A stranger claimed the history of genome modification; the world has attracted attention



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IIn 2010, He Jiankui, a graduate student at Rice University, published an article describing the basic details of a so-called mysterious bacterial immune system called CRISPR. It was well before scientists discovered that CRISPR could be used to manipulate DNA with a precision and ease that was lacking to all genome publishers.

Barely eight years later, after returning to his native China, he made his world debut in the most dramatic way – an entry that he seems to have meticulously choreographed, while ignoring the guidelines set by groups. world scientists. Using YouTube rather than a university newspaper, he said that with the help of CRISPR he helped create the world's first baby – binoculars born a few weeks ago – whose genomes had been modified in the form of embryos. The announcement dropped as a surprise album of Beyonce.

This assertion, which has not been verified by outside researchers, has been presented by some as a scientific milestone, an unprecedented step in the prevention of all kinds of diseases. But others have seen the exact opposite: unscrupulously breaking a scientific taboo for personal gain. After all, many much more experienced and respected researchers had the technical know-how to try what he had done, but they respected the widely accepted ethical barriers. Such research is also illegal in the United States.

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He Jiankui (pronounced HEH JEE & # 39; an-qway), who was previously unknown to many Western CRISPR experts, immediately found himself at the center of a wave of criticism over the lack of transparency of his research, the choice of the edited gene, and its continuation of this research at all.

"I'm trying to understand what may have motivated the work that he describes," said a scientist who helped organize a major summit in Hong Kong on the human genome edition that begins on Tuesday. and who asked not to be named. "As far as I know, it was a combination of pride, naivety and perhaps a genuine desire to help those in need. He does not seem to have anticipated the deep reaction of the public against his work and the way it was conducted and made public. "

He clearly knew the attention that his ad would attract. He reportedly worked with a US public relations specialist. gave prior interviews to the Associated Press, which has a global reach; timed the great revelation at the beginning of the summit; and posted a series of YouTube videos in English celebrating this feat.

But he also caught the world off guard, hiding his activities from the broader scientific community. Information about his clinical trial, for example, was published on a Chinese online registry only this month. The experts imagined that the first published baby would be born after rigorous discussions on regulations and ethics and with strict safeguards in place, all in conditions that did not worry the public.

Even his own university, which he has been on leave since February, distanced himself from the research, claiming that she knew nothing about the work done and that it had been "conducted off campus" and "seriously violated academic ethics and codes of conduct". . "

Beyond this condemnation, the researcher who hides behind the ad has simply puzzled the top experts in genome editing. He has no long experience in publishing articles on the genome, embryology or gene that he deactivated in embryos, CCR5, to try to confer resistance to HIV infection. Much of the social media confusion has come back to this question: this guy do the edition of embryos?

Perhaps he should have been better known. At a conference held last year at the Cold Spring Harbor Laboratory, he discussed editing genomes of mouse, monkey, and human embryos (editing human embryos in the lab, it's ie not for transfer into the uterus and the beginning of pregnancy).

This conversation earned him a top spot at this week's summit in Hong Kong; his panel is scheduled for Wednesday morning, Hong Kong time. Evidence of awareness by all its project CRISPR'd embryos by the world scientific community, however, his speaking time is not a plenary session, usually reserved for the largest media outlets of a conference.

He also co-authored an article published this week in the CRISPR journal proposing five "ethical principles" to guide the use of genome editing in the clinic. The second author: Ryan Ferrell, the US public relations professional who worked with He on the CRISPR'd embryos project deployment.

Among the elements he claimed: an open dialogue.

But he does not seem to have followed his own recommendations.

In April 2016, he wrote to CRISPR pioneer, Feng Zhang, of the Broad Institute, identifying himself as CEO of his DNA sequencing company, Direct Genomics, and requesting a visit from the laboratory of Zhang in Cambridge, Massachusetts. He did not go back then, but he gave up briefly. In August, Zhang told STAT the top genome editing on the genome.

What did he want to talk about? Methods to reduce off-target effects – clippings that CRISPR can perform at unwanted locations – when editing mouse and human embryos, Zhang recalled.

"It was clear to me that he had the same challenges as other researchers regarding lack of efficiency and lack of precision," Zhang said. "I told him that the technology was neither efficient enough nor accurate enough for a real application on embryos, including human IVF applications."

