CRISPR-baby scientist fails to satisfy critics –

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He Jiankui gives talk about controversial genome-edited baby claim, but ethical questions remain.

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He Jiankui talks at a podium during his presentation on the 28th November.

He Jiankui spoke at the second international summit on human genome editing 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 edited genomes — twin girls — appeared today at a gene-editing summit in Hong Kong to explain his experiment. He gave his talk amid threats of legal action and mounting questions, from the scientific community and beyond, about the ethics of his work and the way in which he released the results.

He had never before presented his work publicly outside of a handful of videos he posted on YouTube. Scientists welcomed the fact that he appeared at all — but his talk left many hungry for more answers, and still not completely certain that He has achieved what he claims.

“There’s no reason not to believe him,” says Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London. “I’m just not completely convinced.”

The talk encompassed He’s work in animals and the details of how he genetically modified embryos and implanted them in women. He explained how he verified the gene edits — and revealed that another woman is pregnant with a gene-edited embryo.

Lovell-Badge, like others at the conference, says that an independent body should confirm the test results by performing an in-depth comparison of the parents’ and childrens’ genes.

Many scientists faulted He for a lack of transparency and the seemingly cavalier nature in which he embarked on such a landmark, and potentially risky, project.

“I’m happy he came but I was really horrified and stunned when he described the process he used,” says Jennifer Doudna, a biochemist at the University of California, Berkeley and a pioneer of the CRISPR/Cas-9 gene-editing technique that He used. “It was so inappropriate on so many levels.”

Alta Charo, a bioethicist at the University of Wisconsin–Madison who is a member of the summit’s organizing committee, is also critical. “Having listened to Dr. He, I can only conclude that this was misguided, premature, unnecessary and largely useless,” she says.

He answers questions during his presentation on the 28th November.
He answers questions during his presentation on the 28th November.

Scientists peppered He Jiankui with questions after he elaborated on his claim to have helped create the first genome-edited babies.Credit: Kin Cheung/AP/Shutterstock

Nervous talk

He seemed shaky approaching the stage and nervous during the talk. “I think he was scared,” says Matthew Porteus, who researches genome-editing at Stanford University in California and co-hosted a question-and-answer session with He after his presentation. Porteus attributes this either to the legal pressures that He faces or the mounting criticism from the scientists and media he was about to address.

He began by apologizing for the commotion he caused after news of his work first emerged on 26 November. He then spent 20 minutes firing through his presentation — entitled “CCR5 gene editing in mouse, monkey, and human embryos using CRISPR/Cas9” — before taking 40 minutes of questions.

CCR5, the gene that He edited, is used by some strains of HIV to infect immune cells. Many scientists have criticised this choice, in part because there are other ways to stop people from contracting HIV ― such as using caesarean sections to deliver the babies of mothers with the virus. Critics also say that other diseases are more obvious targets to eliminate by editing embryos’ genomes.

In the opening presentation of the day, George Daley, dean of Harvard Medical School in Boston, Massachusetts, pointed to Huntington’s Disease or Tay Sachs as examples of diseases that, in some circumstances, might only be averted by gene-editing.

HIV-resistant twin

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

He’s decision to implant the second embryo drew strong criticism. “Why choose this embryo? It just doesn’t make sense scientifically,” said Seoul National University geneticist Jin Soo Kim. During his talk, He said he had explained the situation to the parents and they decided they wanted to do it anyway.

And as He made clear in the question-and-answer session, his aim is prepare the technique for global use. “Do you see your friends or relatives who may have a disease? They need help,” He said. “For millions of families with inherited disease or infectious disease, if we have this technology we can help them.”

He didn’t just work with the parents of the twins, he said, but with eight couples that all consisted of HIV-positive fathers and HIV-negative mothers. One couple later dropped out.

He’s team washed sperm from the men to ensure that HIV was not present. The researchers then injected the sperm, and CRISPR/Cas-9 enzymes, into unfertilized eggs from the men’s partners. This produced a total of 30 fertilized embryos, of which 19 were viable and appeared healthy, He said. Two of the four embryos from one couple contained modifications to CCR5, and He implanted these in the woman, even though one embryo also had an intact copy of the CCR5 gene. This pregnancy produced the twins.

It is not clear what has happened to the other embryos, but He says there is one other “early-stage” pregnancy with a gene-edited embryo.

