Modules

Gene Editing: Ethics Issues

Instructions for:TraineeTrainer

Goal

To support students, researchers, and research ethics reviewers in learning about and reflecting upon the ethics issues associated with the development and use of gene editing.

Learning outcomes

At the end of this module, learners will be able to:

Weigh the potential harms and benefits of different areas of gene editing.
Identify safety issues related to the techniques and applications of gene editing.
Reflect upon some of the broader ethics issues (like dual use/misuse or slippery slope) associated with gene editing.
Access the relevant guidelines and regulations for gene editing

Duration (hours)

2

For whom is this important?

All stakeholders in researchStudents

Part of

iRECS

1

Module Introduction

From the eradication of genetic diseases to potential human enhancements, and the place of genetically modified organisms in agriculture, the number of potential uses of gene editing is vast. This module touches upon a wide variety of ethics issues that are associated with research involving gene editing. It includes ethics issues related to both human and non-human applications and the way in which these issues might be assessed and governed.

Irecs-Gene Editing Ethics-Step 1

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A Case of Gene Editing in Human Embryos

In November 2018, an international news story broke about a scientist in China who had genetically altered a gene in human embryos that had resulted in the birth of IVF twins, Lulu and Nana. The gene editing involved the use of CRISPR-Cas9 technology to disable the CCR5 gene with the aim that this would lead to HIV resistance. The scientist, He Jiankui, introduced the CRISPR technology very soon after the embryos were created when they were formed of only one cell each. He Jiankui’s actions were widely condemned as unethical, and the news sparked intense debate about the potential impacts upon the children.

How might this genetic modification affect the development, the health and the wellbeing of Lulu and Nana? In the years since their birth there have been many rumours and suggestions about the impacts, including that the twins have enhanced memories and learning abilities, and others that their lives will be shortened. We don’t yet know what attributes can be attributed to the gene editing.

Irecs-Gene Editing Ethics-A case of gene editing in human embryos

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A Case of Gene Editing in Human Embryos cont.

What do you think are the main ethics issues for this case? Some of the main ones are listed below. Sort each issue into one of the four categories: Autonomy, Future generations; Potential harms and benefits; and Slippery slope.

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Germline Gene Editing

Germline gene editing needs to be undertaken at the earliest stage of embryo development to ensure that all cells carry the changes. When used to correct mutations, it can enable people who are at risk of passing genetic disease to their children to have a child free from severe genetic diseases. It might also be used to enhance immunity or protective factors for many other diseases (as was the intention for Lulu and Nana).

Additionally, it may offer the only hope of a biological child in cases where people, due to genetic mutations, face challenges in conceiving healthy embryos through conventional means or in vitro fertilisation. Nevertheless, the long-term risks associated with germline manipulation remain uncertain. Errors in this process could have far-reaching consequences for future generations because germline gene editing affects all cells, germ cells, as well as somatic cells. Hence, the changes will be heritable, and any harmful effects may only be rectified if none of these individuals ever have children of their own.

Regarding germline editing regulations, the Lancet reported in 2023 that there is broad consensus around the world that altering embryo DNA should remain forbidden. However, many countries do not have effective oversight and governance mechanisms to enforce existing regulations. In some countries, although altering embryo DNA is generally forbidden, exceptions are allowed. In Europe, the Oviedo Convention, a legally binding instrument established by the Council of Europe, permits somatic genome modifications for preventive, diagnostic, or therapeutic purposes, and prohibits germline editing, but only 29 countries have written it into law.

While there is a lack of policy and oversight alignment between countries, there is a risk of ethics dumping – the off-shoring of research that would be forbidden or considered unethical in the researcher’s home country to a region where regulation is lacking, of a lower standard or less well enforced.

Irecs-Gene Editing Ethics-Germline gene editing

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Gene Editing and Human Embryos

To develop and improve methods of gene editing, both germline and somatic, research on human embryos is currently necessary, although it may be possible in the future through generating germ cells in vitro. Research with human embryos raises moral objections for many, not least because the embryos will be destroyed when used for research.

