Ethical issues regarding CRISPR-mediated gene editing (Part 49- CRISPR in gene editing and beyond)
Welcome to the 49th part of the multi-part series on applications of CRISPR in gene editing and beyond.
CRISPR-mediated gene editing can be classified into two types: germline editing and somatic cell editing. Germline editing involves editing genes in the reproductive cells, such as sperm and egg cells, which means that any changes made would be inherited by future generations. Somatic cell editing involves editing genes in non-reproductive cells, such as cells in the liver or lungs, which means that any changes made would not be passed on to future generations.
Both types of gene editing raise ethical concerns, but germline editing is considered to be more controversial due to its potential long-term impact on future generations.
Here are some of the ethical concerns of gene editing:
(i) Safety: Gene editing techniques, such as CRISPR/Cas9, can cause undesired changes in the genome, in which the Cas9-gRNA complex can cut DNA at unintended locations in the genome, potentially causing mutations and altering genes that were not desired to be edited (Doudna and Charpentier, 2014; Cribbs and Perera, 2017; Shinwari et al., 2018; Brokowski and Adli, 2019). Another safety concern is the possibility of long-term effects on human health and the environment. While CRISPR has the potential to treat genetic diseases, there is still much that is unknown about the long-term effects of these treatments. It is still unclear how the edited genes will interact with other genes in the body and what will be the effects of these interactions over time. For example, editing the CCR5 gene has been shown to be effective in preventing HIV infection, as the CCR5 protein is a co-receptor that HIV uses to enter immune cells. So editing this gene can potentially make cells resistant to HIV infection. But there are some concerns that deleting the CCR5 gene could have unintended effects on the immune system, as this gene plays a role in immune function beyond its role as an HIV co-receptor. For example, a study published in Nature in 2019 found that deleting the CCR5 gene in mice led to increased susceptibility to West Nile virus and reduced survival rates.
It is critical to understand that the consequences of altering the human genome in the germline are not just limited to the individual but can also affect future generations (Lanphier et al., 2015; Tang et al., 2017; Lander et al., 2019; Schleidgen et al., 2020). Undoubtedly, gene editing could potentially eliminate genetic diseases from a family’s lineage, but it could also introduce unintended mutations or genetic changes that could have negative consequences for future generations.
Therefore, it is crucial to ensure that the safety of gene editing is thoroughly evaluated before it is used in humans. It is essential to take a cautious approach to gene editing and carefully consider the potential risks and consequences. As we continue to explore the possibilities of gene editing, it is essential to keep in mind that any decision to alter the germline DNA could have significant implications for future generations and the course of human history.
(ii) Equity: Equity is a concern because access to gene editing technology may not be available to everyone equally. There is a risk that technology could become a tool for the wealthy, leading to greater disparities between the rich and the poor. Gene editing could also exacerbate existing health disparities. For example, certain genetic diseases are more prevalent in certain populations, such as sickle cell anemia in people of African descent. The cost of gene editing technology is likely to be very high initially, and it may take time before the technology becomes more widely available and affordable. This means that if gene editing technology is only accessible to those who can afford it, it will prevent those in poorer regions or people from certain populations with a higher incidence of certain genetic diseases from having access to gene editing technology. Thus, widening the health disparities between different populations.
(iii) Genetic enhancements: Once we fully understand the genetic factors determining human health and performance, genetic enhancements will become another ethical concern. The gene editing of human embryos could potentially be used to enhance certain traits, such as intelligence or athletic ability. This raises concern that genetic enhancement could be used to create “designer babies,” in which parents select certain genetic traits for their offspring. This raises serious ethical questions about the extent to which parents should be allowed to manipulate the genetic makeup of their children and whether it is ethical to manipulate genomes for non-medical purposes (Ishii, 2017; Enriquez, 2018; Baylis, 2019; Al Shakaki, 2022).
Additionally, the potential for genetic enhancements to create a societal divide between those who have access to gene editing technology and those who do not is a significant concern. If only certain segments of the population have access to genetic enhancements, it could lead to a new form of discrimination based on genetic traits. This would exacerbate existing societal inequalities based on factors such as socioeconomic status or race.
(iv) Consent: Gene editing also raises questions about informed consent before undergoing gene editing procedures. Patients need to fully understand the risks and benefits of gene editing and give their informed consent before undergoing the procedure. There is also a question of how consent can be obtained for future generations, who may not have the ability to give their own consent.
