World of Genomics: The United Kingdom

Being a UK based company in the genomics field, we know the space here better than in any other country (or so we hope)! As we have seen with the COVID-19 pandemic, research in the UK has been central to understanding the virus and developing vaccines. The UK has been at the forefront of genomic sequencing to identify and track variants of significance. Simultaneously, the UK continues to be a leader in genomics within healthcare, being home to many notable geneticists, institutions and organisations. In this World of Genomics entry, we showcase some of the leading projects and organisations within the UK that are helping to integrate genomics into mainstay clinical care.

The population of the United Kingdom

The UK is a sovereign state located off the north-western coast of Europe. The history of the UK began in the early eighteenth century with the Treaty of Union and Acts of Union. In 1707, the UK became a unified state with the political union of the Kingdoms of England (which included Wales) and Scotland. The Act of Union 1800 then added the Kingdom of Ireland into this state. Most of Ireland seceded from the UK in 1922, leaving the present formulation of England, Scotland, Wales and Northern Ireland. Over the past 2,000 years the UK population has fluctuated due to famines, wars and diseases.

Geographic and demographic information

Summary statistics:

• Land area: 242,495 km²
• Gross domestic product (GDP):
  • Total: $3.124 trillion
  • Per capita: $46,344

Population statistics

• Population size: In mid-2019, the UK population was estimated to be 66,796,807.
• Birth rate: In 2019, the crude birth rate was 10.7 per 1,000 people.
• Death rate: In 2019, the crude death rate was 9 per 1,000 people.
• Infant mortality rate: The crude infant mortality rate is 4.27 per 1,000 people.
• Average life expectancy: The average life expectancy in 2018 was 81.26 years.
• Ethnicity: The most recent 2011 census data indicates that the UK is an ethnically diverse society with fast-growing migration. The largest ethnic group is White British, yet in 2011 8 million people in the UK were from ethnic minorities. Of those, 4.3 million were Asian or British Asian, 1.9 million were Black or Black British and 1.2 million were from mixed ethnicity.

Healthcare system

The National Health Service (NHS) was founded in 1946 and is responsible for the public healthcare sector of the UK. The UK healthcare system is comprised of four separate healthcare systems including NHS England, NHS Scotland, NHS Wales and Health, Social Services and Public Safety in Northern Ireland. Each of these systems are funded by and accountable to separate governments and parliaments. As a result, there are a variety of differences between these systems, including prescription and parking charges and cost control analysis. Nonetheless, all four countries have universal health coverage, with citizens entitled to buy private health insurance as well.

Health priorities

In 2018, the leading cause of death in the UK was dementia and Alzheimer’s disease, accounting for 12.7% of all deaths registered. It has also become the leading cause of death for females. Despite a decrease in deaths, ischaemic heart disease remains the leading cause of death in males. Most importantly, while people are living longer, many of these additional years are spent with health problems. For example, in England, 44% of people aged 65 years and over have reported having one chronic disease and 16% at least two. Shockingly, over one third of all deaths in the UK can be attributed to behavioural risk factors, including tobacco smoking, poor diet, alcohol consumption and low physical activity.

Some of the other priorities across the UK include improving healthcare equality, promoting a healthier nation (e.g., healthier diets), improving mental health and reducing the risk from antimicrobial resistance. Other challenges include underfunding and shortages in the health workforce as the UK relies heavily on migration to sustain its health system.

Genomic medicine capabilities

The NHS is a world-leading health system in its use of cutting-edge genomic technologies. From birth, the NHS has a newborn screening programme that helps identify several rare diseases through a small blood sample (heel prick test). More recently, NHS Wales have been leading in the use of whole-genome sequencing to diagnosis critically ill children with their new service – WINGS (Wales Infants’ and Children’s Genome Service). The NHS also offers screening during pregnancy to determine whether the foetus has specific conditions, such as Down Syndrome.

Other capabilities include systematic family history and subsequent genetic counselling services, for example, for inherited disorders like Huntington’s disease. This extends to inherited cancers, such as BRCA testing.

Current pharmacogenomic tested is limited to specific polymorphisms. For example, pharmacogenomic testing for DPYD polymorphisms which cause dihydropyrimidine dehydrogenase (DPD) deficiency is recommended as a pre-treatment screening test prior to the administration of fluoropyrimidine-based therapies.

Other applications, such as tumour sequencing and microbial pathogen identification and tracking, are largely limited to a research capacity.

