By Amrit Kaur Sidhu
The up and coming field of gene editing, specifically in regards to the advancements of the innovative CRISPR-Cas9 technology, is revolutionizing the world. Advancements in genetic discoveries hold the potential for significant societal impact, providing unprecedented opportunities and challenges. The spectrum of these possibilities that gene editing controls ranges from: cures to genetic diseases, enhanced human capabilities, or on the more intense side, even creating the ‘perfect’ man. These god-like powers raise many questions regarding the ethics of human-driven genetic manipulation. To properly advance through this complex venture and expand its influence over society, recognizing society’s moral and ethical implications is key to success.
As gene-editing technologies advance, they offer extraordinary potential for medical breakthroughs, yet also raise concerns surrounding major ethical issues, specifically regarding the risks for social inequality, unexpected outcomes, and the potential destruction of what it means to be human.
Through the study of various literary sources, such as case studies, professional philosophies, and regulations, three prominent themes emerged: human dignity and the ethical responsibility in manipulating life, potential cures and treatments for genetic mutations or diseases, and the possible social divide due to unequal access to this revolutionary technology. In recent years, gene modification experimentation and application have grown exponentially, leading to significant controversy over the morality of certain cases published by the scientific community. This summative review contributes to these debates by analyzing both public and academic viewpoints.
Before exploring case studies or analyzing the moral debates on genome editing, one must first understand genealogy and the actuality of gene altering. “A gene is the basic physical and functional unit of heredity” (What Is a Gene?: MedlinePlus Genetics, n.d.). Genes, made of deoxyribonucleic acid (DNA), control all inherited traits passed down through generations, shaped by countless evolutionary changes (NCI Dictionary of Genetics Terms, n.d.). This gives them a unique sentimental value, forming a collaborative script to which all of your ancestors have contributed. Genome editing, meanwhile, is the process of removing, adding, or altering parts of DNA within the genome. (Ethical Issues: Germline Gene Editing | ASGCT - American Society of Gene & Cell Therapy |, n.d.) There are also various types of genome editing. The Harvard Gazette describes the two main types of genome editing as follows, “While somatic gene editing affects only the patient being treated (and only some of his or her cells), germline editing affects all cells in an organism, including eggs and sperm, and so is passed onto future generations” (Cannon & Cannon, 2024). Knowing these foundational aspects of genealogy is necessary when discussing all moral aspects of genome editing.
Popularized for its efficiency, accuracy, lower cost, and speed, the technology known as the CRISPR Cas-9 rose to fame and is the most widely used genetic editor. CRISPR is the abbreviation for Clustered Regularly Interspaced Short Palindromic Repeats, and Cas9 is abbreviated for CRISPR-associated protein 9 Liu (2020). It was adapted from a naturally occurring enzyme found in bacterial immune defense systems. It enables the bacteria to remember viruses by storing specific patterns from the viruses’ DNA, inserting it into its own DNA, forming what are known as CRISPR Arrays. When the viruses attack the second time, the bacteria produces Ribonucleic Acid (RNA) segments from the previously copied patterns which recognize and target the viruses DNA, essentially disabling the virus and providing immunity (What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics, n.d.-b). This process was adapted to purposely edit DNA. A segment of RNA is manually synthesized in a lab and attached to the target DNA similar to the bacteria’s CRISPR Arrays. Then, the RNA attaches to the Cas-9 enzyme. (“What Is CRISPR-Cas9?,” n.d.) The next time the RNA is introduced to the cell, it recognizes the DNA that it previously copied and the enzyme (Cas-9 enzyme is most commonly used however the enzyme Cpf1 can also be used (What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics, n.d.-b)) cuts the DNA at that location. The cell’s natural DNA repair system is then utilized by the scientist to edit base pairs or replace segments with customized DNA sequences. (What Are Genome Editing and CRISPR-Cas9?: MedlinePlus Genetics, n.d.-b).
