Genomics: Technology helping deliver better health care

Technology is helping deliver better health care and inform the response to the global pandemic.

Discover

Cambridge is arguably the birthplace of modern genetics. Even the term ‘genetics’ was coined at the university by William Bateson in 1905. In 1953, Francis Crick and James Watson published a paper in Nature proposing the double helix structure of DNA – a discovery that was to lay the groundwork of modern-day genomics, the study of our entire genetic makeup. In 1977, Cambridge alumnus Fred Sanger, working at the Medical Research Council Laboratory of Molecular Biology, became the first person to sequence a DNA genome – that of the bacteriophage φX174 – having developed methods for sequencing RNA and DNA. At the end of the 20th century, the Wellcome Trust Sanger Institute, at Hinxton, just outside Cambridge, played a crucial role in the Human Genome Project, helping sequence the first human genome and ensuring the data produced were made available for the research community to access free of charge.

Develop

In the mid-1990s, Cambridge professors Shankar Balasubramanian and David Klenerman were carrying out research into DNA polymerases, enzymes that create DNA molecules by assembling nucleotides – the A, C, G and T ‘building blocks’ of DNA . Sitting in the beer garden of Cambridge’s Panton Arms pub, the pair sketched out their plans to watch DNA polymerase as it assembled these building blocks. It was at this point that they realised, if they could watch the Genomics enzyme copying a genome, they were inadvertently also reading the genome. They had discovered a radically new way to sequence DNA that would be fast, accurate, low-cost and scalable. Within a year, the pair had co-founded the spin-out company Solexa to make the technology more broadly available to the world; in 2007, the company was acquired by US biotech company Illumina.

Deliver

Today, Solexa-Illumina’s ‘next-generation sequencing’ is used to sequence one million genomes per year. It is responsible for as much as 90% of the total DNA and RNA sequences produced worldwide. The technology has enabled a profound increase in the rate of sequencing. In 2000, sequencing of one human genome took more than 10 years and cost more than a billion dollars; today, the human genome can be sequenced in a single day at a cost of $1,000.

The technology has had – and continues to have – a transformative impact in the fields of genomics, medicine and biology. It is helping Cambridge teams DEVELOP new ways of treating disease and DELIVER improvements in health care. Examples include:

COVID-19 Genomics UK (COG-UK) Consortium: Cambridge-led COG-UK has been at the forefront of the use of large-scale, rapid, whole-genome sequencing of SARS-CoV-2 to understand viral transmission and evolution – including the emergence of new variants of concern – and to inform public health responses and vaccine development. By December 2021, COG-UK scientists had sequenced more than 1,500,000 virus samples, contributing around a quarter of all global SARSCoV-2 sequence data deposited in the international open-access database GISAID. Led by Professor Sharon Peacock, COG-UK builds on her previous work using whole-genome sequencing to understand outbreaks of hospital-associated pathogens at Addenbrooke’s Hospital. In 2012, Peacock was one of the first to use pathogen whole-genome sequencing to understand the basis of a clinical infectious disease scenario – an MRSA outbreak in a neonatal intensive care unit.

Personalised Breast Cancer Programme: Cambridge is home to the world’s first precision breast cancer programme. Whole-genome and RNA sequencing is offered to all breast cancer patients at Addenbrooke’s Hospital. This data is used to guide patient care decisions. The programme builds on a pilot carried out in Cambridge in 2016. Patients’ tumour cells were compared with their healthy cells to study which genetic mistakes were causing the disease and which weaknesses could be targeted with cancer drugs. The technology has had – and continues to have – a transformative impact in the fields of genomics, medicine and biology. It is helping Cambridge teams DEVELOP new ways of treating disease and DELIVER improvements in health care. Examples include: The results also identified whether the patient had any inherited genetic faults that increase the risk of breast cancer or cause toxic side-effects to chemotherapy. For the majority of patients, their results confirmed that they were receiving the best treatment available. A small number were found to be better suited to a different drug. The Personalised Breast Cancer Programme – a partnership between The Mark Foundation for Cancer Research, Cancer Research UK, Illumina and AstraZeneca – will form an integral part of the new Cambridge Cancer Research Hospital.