In November 2018, Chinese biophysicist He Jiankui announced that twin girls, pseudonymously called Lulu and Nana, had been born after he used CRISPR-Cas9 to edit their embryos before implantation. His stated goal was to disable the CCR5 gene and make the children resistant to HIV. The announcement, made not through a peer-reviewed journal but via YouTube and a genetics conference in Hong Kong, provoked immediate condemnation from scientists, ethicists, and governments worldwide. What followed was a criminal conviction, sweeping regulatory reform in China, and a still-unresolved global debate about whether heritable human genome editing should ever be permitted.
What He Jiankui Actually Did
He Jiankui recruited couples in which the father was HIV-positive and the mother was HIV-negative, then used CRISPR-Cas9 to target the CCR5 gene in their embryos during in vitro fertilization. CCR5 encodes a protein on the surface of certain immune cells that HIV uses as a doorway to enter and infect them. A naturally occurring mutation, a 32-base-pair deletion known as CCR5-Δ32, had already been identified in a small percentage of people of European descent. Those who carry two copies of this deletion are nearly completely resistant to most strains of HIV.
He’s idea was to recreate something like this natural mutation using gene editing. But the edits he introduced were not identical to CCR5-Δ32. Instead, the CRISPR tool made cuts at the target site, and the cell’s own repair machinery stitched things back together in ways that created novel deletions and insertions. In other words, the children ended up with disruptions to CCR5 that had never been observed in any human population before, making it impossible to predict their biological effects by looking at studies of the natural Δ32 variant.
Why CCR5 Was Chosen and Why the Choice Was Flawed
CCR5 became an attractive target in HIV research because of the well-documented protection conferred by the Δ32 deletion. People homozygous for CCR5-Δ32 display near-complete resistance to HIV infection regardless of exposure, and this discovery had already inspired therapeutic strategies including the famous “Berlin Patient,” who was cured of HIV after receiving a bone marrow transplant from a Δ32 homozygous donor.
But choosing CCR5 for germline editing in healthy embryos was a different matter entirely. The fathers in He’s study were HIV-positive, yet the mothers were not, and standard assisted reproduction techniques like sperm washing already reduce the risk of HIV transmission during IVF to negligible levels. There was no pressing medical need that could not be met by existing, far less risky interventions. This is a point that many critics returned to repeatedly: even if the editing had worked flawlessly, the procedure solved a problem that did not exist for these particular children.
The Editing Was Incomplete
Beyond the questionable rationale, the technical execution raised serious concerns. One of the core problems with applying CRISPR to human embryos is mosaicism, a situation in which some cells in the developing embryo carry the edit while others do not. Numerous studies have reported unexpected genomic mutation and mosaicism following the use of CRISPR-Cas nucleases, and researchers still do not fully understand how common these events are or how reliably current methods can detect them.
Earlier laboratory research on human embryos had already demonstrated the difficulty of controlling edits at the CCR5 locus. When researchers attempted to engineer CCR5-Δ32 in tripronuclear embryos (embryos unsuitable for implantation), they found that even in embryos containing the desired allele, the other copies at the same locus could not be fully controlled, remaining either wild-type or harboring random insertions and deletions.
He Jiankui’s own unpublished data, later reviewed by outside scientists, suggested that neither twin carried a clean, biallelic knockout of CCR5. One of the twins appeared to be mosaic, meaning that not all of her cells carried the same edit. The other appeared to have one disrupted copy and one normal copy, which would not confer meaningful HIV resistance even under the best interpretation. The children did not carry the exact CCR5-Δ32 mutation that occurs naturally, raising questions about their future health that no existing research could answer.
Hidden Costs of Losing CCR5
CCR5 does much more than serve as an entry point for HIV. It plays roles in immune signaling, inflammatory responses, and brain function. Knocking it out does not simply remove a vulnerability; it removes a working part of the immune system.
One well-documented risk involves West Nile virus. Studies of two independent patient cohorts, one in Arizona and one in Colorado, found that people homozygous for CCR5-Δ32 were significantly overrepresented among those with symptomatic West Nile virus infections. In the Arizona cohort, Δ32 homozygotes had roughly four times the odds of symptomatic infection compared to the general Caucasian population, and Δ32 homozygosity was significantly associated with fatal outcome. The Colorado cohort showed an even starker picture, with about nine times the odds of symptomatic disease. Follow-up research confirmed that CCR5 deficiency is a risk factor for clinical manifestations of West Nile virus infection, with the receptor apparently functioning to limit disease severity in humans.
