Claim of CRISPR’d baby girls stuns genome editing summit

HONG KONG — A Chinese scientist’s claim that he used the genome editing technology CRISPR-Cas9 to alter the DNA of human embryos, resulting in the birth a few weeks ago of twin girls, stunned organizers of the Second International Summit on Human Genome Editing, leaving them scrambling to evaluate the claim two days before the scientist is scheduled to speak at the meeting.

“I don’t know the details” of the claim by He Jiankui, said David Baltimore of the California Institute of Technology, chairman of the organizing committee of the summit, which begins on Tuesday in Hong Kong. “We don’t know what will be said” when He speaks at a session on human embryo editing.

The summit’s organizing committee issued a statement Monday saying they had only just learned of He’s research in Shenzhen, China. “Whether the clinical protocols that resulted in the births in China conformed with the guidance” of leading scientific bodies for conducting clinical trials of heritable genome editing “remains to be determined,” the statement said. “We hope that the dialogue at our summit further advances the world’s understanding of the issues surrounding human genome editing. Our goal is to help ensure that human genome editing research be pursued responsibly, for the benefit of all society.”

Harvard biologist and genetics pioneer George Church said the claims were “probably accurate.

“I’ve been in contact with the Shenzhen team and have seen the data,” he said by email from Indianapolis. “The sequencing assays used are generally unambiguous especially when done in multiple cell types at different developmental stages and in two children.”

Church added: “Is the genie really out of the bottle? Yes.”

Dr. George Daley, dean of Harvard Medical School and a member of the organizing committee for the summit here, said He had been invited to speak because of a 2017 talk he gave at Cold Spring Harbor Laboratory about genome editing in human, monkey, and mouse embryos. At that session, He described altering target DNA in human embryos created through in vitro fertilization, resulting in few unintended edits (“off-target effects“). The most serious problem was that only some of the embryos’ cells were successfully edited, resulting in what’s called mosaicism.

But He said then that he was able to increase the proportion of edited cells by injecting the very early embryos with CRISPR-Cas9 twice: once when they consisted of only a single cell, and again when they consisted of two cells.

In his 2017 talk, He had not said he planned to use the edited IVF embryos to initiate a pregnancy. He ended his presentation by citing the case of Jesse Gelsinger, whose 1999 death in a trial of gene therapy — the much less precise forerunner of genome editing — set that field back by more than a decade. He urged scientists who are contemplating embryo editing to proceed slowly and “with caution,” since “a single case of failure will kill the entire field.”

The Chinese university where He is an associate professor issued a statement saying that it had been unaware of his research project and that He had been on leave without pay since February. The work has “seriously violated academic ethics and codes of conduct,” Southern University of Science and Technology in Shenzhen said in the statement. The university called on international experts to investigate.

He’s claim, first reported by the Associated Press, has not been backed up by a scientific paper, leaving scientists in the dark about how well the genome editing worked. He used CRISPR-Cas9 to disable a gene called CCR5, which produces a receptor that allows HIV, which causes AIDS, to enter cells. People who lack functional CCR5 genes are therefore immune from HIV infection.

A 2017 National Academies report on genome editing identified CCR5 as a potential target for embryo editing by CRISPR-Cas9. “We did discuss that, but it wasn’t a focus of the report,” said bioethicist R. Alta Charo of the University of Wisconsin, who co-chaired the Academies panel that produced the report. Because editing an embryo changes its sperm- or egg-producing cells, or germline, the changes would be passed on to any future progeny.

Germline editing is considered more ethically fraught than using genome editing to treat a child or adult, which would alter only, say, the blood-making cells in someone with sickle cell disease and not heritable DNA. Germline editing therefore has to clear a higher ethical bar, Charo said on the eve of the genome editing summit: The risks and potential benefits to the child who would develop from an edited embryo must be carefully evaluated, she said.

In the case of the twin girls, any benefits are not clear. Their father is HIV-positive, and semen can carry HIV, said Daley. But there are other ways to prevent a father from transmitting HIV to his children, such as washing sperm.

And HIV is both preventable and treatable, said biologist Richard Hynes of the Massachusetts Institute of Technology, who is attending the Hong Kong meeting and co-chaired the National Academies panel: “We set out stringent criteria that would need to be met” to justify embryo editing, he said. “It should only be for serious unmet medical needs, and informed consent has to be in place. All of those things need to be looked into” to see if He’s experiment met the criteria. For instance, on consent forms parents were asked to sign, He called his work “AIDS vaccine development,” the AP reported, so it is not clear if the parents of the girls understood what he planned to do.

The risks of genome editing in general include altering DNA other than the targeted genes, which could have unintended health consequences, and without a detailed scientific paper, no one knows whether CRISPR altered the girls’ DNA anywhere except in their CCR5 gene. The specific risks of having a disabled CCR5 gene include a higher chance of infection with the West Nile virus and of dying from influenza. He has not said whether he clearly communicated those risks to the parents.

He’s work would be illegal in the U.S., which bars embryo editing, and in many other countries.

Dr. Francis Collins, director of the National Institutes of Health in the U.S., said in a statement, “The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed.”

Watchdog groups quickly denounced He’s work. “If true, this amounts to unethical and reckless experimentation on human beings, and a grave abuse of human rights,” Marcy Darnovsky, executive director of the Center for Genetics and Society, said in a statement. “We wish the best for the health of these babies, but strongly condemn the stunt that threatens their safety, and puts the rest of us at risk. Throwing open the door to a society of genetic haves and have-nots undermines our chances for a fair and just future.”

The concern about “haves and have-nots” refers to fears that embryo editing for desirable traits will one day become available to parents who can afford it, exacerbating social inequality.

“It’s possible that in the circumstances [the experiment] was felt to be justifiable,” Robin Lovell-Badge of the London-based Francis Crick Institute told reporters Monday ahead of the genome editing summit. “But we just don’t know that. We have to wait to hear from him,” he said, referring to He’s upcoming summit presentation.