While the CRISPR Cas-9 gene editing technology holds great potential in curing genetic disorders and enhancing performance, however, its applications have led to great controversy. In 2018, Chinese scientist He Jiankui used CRISPR to genetically edit the genes of a set of twin girls, triggering intense moral debates across the world (Raposo, 2019). He conducted this “experiment” with couples where the male carried a gene for HIV. Jiankui used the CRISPR Cas-9 method to disable the CCR5 gene which causes HIV infection, leaving the girls immune to HIV. This specific case sparked intense controversy because of the regulations in China. The 2003 “Ethical Guiding Principles for Research on Embryonic Stem Cell” issued by China's Ministry of Science and Technology and the National Health Commission (Liao et al., 2007) stated that “research to be performed on human in vitro embryos after the 14th day of existence, and its subsequent implantation into a human uterus,” is banned (Raposo, 2019). Additionally, the scientific community pointed out that the CCR5 gene heavily influences major brain functions. Implying that Jiankui may have intended to enhance the girls’ brain functions (better memory or higher IQ) with the excuse of curing HIV. Furthering the possibility of creating “designer babies”, leading to further public divide and status based inequality (The Designer Baby Distraction | ASM.org, n.d.). This caused significant controversy due to the threat of harming long term implications of gene editing and breaking public trust.
As mentioned above, during the 2018 Chinese CRISPR babies controversy, law in China states that Scientist He Jiankui’s actions were illegal and immoral, punishing him to 3 years in jail (Liu, 2020). Similarly, countries have their own legal regulations on the limits of genetic modifications and testing. In a 2020 Forbes article, researchers found stricter regulations for heritable germline gene alterations for reproduction as compared to somatic genome editing, not for reproduction (not heritable) (Qaiser, 2020). They discover that, “When it comes to germline genome editing (i.e. not for reproduction), only 40 out of 96 countries have specific policies to address this, where 23 countries prohibit this research, and 11 explicitly permit it. In contrast, 78 out of 96 countries have policies to address heritable genome editing (i.e. for reproduction), where 70 prohibit this type of editing outright, five prohibit it with potential exceptions (Columbia, Panama, Belgium, Italy and the United Arab Emirates (UAE)) and three are indeterminate (Burkina Faso, Singapore and Ukraine). None of the 96 countries explicitly permit heritable human genome editing,” (Qaiser, 2020). These findings support the notion that germline genome editing (heritable and inheritable) would contribute to social divide. Less than half of the total countries worldwide were considered, excluding countries with less scientific advancements (known as third world countries). From these selected countries, less than half have policies regarding genetic modifications, further backing the fact that only countries with enough knowledge surrounding modern genome editing can make a decision. This already creates a system of global ranking. If germline genome editing were to be approved for use within society, those who can afford the treatments would have an immense advantage over those who do not have access to it. This unequal distribution of resources and abilities would result in a surge of socioeconomic inequality.
On a smaller scale yet in a similar fashion, sub-societies within the scientific community hold their own regulatory frameworks, just without the legal repercussions large scale governments have the authority to implement. The American Society of Gene & Cell Therapy (ASGCT) put out a statement in 2018 (after the controversy in China) stating that they consider it “wholly unacceptable to use germline gene editing and the implantation of gene-edited embryos to achieve a pregnancy without extensive research into the safety, efficacy, and legality of such applications. Any announcements of, or claims to have begun, such studies in germline gene editing are compromised, both ethically and scientifically” (ASGCT Statement on Germline Gene Editing Practices, n.d.). They reference government regulations and believe that without proper approval and testing, such applications of genetic manipulatory technologies are neither safe nor morally acceptable. Furthermore, the International Society for Stem Cell Research (ISSCR) includes in their guidelines of Fundamental Ethical Principles the importance of transparency and social responsibility to work hand in hand with lawmakers and the general public to ensure that their work is respectful to life (Alm, 2023). In their guidelines for Laboratory-based Human Embryonic Stem Cell Research, Embryo Research, and Related Research Activities, they bring attention to their strict ethical standards in working with human embryos and embryonic stem cells. The ISSCR highlights their ethical limits of research when working with human embryos. Boundaries ensure that scientific research does not violate natural life. Reproductive cloning and inter-species chimeras (human hybrids with other animals) are prohibited. A widely accepted rule across the scientific community is that human embryos are not allowed to be cultured 14 days after fertilization. This “14 day rule” is in respect to the growth of complex human features, preserving their humanity (Alm, 2023b). This rule has been greatly emphasized in recent years because of the CRISPR baby case by scientist He Jiankui in China. Jiankui’s “experiment” included human interventions after the 14th day following fertilization as he continued to conduct research. Additionally, to maintain the integrity of human embryos, this rule is implemented: “The research should use the minimum number of embryos necessary to achieve the scientific objective” (Alm, 2023b). It is important that in cases of germline genome editing, the scientist must remember that the “test subjects” are actual humans. Embryos should not be fertilized solely for the purpose of conducting an “experiment” as it is dehumanizing and has been collectively decided to be morally unacceptable.