Kim says he’s 90% sure that the twins are the first babies born with edited genomes, as He claims. That’s in part 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 the embryos — one possible drawback of the process. “I was impressed,” says Kim.

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

Unanswered questions

He’s talk leaves a host of other questions unanswered, including whether the prospective parents were properly informed of the risks; why He selected CCR5 when there are other, proven ways to prevent HIV; why he chose to do the experiment with couples in which the fathers have HIV, rather than mothers who have a higher chance of passing the virus on to their children; and whether the risks of knocking out CCR5 — a gene normally present in people, which could have necessary but still unknown functions — outweighed the benefits in this case.

In the discussion following He’s talk, one scientist asked why He proceeded with the experiments despite the clear consensus among scientists worldwide that such research shouldn’t be done. He didn’t answer the question.

David Baltimore, one of the summit’s organizers, called He’s experiment “irresponsible” and criticized his lack of transparency. Baltimore also accepted blame on behalf of the scientific community. “There has been a failure of self regulation by the scientific community,” he said.

He’s attempts to justify his actions mainly fell flat. In response to questions about why the science community had not been informed of the experiments before the first women were impregnated, he cited presentations that he gave last year at meetings at the University of California, Berkeley, and at the Cold Spring Harbor Laboratory in New York. But Doudna, who organized the Berkeley meeting, says He did not present anything that showed he was ready to experiment in people. She called his defence “disingenuous at best”.

He also said he discussed the human experiment with unnamed scientists in the United States. But Porteus says that’s not enough for such an extraordinary experiment: “You need feedback not from your two closest friends but from the whole community.” Porteus wants He to post data from his experiments with people and monkeys to a website such as BioArxiv as soon as possible so other scientists can check it.

Mounting pressure

Pressure was mounting on He ahead of the presentation. On 27 November, the Chinese national health commission ordered the Guangdong health commission, in the province where He’s university is located, to investigate.

On the same day, the Chinese Academy of Sciences issued a statement condemning his work, and the Genetics Society of China and the Chinese Society for Stem Cell Research jointly issued a statement saying the experiment “violates internationally accepted ethical principles regulating human experimentation and human rights law”.

The hospital cited in China’s clinical-trial registry as the that gave ethical approval for He’s work posted a press release on 27 November saying it did not give any approval. It questioned the signatures on the approval form and said that the hospital’s medical-ethics committee never held a meeting related to He’s research. The hospital, which itself is under investigation by the Shenzhen health authorities following He’s revelations, wrote: “The Company does not condone the means of the Claimed Project, and has reservations as to the accuracy, reliability and truthfulness of its contents and results.”

He has not yet responded to requests for comment on these statements and investigations, nor on why the hospital was listed in the registry and the claim of apparent forged signatures.

Other governments have also begun to weigh in on He’s experiments. On 28 November, the US National Institutes of Health (NIH) said that it does not support the use of gene-editing technologies in human embryos. “This work represents a deeply disturbing willingness by Dr. He and his team to flaunt international ethical norms,” said NIH director Francis Collins in a statement. “The need for development of binding international consensus on setting limits for this kind of research, now being debated in Hong Kong, has never been more apparent.”

Chilling effect?

Fears are now growing in the gene-editing community that He’s actions could stall the responsible development of gene editing of babies. In a lecture on the second day of the summit, ahead of He’s talk, Daley, urged support for germline gene-editing despite recent events. “It’s possible that the first instance came forward as a misstep, but that should not lead us to stick our heads in sand and not consider more responsible pathway to clinical translation,” he said.

The pressures and opprobrium facing He were clear ahead of his talk, from opening remarks by Lovell-Badge, who made a plea uncharacteristic of scientific meetings. “He has to be given a chance to explain what he did,” said Lovell Badge. “We cannot have unruly behavior. If that happens, we will close the session and you won’t have the chance to hear what he has to say.”

There was also heightened security, with men in dark suits near the stage and cameras lining the back of the auditorium. After He started speaking, Lovell-Badge had to ask the photographers to stop clicking so that He could be heard.

Porteus says that He’s appearance was a first step, but that He will have to start answering lingering questions soon. “He’s already at risk of becoming a pariah,”

doi: 10.1038/d41586-018-07573-w
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