BEIJING — Three government institutions in China, including the nation’s science ministry, may have funded the “CRISPR babies” study that led to the birth last November of two genetically modified twin girls, according to documents reviewed by STAT.
These findings appear to support what many researchers inside and outside China have suspected since scientist He Jiankui revealed the births in late November, sparking international condemnation for violating scientific guidelines against the use of gene-edited human embryos to start pregnancies. “I don’t think He Jiankui could have done it without the government encouragement to press ahead” with research they thought would merit a Nobel Prize, said Jing-Bao Nie, a bioethicist at the University of Otago in New Zealand.
If the documents are correct, they would suggest China is supporting research that the U.S. and other countries consider unethical, and raise doubts about the preliminary conclusion of a government investigation that He acted mostly on his own. That inquiry, which was led by the Guangdong provincial health commission and involved the science ministry and the National Health Commission, determined that He raised funding for the experiment on his own without official endorsement. It also concluded that He forged an informed-consent form and violated scientific ethics and Chinese regulations, according to the official Xinhua News Agency.
“They want him to be the scapegoat, so everybody else can be vindicated,” Nie said. “But this would disguise serious institutional failures.”
The documents examined by STAT — a slide presentation prepared by He’s team, Chinese-language patient consent forms, and China’s clinical trial registry — list three funding sources for the study that led to the twins’ birth: the Ministry of Science and Technology; Shenzhen Science and Technology Innovation Commission, part of the municipal government; and Southern University of Science and Technology, where He worked.
It’s not clear, however, whether the institutions knew how their grants would be used. Scientists applying for grants in China typically have to itemize in detail how they would use the money. But it’s possible that for the CRISPR babies study, He could have used money that had been given to his lab for earlier research. The science ministry and the Shenzhen innovation commission both funded He’s preclinical research that tested the CRISPR technology without establishing pregnancies in humans.
The university and the Shenzhen government denied any knowledge of He’s CRISPR babies work soon after it was revealed. In an email on Sunday, the science ministry told STAT that, “based on the preliminary investigation, it did not fund He’s activities of human genome editing.” The Shenzhen innovation commission did not respond to a request for comment, and neither did He Jiankui.
STAT also found that five Chinese fertility clinics are associated with He’s various gene-editing studies, based on mentions in China’s clinical trial registry or in papers He submitted to journals. It’s unclear whether any of them was involved in the CRISPR babies work, or if so, whether they knew what He was doing; most appear to have provided eggs and embryos for some of He’s preclinical studies.
“It’s unlikely that He acted alone,” said Lei Ruipeng, executive director of the Centre for Bioethics at Huazhong University of Science and Technology in Wuhan. “I hope the ongoing investigation addresses the institutional issues that culminated in the affair. Otherwise, it would leave open the possibility of similar scandals.”
Bioethics did not take root in China until a quarter of a century ago. Since then, it has been trying to make laws and struggling to regulate the rapid development of biotechnologies. “It’s hard in the best of cases, and it’s really hard when you have 1.3 billion people spread over a large area,” said Hank Greely, a lawyer and bioethicist at Stanford University.
“But China has to acknowledge that it’s a problem,” he said. “In order to hold its head up high, and in order to be a respectable member of the international research community, China needs much better systems to prevent abuse.”
He Jiankui was a rising star and had received generous financial support from the Chinese government since his return in 2012 after completing a Ph.D. and postdoctoral research in the United States.
Jia Ping, a human rights lawyer and founder of the Beijing-based nongovernment organization Health Governance Initiative, said He was a darling of the science ministry. In September 2017, a flamboyant He appeared on China’s state television news channel CCTV13, showcasing a DNA-sequencing device that He claimed he had developed and had sent shock waves around the world.
“Not every piece of scientific breakthrough can make it onto television, let alone a major profile like this,” Jia said. “You’d need government agencies to back you up.” Indeed, the TV program featured a statement issued by the science ministry, describing He’s work as a significant achievement.
The science ministry then appears to have provided funding for He’s CRISPR babies work, which involved editing a gene called CCR5 in embryos to protect the resulting children from infection with HIV. This could be gleaned from a 14-slide, Chinese-language presentation on the recruitment of volunteers for the clinical trial, which was provided to STAT by a Chinese scientist involved in the project. The sixth slide outlines the aim of the research and claims that the funding source was the State Key Research Program of China’s science ministry.