As genetic engineering is a relatively new concept, the risks and rewards are not fully understood. The theoretical goal is that harmful diseases may be prevented for unborn children while still in embryonic forms, creating a utopian scene, free of genetic illness. Two common risks that are known to be side effects of germline genome editing as described in Ethical Issues: Germline Gene Editing by The American Society of Gene & Cell Therapy (ASGCT) include off-target effects and mosaicism (Ethical Issues: Germline Gene Editing | ASGCT - American Society of Gene & Cell Therapy |, n.d.). Off-target effects of germline genome editing occur when the mutation impacts unintended areas of the genome, leading to unexpected outcomes. This results in a different section of the DNA helix to be changed and thus can lead to disorders affecting multiple larger scale bodily systems and organs (Alm, 2023). This is a side effect that scientist He Jiankui experienced in his “CRISPR Babies Experiment,” causing outrage and controversy. A second known risk of germline genome editing is referred to as mosaicism. Mosaicism is the condition where in a genetically modified person’s body, there exist multiple populations of cells, each having distinct genetic compositions (Mosaicism: MedlinePlus Medical Encyclopedia, n.d.). This may occur in the short period of time after fertilization where the cells begin to divide and grow. For example, during the 2 cell stage, if only one of the cells contains the genome edit but the other cell does not, then the edit may not work. (Ethical Issues: Germline Gene Editing | ASGCT - American Society of Gene & Cell Therapy |, n.d.) Additional results of mosaicism have yet to be noted but possibilities include: genetic modification not having any effect, failed embryo development, fetus not carried to term, etc. These dangers highlight the unpredictability of gene editing, further emphasizing the need for strict control over these novel technologies.
In a 2021 survey endorsed by the Pew Research Center, Americans were asked their thoughts on editing babies’ genes to prevent serious diseases (Nadeem & Nadeem, 2024). In the first survey (Photo 1A), results were divided, about one third (⅓) said that it is a “good idea,” one third said it was a “bad idea,” and the remaining said that they were “not sure”, suggesting that they did not have enough knowledge on the topic to form an opinion. In another survey (Photo 1B), Americans were asked their thoughts on genetic modification to treat disease VS. to manually beautify the child. This poll is unanimous and clearly shows a swing towards one side. About 71% agreed with using genetic editing to immunize children from serious diseases and contrastingly, about 74% said that they opposed using genetic editing to enhance children’s physical appearances or intelligence (Nadeem & Nadeem, 2024). Pew Research Center analyzes these statistics and publishes a statement on how far is too far in terms of genetic engineering? They write, “the use of gene editing in babies to make a baby more intelligent would be taking technology too far but that gene editing for treating a baby’s serious disease or health condition would be an appropriate use of the technology” (Nadeem & Nadeem, 2024). These results reveal the ethical concerns that gene editing may bring which, despite their immense power to revolutionize medicine, raise serious questions about social inequality, unexpected results, and the man-made changing of what it means to be human.
The overall societal consensus on whether gene editing is good or bad remains split and undecided, however, these survey results bring attention to the moral tension surrounding genetic engineering. Ethics and humanity play crucial roles in modern medicine and both come into play when considering the morality of genetic manipulation. Both scientists and researchers need to hold a level of ethical responsibility in the work that they do. In the case of manually modifying human genetics, having integrity and responsibility is of the utmost importance. This long time debate has deep roots within the field of philosophy. Various philosophers have spoken about this matter, setting their own boundaries to where human interference of a genetic scale becomes inhumane.
