The researcher who created CRISPR twins defends his work but leaves many unanswered questions | Science

HONG KONG, CHINA-The researcher who unleashed a global storm 2 days ago when he announced the birth of the first baby in the world to have been subjected to genetic modification, defended his study at a meeting held this morning . He Jiankui of the South University of Science and Technology of the neighboring city of Shenzhen, China, said "proud" of the work, which could lead to the prevention of disease "for Millions of children, "and provided details on the unpublished research of many scientists and bioethicists, as well as a phalanx of reporters, clamoring to hear. Thousands of people around the world watched his live broadcast on the Web.

But it failed to provide many essential details, elusive about the ethical debate conducted before the studies and providing sometimes confusing answers as to the balance between risks and supposed benefits. And his speech immediately triggered new criticisms.

The work should be "considered irresponsible," said biologist David Baltimore of the California Institute of Technology in Pasadena after hearing the presentation. "I do not think it's a transparent process, we learned it after that … after the birth of the children. Personally, I do not think it's medically necessary, "said Baltimore, reflecting concerns that were widely expressed even before all the details of the study were available. "I think the scientific community has failed to self-regulate because of a lack of transparency."

In fact, I feel proud of this particular case. I am most proud because [the father] had lost the hope of living.

The conference was held at the International Summit on the Modification of the Human Genome, a global forum to discuss scientific progress and ethical issues in one of the most challenging areas of biomedical research. Earlier this week, he announced in an interview with The Associated Press (AP) and a series of videos on YouTube that his team had designed twin genomes to paralyze a key receptor, CCR5, used by HIV to infect white blood cells – a modification they can pass on their descendants.

The father of the girls is infected with HIV, but the purported justification for the study was not to protect girls from the AIDS virus during pregnancy. The parents used in vitro fertilization and the father's sperm was washed to eliminate HIV, which virtually eliminated the risk of embryo infection. His goal was to protect them later in life, he told AP, although experts agree that there are other safe and effective ways to prevent HIV.

The news completely dominated the summit discussions even before his appearance; To respond to this sudden interest, he created today a special time slot of one hour for He. The room was packed; Hundreds of videographers, photographers and journalists have crowded together in one area. "I have the right to cancel the session if there is too much noise or interruption," Robin Lovell-Badge from the Francis Crick Institute in London warned early on. When he started his speech, clickable shutters almost drowned him, prompting Lovell-Badge to repeat his warning.

He began by apologizing for how his statements had "fled unexpectedly" earlier this week; he said that an article had been submitted to a peer-reviewed journal. (The news of the breakthrough was reported for the first time by Review of MIT technologyafter which AP published an article on the work and made public YouTube videos and several documents related to the experience.)

He also justified his research goal by explaining that HIV / AIDS still imposes a heavy burden of disease on much of Africa and that infected people often face serious discrimination. Mutations in the CCR5 gene confers resistance to HIV, and stated that previous experiences had suggested CCR5 was a promising target for publishing. But he did not explain how gene editing could help the world prevent the disease; nobody thinks that it is possible to edit the genomes of whole populations.

He explained how he conducted his research on mice, from nonhuman primates to in vitro human embryos – much of it, he said, which he had already presented in earlier discussions. Then he added some details about human studies. His research focused on optimizing the accuracy with which CRISPR cut the genome to minimize the possibility of altered non-targeted genes.

He recruited couples who wanted to start a family in which the man was infected with HIV and the woman was not. There was a two-step informed consent process with a member of the team who first visited the couple at home and then an hour-long discussion at He's laboratory in Shenzhen.

In the many questions and answers that followed, Lovell-Badge noted that the CCR5 The gene has multiple functions in the immune system, its absence leaves individuals at greater risk of contracting West Nile virus and potentially other diseases. Did he "know enough about CCR5 and its role in the immune system to choose this as a treatment? Asked Lovell-Badge. He replied that his team had chosen CCR5 because it is a well understood monococcal target that is suitable for a first trial before switching to multi-gene diseases. But he did not address the issue of potential side effects inadvertently.

"I just do not see an unmet medical need for these girls," said David Liu, a biochemist at the Broad Institute in Cambridge, Massachusetts. The technology could benefit millions of children potentially exposed to HIV by their parents, he added, without explaining it further. Speaking of babies, he added, somewhat mysteriously: "For this particular case, I am proud. I'm most proud, because Mark, [the babies’ HIV-infected father]had lost all hope of life. But with this protection, he sent a message saying that he would work hard, earn money and take care of his two daughters and his wife all his life. He did not explain the fact that there are safe and effective ways to prevent HIV transmission, or why gene editing might be better.

I think the scientific community has failed to self-regulate due to a lack of transparency.

This served as a model for the rest of the Q & A period: he answered a few questions but left many in part – or did not answer at all. He took a tangent when asked directly why he had chosen to conduct a study that, according to the international scientific consensus, should not be done. He asked if the study had been approved by an institutional review committee. He said that he personally paid the medical expenses of the study participants, but he did not specify the amount or whether he could maintain this support in the long term. We still do not know where he directed the lab work and which hospital was involved.

Assistance issues revealed widespread dissatisfaction with his responses regarding his informed consent procedures. He stated that four people had reviewed the consent form before it was given to couples; In the United States, "hundreds of people would review a consent form" before putting it into service, says Matthew Porteus, a pediatric stem cell researcher at Stanford University in Palo Alto, California. Although the broad outlines of his work globally indicate a "reasonable approach", moving from mice to non-human primates, Mr. Porteus adds that "there are still gaps" in the information provided, such as the number Eggs used, the success rate in the gene modification stage, if there had been miscarriages, and the date of births.

In addition, "There are questions about secrecy," says Porteus. For example, he claimed to have discussed his work at several conferences. "But I was at these conferences and he did not say he was going in that direction." Unless he produces more information and better answers, "he risks becoming an outcast," Porteus explains.

The fact that it is possible that the first case of modification of the human germ line appeared as a false step should in no case lead us to break our head in the sand.

With the ongoing investigations of national and local authorities and his university, his saga is about to shake the scientific and biomedical community for months or even years. It remains to be seen what impact his independent approach could have on the ground. Prior to his presentation, George Daley of Harvard Medical School in Boston expressed his concern, while urging researchers to trust the self-regulation of the research community while recognizing that it required transparency and external control.

"The fact that it is possible that the first case of modification of the human germline has been presented as a misstep should not in any way cause us to break our head in the sand," said Daley. Rather than being on the defensive, he proposed "that it be time for us to consider at least one pathway responsible for the clinical translation" of the germ line modification.

With reporting by Jon Cohen.