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Issue 3 » January 2014 Civil Service Quarterly 100,000

» In December 2012 the Prime Minister announced an ambitious plan to sequence the genomes of 100,000 NHS patients over the next five years. To meet the ambitious target, the Department of Health has established Genomics England. By Professor Dame , Chief Medical Officer, and Dr Mark Bale, Deputy Head of Health Science and Bioethics Division, Department of Health.

In December 2012, the Prime has not been a whole diagnoses genetic conditions Minister announced a plan to sequence for any NHS patient by testing for single changes, sequence the whole genomes in the UK to date. The machines known as mutations in a gene. of 100,000 NHS patients of the current market leader They often sequence (decode) and use this to push forward that sequence whole genomes the four letters of DNA in a understanding of diseases and to to clinical quality cost around whole gene or several genes. inform the treatment of patients £500,000 each. If all 50 of these Genetic testing is also proving with rare diseases, cancer and machines in the UK were put to vital in understanding the infections. work sequencing the 100,000 genetic changes in tumours and genomes, it would take eight the origins of, and risks from, years. Meanwhile, the genome infectious organisms such as It is crucial that sequences will need to be linked E.coli O104:H4 which caused to patient data, diagnosis, a food poisoning outbreak in we continue to treatment and response. Germany in 2011. push the boundaries and The Department of Health By contrast, focus group this new plan will mean we (DH) has established a wholly- research conducted for DH are the first country in the owned company, Genomics in 2012 showed the public's world to use DNA codes England, to overcome these understanding of genomics is in the mainstream of the challenges and deliver on the very limited. Some just said "I've Prime Minister’s commitment. never seen that word before". Our health service. – favourite question asked was: "Is The Prime Minister, it the economics of genetics?" 10 December 2012 What is a genome? Actually genomics is the study of genomes; and a genome is all Most of us know something of the genes in a cell, all of the Without wishing to over- about genetics, the study of DNA that codes for a human (or exaggerate, there are parallels the way particular features are mouse or elephant). Genomics with US President John F inherited by children through relates to the way that all of Kennedy's public commitment genes contributed by their the different combinations of in 1961 that his government mother and father. genes interact to determine the would land a man on the moon In healthcare terms, genetics characteristics of an individual. by the end of the decade. The is a medical speciality that deals President made this commitment with inherited disorders. These before NASA had successfully may be common and relate to sent an astronaut into orbit. changes in single genes, like Huge technical challenges had Cystic Fibrosis or Muscular There are a large number of to be overcome, and significant Dystrophy. Or they may be more research initiatives around the advances had to be made to complex due to the spontaneous world aimed at sequencing achieve a moon landing. changes in more than one gene – partial or whole genomes. Many The Prime Minister has laid sometimes whole chromosomes, of these projects, such as the down a similar bold challenge in as in Down's Syndrome. the funded the field of life sciences. There At present, the NHS UK10K Genomes project, 24

Issue 3 » January 2014 Civil Service Quarterly

have looked at sequencing the software is that it is correct. more affordable and further different healthy populations For research purposes it is external investment to develop worldwide, or focused on often sufficient for each letter firm delivery plans. people who are over 100 years to be tested (read) five times. old. Others have focussed However, for clinical use each on particular diseases, such letter has to be read many The data challenge as the International Cancer times, even up to 100 times to Genome Consortium. Most help diagnose tumours. This The sequencing of a whole focus on the small part of dramatically increases the cost genome is relatively easy the genome that codes for and the data challenges. compared to the handling of proteins, known as the exome. Sequencing whole genomes the resulting data. Each 'raw' UK investment in genomic to clinical quality at this scale sequence is over two terabytes research this century, led by the is not routine anywhere in of information, more than would Wellcome Trust, has put us at the the world. Although there are fit on 500 DVDs. With processing forefront of genomics research around four or five promising this can be reduced to less than internationally. technologies, currently the 300 gigabytes, or just over Sequencing a genome for market leader is Illumina (a US five DVDs. Once the variation research purposes, however, company that uses Cambridge from the reference genome is is a totally different prospect technology developed in the calculated this shrinks to around to sequencing for a clinical UK). There are approximately one gigabyte of information, diagnosis. Genome sequencing 50 of these machines in various mapping millions of differences is inherently prone to errors. It UK laboratories, with a further between the patient's genome requires the DNA to be broken 100 in the USA and 100 in China. and the reference genome. into thousands of pieces, The current quoted cost of a Once we have the information, probed through complex clinical whole genome is around the challenge is then to chemical reactions and then $3-5,000, and although price interpret the significance of re-assembled like a giant jigsaw reductions and new entrants the differences and arrive at puzzle so it can be compared to the UK market are already a diagnosis of the patient's with a reference genome map to being catalysed by early pilots, condition. The vast majority of highlight the differences. During Genomics England does not yet these differences are harmless the sequencing process each have the budget to complete natural variations between DNA letter is assigned a value the 100,000 Genomes project. individuals. Some of the depending on how confident We need sequencing to become differences will be obviously 25

