Songs of Genomics

On Saturday 2nd November 2024, in collaboration with HIVE Choir, a vocal ensemble based in Belfast, we hosted Songs of Genomics at Pegasus Theatre.

Together with HIVE Choir we transformed our research into songs that capture the complexities of genomics medicine. The choir performed these songs, featuring new pieces created during a workshop earlier in the day with individuals affected by genomic testing. The performance was followed by an engaging panel discussion.   

The Songbook can be found here.

Genetics and insurance: Complexities in the genomic era

This event took place on 15th May 2024, at the Wellcome Collection, London. Below is the programme and some background information; a summary paper is in process and will be added to this page in due course.

10:30 – 11:30 Session 1 – Chair: Professor Anneke Lucassen
Introduction: Anneke Lucassen, CPM
2023 consultation and its findings: Ana Hallgarten la Casta, DHSC
A summary of patients’ and families’ experiences and concerns: Sophie Peet, Genetic Alliance
Emerging challenges: Dr Padraig Dixon, CPM
Insurance industry view: William Meredew, ABI

11:30 – 11:45 Coffee

11:45 – 12:45 Session 2 – Chair: Professor Michael Parker, University of Oxford
Q+A session for all speakers from first session

12:45 – 13:30 Lunch

13:30 – 15:00 Session 3 – Chair: Sophie Peet, Genetics Alliance
Focused conversations

15:00 – 15:20 Coffee

15:20 – 16:00 Session 4 – Chaired by Tara Clancy, BSGM

Summary, conclusion, and final reflections

BRIEFING NOTE

Background information

This event was jointly organized and supported by the Centre for Personalised Medicine at Oxford and the British Society for Genetic Medicine. The focus for the event was on existing and emerging issues that might challenge current arrangements in the UK about how genetic information can, and should, be used for insurance purposes.

There is a long-standing concern that people might be treated differently or in some sense unfairly because of their genetic background. This might involve being denied access to insurance or being offered lower coverage or higher costs. People may also avoid genetic testing, even where this might be beneficial (e.g. to access extra screening), because of how they perceive it might affect their insurance. On the other hand, if insurance companies can’t use any genetic information to price their policies, this could lead to price increases or unavailability of certain types of insurance plans. Insurers might exit from parts of the market.

Reports from the operation of the Code on Genetic testing and Insurance (see further reading) in the UK show that, for now, genetic information has not had wide-ranging impacts on insurance decisions in the UK, although there are many examples of individuals experiencing difficulties in accessing affordable insurance. Nevertheless, there is a strong case for considering if the current arrangements are fit for purpose because of recent expansions in the scale, speed and sophistication of genetic testing.

Genetic testing: some key information

Genetics involves studying genes and their impact on health. Genomics involves studying the whole genome (both genes and non-coding regions). In practice they are overlapping terms and often used interchangeably. We use the term ‘genetics’ in this document for reasons of continuity and consistency with the Code on Genetic Testing and Insurance.

Each of us has around 5 million genetic variants. Many of these variants contribute to human diversity and do not influence health. Others may subtly, or significantly, increase the chance of certain conditions or how someone responds to medication. Variants can be inherited from parents or can occur for the first time in an individual (i.e. are not inherited from parents).  

Genetic tests look for variants. The results of a genetic test can be

• positive: variant(s) known to cause the condition are found
• negative: variant(s) known to cause the condition are not found
• uncertain: variant(s) are found that are of unknown or uncertain significance; this means there isn’t enough information about the variant to establish if it does or does not influence the condition

Different members of a family may have the same variant linked to a condition (for example a BRCA1 gene variant) but not everyone will develop the condition, or people might have more or less symptoms or complications of the condition. This is known as penetrance and expressivity: a genetic variant with less than 100% penetrance will not cause the disease in everyone who has it; a variant with variable expressivity can lead to mild symptoms in some people and severe symptoms in others. Reduced penetrance and variable expressivity are likely to be due to a combination of genetic, environmental and lifestyle factors; many of these other factors are not yet known and/or cannot be measured.

There are many different types of genetic tests, including diagnostic tests, predictive tests, pharmacogenomic tests and polygenic risk scores.

• Diagnostic genetic tests are usually offered when an individual has symptoms that suggest they have a particular condition. These tests usually give a positive or negative result.