Some countries have enacted outright bans on certain types of embryo research, such as research involving the creation of embryos solely for research purposes or research aimed at modifying the human germline. Consensus does not exist regarding the moral status of an embryo, and many people oppose research on embryos categorically.

Regulations for embryo research often impose limits on the duration embryos can be cultured for research purposes. For example, some jurisdictions allow research only on embryos up to 14 days old, as this is when the primitive streak (an early stage of nervous system development) typically forms. However, an extension of the 14-day rule for embryo research (which is legally binding in some countries) has been under discussion for many years. The International Society for Stem Cell Research (ISSCR) relaxed its guideline on this limit in 2021.

Therein, it is suggested that studies proposing to grow human embryos beyond the two-week mark be considered on a case-by-case basis, involving institutional or national bodies as well as extensive public engagement. Allowing embryos to grow past 14 days might improve understanding of human development and many health-related questions, for example, why many pregnancies fail.

Irecs-Gene Editing Ethics-Gene editing and human embryos

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Reflection Activity

The ISSCR suggests that studies proposing to grow human embryos beyond two weeks should be considered on a case-by-case basis. Imagine that you are a member of a committee that has been asked to approve a study that involves gene editing of embryos that will be grown for 28 days. How would you go about this, and what sort of things might you include in your deliberations?

There are many important factors to consider. These may include the following:

Does the research comply with relevant laws, regulations, and ethics guidelines in the jurisdiction where it is conducted?
What is the scientific rationale for use of this approach?
Do the research goals clearly justify the gene editing and growth of embryos beyond 14 days old?
Are there any alternative methods or models that could achieve similar research objectives without using human embryos or extending beyond the 14-day limit?
How have the opinions of stakeholders (including researchers, policymakers, ethicists, society, experts etc.) been taken into account?
What are the broad-based and longer-term implications of this study?

Decision-making in complex circumstances like this needs to be evidence-informed. By taking time to consider factors carefully, with the involvement of various experts (scientific, legal, ethics) and the general public, informed decisions can be taken about implementation, modification, or potential revision in light of evolving ethical, scientific, and social considerations.

Furthermore, these issues need to be navigated within the framework of the national legislation, which can be stricter than the 14-day rule. For research with embryos, or their modification through genome editing, the legal requirements vary, even within the EU. Where it is permitted, the procedures and the requirements for ethical assessments also vary.

In the USA, experiments with embryos or with the production of embryos are not publicly funded, but privately funded experiments are possible. Given that the legal and governance frameworks can be very different from country to country, international cooperation for projects involving gene editing of human embryos can be especially difficult.

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Expert Interview on Slippery Slope

The term Slippery Slope is an argument that claims that an initial action will trigger a series of other events that will lead to basically some undesirable outcomes in the end. So, if we decide to allow

a procedure that heals cystic fibrosis in patients, for example. The argument claims that this will lead to

more controversial procedures, such as basically, for example, editing cells in terms of, let's say, growth, editing the height of people, and this will then lead to enhancements such as choosing the eye colour of people or other very controversial procedures.

The problem with human enhancement is that there is no consent, because human enhancement needs to be done before the birth of a baby. So, there's no consent from the baby, obviously. So, we would need to ask the parents. And that could be a problem, because the parents' intentions might not be aligned with the baby's intentions.

There's also the problem of accessibility, because obviously if people have to pay for it, then it would be accessible for rich people, but not for poorer ones. And that also leads to a problem of fairness.

And it could lead to a two-class system where rich people have access to enhancement, whereas poorer people don't have access. And that would be a problem for society as well.

8

Human Enhancement

Some ethicists argue that we have a moral duty to use gene editing to eliminate hereditary diseases.