Influenza is another concern. A study of patients with severe influenza found that those carrying the CCR5-Δ32 allele had a mortality rate of about 17%, compared with roughly 5% among those with normal CCR5. The difference was statistically significant, suggesting that people without functional CCR5 face a meaningfully higher risk of dying from the flu.
On the other side of the ledger, there are hints that reduced CCR5 activity could have cognitive benefits. Research in mice found that decreasing CCR5 function enhanced signaling pathways associated with learning, increased long-term potentiation (a cellular mechanism tied to memory formation), and improved performance on memory tasks. The same study showed that reducing CCR5 in the brain’s sensory cortex dramatically accelerated experience-dependent plasticity. These findings are intriguing but preliminary, drawn from animal work, and the leap to predicting what happens in a human child carrying novel, untested CCR5 disruptions is enormous.
The broader point is that CCR5 is not a junk gene that evolution failed to clean up. It persists in most human populations at full function because it does useful things. Trading away those functions to prevent an infection that could have been avoided through conventional medicine was, in the view of nearly every expert who weighed in, a bad bargain.
Ethical Failures and Consent
The ethical violations extended well beyond the science. He Jiankui bypassed normal institutional oversight. His university, the Southern University of Science and Technology in Shenzhen, stated that it was unaware of the research and that He had been on unpaid leave. The informed consent process was deeply problematic: the participating couples were recruited through an HIV/AIDS advocacy group, and critics raised serious questions about whether the parents, who were not scientists, could have genuinely understood what was being done to their future children and what the long-term risks might be.
Informed consent for something as unprecedented as heritable genome editing is an unsolved problem even in theory. The individuals most affected by the procedure, the children themselves, obviously cannot consent before they exist. Any risks from off-target mutations or mosaicism would follow them for life and could potentially be passed to their own children. Researchers who have examined the question argue that informed consent for embryo genome editing, if it ever becomes clinically appropriate, will require extraordinary standards of truthfulness, sensitivity, and regulatory compliance that simply did not exist in He’s experiment.
Criminal Conviction and Punishment
In December 2019, a court in Shenzhen found He Jiankui guilty of illegal medical practices. He was sentenced to three years in prison and fined 3 million yuan, equivalent to roughly $430,000. Two collaborators, Zhang Renli and Qin Jinzhou, received lesser prison sentences and fines. He was released from prison in April 2022.
The charges were notably narrow. He was not convicted of a specific crime related to germline editing, because at the time of his experiment, China did not have a law that explicitly criminalized heritable human genome editing. Instead, the court relied on a broader statute against practicing medicine without proper authorization. This legal gap itself became a catalyst for reform.
China’s Regulatory Overhaul
The scandal prompted a rapid and far-reaching tightening of China’s regulatory framework for biotechnology. In October 2019, China established the National Science and Technology Ethics Committee, with a dedicated Life Science Ethics Sub-Committee. In March 2022, the government issued national guidelines on science and technology ethics governance that detailed principles, management systems, and enforcement responsibilities.
Several major laws followed. The Chinese Civil Code, enacted in May 2020, explicitly states that medical and scientific research involving human genes and embryos must comply with laws and regulations without endangering human health, violating moral principles, or damaging the public interest. Violators can now face civil liabilities for personal rights infringement. More pointedly, China’s Criminal Law Amendment XI now explicitly prohibits both human cloning and human germline genome editing for clinical purposes. The Biosecurity Law, also promulgated in 2020, established a broader framework for biosafety risk prevention and requires that biotechnology research and applications conform to ethical principles.
The legislative response also went through China’s highest legislative body, the National People’s Congress, along with the Ministry of Science and Technology and the National Health Committee. Together, these bodies undertook what legal scholars have described as a seemingly far-reaching regulatory reform, with the most significant step being the regulation of genetic research and human embryo research directly within the Civil Code.
The International Response and the Moratorium Debate
The scandal did not just reshape policy in China. It forced a global reckoning. Within months, an international group of prominent scientists and ethicists published a call for a global moratorium on heritable genome editing. The proposal was controversial from the start. Supporters argued that a moratorium was the only way to prevent another rogue actor from implanting edited embryos while safety and ethical standards remained undeveloped. Opponents worried that a blanket moratorium could stifle basic research, push clinical attempts underground, and be unenforceable in practice.