The Chinese Clinical Trial Registry lists another funder for He’s trial: the Shenzhen Science and Technology Innovation Free Exploration Project, a program funded by the Shenzhen innovation commission. It makes no mention of the science ministry or Southern University of Science and Technology.
When asked about the funding sources last November, after talking about his clinical trial at the Second International Summit on Human Genome Editing in Hong Kong, He said the work was paid for in part by his own savings and in part by a generous startup fund provided by the university when he was first recruited. Indeed, the university is listed as the funding source on two Chinese-language informed-consent forms provided to STAT, which He used to recruit male and female volunteers, respectively.
He may also have been seeking support from another government entity. A source close to the Chinese health ministry told STAT that He’s team had been lobbying the government of the southern province of Hainan to set up IVF clinics specialized in germline editing — changing the DNA of embryos, eggs, or sperm.
Some Chinese researchers say that He may have untruthfully listed some of the government grants to lend himself credibility. “I would be very surprised if government agencies officially funded the CRISPR babies project,” said Mu-ming Poo, director of the Chinese Academy of Sciences’ Institute of Neuroscience in Shanghai. “But it’s possible He used other government grants of his to fund the CRISPR babies work because there is some flexibility in how the money can be spent.”
Where He’s team carried out the in vitro fertilization work and gene editing remains a mystery. The page for the CRISPR babies project on the Chinese Clinical Trial Registry contains an approval form from the medical-ethics committee of the Shenzhen HarMoniCare Women and Children’s Hospital, which claimed to have no knowledge of the project. Regardless of the authenticity of the approval, the IVF and the implantation of genetically modified embryos could not have taken place at the hospital because it does not have an IVF clinic.
One clue may come from a manuscript He submitted to Nature last November titled “Birth of twins after genome editing for HIV resistance.” The only hospital listed on the paper (which the journal rejected) is Shenzhen University’s Third Affiliated Hospital (also known as Shenzhen Luohu District People’s Hospital). And the only hospital-affiliated researcher on the author list is Qin Jinzhou, who is the second author — after He, who is the lead author.
Qin was a key member of the project. He is listed as its co-principal investigator on the clinical trial registry and the point of contact on the patient-recruitment slide presentation. Qin is also a co-author of He’s on two preclinical studies of gene editing.
On the website of the hospital’s IVF clinic, Qin was listed last December as an “IVF laboratory expert” — rather than a “clinical expert” — suggesting he is an IVF technician rather than a fertility doctor. Qin’s role in the CRISPR babies work is unclear. But he has since been removed from the website, and neither he nor the hospital responded to STAT’s request to comment.
Four other IVF clinics are associated with He’s preclinical studies of gene editing, which involved more than 300 embryos. Two of the clinics — the Third Affiliated Hospital of Zhengzhou University and the CITIC-Xiangya Genetics and Reproduction Hospital in Changsha — are listed as collaborating hospitals of the projects in the clinical trial registry. Both hospitals, along with Guangdong General Hospital and Shenzhen Armed Police Hospital Reproductive Centre, are listed as contributing affiliates on the two preclinical papers that He and Qin co-authored.
“What’s their role in the CRISPR babies work? Did they follow due process when providing He the eggs and embryos? Are they being investigated?” asked Lei, of Huazhong University of Science and Technology. None of the IVF clinics responded to STAT’s requests for an interview. Nor did the national health commission, or the Guangdong provincial health commission.
On the day of the Xinhua report, He was fired by his university. An unidentified official involved in the investigation told the news agency that those suspected of criminal offenses would be handed over to relevant public security bureaus.
“This would be a step forward from previous such incidents,” said Jia, the human rights lawyer. In China, the penalties for ethical breaches are light, if there are any at all. “Few get the sack, let alone going to prison,” said Jia.
But punishing He alone, no matter how harshly, is far from enough, researchers say. “While it’s important to penalize the individuals, the focus should not be why they behave so badly, but why good people do bad things, and why the system has let that happen,” said Nie, the New Zealand bioethicist.
And “you need more than just deterrent to have good quality control,” Stanford’s Greely said. “Even if He acted alone, which is a big if, there should have been institutions that could have prevented that. A good system creates redundant safeguards that limit the harm a bad actor can do.”
“China should turn this medical scandal into positive institutional reforms to prevent similar incidents from happening again,” Lei said. “Let’s hope it will not be a missed opportunity.”