The hard labor of delivering designer babies
During the Human Genome Editing Summit in Hong Kong last November 2018, Chinese scientist He Jiankui shocked the world when he announced that he had successfully made the world’s first genetically engineered babies [1,2].
It was a scientific breakthrough riddled with much skepticism — and with good reason.
The experiment
Seventeen months prior to his announcement, He Jiankui was looking for willing participants — couples with an HIV-positive male — for his designer baby experiment. He, alongside two co-workers, obtained informed consent from eight volunteers (one dropped out after) [3]. Allegedly, He downplayed the procedure as a standard in vitro fertilization (IVF) in the consent forms when, in fact, the proposition was far more intricate and frightening [4].
With the goal to create a genetically engineered embryo that is resistant to HIV, the CRISPR-Cas9 system was used by He Jiankui to render HIV resistance. Specifically, the system he used targeted and removed part of the CCR5 gene — a gene that encodes an important co-receptor for macrophage-tropic virus like HIV — to induce a mutation that disables the entry of HIV into the cells and confer the cells’ resistance [5]. IVF was carried out first to form the embryo where the CRISPR-Cas9 system was added [6]. After gene editing and during embryo development, He arrested a few cells from the embryos to check for changes in the genome [6]. Successfully modified CRISPR-Cas9 embryos were implanted into the mothers’ uterus for the mothers to carry them to term [6].
By the day of his announcement, He Jiankui’s experiment had birthed the first gene-edited twins Lulu and Nana.
Actions and reactions
While IVF has long been accepted, human genome editing has not. The local court in Shenzhen City, China ruled that He and his two co-workers did not have license to practice medicine and, at the same time, used a prohibited method for reproductive medicine [7]. By the end of 2019, He Jiankui was sentenced to three years in prison for committing illegal medical practice [7].
Many countries have laws and guidelines that prohibit human genome editing — 25 countries ban them based on legislation, four based on existing guidelines, nine based on the ambiguity of the technique, and one based on restrictions [8]. China does not allow genome editing based on their own set guidelines. He Jiankui’s case has proven that countries with regulations against human genome editing take these matters seriously.
Aside from the legal reflections of human genome editing, questions regarding the safety and necessity of the technique arose. While CRISPR is known for its high level of precision and efficiency, there are still risks that off-target effects and mosaicism would ensue [9]. For the CCR5 gene that was modified in the twins, studies show that people with mutated CCR5 may have higher risk of infection from the West Nile virus and severe flu [10]. Due to its unpredictability, future health consequences of the experiment would be difficult to account for and address. Furthermore, a lot of researchers and medical experts argue that there is low risk of HIV transmission from the parent to the baby with the use of existing preventative measures and assisted reproductive technology anyway [6]. This then renders the experiment unnecessary, and tips the risk-to-benefit ratio against the experiment.
The birth of Lulu and Nana — and what it means for science
He Jiankui’s experiment not only increased the curiosity towards human genome editing but also exposed the lack of adequate regulation and safeguarding of the public towards these practices.
The potentials and risks of human genome editing have been brought to light due to the experiment. Following this, the World Health Organization (WHO) has established an 18-man committee to formulate standards for human genome editing. On the 12th of July 2021, WHO released a set of recommendations regarding the use of human genome editing for the “advancement of public health.” It contains a governance framework in which countries can base their guidelines and regulations on [11]. Specific recommendations include establishing international agreements, having human genome editing registries, and facilitating education, engagement, and empowerment regarding human genome editing, among six others. These WHO recommendations establish a more global approach to human genome editing.
Today, more countries are developing and amending their regulations to cater to a more blunt and specific approach to the checks and balances in place for human genome editing.
In the spring of 1904, Francis Galton stood in front of an elite audience and spoke of the idea of eugenics — the selection of the fitter and more desirable heritable traits to improve future generations [12]. The idea was met with skepticism and restlessness. At least a century later and using a more contemporary approach, He Jiankui has brought about the same principle, now in conjunction with the current technological advancements; the reception was all the same. It does not mean, however, that nothing has changed since then.
Today, aside from scientists, medical professionals, and world leaders, more and more people are joining in on discussions regarding human genome editing. Public engagement has brought about insightful perceptions. The potentials and limitations of CRISPR technology are being talked about on a wider scale, which further increase its impact and relevance. Scientists could not be any happier; it is a testament that science is alive and well.
CRISPR and human genome editing is one powerful tool for treatment and prevention of diseases, and for the enhancement of one generation and the next. Are we amenable to using human genome editing for these purposes today? That depends on who we are asking. Are we ready to use this technology? No, not yet.
References
[1] Regalado, A. (2018, November 25). EXCLUSIVE: Chinese scientists are creating CRISPR babies. MIT Technology Review. https://www.technologyreview.com/2018/11/25/138962/exclusive-chinese-scientists-are-creating-crispr-babies/
[2] Associated Press. (2018, November 25). Chinese researcher claims birth of first gene-edited babies — twin girls. STAT. https://www.statnews.com/2018/11/25/china-first-gene-edited-babies-born/
[3] BBC News. (2018, November 28). He Jiankui defends ‘world’s first gene-edited babies’. BBC. https://www.bbc.com/news/world-asia-china-46368731
[4] Cohen, J. (2019, August 1). The untold story of the ‘circle of trust’ behind the world’s first gene-edited babies. Science. https://www.science.org/news/2019/08/untold-story-circle-trust-behind-world-s-first-gene-edited-babies
[5] Blanpain, C., Libert, F., Vassart, G., & Parmentier, M. (2002). CCR5 and HIV infection. Recept Channels, 8(1), 19–31.
[6] Wang, H., & Yang, H. (2019). Gene-edited babies: What went wrong and what could go wrong. PLoS Biol, 17(4), e3000224. https://doi.org/10.1371/journal.pbio.3000224
[7] Normille, D. (2019, December 30). Chinese scientist who produced genetically altered babies sentenced to 3 years in jail. Science. https://www.science.org/news/2019/12/chinese-scientist-who-produced-genetically-altered-babies-sentenced-3-years-jail
[8] Liu, S. (2020). Legal reflections on the case of genome-edited babies. Glob Health Res Policy, 5(24), 1–3. https://doi.org/10.1186/s41256-020-00153-4
[9] Raposo, V. (2019). The First Chinese Edited Babies: A Leap of Faith in Science. JBRA Assist Reprod, 23(3), 197–199. https://doi.org10.5935/1518-0557.20190042
[10] Glass, W., McDermott, D., Lim, J., Lekhong, S., Yu, S., Frank, W., Pape, J., Cheshier, R., & Murphy, P. (2006). CCR5 deficiency increases risk of symptomatic West Nile virus infection. J Exp Med, 203(1), 35–40. https://doi.org/10.1084/jem.20051970
[11] World Health Organization. (2021, July 12). WHO issues new recommendations on human genome editing for the advancement of public health. World Health Organization. https://www.who.int/news/item/12-07-2021-who-issues-new-recommendations-on-human-genome-editing-for-the-advancement-of-public-health
[12] Rich, P. (1986). Race and Empire in British Politics. Cambridge University Press.
Written by Rhaena Pablo
Art by Bobet Malaluan
