Rachel Lim ‘29
On November 28, 2018, Chinese geneticist He Jiankui announced the birth of the first gene-edited human babies in the world. As soon as he finished presenting his work at the Second International Summit on Human Genome Editing in Hong Kong, he was promptly bombarded by questions from scientists and journalists in the audience. Soon, the media had reported to the whole world that two twin babies, nicknamed ‘Lulu’ and ‘Nana’, had been born with genes modified to make them resistant to HIV infection.
However, the international science community swiftly condemned Dr. He and the ethics of his work – the Chinese government suspended Dr. He’s research activities the day after the summit, and on December 30, 2019, Dr. He was sentenced to three years in prison for violating informed consent and deceiving medical authorities. Since then, the story of He Jiankui and the “CRISPR Babies” has generally been hailed as a “deeply unfortunate, misguided misadventure of the most dramatic sort,” as described by former U.S. National Institutes of Health director Francis Collins (Stein, 2018). Controversy surrounding Dr. He’s case has been central to the debate around the future of human genome editing research.
So, what happened? While working at the Southern University of Science and Technology in Shenzhen, China in June 2017, Dr. He recruited two couples for his experiment. In each couple, the would-be father was HIV-positive. Dr. He planned to perform an in-vitro fertilization (IVF) procedure, but with a catch – he would attempt to genetically modify the embryonic cells so that the couples’ children would supposedly be resistant to HIV infection in the future. To do so, he targeted the CCR5 gene, which codes for a protein that has been shown to serve as a method of entry for HIV. Prior research had suggested that when people inherit two disabled copies of CCR5 with the delta-32 mutation, a 32 base-pair deletion in a specific region of the gene, they tend to have a reduced risk for HIV infection (Ni et al., 2018).
Dr. He planned to create this specific mutation using CRISPR-Cas9 gene editing, the revolutionary technique that allows for precise edits of DNA sequences. CRISPR-Cas9 gene editing is based on the naturally occurring adaptive immune system of many bacterial species. In this system, bacteriophage DNA is captured, stored, and used to identify and destroy incoming phages with matching DNA sequences (Doudna, 2022). CRISPR-Cas9 revolutionized genome editing by making it much simpler to specify target sequences; this was due to its reliance on DNA-RNA binding rather than DNA-protein binding, since it is easier to design guide RNA molecules than specific proteins (Guo et al., 2023). In the case of Lulu and Nana, Dr. He planned to target the CCR5 sequence; according to him, he and his team injected “protein[s] and instructions for a gene surgery” into the fertilized zygotes (The He Lab, 2018).
On paper, Dr. He’s intentions may seem noble. However, scientists and ethicists who investigated Dr. He’s research process have claimed to unravel the morality and effectiveness of what the researcher asserted to be a successful “gene surgery”. One big argument against Dr. He’s work is that there was no unmet medical need that justified editing Lulu and Nana’s genes. According to physician and biologist Siddhartha Mukherjee, the threat of HIV infection is eliminated during the IVF procedure; even though the twins’ father was HIV-positive, it would have been highly unlikely for him to pass on the risk of HIV infection to Lulu and Nana because of their HIV-negative mothers and the process of sperm washing and IVF (Mukherjee, 2023, p. 128). As HIV is also not an untreatable or immediately fatal disease, some scientists have questioned the validity of resorting to risky genome editing to prevent it (Cyranoski & Ledford, 2018). In addition, HIV researcher Paula Cannon doubts the effectiveness of targeting CCR5 to promote HIV resistance – some strains of HIV do not use the CCR5 protein to enter cells, and even people who do not possess the CCR5 genes at all are susceptible to forms of HIV that use another protein called CXCR4 (Cyranoski & Ledford, 2018).
Another source of controversy was the question of whether the “gene surgery” was actually as successful as Dr. He claimed. Despite improved precision with the development of CRISPR-Cas9, gene editing can still go wrong in a few ways. Off-target edits are possible “typos” made in a DNA sequence, where the Cas9 protein cleaves the DNA in incorrect spots (Guo et al., 2023). Also, when instructions for CRISPR-Cas9 editing are injected into fertilized zygotes as DNA, RNA, or protein molecules, they can cause edits to occur at varying stages of embryo development. This results in genetic mosaicism, where the developed individual possesses different genotypes across their body (Mehravar et al., 2019). Viewing the DNA sequencing data for Lulu and Nana’s edited genomes, cardiologist and gene editing expert Kiran Musunuru reportedly observed both off-target edits and mosaicism; he says, “the fact that there were actually two live-born twin girls who had genomes that looked like [this] … made me start crying and screaming in my office because I couldn’t believe it” (Pedrick, 2025).