• Predictive (sometimes called presymptomatic) tests are often offered when an individual has a family history of a genetic condition and a variant known to cause that condition has been identified in a relative. However, direct to consumer genetic tests, for example, may provide predictive results outside this setting.

• Pharmacogenomic tests are offered to provide information about how an individual will respond to medication. This includes information about whether a particular drug will be effective or how likely it is to cause significant side-effects.  Just like other genetic tests, the results of these may be strongly or weakly predictive.

Common diseases, such as heart disease, cancer or diabetes, are influenced by genetic, environmental and other factors. About 20-30% of the risk of common diseases is explained by genetic variants. These variants are usually weak risk factors individually, but thousands of variants together may explain an important part of the genetic component to common disease.  Polygenic risk scores (PRS) measure the contribution of these multiple variants to risk. PRS may, when taken together with other risk factors such as age, enable more targeted screening or other interventions.

Life insurance, critical illness insurance and income protection insurance: some key information

Life insurance pays a lump sum on the insured person’s death. Critical illness insurance pays a sum assured on occurrence/diagnosis of a specified list of serious illnesses, e.g. cancer. Income protection insurance pays out a regular amount to replace a portion of income if a person is unable to work because of injury or illness.

These types of insurance serves as a safeguard for individuals against the harmful financial impact of unforeseen or unpredictable events. Prolonged serious illness and death are foreseeable to some extent, but their timing and impact are largely unpredictable. Insurance involves the pooling of risk by individuals at risk of particular events who contribute premiums to a risk pool. Individuals who suffer the event are compensated from the risk pool.

Within this risk pool, the collective contributions of the majority, who do not file claims, support the expenses incurred by the minority who do. For life insurance, the principles of risk pooling also apply, but the payouts are to the beneficiaries (such as spouses or dependents).

The premiums of risk-rated insurance contracts reflect the likelihood of a prospective policyholder experiencing an insurable event and the associated costs borne by the insurer. Greater assessed risk typically translates to higher premiums and/or more stringent contract terms. Lower assessed risk generally results in more favourable terms and lower premiums. Actuarially, a fair insurance contract accurately appraises and prices risk.

Persistent mispricing of insurance, by either overcharging or undercharging certain groups relative to their risk exposure and associated costs, places insurers at a competitive disadvantage and is ultimately unsustainable.

The Code on Genetic testing and Insurance (the “Code”): some key information  

In the 1990s, the increasing use of genetic tests and concern over their implications for access and costs of insurance led to the “Genetic Testing Code of Practice”, published in December 1997. This has been updated over time and is now known as the Code on Genetic testing and Insurance. It covers two main types of genetic tests, which are defined in the Code as follows:

• Diagnostic tests: “confirm or rule out a diagnosis based on existing symptoms, signs or abnormal non-genetic test results which indicate that the condition in question may be present.”
• Predictive tests: “predict a future risk of disease in individuals without symptoms of a genetic disorder.”

The Code applies to life insurance, critical illness, and income protection. It has two main principles:

• Insurance companies can’t require or pressure people to take diagnostic or predictive genetic tests to obtain insurance.
• For predictive tests, insurers can only consider the results if the test is listed in the Code and if the amount of insurance requested is over a certain limit.

At present, the only condition for which insurers may ask for and take account of predictive test results is Huntington’s disease in applications for life insurance policies totalling over £500,000.

The Code doesn’t stop insurance companies from using family history (and other factors such as age) to assess disease risk.

Explanation of terms

DNA (deoxyribonucleic acid): the molecule that contains/encodes genetic information

Gene: a DNA sequence that usually codes for a protein or component of a protein

Genetic variants: changes in a gene that can lead to the protein it codes for not working properly or not being formed

Polygenic: multiple genes   

Proteins: large complex molecules that play critical roles in how the body functions

Some further reading

Code on Genetic Testing and Insurance, https://www.abi.org.uk/data-and-resources/tools-and-resources/genetics/code-on-genetic-testing-and-insurance/

Code on Genetic Testing and Insurance: the government’s annual report 2023: https://www.gov.uk/government/publications/code-on-genetic-testing-and-insurance-annual-report-2023/code-on-genetic-testing-and-insurance-the-governments-annual-report-2023

Code on Genetic Testing and Insurance: call for evidence: https://www.gov.uk/government/calls-for-evidence/code-on-genetic-testing-and-insurance-call-for-evidence/code-on-genetic-testing-and-insurance-call-for-evidence

Dixon P, Horton R, Newman W, McDermott J, Lucassen A, Genomics and Insurance in the United Kingdom: Increasing Complexity and Emerging Challenges, Health Economics, Policy, and Law, in press. https://dx.doi.org/10.1017/S1744133124000070

Results of the Code on Genetic Testing and Insurance call for evidence  https://www.gov.uk/government/calls-for-evidence/code-on-genetic-testing-and-insurance-call-for-evidence/outcome/results-of-the-code-on-genetic-testing-and-insurance-call-for-evidence

The full report from the event can be found below.