Philosophical Views:
German philosopher and key Enlightenment thinker Immanuel Kant has produced many well-known ideologies on morality. The Corporate Finance Institute (CFI) describes his definition of morality as: “the motive (or means), and not consequence (or end), of an action determines its moral value.” Kant rejects the common utilitarian ideology that “the rightness of an action is a function of how fruitful its outcome is” (Schmidt, 2024). His theory can be applied to argue against the usage of germline genome editing as even though it is for a “good cause,” the road there can be considered disrespectful and unnatural. Germline genome editing involves the use and manipulation of thousands of embryos, which could have become people, but are instead experimented on and discarded. He emphasizes that, “To live ethically, one must never treat another human being as a means to some greater end” (Schmidt, 2024). Kantian Philosophy suggests scientists should avoid interfering with the humanity and dignity of future generations by permanently altering their genetic makeup as it may impact their individuality and uniqueness. Many researchers worry that if permanent heritable germline genome editing becomes more normalized and used throughout society, the genetic pool will shrink. A smaller genetic pool means less individuality, and heterozygosity. Heterozygosity, as defined in Science Direct is, “the probability that two alleles from one individual and at one locus (all randomly drawn) in a population (or subsample) are different.” This indicates increased uniformity and loss of genetic diversity where scientists are prioritizing collectivism over individuality (Joseph et al., 2022).
Jürgen Habermas was a German philosopher and social theorist during the 1900’s. In his book The Future of Human Nature, Habermas argues that genetic manipulation of human embryos dehumanizes them. In Nicole Morar’s article An empirically informed critique of Habermas' argument from human nature, she writes about how any genetic modification that has the power to “alter human nature” should not be allowed as the very thing that makes a child a child is taken away. Additionally, Habermas explained how using human embryos as subjects for an experiment binds them to a life of restraint. As the child’s life is someone's experimental project, the child has no choice but to live his life out with various restrictions and constant testing. His unique view on the issue shines light on the after effects of the experiment rather than the equally dehumanizing process to get there.
Award-winning author Siddhartha Mukherjee’s The Gene: An Intimate History is an elaborate and well written book that covers all aspects of genealogy. The author covers his family’s history with genetic mental illness and the history of genes. From Charles Darwin Gregor Mendel to more modern scientists, Mukherjee references each model and the logistics of gene editing. Additionally, he talks about the possible societal implications of genetic manipulation of peoples. He writes, “the idea that the human genome might contain the answers not just to medical illnesses, but to social maladies such as deviance, alcoholism, violence, moral corruption, perversion, or addiction, was potently seductive”(Mukherjee, 2016a, p. 253). Here, he talks about the possibility that genes can control behavioral aspects and the possibility of manipulating those specific genes to shape a person's actions. Later on, he expands on the prospect that those who are more likely to commit crimes could be “identified, quarantined, and treated before they had committed crimes—i.e., via genetic profiling of pre-criminals.”(Mukherjee, 2016a, p. 253).This idea further enhances the social divide and system of stereotypical ranking that may occur as a result of manipulatory and dehumanizing genetic engineering.
The possibility of genes controlling one’s behavior and person has been studied and expanded on by American Clinical Psychologist Erik Turkheimer. Turkheimer studied the correlation between genetics and behavior extensively and created three laws to represent his findings:
- “All human behavioral traits are heritable. [That is, they are affected to some degree by genetic variation.]” (Chabris et al., 2015)
- “The effect of being raised in the same family is smaller than the effect of genes.” (Chabris et al., 2015) 3. “A substantial portion of the variation in complex human behavioral traits is not accounted for by the effects of genes or families.” (Chabris et al., 2015)
Turkheimers three laws on behavioral genetics stem from his research on twins, adopted children, siblings, as well as many other kinships. Though his findings provide valuable information on the role that heritable traits play on a person’s character, they can not answer other more specific questions as behavior is not something that can be predicted but rather is spontaneous and is what makes the children he researched themselves. Erik Turkheimer’s research does nevertheless provide insight on the morality of permanent heritable germline genome modification. Prior to his research, the most prominent issue with adding, subtracting, or wholly changing a genetic sequence was the loss of physical individuality. However, his research on the connection between character and heredity leads us to realize that changing manually modifying one’s genes may in fact lead to them losing the very characteristics that make them human.
