The Ethics Regarding the Conduct and Oversight of Experimental Treatment Proceedings

A new experimental CRISPR-based treatment leads to complications of thrombotic microangiopathy and death in a six-year-old girl, raising concerns on whether the trials were conducted properly.

By JOHN LEE

An illustration of CRISPR gene-editing technology, which allows scientists to precisely modify DNA and is increasingly being explored for medical treatments. (Photo: Stanford University)

Throughout history, humanity has overlooked the consequences of its technological advancements, perhaps forgetting that the purpose of development is for betterment. Nuclear technology leading to mass destruction of the environment, fossil fuel usage perpetuating climate change, and insecticides like DDT causing severe declines in animal populations are just a few of countless examples. This is what makes setting and following regulations of ethics committees in the context of the medical field so important: with human lives—something we hold to the utmost importance—at stake, consequences like death cannot be taken lightly.

Mei

In the case of Mei (a pseudonym for anonymity), a six-year-old Chinese girl who died after receiving a gene-editing treatment based on CRISPR, there is serious discourse on whether the pre-existing recommendations of leading bodies of ethics review were followed. CRISPR, short for clustered regularly interspaced short palindromic repeats, is a DNA editing technology that cuts both strands of DNA. Once that happens, the cell can either repair the DNA while deactivating the targeted gene, or scientists can insert a custom DNA template, fixing the mutation. The gene editing tool that Mei was subject to was a base editor, a more precise technology that breaks only one strand and chemically modifies the base on the intact strand. While CRISPR’s effectiveness in human cells has been proven since 2013, and a gene therapy treatment, Casgevy, has been approved by the FDA since 2023, base editing is a much newer technology.

Mei’s specific mutation was in the CHD3 gene, which influenced the way DNA coiled into chromosomes. This caused developmental issues, both mentally and physically, in Mei, leading her parents to come into contact with Zilong Qiu, a neuroscientist at Shanghai Jiao Tong University School of Medicine’s affiliate Xinhua Hospital.

Concerns with the Procedure

The conduct of Qiu’s treatment of Mei raises concerns in several ways. First, the consent form given to Mei's parents did not mention death as a possible outcome of the treatments, and the doctors they interacted with never mentioned it as a risk. The National Health Commission of China, in its 2023 "Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects," clearly states in Article 36, Section iii, that the informed consent form must contain the potential risks to the participants. By not even mentioning death as a possible outcome, Qiu (whether through oversight or intention) misled the parents. In fact, though Qiu acknowledged that the treatment was not a guarantee, he reassured the parents that safety was a given, even being quoted in a recording stating that the institution he worked at could ensure there would be no pressing safety concerns.

The parents of Mei also paid Qiu and his team roughly $860,000 in US currency for the treatment. The consent form they were given said that participation in the development and testing of the treatment would not involve additional costs and that the sponsoring company would pay for it, yet Qiu continuously solicited payments through informal arrangements. This burdening of funding raises questions about compliance with Article 17, Section iv in the previously mentioned "Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects.” The article states that no research-related fees should be charged to participants, and that participants who suffer harm through the research would receive compensation by laws, regulations, and agreement between the parties. According to their account, the parents never received an offer for compensation for the death of their child.

Qiu’s team also did not present clear results on the trials they showed to the parents. Qiu revealed zoomed-in images of two monkeys’ brain slices where the gene editor was highlighted, which implied that it contacted every targeted neuron where the CHD3 gene was expressed. He then stated that this was proof that the clinical trial of Mei should go ahead. This result reportedly helped persuade the hospital ethics committee to approve the clinical trial. However, several expert reviews of the images had doubts. There were no control samples, which meant that there was no way to prove that the highlighting was truly representative of the gene editor: in other words, it may have just been background staining, the coloration of areas in a sample where no target molecule is present. In fact, another graph in Qiu’s paper suggested the gene editing technology only affected delivery to 30% of targeted neurons, but even that number has been doubted when compared with similar treatments in other studies that suggest a much lower number.

Another issue arises with the toxicology study released around a month before Mei was treated. All four monkeys in the trial, regardless of dosage in treatment, developed moderate to severe liver damage, and one monkey had kidney damage. This was suspected to be connected to thrombotic microangiopathy, a well-documented reaction to the gene therapy that Mei was subject to. This same reaction happened in Mei and caused her death. Though the parents were made aware of these complications in the monkeys, Qiu was reported as being “unconcerned about their significance.” The hospital ethics committee did not review the toxicology report before it approved Mei’s trial. Article 25 of the Chinese National Health Commission’s 2023 ethics-review measures previously mentioned addresses this, requiring that ethics review committees conduct follow-up reviews based on the reports of the researchers.

After Mei died, Nature, a scientific journal, published a paper on the base editor technology that Qiu had submitted during the trials. New images containing what were presented as control samples, produced at the request of peer reviewers, appeared to have been taken at a different time than the experimental samples, with different microscope settings. The paper no longer contained any information regarding Mei and her treatment, and rather focused on the results that happened with the monkey trials. It never mentioned the kidney and liver complications that the monkeys developed.

The Larger Scope

Mei’s condition was not life-threatening. This raises questions on whether this treatment was justified, and if the benefits outweighed the risks. Though an attempt at experimental treatment of a nonfatal condition cannot be inherently deemed unethical, there must be compelling reasons to expose human life to unknown dangers.

Ethical approval is integral in each step of uncertain trials such as these. When the monkey trials produced results of kidney and liver damage that indicated concern for complications due to thrombotic microangiopathy, the ethical committee should have been alerted to review it. Parents who base their decision to sign a consent form solely on information provided by those seeking their consent are not sufficiently informed. If the complications of the animal trials were presented to the ethical committee, there may have been reason to delay the trials to postpone Mei’s treatment, mitigating the risk of those same complications leading to her death.

The way Qiu’s research was presented to Nature also raises a question about how medicine judges progress. Of course, the prestige and recognition that comes with being a trailblazer in a new field such as base editing technology may be attractive, but it must never come before the well-being of human lives. It’s the same case with medical students who are incentivized to mass-produce research papers to match with competitive residency programs in the race to “outdo” others, potentially producing superficially hollow papers with poorly designed or rushed studies. It’s irresponsible to withhold the negative results of research or warp it so that it is beneficial for the ones publishing, as it has the power to mislead people. The purpose of research is to progress humanity, and presenting incomplete information is antithetical to that intention.

Sources & Further Reading

Shanghai Jiao Tong University School of Medicine. “Measures for Ethical Review of Life Science and Medical Research Involving Human Subjects.” Institutional Review Board, 2023.

Servick, Kelly. “Exclusive: Death of Girl in Chinese Gene-Editing Trial Was Never Made Public.” Science, 2026.

U.S. Food and Drug Administration. “FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease.” FDA, 2023.

World Medical Association. “WMA Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Participants.” World Medical Association.