Scientists condemn ‘high-risk’ gene editing breakthrough

In an apparent backlash against uncontrolled and unethical human embryo research in China, more than 120 Chinese scientists have signed a letter condemning the use of gene editing technology on humans, which reportedly led to two babies born this year using the technologies.

Chinese authorities also moved to order the suspension of "research activities of persons involved in the gene-edited babies incidents", denouncing the matter as "extremely abominable in nature" and in violation of Chinese laws and science ethics, according to the state-run Xinhua news agency, quoting Xu Nanping, vice minister of science and technology, as saying the incident "is both shocking and unacceptable".

China’s Southern University of Science and Technology (SUSTech) took the highly unusual step of issuing a statement disassociating itself from the research by one of its associate professors. The move to condemn the announcement last Monday by SUSTech’s He Jiankui that he carried out genetic editing on human embryos is a rare public joint statement by Chinese scientists on ethics of research which could have implications for other scientific fields being pushed by China, such as artificial intelligence.

The use of the cheap and easy to use gene editing tool known as CRISPR – which can disable a defective gene in DNA or add a gene – was deployed to modify human embryos before they were transferred into the human uterus. He and his research team modified embryos to switch off a gene related to HIV, that he hopes will provide babies with immunity from the disease.

Academics in the West were quick to condemn such research on humans. But compared with the United States and Europe, which have strict curbs on human trials for gene editing, China has fewer restrictions.

The outcry by Chinese scientists from top universities – such as Peking University and Tsinghua University in Beijing and Fudan University in Shanghai – and many members of the prestigious Chinese Academy of Sciences, including some at universities in the US, United Kingdom, Germany and Singapore, is highly unusual in China.

In a rare open letter posted on China’s social media platform Weibo, the scientists said such research would affect the reputation and development of China’s science, particularly in the biomedical field, and was unfair to most of the scientists who adhere to ethical guidelines.

They condemned the research conducted against international ethical norms as “crazy”.

“The bioethics approval for this so-called ‘study’ was insufficient,” they said.

Irreversible alterations

“It is scientifically possible but scientists and medical experts have chosen not to use the technology on human beings because of uncertainties, risks, and most importantly, the ethical problems that follow,” they said, noting that irreversible alterations on human genes will inevitably become part of the human gene pool.

Even if the babies born using the technology can be healthy for a period of time, “the potential risks and dangers brought about by the unjustified procedure are hard to assess, particularly if such experiments continue.”

“The Pandora’s box has been opened. We need to close it before it is too late. We, as biomedical researchers, strongly oppose and condemn any attempts on editing human embryo genes without ethics and safety oversight.”

Li Jinsong, a researcher from the Institute of Biochemistry and Cell Biology of the Chinese Academy of Sciences, has said the research is "unbelievable, totally unacceptable".

He Jiankui, an associate professor of biology at SuSTech, was previously at Rice University, Houston, and Stanford University in the United States before returning under China’s ‘Thousand Talents’ programme designed to lure top scientists home with generous financial benefits. He set up a laboratory at the university in Shenzhen, part of China’s drive to become a global leader in biomedical research.

SUSTech disowns the research

SusTech said in a rare statement in English posted on its website last Monday that it was “deeply shocked” by He’s announcement and was seeking clarification from the scientist.

The research was conducted outside of the campus and was not reported to the university or the institution’s biology department. “The university and the [biology] department were unaware of the research project and its nature,” the statement said, noting that He had been on “no-paid leave” from the university since February this year.

“All research conducted at SUSTech is required to abide by laws and regulations and comply with international academic ethics and codes of conduct,” the university said, adding that it would call for international experts to form an independent committee to investigate “and release the results to the public”.

The department of biology at SUSTech called an emergency meeting on Monday 26 November of its academic committee, which said He’s use of CRISPR to edit human embryos “seriously violated academic ethics and codes of conduct”.

He’s research has not been published and has not been peer reviewed or independently verified.

Chinese-American scientist Feng Zhang, a co-inventor of CRISPR, now at Massachusetts Institute of Technology (MIT) in the US, called for a global moratorium on use of the technology for gene-edited babies after the furore broke. Zhang said in a statement to MIT Technology Review that the risks of the experiment outweigh the benefits.

Zhang said he was "deeply concerned" that the Chinese project was undertaken in secrecy. “Not only do I see this as risky, but I am also deeply concerned about the lack of transparency surrounding this trial.”

Risk of ‘off-target’ mutations

One concern is that CRISPR can introduce accidental so-called “off-target” mutations.

Chinese law currently stipulates that biomedical research on human diseases must first be reviewed by ethics authorities, according to 2016 guidelines from the country’s National Population and Family Planning Commission.

According to documents at the World Health Organization-affiliated Chinese Clinical Trial Registry, an application for registration was lodged retrospectively on 8 November for a ‘safety and validity evaluation’ of HIV immune gene editing in human embryos. The application documents stated it had been approved by the medical ethics committee of Shenzhen HarMoniCare Women’s and Children’s Hospital, although hospital officials quoted by Shenzhen newspapers said the experiments were not conducted at the hospital.

The genetically-modified twin sisters were not born at the hospital, health officials said.

Beijing News reported that Shenzhen city medical ethics officials said they had not received any application to conduct such an experiment and are now investigating the case.

International meeting issued statement

The Second International Summit on Human Genome Editing, which took place last week at the University of Hong Kong, and was organised by the Academy of Sciences of Hong Kong, the UK’s Royal Society, the US National Academy of Sciences and the US National Academy of Medicine, gathered world experts on the subject and issued a statement after a debate on what is acceptable in gene editing and how it should be regulated.

The organising committee of the Hong Kong conference issued the statement on 29 November condemning He's procedures as "irresponsible" and said they "failed to conform with international norms", but stopped short of calling for a moratorium on such work as demanded by some scientists.

"The scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time. Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials," the statement said.

However, Xu Nanping, China's vice-minister for science and technology, said on state-run CCTV on Thursday that the work blatantly violated "China's relevant laws and regulations" and called for activities related to He's work to be suspended.

China had earlier withdrawn from the summit, according to the organisers, prompting speculation that it did not wish to be in the spotlight over ethical issues and general research transparency. The Chinese Academy of Sciences co-sponsored the first gene editing summit held in 2015 in Washington DC in the US.

At the 2015 summit, a science ministry official sparked controversy, saying that although China has strict regulations on the use of gene editing in human embryos, he could not guarantee that rogue labs and clinics were not conducting experiments.

This article was amended on 29 November to reflect the outcome at the Second International Summit on Human Genome Editing in Hong Kong.