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First gene-edited babies born, scientist claims

As an international genome editing summit kicks off in Hong Kong, Chinese researcher He Jiankui steals the spotlight by announcing his project using CRISPR to install HIV resistance in a pair of embryos

by Ryan Cross , Megha Satyanarayana , Rick Mullin
November 27, 2018 | A version of this story appeared in Volume 96, Issue 48


Credit: He Jiankui
He Jiankui announced and explained his embryo editing project in a series of videos on Youtube.

As the Second International Summit on Human Genome Editing opens in Hong Kong, huge questions remain unanswered about the work of Chinese scientists who claimed earlier this week to have used CRISPR/Cas9 gene editing to create embryos resistant to HIV, then implanted the embryos into a woman’s uterus to develop. The babies were reportedly born just weeks ago.

Scientists and ethicists, united in a state of alarm, are concerned about the lack of transparency and disregard for established ethical guidelines in the clinical work done by the team, led by He Jiankui of the Southern University of Science and Technology. The overriding question is simply whether He’s project to genetically engineer humans before birth can be verified. If such babies exist, there is broad agreement that the experiment occupies the gray zone between treating disease and enhancing the human species through gene editing, an endeavor widely renounced as unethical.

Credit: Darren Weaver/Andrew Sobey/ACS Productions/C&EN
CORRECTION: This video was updated on 10/14/20 to correct video footage of cuttlefish. The original clip showed a species of squid.

The news, which was first reported by MIT Technology Review and the Associated Press, has not been presented at a scientific conference or published in a peer-reviewed journal. Instead, lead researcher He Jiankui, from the Southern University of Science and Technology, announced and explained his gene modification experiment through a series of YouTube videos published on Nov. 25.

According to the AP report, seven couples donated their eggs and sperm to create embryos for He’s experiment. All of the fathers had HIV. He used CRISPR to change the embryos’ DNA to prevent the children from succumbing to an HIV infection. Eleven edited embryos were ultimately used for in vitro fertilization (IVF). The IVF procedures led to one pregnancy and the birth of twin girls, who He calls Lulu and Nana. Editing the genes in embryos, if done early enough in development, means that the girls should carry the edited genes in their reproductive cells and pass them on to their own children.

“The girls are [as] safe and healthy as any other babies,” He claims in one of his videos. “I understand my work will be controversial, but I believe families need this technology, and I’m willing to take the criticism for them.”

That anticipated criticism came rapidly from a slew of scientists and ethicists who characterized the research as impulsive and unnecessary. For one, there are several ways to prevent HIV infection that do not involve editing human DNA in a way that will be passed to future generations, with possible unanticipated consequences. David Liu, a chemist who has invented new versions of CRISPR at the Broad Institute, says He’s work “represents a serious breach of ethics that I hope will serve as a wake-up call for the community.”

He isn’t the first scientist to use CRISPR on human embryos, and the technical accomplishment itself is not particularly remarkable, says Sam Sternberg, a CRISPR scientist at Columbia University. However, none of the previous work involved implanting the embryos to try for pregnancy.

“I’ve long suspected that scientists, somewhere, would rush to claim the ‘prize’ of being first to apply CRISPR clinically to edit the DNA of human embryos, and use those embryos to establish pregnancies,” Sternberg says. “But still, I’m shocked to find out it’s allegedly happened this quickly.”

Furthermore, the news came just two days before CRISPR experts were due to gather in Hong Kong for the genome editing summit, an event designed to discuss and debate the merits of using CRISPR in humans.

“This announcement looks like a cynical attempt to seize headlines,” says Pete Mills, assistant director of the Nuffield Council on Bioethics, a U.K. policy group. “If the claims are true, it is a premature, inexplicable, and possibly reckless intervention that may threaten the responsible development of future applications of genome editing.”

These two lives are now an experiment, a matter of scientific curiosity, which is an outrageous way to relate to human lives.
Ben Hurlbut, professor of biology and society, Arizona State University

HIV-resistant babies

He calls his work gene surgery rather than gene editing. He characterizes it as “another IVF advancement and is only meant to help a small number of families,” he says. “Their parents don’t want a designer baby, just a child who won’t suffer from a disease which medicine can now prevent.”

He aimed to edit the gene for CCR5, a receptor protein found on the surface of T cells and macrophages. The majority of HIV infections in humans occur through CCR5, which HIV co-opts to enter immune cells, says Bryan Cullen, a virologist at Duke University. Several years ago, a group of researchers found a mutation in CCR5 that made people with that mutation mostly resistant to HIV.

Since then, people have been trying to understand and mimic that mutation. In one famous case, an HIV-positive man received a bone marrow transplant from a donor with a CCR5 mutation, Cullen says. The man’s viral load dropped to undetectable levels.

That CCR5 mutation is only prevalent in a group of northern European people, however, and HIV infection is a growing problem in China. In September, China reported that more than 820,000 people in the country are infected.

He’s experiment aimed to use CRISPR to introduce that HIV-protective CCR5 mutation into embryonic DNA, so that children born from those embryos would resist HIV infection. There is precedent for this approach: Sangamo Therapeutics is currently running clinical trials for a different type of CCR5 gene editing in HIV-positive adults. But doing this in embryos “is totally absurd,” Cullen says. “It’s irresponsible. We don’t know enough to do that.”

For one, the gene editing system is not exact. The procedure could snip DNA and introduce a mutation in a region that happens to have the same sequence as the one being targeted in the CCR5 gene. He suggests that such off-target effects were undetectable in the twin girls whose embryos he edited.

