Exploring 10 ethical considerations in genome editing

1. Informed Consent

Informed consent is a complicated issue in genome editing based on multiple factors. Because genome editing can alter germline cells, there is a concern that the therapeutic intervention is affecting embryos and future generations not consenting to the treatment.

In general, the principle of informed consent is essential when conducting any medical intervention, including genome editing. Before giving consent, individuals or their legal guardians should comprehensively understand the risks, benefits, and potential long-term consequences of the procedure.

2. Safety and Efficacy

Safety concerns are also an ethical consideration in genome editing. Like any therapeutic intervention, there is a risk of adverse effects and safety issues; however, the risks may be more pronounced with genome editing technologies.

Genome editing techniques are still evolving, and these interventions' long-term effects and safety profiles are not yet fully understood. Ethical considerations require thorough preclinical and clinical trials to establish safety and efficacy before applying genome editing technologies to humans.

Edits in the wrong place in the genome, also called off-target effects, pose a safety concern to patients undergoing treatment. For example, a 2021 article in the Proceedings of the National Academy of Sciences evaluating OCT4 CRISPR-Cas9–targeted embryos notes that approximately 16% had unintended gene editing outcomes.

Another risk is genetic mosaicism, which occurs when some cells carry the gene edits but others do not. According to the American Society of Gene and Cell Therapy, “Mosaicism is problematic because the genetic disease to be prevented may still occur if all the cells in the embryo do not have the desired edit. Perhaps more importantly, at present, the effects of mosaicism are unpredictable; it could lead to entirely different kinds of disease or impact embryo development, potentially preventing development to term.”

3. Equity and Access

Equity and access issues remain constant across the entire healthcare system; however, genome editing technologies underscore ongoing healthcare disparities, as exorbitant costs present a barrier to accessing care.

For example, many existing gene therapies to address chronic conditions are too expensive for the average person to afford. Recently, the FDA approved the most expensive gene therapy, Lenmeldy, for pre-symptomatic early juvenile or early symptomatic early juvenile metachromatic leukodystrophy (MLD), topping existing prices at a wholesale acquisition cost of $4.25 million per one-time treatment.

There is a risk that only those with sufficient resources or access to advanced medical care will benefit. Ethical considerations call for ensuring equitable access to genome editing technologies, particularly for medically necessary interventions.

4. Germline Editing

Germline editing involves modifying the genetic material of eggs, sperm, or embryos, resulting in permanent changes that can be passed on to future generations. This raises significant ethical concerns due to the potential for unintended consequences and the potential for creating a "designer baby" scenario. Many countries have imposed restrictions or outright bans on germline editing to prevent unethical uses and to allow for further ethical and scientific deliberation.

The Journal of Applied Philosophy poses two primary concerns associated with germline changes. The first concern considers unintended changes to the germline caused by off-target mutations, which can potentially negatively affect future generations.

Another concern is the intended changes made to the germline that may have unforeseen consequences. While some edits may intentionally eliminate diseases and address critical health concerns, their long-term impacts could be detrimental. For example, the journal points to a variant of the DARC gene that makes some individuals more susceptible to human immunodeficiency virus (HIV). Although editing this variant to decrease susceptibility may be beneficial for minimizing HIV, the gene variant is also known to protect against malaria. If eliminated from the human genome, malaria risk could increase significantly for future generations.

5. Unintended Consequences

Genome editing techniques are precise but not perfect. There is a risk of off-target effects, where unintended changes occur in the genome, leading to unforeseen health problems.

For example, a 2020 article from the American Society of Hematology (ASH) notes that CRISPR genome editing results in unintended changes in human embryos. The organization cites a study in Cell that used CRISPR to edit mutations on the EYS gene to address hereditary blindness; however, these gene editing technologies resulted in a loss of chromosome 6 segments.

"This study is not going to stop the [gene editing] field. But we have to ask what to do with these powerful tools, and in which context they are safe and efficacious," the study author Dieter Egli, PhD, told ASH.

Ethical considerations dictate the need for rigorous testing, transparency, and ongoing monitoring to minimize the potential for unintended consequences.

6. Enhancements v. Therapeutics

There is a distinction between using genome editing for therapeutic purposes, such as correcting genetic diseases, and using it for non-therapeutic purposes, such as enhancing physical or cognitive traits. Using genome editing for enhancement purposes poses a serious ethical concern.

Ethical considerations call for scrutiny of the motivations and potential consequences of non-therapeutic genome editing, as it raises concerns about creating a society with increased inequalities and a loss of human diversity.

7. Regulatory Oversight

Robust regulatory frameworks are necessary to ensure the responsible and ethical use of genome editing technologies. Oversight should balance facilitating scientific progress and protecting individuals’ rights and welfare.

The CRISPR Journal states, “Multiple national and international bodies have formed, and numerous position statements have been published. While opposition against GGE has continued, others have begun to consider theoretical conditions where germline editing may someday be ethically warranted.”

8. Long-Term Implications

Genome editing interventions may have far-reaching implications for future generations and the human gene pool. Ethical considerations should extend beyond immediate benefits and account for potential long-term effects on human diversity, evolution, and societal norms.

9. Public Engagement

Ethical decision-making regarding genome editing should involve public engagement and open dialogue to incorporate diverse perspectives. Public input can help shape policies, regulations, and guidelines that reflect societal values and avoid undue concentration of power.

The CRISPR Journal notes that public participation in gene editing policy is critical for comprehensively understanding varying ethical viewpoints, establishing transparency, and disseminating information.

Despite many sources emphasizing public participation, existing efforts remain insufficient. 

10. International Collaboration

Given the global implications of genome editing, international collaboration and cooperation are essential. Harmonizing ethical standards and guidelines across countries and regions can promote responsible and consistent use of genome editing technologies.