Instruction:E0b76d6a-5261-473a-9f2d-a7fedc2607da

Modules

Gene Editing Case Study with Human Application

Instructions for:TraineeTrainer

Related Initiative

iRECS

Goal

The aim of this module is to facilitate reflection upon the ethics issues associated with the development and use of gene editing in humans.

Learning outcomes

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

1. Identify and analyse the ethics issues and dilemmas associated with an example research proposal.
2. Make suggestions for how the ethics issues might be addressed.
3. Identify ethics guidelines and policies that are relevant to the proposed research.

Duration (hours)

1

For whom is this important?

All stakeholders in researchBachelor studentsMaster students

Part of

iRECS

Steps

1Introduction

2Further Reading

3Glossary

4What is Hunter Syndrome?

5Hunter Syndrome Poll

6The Research Proposal and Ethics Approval

7Is the Research Justified?

8The Governance of Gene Editing Research

9A Checklist for Research Ethics Committees

10Would you Approve the Study?

11Module Evaluation

1

Introduction

In humans, gene therapy via gene editing is a rapidly growing field of research with many potential benefits for health and wellbeing. It involves the editing of genes to modify or knock out specific genes to achieve desired traits, to correct genetic defects, to treat or prevent disease, or to enhance cellular functions.

In this module we consider an example proposal for a research project that is based upon a real-world study. The study aims to trial gene therapy for Hunter syndrome in a small group of young children.  As you work through the module, we invite you to consider the ethics issues that are associated with this type of study from a variety of perspectives as well as how they might be addressed. We begin with some information about the disease.

2

What is Hunter Syndrome?

What is Hunter syndrome?

Hunter syndrome is a rare genetic disorder that primarily affects males. It is part of a group of diseases known as mucopolysaccharidoses or MPS, which are caused by the body's inability to break down certain complex sugars called glycosaminoglycans or GAGs. For people with Hunter syndrome, a lack of the enzyme iduronate-2-sulfatase or IDS, means that GAGs build up inside the body leading to a wide variety of symptoms including developmental issues, physical problems and mental decline. For example:

• Physical development impacts like coarse facial features, thickened skin, enlarged tongue, and joint stiffness.
• Developmental delays in children affecting motor skills, speech, and learning.
• Respiratory problems with frequent respiratory infections, sleep apnoea, and other breathing difficulties.
• Hearing loss.
• Enlarged liver and spleen, leading to abdominal distension.
• Heart problems with heart valve abnormalities and other cardiac issues.
• Skeletal abnormalities like joint stiffness, short stature, and abnormal bone development.

The onset of the disease is usually between the ages of 2 and 4 years and developmental decline is usually evident between the ages of 18 and 36 months.

There is currently no cure for Hunter syndrome, but treatments can help to manage the symptoms and improve quality of life. Options include:

1. Enzyme replacement therapy (ERT). Regular, often weekly, infusions of a synthetic version of the missing enzyme can help reduce the buildup of GAGs. However, the enzyme is not able to pass the blood-brain-barrier, so this form of treatment does not help to protect against brain damage.

1. Symptomatic treatments for specific issues including physical therapy for joint problems, medications for respiratory and heart problems, and surgical interventions for specific complications.

Despite treatment, those with severe disease usually die in their teens. Those with a milder form of Hunter syndrome might live with more gradual deterioration in health until middle age.

3

Hunter Syndrome Poll

Now that you know a little about the syndrome, imagine that you are the parent of a 12-month-old child who has been diagnosed with severe Hunter syndrome. Your child is being offered the chance to try a new experimental therapy for the disease, but the treatment is untested in humans.

Are you likely to agree to their participation? Please select a response and then check to see how others have responded.

Feedback Decisions about whether or not to participate in studies that are testing novel interventions can be challenging for anyone. Why not just let others take the risk in an experimental trial and wait to see what the outcomes are? For the parents or guardians of young children who are unable to consent for themselves, the decision-making is much more complex. As you work through the rest of the module, see whether you change your mind about your response.

4

The Research Proposal and Ethics Approval

Let’s find out more about the proposed study. While watching the next video, imagine that you are a member of an ethics review committee and your role is to make an assessment about whether or not to approve the study, to ask for changes to be made / further information, or to disallow the study. Make a note of any points or questions that arise for you.

There may be opposing views on the research ethics committee about whether this study can be approved. It is certainly a proposal that demands careful ethical scrutiny. In the audio below you will hear from some REC members who discuss some of the issues that need to be considered. Check to see whether they address all of the points or queries that you noted.

Error creating thumbnail: File with dimensions greater than 12.5 MP

5

Is the Research Justified?

Justification for this type of research cannot rest purely upon the assessment of harms and benefits for the participants. There are many other factors to take into account when assessing the ethical permissibility of leading-edge gene editing research with humans. Work through the presentation below to reveal some other important factors that might need to be considered.

The assessment of proposals like this is a complex matter and it may demand input from a wide range of perspectives. There are specific technical questions (for instance, regarding what the therapy will involve and the potential for off-target or on-target effects), as well as broader and more general questions, (for instance, ‘does this research need to be done?’ and ‘who stands to benefit from the research?’). The involvement of young children also demands careful consideration, ‘Is children's participation in the research necessary or could the information be obtained in other ways?’; ‘What would be the likely consequences of not involving children?’. These considerations require individual, case by case scrutiny, from a committee with wide-ranging expertise.

6

The Governance of Gene Editing Research

Governance at the international level

The governance of gene editing research is not straightforward because it varies across countries, and encompasses legal, ethical, scientific, and societal dimensions. There have been steps towards development of an international regulatory framework. For instance:

The World Health Organization has established advisory committees to provide guidelines on human genome editing. In 2021, the WHO published two reports offering recommendations on the governance and oversight of human genome editing, particularly emphasizing international collaboration and transparency.

Human genome editing: recommendations: https://www.who.int/publications/i/item/9789240030381

Human genome editing: a framework for governance: https://www.who.int/publications/i/item/9789240030060

In 2022, the EU published a survey of law, governing and regulation principles

https://www.europarl.europa.eu/RegData/etudes/STUD/2022/729506/E PRS_STU(2022)729506_EN.pdf

The EU’s approach to genome editing is highly precautionary, particularly when it comes to germline editing. Regulations are largely guided by the European Medicines Agency (EMA), which oversees clinical applications of genome editing therapies.

Error creating thumbnail: File with dimensions greater than 12.5 MP

Steps

Other information