The World Health Organization formed an expert advisory committee in 2019 specifically to develop a governance framework for human genome editing. After two years of deliberation, the committee recommended against any country allowing heritable genome editing to proceed to clinical application until safety and efficacy standards could be established, but stopped short of endorsing a formal moratorium. Instead, it proposed a global registry for gene-editing research and called for stronger international coordination.
Researchers advocating for anticipatory governance have pushed for continued participatory public engagement, international harmonization across regulatory bodies and scientific societies, and the development of a formal whistleblower framework so that scientists who learn of unauthorized experiments have a clear, protected channel to report them. That last recommendation speaks directly to the He Jiankui case: several colleagues reportedly knew about his plans before the announcement but lacked a mechanism, or perhaps the courage, to intervene.
Public Reaction Across Different Spheres
The controversy played out differently depending on where you looked. Within the scientific community, the response was overwhelmingly critical, focused on technical shortcomings, safety risks, and violations of research ethics. In the press and on social media, the conversation was broader and more emotionally charged. Analysis of how the debate unfolded across these spheres shows that while scientific and legal aspects were discussed everywhere, the public conversation was layered with fear, anger, hope, pride, disgust, and shame in ways that the technical debate was not.
In China specifically, the reaction was complicated by national pride in the country’s rapidly growing biotech sector, embarrassment at the global condemnation, and genuine concern for the children. Internationally, the case became a touchstone for fears about designer babies, genetic inequality, and the pace of biotechnological change outrunning ethical guardrails. For many people who had never heard of CRISPR before November 2018, the gene-edited babies were their introduction to the technology, which colored public perception of genome editing as a whole in ways that researchers working on legitimate therapeutic applications have struggled to counterbalance.
What Has Happened Since
He Jiankui was released from prison in April 2022 and has since attempted a return to scientific work, which has drawn fresh criticism. A third child, conceived during the same period as the twins but born later, is also known to exist. Very little public information is available about the health or development of any of the three children. Chinese authorities have not released medical follow-up data, and it remains unclear what monitoring, if any, is in place.
The state of the underlying science has continued to advance, but the safety bar for clinical germline editing remains unmet. Research on editing human embryos in the lab, without implantation, has continued in several countries and has repeatedly confirmed the problems that plagued He’s work. Off-target edits and mosaicism remain common enough that no responsible scientist has proposed moving to clinical application. The 2017 study that demonstrated correction of a disease-causing heart mutation in human embryos, often cited as a landmark, achieved its results only under carefully controlled laboratory conditions and was itself the subject of scientific debate about the mechanism involved.
Meanwhile, somatic gene editing, which targets cells in a living patient without affecting future generations, has moved forward rapidly. Approved therapies now use CRISPR to treat sickle cell disease and beta-thalassemia in adults, with the edits confined to blood stem cells. These treatments sidestep the most fraught ethical questions by leaving the patient’s reproductive cells untouched. The distinction between somatic and germline editing is, for many in the field, the bright line that He Jiankui crossed and that the scientific community is determined to maintain until the risks are far better understood.
CCR5 Research Beyond the Scandal
Despite the damage He Jiankui did to public trust, research on CCR5 as a therapeutic target has not stopped. The receptor remains a compelling piece of human biology. Its role as a co-receptor for HIV entry is well established, and naturally occurring CCR5 mutations have allowed scientists to pursue the molecule as a promising target for preventing or limiting HIV infection through approaches that do not involve editing embryos.
CCR5-blocking drugs like maraviroc have been approved for HIV treatment for years. Researchers are also exploring whether CCR5 can be safely disrupted in adult immune cells using gene editing, with several clinical trials underway. These approaches carry their own risks, but they differ fundamentally from what He did: they affect only the patient who consents to treatment, and they can be monitored and, in some cases, reversed. The mouse studies showing that reduced CCR5 function enhanced memory and neural plasticity have also sparked interest in neurological applications, though that work remains far from clinical relevance.
The irony of the He Jiankui case is that CCR5 biology is genuinely fascinating and holds real therapeutic promise. But by racing ahead of both the science and the ethics, He did not accelerate progress toward HIV prevention. He may have slowed it, by making regulators more cautious and by associating CCR5 research in the public mind with recklessness rather than careful medicine.