When analyzing these findings of various researchers and the issues they bring attention to, there is an unsettling sense of overperfection. Both Habermas and Turkheimer emphasize the idea that altering human DNA to conform to socially idealized traits such as for intelligence or beauty risks homogenizing our heterogeneous society. This stems from the prioritization of a “genetically optimized” collective society that prioritizes efficiency and performance over the humane qualities of individuality and diversity, similar to that of a dystopian society. These risks push for increased control over the praised modern gene editing technologies. However, it is crucial to consider that these advancements might lead us to or perhaps lose touch with or even redefine what our life means.
While gene editing offers a multitude of groundbreaking opportunities to eradicate harmful genetic diseases, a balance with ethical responsibility is essential to success. The miraculous benefits can be easily outweighed by the risk of misuse and irresponsible genetic editing. Germline modification to reduce the risks of genetic disease is a situation where genetic manipulation should be considered morally acceptable, however, the utilization of genetic manipulation to make a child smarter or prettier is in all cases morally unacceptable. Firm ethical boundaries are needed to ensure morality in our modern age of unprecedented genetic engineering. To truly understand these boundaries, we must ultimately ask ourselves, "What does it really mean to be human…?"
Annotated Bibliography
ASGCT Statement on Germline Gene Editing Practices. (n.d.). https://www.asgct.org/publications/news/november-2018/asgct-statement-on-germline-gene-editing-practic es
Cannon, W., & Cannon, W. (2024, January 10). Perspectives on gene editing. Harvard Gazette. https://news.harvard.edu/gazette/story/2019/01/perspectives-on-gene-editing/
Chabris, C. F., Lee, J. J., Cesarini, D., Benjamin, D. J., & Laibson, D. I. (2015). The Fourth Law of Behavior Genetics. Current Directions in Psychological Science, 24(4), 304–312. https://doi.org/10.1177/0963721415580430
Clarke, S., Savulescu, J., Coady, C. a. J., Giubilini, A., & Sanyal, S. (2016). The ethics of human enhancement: Understanding the Debate. Oxford University Press.
Ethical issues: Germline Gene Editing | ASGCT - American Society of Gene & Cell Therapy |. (n.d.). https://patienteducation.asgct.org/patient-journey/ethical-issues-germline-gene-editing#:~:text=Ethical%20 Concerns%20for%20Germline%20Gene%20Editing&text=Because%20genetic%20diseases%20are%20in herited,to%20children%20of%20their%20own.
Genetic Testing (PGT & PGS) | UCSF Center for Reproductive Health. (n.d.). UCSF. https://crh.ucsf.edu/fertility-treatment/preimplantation-genetic-testing-pgt/
Guidelines — International Society for Stem Cell Research. (2022, July 14). International Society for Stem Cell Research. https://www.isscr.org/guidelines
Gunderson, M. (2007a). Seeking Perfection: A Kantian look at human genetic engineering. Theoretical Medicine and Bioethics, 28(2), 87–102. https://doi.org/10.1007/s11017-007-9030-4
Gunderson, M. (2007b). Seeking Perfection: A Kantian look at human genetic engineering. Theoretical Medicine and Bioethics, 28(2), 87–102. https://doi.org/10.1007/s11017-007-9030-4
Gunderson, M. (2007c). Seeking Perfection: A Kantian look at human genetic engineering. Theoretical Medicine and Bioethics, 28(2), 87–102. https://doi.org/10.1007/s11017-007-9030-4
Habermas, J. (2003). The future of human nature. http://ci.nii.ac.jp/ncid/BA61157622
Immunology and Microbiology: Heterozygosity. (n.d.). ScienceDirect. https://www.sciencedirect.com/topics/immunology-and-microbiology/heterozygosity#recommended-public ations
