

The gene editing community is increasingly concerned that its actions will hinder the responsible development of gene editing in babies. At a conference on the second day of the summit, Daley, before He's speech, called for support for the modification of the germlin gene despite recent events. "It is possible that the first instance appeared as a misstep, but it should not lead us to stick our head in the sand and not to consider a more responsible path to clinical translation," he said. declared.

The pressures and opprobrium he faced were clear before his speech, according to Lovell-Badge's introductory remarks, which made an unusual plea for scientific meetings. "We have to give him a chance to explain what he did," Lovell said. "We can not have unruly behavior. If that happens, we will close the meeting and you will not have the chance to hear what he has to say. "

Security was also enhanced, with men in dark suits near the scene and cameras lined up at the back of the auditorium. After he started talking, Lovell-Badge had to ask the photographers to stop clicking for him to be heard.

Porteus said his appearance was a first step, but he should start answering the outstanding questions as soon as possible. "He's already in danger of becoming an outcast,"


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