Others assert that gene editing, initially aimed at therapy, might lead to non-therapeutic enhancements and the application of gene editing for enhancing the human body and brain raises numerous ethical concerns. These include matters of safety, the concept of 'designer babies', potential discrimination against non-enhanced individuals, and potential longer-term effects. Let's hear from someone who has many concerns.

In the realm of enhancement, I’m concerned about children being subjected to parental experimentation without the children’s informed consent. The procedures involved carry significant risks that may impact their entire lives as well as those of their children.

There are also ‘slippery slope’ risks. If genetic enhancement becomes acceptable for certain characteristics, the boundaries of what is considered acceptable will soon be pushed. Additionally, people may begin to feel pressure to enhance to ensure that their children are not disadvantaged in comparison with those who benefit from enhancements.

Additionally, the possibility of enhancement and ‘designer babies’ raises serious issues about equity regarding equal access and the unfair distribution of benefits, as well as a potential drift towards eugenics. If gene editing becomes widely available, there's a risk of selectively enhancing desirable traits and suppressing undesirable ones, which might foster societal intolerance for imperfection.

While individuals may benefit personally, there are broader societal impacts. How might it affect those already living with disabilities? This raises questions about inclusivity, diversity, resource allocation, and the rights of individuals with disabilities. Balancing individual autonomy with societal wellbeing is at the core of this dilemma.

A major problem for ethics assessment is that there are currently no clear guidelines about human enhancements. Furthermore, the line between therapy and enhancement is often blurred and there can be dual effects, both therapy and enhancement, in some cases.

Research ethics committee members need to be aware of the mechanisms and drivers of the use of genome editing and related technologies by the global fertility industry. This is necessary to ensure that research ethics reviewers can support the research community in applying the precautionary principle to specific research fields with dual benefit potential. For instance, therapy of life-threatening diseases versus selection of desirable traits.

Feedback

The precautionary principle states that if an activity or technology has the potential to cause harm, and if there is scientific uncertainty about the extent or nature of that harm, then precautionary measures should be taken to prevent or minimise the harm, even if conclusive evidence of harm is lacking. Given the gaps in our understanding of the consequences, and the lack of clear, shared guidelines, adoption of a precautionary approach to the use of gene editing for non-therapeutic human enhancements seems most appropriate.

Irecs-Gene Editing Ethics-Human enhancement

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Human Enhancement - Poll

Take a moment to reflect on how you feel about the use of gene editing for some non-therapeutic human enhancements.

Feedback

The use of gene editing for non-therapeutic human enhancements is a complex matter which many people feel conflicted about. On one hand, the potential to improve human capabilities is exciting and could lead to incredible advancements. On the other hand, there are concerns about the ethical implications and the possibility of creating a society with even greater inequality and unforeseen health risks.

10

Gene Editing, Justice, and Equality

Treatments and therapies involving gene editing are already undergoing clinical trials for marketing approval in the EU and the US for certain diseases and are likely to incur equivalent costs to those of conventional gene-based therapies that are used for rare genetic diseases. However, they are very costly and may thus be restricted to wealthy patients or citizens in countries with corresponding health insurance or social security systems. The dilemma of resource allocation poses questions about the development of extremely expensive therapies.

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Gene Editing, Justice, And Equality - Poll

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Gene Editing, Justice, and Equality cont.

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Who Profits Financially From CRISPR-Cas9?

Irecs- Gene Editing Ethics- Who profits financially from CRISPR-Cas9

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Gene Editing, Misuse, and Dual Use

Irecs-Gene Editing Ethics- The Insect Allies Program

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Ethical Challenges for Non-Human Gene Editing

Irecs-Gene Editing Ethics-Environmental impacts

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Food Safety

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Broader Ethics Issues

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Gene Editing In Animals

Irecs- Gene Editing Ethics- Gene editing in animals

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Gene Editing in Animals cont.

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Governance of Gene Editing Research

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Expert Interview about Research Considerations

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End of Module Quiz

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Module Evaluation

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References and further resources

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Bibliography

Steps

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