Science news 原文（部分）：CRISPR bombshell: Chinese researcher claims to have created gene-edited twins！

HONG KONG, CHINA—On the eve of an international summit here on genome editing, a Chinese researcher has shocked many by claiming to have altered the genomes of twin baby girls born this month in a way that will pass the modification on to future generations. The alteration is intended to make the children’s cells resistant to infection by HIV, says the scientist, He Jiankui of the Southern University of Science and Technology in Shenzhen, China.

The claim—yet to be reported in a scientific paper—initiated a firestorm of criticism today, with some scientists and bioethicists calling the work “premature,” “ethically problematic,” and even “monstrous.” The Chinese Society for Cell Biology issued a statement calling the research “a serious violation of the Chinese government’s laws and regulations and the consensus of the Chinese scientific community.” And He’s university issued a statement saying it has launched an investigation into the research, which it says may “seriously violate academic ethics and academic norms.” Other scientists, meanwhile, asked to see details of the experiment and its justification before passing judgment.

He told The Associated Press (AP) that he altered embryos for seven couples during fertility treatments, with one pregnancy resulting thus far. In each case, the father was infected with HIV; the mothers were HIV-negative. He’s goal was to introduce a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Specifically, He deleted a region of a receptor on the surface of white blood cells known as CCR5 using the revolutionary genome-editing technique called CRISPR-Cas9.

According to the AP report, He was not trying to prevent transmission of HIV from the father’s sperm to the embryo, a highly unlikely event. The risk of transmission drops even lower when the sperm is washed before insemination through in vitro fertilization, as occurred here. Rather, He said he wanted to protect the babies from infection later in life. The International Summit on Human Genome Editing begins here on Tuesday and many researchers, ethicists, and policymakers attending the meeting first learned of He’s claim through media reports. Organizers of the conference told reporters at a pre-event briefing they were awaiting further details.

Scientists are investigating the use of CRISPR-Cas9 as a treatment for many genetic diseases, such as muscular dystrophy and sickle cell anemia. One long-running study in HIV-infected adults has crippled CCR5 with another genome-editing technology, and a similar study is underway in China with CRISPR. But these cases involved gene editing of so-called somatic cells that are not passed on to the patient’s children. He reportedly went a step further, altering the genome in early stage embryos, which would affect sperm and eggs—the germline—and make the change heritable. Such work is effectively barred in the United States and many other countries. Whether it fits within China’s regulatory environment is not clear.

He is scheduled to speak at the summit on gene editing on Wednesday, but organizers were unsure whether he planned to discuss his experiment. He put a series of videos on YouTube to justify the experiment and explain how it was done. He also invited viewers to send comments to his lab and to the two babies, named Lula and Nana.

Yet many scientists say the experiment was premature and the potential benefits not worth the risk. “The underlying purpose of doing the experiment was obviously to show that they could do gene editing on an embryo, but the purpose for the party involved does not make any sense,” says Anthony Fauci, an HIV/AIDS researcher who heads the U.S. National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. “There are so many ways to adequately, efficiently, and definitively protect yourself against HIV that the thought of editing the genes of an embryo to get to an effect that you could easily do in so many other ways in my mind is unethical.”

Pablo Tebas, a clinical researcher at the University of Pennsylvania who led a small study that crippled CCR5 in HIV-infected adults using what’s known as zinc finger technology, similarly denounced the embryo alteration. “The experiment is not medically justified,” said Tebas, who noted that CCR5 mutants are not benign as people are more susceptible to serious consequences from West Nile infections. “Hopefully these kids will not have any health problems," he says.

“Gene editing itself is experimental and is still associated with off-target mutations, capable of causing genetic problems early and later in life, including the development of cancer,” Julian Savulescu, an ethicist at the University of Oxford in the United Kingdom, said in a statement released today by the U.K. Science Media Centre. “This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit,” he says. Sarah Chan, a bioethicist at the University of Edinburgh, worries that the premature use of gene editing prior to consideration of social aspects of the work “threatens to jeopardize the relationship between science and society … and might potentially set the global development of valuable therapies back by years.”