Download

Familial Disclosure event

Outline

The PHG Foundation, Cambridge, and the Centre for Personalised Medicine at the University of Oxford, in association with the British Society for Genetic Medicine, held a half-day meeting on 23 November 2023 at St Anne’s College, Oxford, on the legal and ethical challenges raised by the discovery of familial genomic information in healthcare through the testing of an individual. This document is a starting point for discussion and agreement on focus and format for the meeting as well as planned outputs and background material.

Background

The question of how genetic and genomic test results that are relevant to more than one family member should be managed has been a topic of debate for several decades in healthcare. However, the difficulties of balancing duties of care where information revealed is both personal and at the same time familial, continues to place clinicians in uncertain situations.

Such issues arise in at least half of all cases discussed at the UK Genethics Forum – a multidisciplinary discussion forum for health professionals, which has held 70 meetings over more than two decades. Professional guidelines such as those from the General Medical Council have long recommended a balancing exercise between one patient’s confidentiality and the prevention of harm to another.  However, the governing legal framework (including common law and legislation relating to patient confidentiality, privacy, human rights, personal data and professional responsibilities) did not offer unambiguous support for this. The seminal 2020 judgment of the High Court in ABC v St George’s Healthcare NHS Trust sets an important precedent by establishing a legal duty to consider disclosure of confidential information without consent if another person is at risk of serious harm in certain circumstances.  But the nuances of this judgment and its precise implications are not necessarily clear to all working in healthcare, or hospital legal teams often called upon to advise. Challenges relating to other aspects of the legal framework (such as how to reconcile multiple individual interests in relation to the same ‘personal data’ under data protection law) also remain.

Approaches that frame the duty of confidentiality differently have been proposed but not yet widely adopted in clinical practice. For example, whether it is possible to alert relatives of their risks without breaching the confidences of another.[1]  Debate continues about the appropriate nature and scope of professional and ethical obligations[2] and relevant conceptual underpinnings, such as the extent to which relational aspects to autonomy should guide decision-making in this area.[3]  

Achieving greater understanding and consensus in relation to these topics could have significant value for professional guidance, professional practice and even the determination of future legal claims or legislative reform. 

The event

Revisiting the legal and ethical framework surrounding familial genomic information in healthcare and research

• The event will consider the ethical aspects and legal framework governing familial genomic information in research and care, as well as professional responses to, and implications of, the ruling in ABC v St George’s Healthcare NHS Trust.
• It will involve discussion of competing conceptions of autonomy, confidentiality and privacy in the genomic context and implications for practice as well as the existing legal framework.
• The aim of the meeting will be to generate recommendations for areas of further research into patient/public thinking about these ethical and legal aspects, as well as highlighting policy considerations for professional bodies and those involved in law reform.

Who should attend?

• The event will assemble a mix of legal and clinical professionals, academic experts and representatives of professional bodies responsible for relevant guidance
• This will include academics active in this area, legal experts in relation to relevant areas of law (Data, Privacy/confidentiality), genomics professionals and representatives of relevant initiatives (e.g. GEL) and bodies (e.g. law commission, Information Commissioner’s Office).
• Whilst we hope to incorporate international perspectives  from other countries/jurisdictions/health systems to provide insight from alternative and related  perspectives in the long term, this meeting will be focussed on the UK landscape and the analysis of how the ABC versus St George’s case has been interpreted thus far

Format

• An afternoon workshop of ~ 45 people in Oxford with Sessions around ethico-legal aspects (e.g. confidentiality, data protection) and examples of how the issue arises in clinical examples practice. Outputs
• A briefing to outline relevant ethical and legal issues and framework, acknowledging the context of genomic information being generated and stored at ever increasing scale in research and healthcare (e.g. Newborn sequencing initiatives).
• A meeting Report providing a high-level summary of presentations/discussions and key conclusions/recommendations, including priorities for further research/deliberation.
• It is hoped the outputs of this meeting will help inform revision of the Joint Committee of Genomics in Medicine report on consent and confidentiality in genetic medicine (2019)[4]

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[1] Alerting relatives about heritable risks: the limits of confidentiality | The BMJ

[2] Lucassen, A, and Clarke A . “In the family: access to, and communication of, familial information in clinical practice.” Human Genetics 141.5 (2022): 1053-1058.