(v) Eugenics: CRISPR-mediated gene editing, a cutting-edge technology, also raises concerns about its potential for eugenics. Eugenics is a social and scientific movement that emerged in the early 20th century, aiming to improve the genetic quality of human populations through selective breeding and forced sterilization of individuals deemed “unfit” or “undesirable” due to disabilities, mental illness, or low intelligence. This movement was widely discredited and condemned after it was used by the Nazi regime in Germany to justify the genocide of millions of people, including Jews, homosexuals, and individuals with disabilities.
Nevertheless, germline CRISPR editing uses methods different from eugenic measures in the past, but there are concerns that eugenic ideologies and practices may reemerge. Some have argued that gene editing could be used for eugenic purposes, leading to the creation of a genetically homogenous society in which only certain traits or characteristics are valued. It may disallow people with genetic differences from coming into the world while simultaneously claiming to “improve” the human race by eliminating certain traits in future generations (Krishan et al., 2016; de Araujo, 2017; Garland-Thomson, 2020). This could result in discrimination and exclusion of individuals who do not meet certain genetic standards, leading to social inequalities and a lack of diversity if certain traits are edited out of the gene pool.
(vi) Moral and religious objections: Some people also have moral or religious objections to the use of human embryos for gene editing, arguing that it is playing with God or interfering with nature. These objections must be taken into account when considering the ethical implications of gene editing.
In summary, gene editing is a powerful technology that has the potential to improve human health, but it must be used responsibly and ethically. The ethical concerns raised by gene editing must be carefully considered and addressed before its widespread use in humans.
To address these concerns, certain steps are required to be taken:
(i) Educating the public: Effective communication between researchers and the public is critical to ensuring that everyone is on the same page when it comes to the use of gene editing technology. Scientists should make an effort to explain the science behind gene editing in a way that is accessible to the general public while also being transparent about the benefits, limitations, and potential risks associated with this technology. This could involve educational materials, public lectures, or engaging with the media to provide accurate and accessible information about gene editing technology.
At the same time, it’s important for the public to be actively engaged in the discussion around gene editing. Providing feedback and input to researchers and policymakers can help ensure that the development and use of gene editing technology is aligned with the ethical values and priorities of the broader community. Public engagement can also help identify concerns and issues that scientists and policymakers may not have fully considered, enabling a more comprehensive and responsible approach to developing and using gene editing technology.
By working together and fostering open communication between scientists and the public, it can be ensured that gene editing technology is used in a responsible and ethical way that benefits society as a whole.
In fact, some researchers have already begun taking steps to engage with the public about gene editing. For example, the Broad Institute of MIT and Harvard launched a public dialogue initiative called the Human Gene Editing Initiative, which aims to encourage discussion and debate about the ethics of gene editing technology. The initiative has also published various resources, including background materials on gene editing technology, summaries of key ethical and policy issues, and reports on public engagement activities.
By engaging with the public in this way, researchers can help ensure that gene editing technology is developed and used in a way that reflects the values and priorities of the broader community.
(ii) Guidelines and regulations: Various guidelines and regulations have been issued by governments, international organizations, and scientific societies to provide guidance on the responsible use of this technology.
In the United States, the National Institutes of Health (NIH) released a policy in 2015 stating that it would not fund research that involves editing the genomes of human embryos. However, research on somatic cells (non-germline cells) is allowed.
In 2017, the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM) released a report that provided recommendations for the use of gene editing technologies in humans, including the importance of informed consent, transparency, and continued monitoring of the technology.
The World Health Organization (WHO) established an Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing, which issued a report in 2019 that called for a global registry to track research on human genome editing and emphasized the importance of transparency and public engagement. The report also recommended that any use of genome editing in human embryos should only be done for the treatment or prevention of serious genetic diseases and not for genetic enhancement or non-medical purposes.
Scientific societies, such as the American Society of Gene and Cell Therapy and the International Society for Stem Cell Research (ISSCR), have issued guidelines and recommendations for the responsible use of genome editing technologies in research. The guidelines also stated that any use of genome editing in human embryos should be subject to rigorous oversight and conducted only for compelling reasons and under strict regulatory and ethical standards. The ISSCR also recommended that germline editing should not be used for clinical purposes until safety and efficacy concerns have been addressed.
It’s important to note that guidelines and regulations related to CRISPR gene editing are still evolving and subject to change as new information and technologies become available. While the specific recommendations and requirements may vary depending on the country or organization, the overall goal is to balance the potential benefits of these technologies with the need to ensure safety, protect human dignity, and respect ethical principles.
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References
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