More importantly, Cullen says, is the problem of mosaicism, when cells in the same individual have different gene sequences. In one of He’s videos, lab member Qin Jinzhou says he typically edits genes in a newly fertilized egg, but it’s not clear if this was the exact protocol used with the twins. Depending on when the editing was done, some cells may have been missed. If any one of those cells gives rise to part or all of the twins’ T cells and macrophages, they may still have some normal CCR5 that would leave them susceptible to HIV infection, Cullen says. In addition, a smaller number of HIV infections happen through other receptors on T cells.

Editing Ethics

Ethical committees have generally looked favorably on using CRISPR to fix an inherited or spontaneous mutation that causes disease in children and adults. Using CRISPR to prevent a disease that people might never acquire demands a higher bar of safety, and many experts question whether the potential benefits outweigh the risks.

Consequently, scientists and ethicists expect the news of He’s experiment to dominate discussions at the Hong Kong Summit.

He previously published a paper that claims the field “lacks concise and plain-language ethics statements on ultimate clinical uses” of technologies such as CRISPR, despite existing guidance from organizations such as the UK’s Nuffield Council and the US National Academies of Sciences, Engineering, and Medicine.

In his paper, He proposes a “core set of fundamental human values to frame, guide, and restrict clinical applications that communities around the world can share and localize based on religious beliefs, culture, and public-health challenges” (The CRISPR J 2018, DOI: 10.1089/crispr.2018.0051; the paper was retracted by the journal on Feb. 21, 2019).

Ethicists in turn raise several concerns about He’s embryo editing experiments, questioning his justification for proceeding on gene editing to prevent HIV, transparency about clinical trials, and timing of the announcement.

“In a sense they are flouting any kind of attempt to engage in reasonable dialogue and debate and discussion,” says Francoise Baylis, a professor of bioethics and philosophy at Dalhousie University, about He and his colleagues.

Until now, ethical conversations about editing genetic material in a way that can be passed through generations “were very much focused on preventing the transmission of serious genetic disorders,” explains Jeantine Lunshof, a philosopher and ethicist working in the biological engineering laboratory of chemist and genetics professor George Church at Harvard University. “And of course HIV is not a genetic disorder.”

Lunshof also questions the timing of clinical trial registration, noting that it is difficult to determine which work began at what time. The trial appears to have been registered with Chinese authorities on Nov. 8 of this year, which Lunshof speculates may have been the day the babies were born. It’s also unclear how much the parents understood about the permanence of gene editing.


Ben Hurlbut, a professor of biology and society at Arizona State University who is in Hong Kong for the conference, says He’s purported achievement “simply leapfrogs completely over anything that would count as treatment into something that is much more unequivocally in the territory of enhancement.” He adds, “These two lives are now an experiment, a matter of scientific curiosity, which is an outrageous way to relate to human lives.”

An embryo-editing moratorium?

Implanting edited human embryos is illegal in the US and the UK. The legality is less clear in China, but He’s own university has distanced itself from the work. “The SUSTech Department of Biology Academic Committee believes that Dr. He Jiankui conduct in utilizing CRISPR/Cas9 to edit human embryos has seriously violated academic ethics and codes of conduct,” the university says in a statement. He has been on unpaid leave since February, the university adds.

Additionally, the Shenzhen City Medical Ethics Expert Board released a statement saying it would initiate an investigation of He’s research. And Rice University, where He trained under bioengineer Michael Deem, said it would launch an investigation as well after the Associated Press reported that Deem assisted He in the experiment and holds stakes in two companies started by He.

Feng Zhang, one of CRISPR’s inventors at the Broad Institute, is calling for a moratorium on implanting gene-edited embryos until a list of safety requirements is constructed. “Not only do I see this as risky, but I am also deeply concerned about the lack of transparency surrounding this trial,” he says in an official statement.

In her own statement, Jennifer Doudna, another of CRISPR’s inventors at the University of California, Berkeley, concurred, calling the news “a break from the cautious and transparent approach of the global scientific community’s application of CRISPR-Cas9 for human germline editing.”

CRISPR’s third inventor, Emmanuelle Charpentier, who directs the Regulation in Infection Biology group at the Max Planck Institute for Infection Biology, says she is waiting for a scientific publication describing the experiment before commenting on it publicly. Other scientists have similarly urged caution reaching conclusions about the research until He provides evidence for his claims.

Others have released statements to defend their own gene editing work in light of He’s announcement. Shoukhrat Mitalipov, director of Oregon Health & Science University’s Center for Embryonic Cell and Gene Therapy, says his work using CRISPR to fix a genetic disease in human embryos—that were not used to attempt pregnancy—was done “only after our university conducted thorough scientific and ethical reviews.”

Researchers lament the possibility that news of He’s experiment will tarnish an emerging technology that could lead to therapeutic breakthroughs. “I think there is a great risk that negative publicity over this unwarranted and premature clinical use of CRISPR on human embryos could mar the public’s perception of gene editing technology,” Columbia’s Sternberg says. Many researchers are developing CRISPR therapies to treat or cure a variety of genetic diseases and cancers in a way that doesn’t involve germline editing. “It would be a shame if enthusiasm and support for this work is negatively impacted by the recent news,” Sternberg adds.

If nothing else, He’s announcement and reactions to it underscore the importance of the summit in Hong Kong and discussions there about the science, application, ethics, and governance of human genome editing. “There will be someone somewhere who is doing this,” He says in a videotaped interview with the Associated Press. “If it is not me, it’s someone else.”


The headline on this story was revised on Nov. 28, 2018, for clarity. The previous headline was "First gene-edited babies allegedly born to Chinese mother. 


This story was modified on Feb. 22, 2019, to note that a paper published in the CRISPR Journal has been retracted.


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