Notable projects

• The 100,000 Genomes Project: First announced in 2012, the 100,000 Genomes Project was a UK Government project established to sequence 100,000 genomes from NHS patients affected by a rare disease or cancer. The project was completed in 2018 and to date, actionable findings have been found for 1 in 4/1 in 5 rare disease patients. Additionally, around 50% of cancer cases so far have been found to contain the potential for a therapy or a clinical trial. Genomics England was set up by the UK Government to oversee this project.
• The UK Biobank: Established in 2007, the UK Biobank is a large long-term biobank study which retrospectively investigates contributions of genetic predisposition and environmental exposure to the development of disease. The study follows 500,000 volunteers from the UK, enrolled at ages 40-69. The UK Biobank continues to obtain additional metrics, with many participants recently sending monthly blood samples for analysis of SARS-CoV-2 antibodies.
• Dolly the Sheep: In 1996, at the Roslin Institute in Scotland, the first mammal was cloned from an adult somatic cell, using the process of nuclear transfer. The sheep, subsequently named Dolly, captivated the world and her legacy still lives on despite her death in 2003.
• The DDD study: The Deciphering Developmental Disorders Project aimed to determine whether new high-throughput genetic technologies could help determine the cause of developmental disorders. The study involved 40,000 saliva samples from children with undiagnosed developmental disorders and their parents. Analysis for this project is still ongoing.

Universities and research centres in the UK have also been involved in several notable international projects, such as the Human Genome Project, a 13-year-long project that sequenced the entire human genome.

Notable organisations and companies

• Genomics England: Genomics England, owned by the Department of Health and Social Care, was set up to help deliver the 100,000 Genomes Project. After the Project reached its goal in late 2018, the UK’s Secretary of State for Health and Social Care, Matt Hancock, announced that the program had been expanded with a new goal of sequencing five million genomes within five years.
• All Wales Medical Genomics Service (AWMGS): AWMGS is an NHS specialist regional health service to help and support patients in Wales who have or may be at risk of developing a genetic condition.
• Oxford Nanopore Technologies: Founded in 2005, Oxford Nanopore Technologies is a company which is developing and selling long-read nanopore sequencing technologies, including the portable MinION.
• The Wellcome Sanger Institute: Established in 1992, the Wellcome Sanger Institute is a non-profit genomics and genetic research institute, primarily funded by the Wellcome Trust. It was conceived as a large-scale DNA sequencing centre to participate in the Human Genome Project. Bioinformatic database resources are one of the main outcomes of programmes at the Institute, including COSMIC, a catalogue of somatic mutations in cancer.
• Institute of Cancer Research: ICR is a public research institute established in 1909 specialising in oncology. It pursues three main research areas: genetic epidemiology, molecular pathology and therapeutic development. The Institute has been responsible for a number of breakthroughs, including identifying that the basic cause of cancer is damage to DNA.

The UK is also home to two of the best academic institutions globally – University of Oxford and University of Cambridge, as well as many other amazing universities that contain both teaching and research facilities.

Notable individuals

Naming all of the amazing UK researchers, both past and present, would be impossible, so below we’ve listed just a few researchers that most people would be familiar with:

• Francis Crick (1916-2004): Crick was a British molecular biologist, biophysicist and neuroscientist who played a crucial role in deciphering the helical structure of the DNA molecule. Alongside James Watson and Maurice Wilkins, Crick was awarded the Nobel Prize in Physiology or Medicine in 1962. The Francis Crick Institute is an institute developed in Crick’s name, with the aim of conducting world-class research to understand life and benefit human health.  
• Rosalind Franklin (1920-1958): Franklin was an English chemist and X-ray crystallographer whose work was central to understanding the molecular structure of DNA and RNA. Franklin died before the Nobel Prize was awarded to her colleagues in 1962.  
• Frederick Sanger (1918-2013): Sanger was a British biochemist who won the Nobel Prize in Chemistry twice for discovering that proteins have a unique molecular structure and for developing the chain-terminating method to sequence DNA (so-called Sanger sequencing).

Next steps

Last year, the UK released its new National Genomic Healthcare Strategy with the goal of cementing its status as a global leader in genomics. Genome UK: The Future of Healthcare sets out a plan to provide world-leading, genomics-driven healthcare to patients in the UK. The three main pillars include:

• Early and precise diagnosis and providing personalised treatments.
• Disease prevention through screening for genetic variants.
• Integration of research into clinical outcomes through improved data sharing.

To achieve this, whole-genome sequencing services will be expanded across NHS England Genomics Medicine Service as part of routine care. They will also ensure that multi-disciplinary teams can draw from a range of information, including genomic and imaging, to improve patient outcomes. In addition, they aim to use genomics to improve population health through improved disease prevention, including better screening. They also expect to develop and integrate non-invasive prenatal testing to help identify diseases earlier. Another important aspect will be the development of standardised infrastructure and tools to improve data storage and access. A part of this will include ensuring diversity within the data and equity of access. Alongside these pillars, the NHS will also focus on improving engagement with the public as well as building trust and also developing the workforce and supporting industrial growth across the UK.

The pandemic has shown the power of genomics and the amazing capabilities that exist within the UK. Despite the devolved healthcare systems, the UK is truly united in trying to improve patient care and work alongside other countries to build our knowledge base as a planet. Being born and raised in the centre of this genomics hub, I am excited to see what is in store next!