In vitro fertilization (IVF) - Mayo Clinic. (n.d.). https://www.mayoclinic.org/tests-procedures/in-vitro-fertilization/about/pac-20384716
Issues. (2022, July 1). The legal and regulatory context for human gene editing. Issues in Science and Technology. https://issues.org/legal-and-regulatory-context-fhuman-gene-editing/
Joseph, A. M., Karas, M., Ramadan, Y., Joubran, E., & Jacobs, R. J. (2022). Ethical Perspectives of Therapeutic Human Genome Editing From Multiple and Diverse Viewpoints: A Scoping review. Cureus. https://doi.org/10.7759/cureus.31927
Lanphier, E., Urnov, F., Haecker, S. E., Werner, M., & Smolenski, J. (2015). Don’t edit the human germ line. Nature, 519(7544), 410–411. https://doi.org/10.1038/519410a
Liu, S. (2020). Legal reflections on the case of genome-edited babies. Global Health Research and Policy, 5(1). https://doi.org/10.1186/s41256-020-00153-4
Mengstie, M. A., Azezew, M. T., Dejenie, T. A., Teshome, A. A., Admasu, F. T., Teklemariam, A. B., Mulu, A. T., Agidew, M. M., Adugna, D. G., Geremew, H., & Abebe, E. C. (2024). Recent advancements in reducing the Off-Target effect of CRISPR-CAS9 genome editing. Biologics, Volume 18, 21–28. https://doi.org/10.2147/btt.s429411
Morar, N. (2014). An Empirically Informed Critique of Habermas’ Argument from Human Nature. Science and Engineering Ethics, 21(1), 95–113. https://doi.org/10.1007/s11948-013-9509-5
Mosaicism: MedlinePlus Medical Encyclopedia. (n.d.). https://medlineplus.gov/ency/article/001317.htm#:~:text=Mosaicism%20is%20a%20condition%20in,Blood %20cells
Mukherjee, S. (2016). The gene: an intimate history. https://en.wikipedia.org/wiki/The_Gene:_An_Intimate_History Nadeem, R., & Nadeem, R. (2024, July 22). 7. Americans are closely divided over editing a baby’s genes to reduce serious health risk. Pew Research Center.
https://www.pewresearch.org/internet/2022/03/17/americans-are-closely-divided-over-editing-a-babys-gene s-to-reduce-serious-health-risk/
NCI Dictionary of Genetics Terms. (n.d.). Cancer.gov. https://www.cancer.gov/publications/dictionaries/genetics-dictionary/def/gene
Neogi, N. (2017, November 22). Government representation in Dystopian Literature – Literature and Digital Diversity. https://litdigitaldiversity.northeastern.edu/government-representation-in-dystopian-literature/ Nhgri. (2019, March 13). What are the Ethical Concerns of Genome Editing? Genome.gov. https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns Qaiser, F. (2020, November 2). Study: There is no country where heritable human genome editing is permitted. Forbes. https://www.forbes.com/sites/farahqaiser/2020/10/31/study-there-is-no-country-where-heritable-human-gen ome-editing-is-permitted/
Raposo, V. L. (2019). The first Chinese edited babies: A Leap of Faith in science. JBRA. https://doi.org/10.5935/1518-0557.20190042
Schmidt, J. (2024, May 7). Kantian ethics. Corporate Finance Institute. https://corporatefinanceinstitute.com/resources/esg/kantian-ethics/#:~:text=Kant's%20moral%20philosophy %20is%20a,action%20determines%20its%20moral%20value.
The designer Baby Distraction | ASM.org. (n.d.-a). ASM.org. https://asm.org/articles/cultures-magazine/volume-4,-issue-4-2017/the-designer-baby-distraction The designer Baby Distraction | ASM.org. (n.d.-b). ASM.org.
https://asm.org/articles/cultures-magazine/volume-4,-issue-4-2017/the-designer-baby-distraction What are genome editing and CRISPR-Cas9?: MedlinePlus Genetics. (n.d.). https://medlineplus.gov/genetics/understanding/genomicresearch/genomeediting/
What is a gene?: MedlinePlus Genetics. (n.d.). https://medlineplus.gov/genetics/understanding/basics/gene/ What is CRISPR-Cas9? (n.d.). Your Genome. https://www.yourgenome.org/theme/what-is-crispr-cas9/
