CRISPR-baby scientist fails to satisfy critics

He Jiankui, a Chinese scientist who claims to have helped produce the first people born with a modified genome – twin babies – 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, about the ethics of his work.

Never before had he presented his work publicly, apart from a handful of videos that he had posted on YouTube. The scientists praised the fact that he appeared – but his speech left many people lacking answers and still are not absolutely sure his claims are accurate.

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

He talked about his work on animals and details of 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 many other scientists, believes that an independent body should confirm test results by thoroughly comparing 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," said Jennifer Doudna, a biochemist at the University of Toronto. 39, University of California at Berkeley and pioneer of the CRISPR – Cas-9 gene. editing technique that he used. "It was so inappropriate at so many levels."

Alta Charo, a bioethicist at 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.

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 gene editing research at Stanford University in California and co-moderated a question-and-answer session with He after his presentation. . Porteus attributed his nervous behavior to the legal pressure he faces or the prospect of addressing a critical audience of scientists and members of the media.

He began by apologizing for the tumult that occurred after the first appearance of his work earlier this week. He then spent 20 minutes listening to his presentation entitledCCR5 editing genes in mouse, monkey and human embryos using CRISPR – Cas9 "- before taking 40 minutes of questions.

CCR5, the gene he edited, is the pathway by which many strains of HIV infect immune cells. Many scientists have criticized He's choice to modify this gene, in part because there are other ways to prevent people from contracting HIV – for example, using Caesarean section to put the gene at risk. babies from mothers infected with the virus. Critics also claim that other diseases could be more obvious elimination targets through the editing of embryonic genomes.

In the keynote presentation of the day, George Daley, Dean of Harvard Medical School in Boston, Massachusetts, referred to Huntington's Disease or Tay-Sachs as examples of diseases that, under certain circumstances, could be avoided only through genetic modification.

HIV-resistant twin

At the summit, he revealed that one of the genetically modified twins will be resistant to HIV because the genetic changes took him off both copies. CCR5 gene. The other twin is still susceptible to infection because the gene modification process has inadvertently left a copy of it. CCR5 intact, he said.

The decision to implant the second embryo provoked sharp criticism. "Why choose this embryo? It does not make sense scientifically, "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 explained 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 an initial total of eight couples of HIV-positive men and HIV-negative women. A couple subsequently left the study.

He first washed men's sperm to make sure HIV was not present. The researchers then injected sperm and CRISPR-Cas9 enzymes into unfertilized eggs of the male partners. This produced a total of 30 fertilized embryos, of which 19 were viable and appeared healthy, according to He. Two of the four embryos of a couple contained modifications to CCR5, and he implanted these two modified embryos in the woman, even if 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 used before and after implantation to show that the embryos contained no unwanted mutations – which could be one of the drawbacks of the process. from He. "I was impressed," says Kim.

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

His speech leaves many questions unanswered, especially if the future parents were properly informed of the risks; why he chose CCR5 modification when there are other proven methods of HIV prevention; why he chose to experiment with couples in which men are HIV-positive, while HIV-positive women are more likely to transmit the virus to their children; and if the risks of knocking out CCR5 – a gene normally present in humans, which could have necessary functions but still unknown – outweighs 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, chair of the summit's organizing committee, described the experience as "irresponsible" and criticized his lack of transparency. Baltimore has also accepted the responsibility of the scientific community. "There has been a failure of self-regulation on the part of the scientific community," he said.

He tried to justify his actions mainly. Answering questions about why the scientific community had not been informed of the experiences before the first women were impregnated, he cited 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 that this is not enough for such an extraordinary experience. "You do not need feedback from your two closest friends, but from the entire community," he said. Porteus wants him to publish as soon as possible data from his experiments with people and monkeys on a website such as bioRxiv so that other scientists can analyze this data themselves.

Mounting pressure

The pressure mounted on He before the presentation. On November 26, the National Health Commission of China asked the health commission of Guangdong, located in the province where his university is located, to conduct an investigation.

The Chinese Academy of Sciences issued a statement condemning the work of Mr. He, and the Chinese Society of Genetics and the Chinese Society for Stem Cell Research issued a statement claiming that the experiment "contravened internationally recognized ethical principles governing human experimentation and human rights law ".

The hospital cited in the clinical trial registry in China as having approved its work ethically. He issued a press release on November 26 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 approve of the means of the claimed project and has reservations about the accuracy, reliability and content of its contents and results.

He did not respond to requests for comment on these statements and inquiries, nor on why the hospital was listed in the registry.

Other governments have also begun to weigh in his experiences. On November 28, Francis Collins, director of the National Institutes of Health (NIH) in the United States, said in a statement that the NIH "do not support the use of gene modification technologies in human embryos" . Collins also noted that "this work represents a deeply disturbing desire on the part of Dr. He and his team to post international ethical standards. The need to reach a binding international consensus on defining limits for this type of research, currently being debated 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 baby gene editing. At a conference on the second day of the summit, just before He's speech, Daley urged his support for further research on germ-line editing despite recent events. "It is possible that the first instance appeared to be a mistake, but that should not lead us to stick our head in the sand and not consider a more responsible way towards clinical translation," he said. .

The pressures and opprobrium he faced were clear before his speech, from the introduction to his speech given by Lovell-Badge, who had made an unusual plea for scientific meetings. "You have to give him a chance to explain what he's done," said Lovell-Badge. "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."