For Zhang, this conversation has taken a new tone in light of this week's news. "Of course, we now know that in August, his work on humans must be advanced enough, at least according to his latest claims," ​​Zhang said. "He certainly never mentioned this job when I saw it."

From China to the United States and back

His career highlights some of the highlights: His scientific background is vast, but he does not have extensive expertise in CRISPR and embryology. Public records indicate that it's only 34 years old, an age when many prominent researchers have just opened their first labs.

He seems to have been born and raised in China. He earned his undergraduate degree in physics from the University of Science and Technology of China in 2006. He then traveled to Texas to obtain a PhD in Biophysics from Rice University. in Houston; His adviser, bioengineering professor Michael Deem, will later collaborate with him on the CRISPR'd embryos project.

After graduating in 2010, he spent about a year doing his post-doctorate in Stanford's bio-engineer lab, Stephen Quake. It's there that he learned the sequencing of a single molecule – then a revolutionary method of sequencing single DNA molecules without having to copy them first using a chain reaction. of polymerase, according to a 2015 article published in the publication Bio-IT World.

He returned to China around 2012. The reason he decided to go home is unclear. Some factors may have played. According to Bio-IT World, he wanted to separate companies from his academic research in China. And financial incentives may have contributed to his decision: he returned to China as part of the Thousand Talents program, an initiative in which the Chinese government offered incentives to try to bring back its brightest scientists and its entrepreneurs. followed a training in the United States

He opened a laboratory at the South China University of Science and Technology in Shenzhen. (His current leave of this role is expected to last until 2021.). He has also launched several companies, including Direct Genomics.

He seems to have kept some of the relationships he forged during his training in the United States – notably with his adviser Rice, Deem.


Deem said the research was a perfect fit with the work they had done on vaccines while in Houston. In addition to their 2010 CRISPR study, Deem and He have collaborated on studies on the speed of gene evolution and ways to detect emerging and dangerous strains of the flu.

They have also been cited as the authors of a study published last year and describing the use of single molecule sequencing to untangle the genome of a patient. virus. The other authors of the 2017 article have worked at Direct Genomics.

Rice announced Monday it had opened an investigation into Deem's role in the CRISPR® embryo project, saying the research "violates scientific guidelines and is inconsistent with the ethical standards of the scientific community and the world." Rice University ". comment.

Move fast preaching with caution

In YouTube videos that he had used to reveal his astonishing claims to the world, he sits in an indescribable lab with instruments in the background; he wears a light button-down shirt without a tie or lab coat. Speaking slowly and in English, he took a remarkably emotional tone.

He described his work as being light years away from creating "baby designers", which he condemned. He also implored his audience to look beyond the criticism that his work would be likely to arouse, declaring himself confident that his project would be favorably viewed through history.

"Do not forget that, even though there are virulent critics, many silent families have seen a child suffer from a genetic disorder and should not have to suffer again," he said. he stated on camera in one of the videos. "They may not be the directors of an ethics center quoted by The New York Times, but they are no less of the authorities when it comes to what is right or wrong, because Is their life at stake. "

It is crucial, however, that he does not claim to have tackled a genetic disease with his CRISPR'd embryo project. Instead, he claims to have contracted HIV, a disease for which there are already relatively simple ways to prevent HIV-positive parents from infecting their children.

And big questions remain as to whether his project will actually help the family whose babies are supposed to be genetically modified. Independent scientists who reviewed some of the documentation indicated that there was not enough evidence yet to determine whether the assembly had gone as planned or was safe. They also expressed concern about the consequences of confessing that one of the twins edited by one gene had modified the two copies of CCR5, while the other had modified only one.

At the end of another of his videos on YouTube, he provides an email address to his lab – and another ([email protected]) to viewers wishing to write to the two newborns at Genetic Modification, named Lulu , and Nana.

Although he was criticized for having done too much too fast, he has already insisted on moving patiently and deliberately during the discussion on the published embryos.

In his 2017 speech, he spoke of the death of Jesse Gelsinger in 1999 as part of an early clinical trial of gene therapy, which allowed this field to retreat more than a decade.

Researchers who might be tempted to use a CRISPR'd embryo to start a pregnancy should remember this case, he suggested.

"I want to remind everyone that we should do this kind of slowness and with a little caution," he said, "because a single case of failure can kill the whole field."

Sharon Begley contributed to reports from Hong Kong.

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