Issue 3 » January 2014 Civil Service Quarterly 100,000 genomes

harmful – for example those personalised, or precision, in the sequencing market, recognised from other patients or medicine from genomic and reducing prices, encouraging from experiments in genetically health data to help patients. new facilities to locate to the UK, modified laboratory animals and helping identify solutions to such as mice, fish or fruit flies. the data challenges. Genomics But the vast majority are not Genomics England England has already developed fully understood and may only a partnership with the University give clues about areas for further DH civil servants have been of Cambridge, and started on the investigation or research. active every step of the way to plan to sequence 10,000 rare Our lack of understanding deliver this challenging initiative, disease patients. A collaboration of the majority of the expected leading a number of key work with Cancer Research UK was differences is the main reason areas on the science, data announced in September 2013 why the 100,000 Genomes and ethics, together with an to sequence 3,000 cancer initiative is so important. By analysis of the most appropriate patients. This will involve the combining patient’s’ whole delivery vehicle and assurance sequencing of both the tumour genomes with their anonymised framework. DH established genome and the patient's normal medical records we can Genomics England (GeL) in June genome to identify the mutations create a vital resource, open and appointed Sir John Chisholm that caused the cancer. In total to carefully controlled access as Executive Chair. He is Chair of Genomics England is committed by researchers. These include NESTA and formerly Chair of the to delivering 8,000 whole academic researchers looking for Medical Research Council, GeL genomes sequences by spring basic understanding of genetic is responsible for procuring the 2015. The scale and speed of changes as well as companies sequencing capacity, the data these pilot phases exceeds any researching new therapies or architecture, and the necessary other clinical whole genome diagnostic tests. But perhaps tools to securely store and initiative in the world. most importantly, the data could interpret the 100,000 sequences provide an opportunity for novel and allow access for clinicians data mining to develop new and researchers. Ethical challenge and public ways of visualising the patterns Sir John’s initial aim is to confidence between different genes, develop and launch the pilot genomes and clinical syndromes. phases of the programme that The development of genomics The Prime Minister's vision is will deliver a large number of since the start of the Human one where the UK is the leader whole genome sequences. This Genome Project has involved in a new industry, developing will help to drive competition a detailed debate around the ethical concerns, particularly around privacy, and fears about the misuse of data. Many of these have been addressed through policy initiatives such as making it a criminal offence to test DNA without consent, a moratorium by the insurance industry on accessing genetic test results and a recent updating by Dame Fiona Caldicott of the principles around patient data confidentiality. Since the 100,000 Genomes project promises the integration Image here. PM? of genomics research into the mainstream of the NHS there is a vital role for Genomics England and DH to play in ensuring public trust and confidence. The Prime Minister's announcement said that I, 26

Issue 3 » January 2014 Civil Service Quarterly

patients, the Government is keen to ensure that the wider aspirations of the public are included. Genomics England has already started holding public events and has plans to work closely with the established expertise such as Sciencewise, the Wellcome Trust, and the Medical The report recommended Research Council. One of five core principles to guide the key challenges is to try the programme: to demystify genetic testing, • The programme should bring genome sequencing and benefit to current patients, other diagnostic testing or future patients and to the NHS. screening. But perhaps the • The findings should be available main challenge is to reassure to patients in the NHS, and patients about how their data drive improved diagnosis or care will be protected, and to build within the NHS. trust that those accessing • Data access should be subject to the data are vital to helping to a transparent and accountable understand and derive benefit governance process and made in the public interest. from the complex information in human genome sequences. This • Consent by participants should be based on an understanding of will need to address the evident the implications of participation concerns by some patients about for themselves and of this access for the development of programme more broadly. commercial products such as • There should be a well-designed medicines or diagnostics. and comprehensive programme of public engagement. A history of advancements

The UK has played a central role in the development and application of the life sciences, Professor Dame Sally Davies, as accepted. Genomics England's from the identification of the Chief Medical Officer would be first phase relies on patients structure of DNA in 1953, responsible for overseeing the who are already recruited for the discovery of methods for interests of patients in matters clinical research, but the main sequencing DNA in 1977 (by Sir of science, data security and sequencing programme will Fred Sanger who died recently), ethics. Immediately after the involve patients being referred to the mapping and sequencing announcement I established by NHS clinicians. The Prime of the human genome in 2001. three rapid working parties which Minister's announcement The Prime Minister's reported in March 2013. The emphasised that this project 100,000 Genomes initiative Ethics Working Party, chaired would require explicit patient is part of a much wider by Professor Michael Parker consent and that all information programme to build on this from Oxford, concluded that would be handled in line with history of achievements and our an appropriate and rational other NHS safeguards. Genomics current strengths in academia, approach to ethical issues would England has established an the infrastructure of the NHS, be vital to maintain public trust Ethics Advisory Group, chaired and our partnerships in the and confidence. This should by Professor Parker, which is life sciences industry. As the build on, rather than duplicate, developing the core policies that 100,000 Genomes project existing good practice drawn will be crucial to the successful progresses we plan that the UK from other projects. delivery of the programme. will stay out in front, in the lead These principles have been As well as the individual in this, a new life sciences field.