CRISPR pioneer Jennifer Doudna of the University of California, Berkeley, notes that the work has not been published and urged caution in a statement released today. However, "Assuming that independent analysis confirms today’s news, this work reinforces the urgent need to confine the use of gene editing in human embryos to settings where a clear unmet medical need exists, and where no other medical approach is a viable option, as recommended by the National Academy of Sciences,” Doudna wrote.

Apparently anticipating the criticism, He boldly proclaimed in one of this videos that his group has reflected deeply on how to help families facing risks of genetic diseases. “We believe ethics are on our side of history,” says He, who calls the term “designer babies” an epithet.

Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology in Cambridge who co-chaired the National Academies of Sciences, Engineering, and Medicine report that Doudna referred to, says it laid out “stringent conditions” that should be met before undertaking genome editing: There had to be a serious, unmet medical need; the effort should be well-monitored and with sufficient follow-up; and there had to be informed consent of the parents.

He adds that the United Kingdom’s Nuffield Council on Bioethics’s report on human genome editing, released in July, reached similar conclusions. “All these questions need to be looked into when we hear what he’s actually done,” Hynes says. Alta Charo, a bioethicist at the University of Wisconsin at Madison, notes that the National Academies report does mention CCR5 as a potential target of gene editing. Whether the current experiment is justified “comes down to a risk-benefit analysis,” she says.

Nature原文（部分）：Genome-edited baby claim provokes international outcry

A Chinese scientist claims to have helped make the world’s first genome-edited babies — twin girls, who were born this month. The announcement has provoked shock and outrage among scientists around the world.

He Jiankui, a genome-editing researcher at the Southern University of Science and Technology of China in Shenzhen, says that he impregnated a woman with embryos that had been edited to disable the genetic pathway HIV uses to infect cells. In a video posted to YouTube, He says the girls are healthy and now at home with their parents. Sequencing of the babies’ DNA has shown that the editing worked, and altered only the target gene, he says.

The scientist’s claims have not been verified through independent genome testing, nor published in a peer-reviewed journal. But, if true, the twins’ birth would represent a significant — and controversial — leap in the use of genome editing. Until now, the use of these tools in embryos has been limited to research, often to investigate the benefit of using the technology to eliminate disease-causing mutations from the human germ line. But some studies have reported off-target effects, raising significant safety concerns.

HIV’s entry point

Documents posted on China’s clinical-trial registry show that He used the popular CRISPR–Cas9 genome-editing tool to disable a gene called CCR5, which encodes a protein that allows HIV to enter a cell. Genome-editing scientist Fyodor Urnov was asked to review documents that described DNA sequence analysis of human embryos and fetuses edited at the CCR5 locus for an article in MIT Technology Review. “The data I reviewed are consistent with the fact that the editing has, in fact, taken place,” says Urnov, who is based at the Altius Institute for Biomedical Sciences in Seattle, Washington. But he adds that the only way to tell whether the children’s genomes have been edited is to independently test their DNA.

Urnov takes issue with the decision to edit an embryo’s genome in order to prevent HIV infection. He is also using genome-editing tools to target the CCR5 gene, but his studies are in patients with HIV, not embryos. He says that there are “safe and effective ways” to use genetics to protect people from HIV that do not involve editing an embryo’s genes. “There is, at present, no unmet medical need that embryo editing addresses,” he says.

Paula Cannon, who studies HIV at the University of Southern California, also questions He’s decision to target the CCR5 gene in embryos. She says some strains of HIV do not even use this protein to enter cells, they use another protein called CXCR4. Even people who are naturally CCR5-negative are not completely resistant to HIV because they could be infected by a CXCR4 strain, says Cannon. “This experiment exposes healthy normal children to risks of gene editing for no real necessary benefit," says Julian Savulescu, director of the Oxford Uehiro Centre for Practical Ethics at the University of Oxford, UK.