[3] Dove, Edward S., et al. “Beyond individualism: Is there a place for relational autonomy in clinical practice and research?.” Clinical ethics 12.3 (2017): 150-165.

[4] Consent-and-confidentiality-in-genomic-medicine-July-2019.pdf (rcpath.org)

Centre for Personalised Medicine Art Competition 2023-24

In the second year of the competition, we looked at screening newborn babies for disease. All babies born in the UK are offered tests shortly after birth to check for health issues:

• They have a baby check after birth, then again when they are six weeks old where a clinician checks them over looking for issues like heart murmurs, eye problems or clicky hips
• They have a bloodspot test at around five days old where some drops of blood are collected from their heel. This blood is tested for nine rare conditions where treatment before the baby begins to seem poorly is important to help the baby stay as healthy as they can.

Currently, the Newborn Genomes Programme is exploring how looking at a baby’s genetic code might help with checking them for diseases. This sort of testing can look for a lot of diseases at once, but the results might be less clear as we are still learning how a person’s genetic code links to the illnesses they develop.

• A small number of babies will be found to have a disease that can be treated better the earlier you know about it
• For some babies, screening might raise worries that they will become unwell at some point in the future, but it might take years until we can be sure whether they actually will get ill or not
• For most babies, screening won’t raise any health worries, but their genetic code will become part of the project database.

The video introducing the competition can be found here.

The artworks were judged on:

• Relevance – does the image communicate something important about screening newborn babies for disease?

• Originality – does the image make you think about newborn screening in new or challenging ways?

• Artistry – does the image capture your attention and make you want to find out more?

A huge thank you to the judges; Dr Rachel Horton (CPM Junior Research Fellow), Dr Ali Kay (CPM Junior Research Fellow), Dr Kate Keohane (St Anne’s College/Ruskin School of Art), Brian Mackenwells (Centre for Human Genetics), Melville Nyatondo (Oxford Personalised Medicine Society) and Taisiia Sazonova (Oxford Personalised Medicine Society).

We were so impressed with the quality of the entries we received. This blog post talks through the winners and finalists – we hope you enjoy these thought-provoking entries as much as we did.

Winner

Our winning entry is this fantastic piece by Laranya, aged 13 from Worksop College, Nottinghamshire. Laranya produced this artwork using the letters ATGC – the types of bases found in a DNA molecule. Laranya wrote, ‘When viewing the picture up close you only see the letters, but when you look from a distance you can see the face of the baby. This shows that when examining our DNA, you must look with a microscope, and these tiny proteins make up a whole person.’

The judges were captivated by this impressive piece of art, and thought it was great how it showed the challenge of detecting health relevant genetic variation.

Runner-up

Our runner-up is this thought-provoking entry from Scarlett, aged 12 from Worksop College, Nottinghamshire. Scarlett wrote. ‘I created a painting that explores the connection between a baby’s future and their genetic makeup. In the centre of the artwork, I depicted a cute baby positioned behind a prominent DNA double helix. The double helix appears like a protective cell, symbolizing the delicate nature of a newborn’s life. Surrounding the baby and the DNA structure are intricate double helix patterns, illustrating the complexity of genetic testing. The intertwining patterns convey the idea that our genes hold a blueprint for our future.’

The judges really liked this artwork, and how it covered the complexities of newborn screening in a captivating and evocative way.

Highly Commended

We were really lucky to receive so many great entries from incredibly talented students – all the following artworks were highly commended by the judges.

Parampreet, aged 11 from Higham Lane School, Warwickshire. The judges thought this was a very vibrant and eye-catching piece covering different elements of health monitoring for newborns.

Rayan, aged 13 from Oaklands Secondary School, London. The judges really liked how colourful and informative this entry was.

Alexa, aged 14 from Worksop College, Nottinghamshire. The judges were really impressed by this illustration, and how the use of colour conveys the heavy emotions that come with newborn screening.