Results from Dr. He’s experiment showed that 15 base pairs were deleted from one of Lulu’s copies of the CCR5 gene, but nothing occurred in Lulu’s other copy of CCR5; because she had one un-touched copy of CCR5, Lulu would not possess HIV resistance (Cohen, 2019). For Nana, bases were apparently added to one of her copies of CCR5 and deleted from the other; according to Science reporter Jon Cohen, this may have crippled Nana’s CCR5 gene, but researchers have raised suspicions about the CRISPR editing being performed after the single cell stage of embryonic development, possibly resulting in mosaicism in Nana’s cells (Cohen, 2019). In any case, neither Lulu nor Nana received the intended delta-32 mutation.
On top of these results, Dr. He and his collaborators were also found guilty of forging ethical review documents and of deceiving doctors into implanting gene-edited embryos into the women participating in his “study” (Normile, 2019). Questions still remain about the details of investigations into Dr. He’s work, and confirmations about Dr. He’s results, which were never formally published, are still needed.
Still, Dr. He has received international backlash for what many scientists have deemed a premature and misguided venture into germline editing. Although somatic gene editing, in which edits are not passed on to offspring, is more openly accepted and used to treat diseases like cancer or hemophilia (Mayo Clinic, 2024), editing the genes of embryonic cells through germline editing has faced more scrutiny in ethical debates. Some have feared that the sensationalized story of the “CRISPR Babies” would prevent public support for further advances in gene editing, while others fear that it would encourage other scientists to use germline editing for dangerous applications with societal implications (Cyranoski, 2018). Jennifer Doudna, gene editing pioneer and cowinner of the 2020 Nobel Prize in Chemistry for the development of CRISPR-Cas9, remarks, “over the last few years, I’ve gone from wide-eyed excitement to realizing that there was real risk and that we really needed to be aware of this and discussing it” (Pedrick, 2025). The question of the ethics of germline editing is a tricky one to answer. But, as the field of genetic engineering propels forward and the need for effective treatments persists, this question remains an important one to address.
He Jiankui presenting at the Second International Summit on Human Genome Editing.
Image credit: Alex Hofford/EPA-EFE/Shutterstock (Cyranoski, 2018).
Rachel Lim is a staff writer and editor at The Princeton Medical Review. She can be reached at rl5352@princeton.edu.
References
Cohen, J. (2019, August 1). Did CRISPR help—or harm—the first-ever gene-edited babies? Science. https://www.science.org/content/article/did-crispr-help-or-harm-first-ever-gene-edited-babies
Cyranoski, D. (2018). First CRISPR babies: six questions that remain. Nature.com. https://www.nature.com/articles/d41586-018-07607-3
Cyranoski, D., & Ledford, H. (2018, November 26). Genome-edited baby claim provokes international outcry. Nature.com. https://www.nature.com/articles/d41586-018-07545-0
Doudna, J. (2022, September 12). CRISPR in Nature. Innovative Genomics Institute (IGI). https://innovativegenomics.org/crisprpedia/crispr-in-nature/
Guo, C., Ma, X., Gao, F., & Guo, Y. (2023). Off-target Effects in CRISPR/Cas9 Gene Editing. Frontiers in Bioengineering and Biotechnology, 11(1143157). https://doi.org/10.3389/fbioe.2023.1143157
Mayo Clinic. (2024, April 23). Gene Therapy. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/gene-therapy/about/pac-20384619
Mehravar, M., Shirazi, A., Nazari, M., & Banan, M. (2019). Mosaicism in CRISPR/Cas9-mediated genome editing. Developmental Biology, 445(2), 156–162. https://doi.org/10.1016/j.ydbio.2018.10.008
Mukherjee, S. (2023). The Song of the Cell. Simon and Schuster.
Ni, J., Wang, D., & Wang, S. (2018). The CCR5-Delta32 genetic polymorphism and HIV-1 infection susceptibility: a meta-analysis. Open Medicine, 13(1), 467–474. https://doi.org/10.1515/med-2018-0062
Normile, D. (2019, December 30). Chinese Scientist Who Produced Genetically Altered Babies Sentenced to 3 Years in Jail. Science; Science. https://www.science.org/content/article/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail
Pedrick, A. (2025, September 16). CRISPR: Big Breakthrough, Big Questions. Science History Institute. https://www.sciencehistory.org/stories/distillations-pod/the-crispr-babies/
Raposo, V. L. (2019). The First Chinese Edited Babies: A Leap of Faith in Science. JBRA Assisted Reproduction, 23(3), 197–199. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724388/
Stein, R. (2018, December 7). Outrage Intensifies Over Claims Of Gene-Edited Babies. NPR.org. https://www.npr.org/sections/health-shots/2018/12/07/673878474/outrage-intensifies-over-claims-of-gene-edited-babies
The He Lab. (2018, November 25). About Lulu and Nana: Twin Girls Born Healthy After Gene Surgery As Single-Cell Embryos. Youtube.com. https://youtu.be/th0vnOmFltc?si=gXGsOztX9gH1frSS
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