A six-year-old girl in China died in March 2025 after receiving what researchers said they believed was the world’s first base-editing therapy directed at the brain, according to an investigation by Science and Retraction Watch.
The investigation has raised important questions about the oversight of an experimental personalised gene-editing trial and the way the researchers and their institutions communicated their choices.
The girl had Snijders Blok-Campeau syndrome, a rare neurodevelopmental disorder caused by a mutation in the CHD3 gene. Although the condition affects intellectual development and its severity varies widely, most people with the condition live full lives.
But that such a case could still clear the bar for an unprecedented, high-risk brain intervention says something about a society uneasy with disability and enamoured of techno-scientific interventions.
The girl’s parents sought the experimental treatment after learning of research led by neuroscientist Zilong Qiu at the Shanghai Jiao Tong University.
Base-editing is a more recent invention than CRISPR-Cas9. The American biochemist David Liu developed it at the Broad Institute in 2016 after finding a way to convert one DNA letter directly into another — say, C to T — without cutting both strands of the DNA double helix, as Cas9-based editing does.
As a result, base-editing is, in principle, more ‘gentle’ and can cause fewer unintended mutations. Its development thus renewed hopes that gene-editing could graduate from being a proof of concept and to treating rare disorders caused by defects in single genes.
That said, the memory of He Jiankui, the Chinese scientist who announced in 2018 that he had edited the genomes of twin girls at the embryonic stage without adequate ethical review, scientific justification, and even disclosure to his own university, has weighed heavily on the field.
He was later sentenced to three years in prison for his actions, and the episode forced China to tighten its rules on human gene-editing research. But as the new investigation by Science and Retraction Watch has found, the rifts between what the law says and how it is enforced have remained wide enough for a similar failure to recur.
Dr. Qiu’s team developed a personalised base-editing therapy designed to correct the genetic mutation in the child’s brain cells.
However, delivering the ‘editor’ to the brain required the researchers to inject large doses of adeno-associated viruses (AAVs), which are known to carry risks of severe immune reactions.
According to the investigation report, the child’s parents helped finance much of the therapy’s development, contributing around $860,000 (Rs 8.3 crore) from their personal savings and money borrowed from relatives.
The treatment proceeded as a clinical trial initiated by the investigator at the Xinhua Hospital in Shanghai. This process did not require the National Medical Products Administration, China’s national drug regulator, to review it first.
However, the report has quoted independent experts expressing concerns with several aspects of the process — including whether preclinical studies (in animals) had adequately proved the treatment’s safety for human use.
Toxicology studies in monkeys reportedly found that all the treated animals had developed liver injury and one monkey’s kidneys were damaged as well.
However, the researchers proceeded to inject the therapy into the girl’s cerebrospinal fluid on March 24, 2025. Within days, she developed a fever and kidney damage, and died a week later.
An internal review at the hospital concluded that the treatment was certainly linked to her death, and listed the cause of death as thrombotic microangiopathy, a complication that has previously been associated with genetic therapies involving high doses of AAVs.
According to Science and Retraction Watch, neither the researchers nor the hospital disclosed the girl’s death at the time. Several months later, local health authorities fined the hospital for shortcomings in trial oversight and registration, but did not sanction the lead researcher.
The family said they later asked that a research paper related to the trial be withdrawn, arguing that it did not reflect the appropriate outcomes.
The investigation also examined a paper published in Nature earlier this year describing the underlying preclinical work. Some independent experts questioned aspects of the reported data and argued that the journal should examine the underlying evidence and funding disclosures.
Nature said it had not been informed of the patient’s death or the regulatory issues before publication and that such information would have been considered during editorial review.
The case has prompted renewed debate about ‘first in human’ gene-editing trials, particularly for rare but serious disorders.
In June 2024, Nature had reported a similar story in India: researchers across the country raced against time to develop a treatment for Uditi Saraf, a 20-year old with familial encephalopathy with neuroserpin inclusion bodies, or FENIB — a rare and aggressive brain disorder with symptoms similar to dementia.
Sadly, Uditi passed away before the treatment was ready, although the Sarafs, who helped fund the tests, and the researchers expressed hope afterwards that their efforts could help other people with FENIB.
The researchers’ challenges included identifying the mutation, engineering the base-editor, manufacturing the AAV vectors, and improving institutional capacity to produce a gene therapy of direct clinical value.
Both instances — Uditi Saraf and the little girl in China — began with researchers committing themselves to a schedule they knew would be uncertain and high-pressure.
But in Uditi’s case, while the researchers worked 12-hour days and called in favours from colleagues abroad, their efforts also had to contend against the friction of collaborating across borders and dealing with the US’s more cautious regulatory system. In India as well, Arkasubhra Ghosh at Narayana Nethralaya Eye Hospital was waiting for approval from Indian regulators to manufacture AAVs when Uditi passed away.
In China, on the other hand, the researchers faced little resistance going from decision to injection.
Of course, this doesn’t mean India treats disability better than China. Stigma against disabled people here is widespread, sustained by misunderstanding, misinformation, and prejudice.
The Sarafs’ experience also opened a window to India’s opportunity to become a centre for affordable gene-editing as it wound through Ghosh’s ambition to manufacture AAVs within the country and Debojyoti Chakraborty’s efforts at the CSIR-Institute of Genomics and Integrative Biology to develop inexpensive CRISPR therapies.
That said, while India offered the possibility of acting before it was too late, the researchers might have faced similar questions over the preclinical evidence and toxicology reports and regulatory penalties against hospitals if the treatment had gone awry.
Finally, none of the regulatory philosophies at work in these episodes guarantees success. One emphasised exhaustive reviews before ‘first in human’ use. Another allowed investigator-initiated trials to proceed more rapidly. A third was willing to devolve trust based on reputation and clinical stature over external reviews, including of safety.
In fact, while the law in China forbids charging patients for unproven therapy, it is also written narrowly enough for informal payments to individual researchers — such as the gifts to Dr. Qiu — to fall outside its purview.
Communicating risk and the possibility of death also have thorny social dimensions, including the optimism surrounding frontier biotechnologies and the emotional entanglement that can develop between families and researchers.