Years of research is needed to show that meddling with the genome of an embryo is not going to cause harm, says Joyce Harper, who studies women’s and reproductive health at University College London. . Legislation and public discussion should also occur before genome editing is used in embryos destined for implantation. “Today’s report of genome editing human embryos for resistance to HIV is premature, dangerous and irresponsible,” says Harper.

University ‘unaware’

Southern University of Science and Technology said in a statement on 26 November that it was unaware of He’s experiments, that the work was not performed at the university and that He has been on leave since February.

“The Southern University of Science and Technology requires scientific research to abide by national laws and regulations and to respect and comply with international academic ethics and academic standards,” the statement said. The university says it will set up an independent committee to investigate the matter.

More than 100 Chinese biomedical researchers have posted a strongly worded statement online condemning He’s claims. “Directly jumping into human experiments can only be described as crazy,” the statement reads. The scientists call on Chinese authorities to investigate the case and introduce strict regulations on this procedure.

A Chinese scientist claims to have helped make the world’s first genome-edited babies — twin girls, who were born this month. The announcement has provoked shock and outrage among scientists around the world.

He Jiankui, a genome-editing researcher at the Southern University of Science and Technology of China in Shenzhen, says that he impregnated a woman with embryos that had been edited to disable the genetic pathway HIV uses to infect cells. In a video posted to YouTube, He says the girls are healthy and now at home with their parents. Sequencing of the babies’ DNA has shown that the editing worked, and altered only the target gene, he says.

Should you edit your children’s genes?

The scientist’s claims have not been verified through independent genome testing, nor published in a peer-reviewed journal. But, if true, the twins’ birth would represent a significant — and controversial — leap in the use of genome editing. Until now, the use of these tools in embryos has been limited to research, often to investigate the benefit of using the technology to eliminate disease-causing mutations from the human germ line. But some studies have reported off-target effects, raising significant safety concerns.

Don’t edit the human germ line

Inevitable advance?

News of the experiment comes as researchers in the field gather in Hong Kong for a major international meeting on genome editing, running from 27 to 29 November. A key goal of the summit is to reach an international consensus on how genome editing to modify eggs, sperm or embryos — known as germline editing — should proceed. Even before the news of He’s work emerged, many in the field believed it was inevitable that someone would use genome-editing tools to make changes to human embryos for implantation into women, and had been pushing for the creation of ethical guidelines.

He supports the use of genome editing in embryos only in cases that relate to disease, and says that genetic tweaks to enhance intelligence or to select for traits such as hair and eye colour should be banned. “I understand my work will be controversial, but I believe families need this technology and I am willing to take the criticism for them,” he says.

Bioethicist Tetsuya Ishii at Hokkaido University in Sapporo, Japan, does not think the application of genome editing in embryos to reduce HIV infection is justified. He says that babies of women with HIV can be delivered by caesarean section to avoid the infection being transmitted during childbirth.

In the case of the twins, the father is HIV positive but the mother is not, says He in the YouTube video. But Cannon says it makes no sense to recruit families with an HIV-positive father because there is no real risk of transmission to the children. “I’m just so angry,” says Cannon. She hopes that as a result of this announcement, scientists and policy makers will discuss how to regulate the practice. In an interview with the Associated Press, He said the goal of the work was not to prevent transmission from the parents, but to offer couples affected by HIV a chance to have a child that might be protected from a similar fate.

Recent surveys suggest that the public supports genome editing in embryos if it fixes disease-causing mutations. In December 2017, the Nuffield Council on Bioethics, a London-based independent advisory committee, published a survey of 319 people. Nearly 70% of those supported gene editing if it allowed infertile couples to have children, or if it allowed a couple to alter a disease-causing mutation in an embryo. A larger survey of 4,196 Chinese citizens, released last month, reported a similar level of support for modifying genes if the goal is to avoid a disease. But respondents were opposed to using it to enhance IQ or athletic ability, or to change skin colour.