By Michael Cape
This new NHS Genomic Medicine Centre is part of a network that is complex but vital
In December 2015, the Yorkshire and Humber region was given a key role to play in the development of personalised medicine through the establishment of a new NHS Genomic Medicine Centre.
The Yorkshire and Humber GMC is part of the national network of GMCs tasked with delivery of the 100,000 Genomes Project, which has been commissioned by the Government to take the new science of genomics to the next level. Dr Andrew Jack, a haematologist working at Leeds Teaching Hospitals NHS Trust, is leading this project as clinical director.
The centre’s role will be to collect samples of DNA (the molecule which contains the genetic code) from those with rare inherited diseases – and their family members – and from patients with a variety of common and rare cancers. Advances in sequencing technology now allow the genetic information in these samples to be read, and linking the data to patient information will provide much greater understanding of how cancers develop and the mechanisms of rare genetic diseases.
As well as offering diagnostic breakthroughs, this also has the potential to lead to new ways of tackling disease through correcting genetic faults by the manipulation of people’s genes, or by designing drugs which can counteract the effect of the abnormal gene. It will “lead to the potential to unlock a series of secrets about devastating diseases,” according to the NHS.
Previous genetics research has shown how different cancers can be, for example revealing that breast cancer is not one disease but at least ten, each with a different cause and life expectancy and each needing a different treatment. The development of targeted drugs such as Herceptin – given only if a patient’s breast tumour has a certain mutation – has been possible because of genetics research.
In the case of rare disorders, thousands of genetic diseases – individually uncommon but affecting large numbers of people when combined – could be identified by finding mistakes in the three billion pairs of letters that make up our genetic code. The resultant knowledge could give a patient an explanation for a disease that has plagued their entire life.
While this all has a long way to go to match some media claims, it shows early signs of promise in that genetics research has recently been used to detect diabetes in babies in the womb, often a hereditary condition, so opening up ways for best forms of treatment.
But what exactly is genomics? Most people will have heard of genetics, the way in which particular characteristics are inherited through genes passed down from one generation to the next. One set of all these genes (along with the DNA between the genes) is called a genome, and it is the blueprint that makes an individual the way they are. Genomics is the study of the whole genome and how it works.
Although DNA was first isolated as early as 1869, it took more than a century for the first genomes to be sequenced. The major breakthrough came in 1953 when James Watson and Francis Crick produced a description of the DNA helix. The first genome, however, was sequenced by Frederick Sanger – winner of two Nobel Prizes – in the 1970s. Along with his team he also created techniques for sequencing, data storage and genome mapping which still play an important role in genomics.
Just as important were the later technological advances and advances in methodology which led to the completion of the Human Genome Project in 2003. So if genomics has been around for some time, why is it back in the medical spotlight today?
“A key reason is that, through advances in technology, gene sequencing can now be undertaken for just a few hundred pounds in a day,” Dr Jack says. “The first human genome sequence took 15 years to complete and cost $1 billion.”
This reduction in cost means that the sequencing of DNA samples is now being offered to patients by the NHS, and a major objective is to make the new technology more widely available and transform practice across many areas of medicine.
The Government has taken a world lead in establishing the 100,000 Genomes Project, a national programme that does what it says on the tin: its target is to sequence 100,000 genomes from around 70,000 people.
The project aims to create a new genomic medicine service for the NHS, transforming the way people are cared for. Patients may be offered a diagnosis where there wasn’t one before – and, over time, there is the potential for new and more effective treatments.
The project will also enable new medical research, as combining genomic sequence data with medical records is a groundbreaking resource. Researchers will study how to use genomics in healthcare and how best to interpret the data to help patients. The causes, diagnosis and treatment of disease will also be investigated.
It is not just patients who stand to benefit from the 100,000 Genomes Project, however, as its potential impact has been compared to the knock-on effect of the introduction of railways in the Victorian era. “The 100,000 Genomes Project has some parallels,” according to the Government literature. “Whilst primarily for the benefit of people who are sick, there are potentially economic benefits for the nation.
“The 100,000 Genomes Project cannot be guaranteed to succeed, in the same way that there was no guarantee for the railways. So only the Government is willing to take the risk and make the necessary investment in it. And just as Victorian England with its great engineers was the perfect place for the birth of the railways, the UK, which not only leads the world in life sciences but has the unique benefit of the NHS, is the best place in the world to initiate the practical use of genome sequencing and interpretation for patient benefit.”
Genomics England’s legacy, the document goes on to state, will be “a genomics service ready for adoption by the NHS, high ethical standards and public support for genomics, new medicines, treatments and diagnostics and a country which hosts the world’s leading genomic companies”.
The prospective GMC had to demonstrate the effectiveness of all procedures and governance and have an IT system capable of collecting data from other systems across the region to meet its target of delivering DNA data from 14,000 people. Also, while the collection of DNA samples will be undertaken in Yorkshire, the actual sequencing will take place in Cambridge.
The regional centre is not yet up and running, but when it is it will collect DNA samples either via blood or from a sample of tumour tissue taken at the time of surgery. Before patients reach the stage of providing samples of their DNA, however, there is the important matter of consent.
“People really have to understand what they are agreeing to,” Andrew Jack says, “in that we are taking their genetic information and putting it into a national database. So people can opt in at different levels depending on the information they want to get back.”
There is also the sheer complexity of the subject, which is likely to create a logjam in demand for information and education from across the region as well as from the healthcare professionals involved in this exciting project. “It is endlessly fascinating, and a huge challenge.” Dr Jack says.
The Yorkshire and Humber Academic Health Science Network (AHSN) co-ordinated the proposal for the establishment of the regional Genomic Medicine Centre (GMC) and played a key role in bringing together the leading trusts in the region: Sheffield Children’s NHS Foundation Trust, Sheffield Teaching Hospitals NHS Foundation Trust and Leeds Teaching Hospitals NHS Trust.
The Yorkshire and Humber AHSN helped to ensure the bid was supported by the other 11 acute trusts in the region along with the major universities, There was also direct input from patients and the public, which places the people of Yorkshire and Humber at the heart of crucial developments and improvements in healthcare.
GMCs are being set up throughout the UK, with four in the North of England including the newly established Yorkshire and Humber centre. “The Yorkshire and Humber AHSN has provided invaluable support to the work to establish a GMC for the region,” says the GMC’s clinical director, Dr Andrew Jack.
“They have facilitated positive collaboration between three organisations, maximising the pooled intelligence and resources. I would thoroughly recommend using the Yorkshire and Humber AHSN as a support function to any organisation working within the health sector.”
Co-ordinating the bid has not been a simple process, requiring a strong clinical and managerial team working across all aspects including operations, IT, laboratories and patient representatives. The Yorkshire and Humber AHSN, along with Ian Atkinson (programme director for the Yorkshire and Humber GMC) and individuals from each of the organisations from the bid all worked tirelessly on the successful application.
New kind of weight-watcher
As a dietitian specialising in undernutrition, Catherine McShane was concerned that she and her colleagues were struggling to meet the demand from an increasingly ageing society with its inevitable impact on long-term conditions.
The fact that they were working in a predominantly rural area meant that house calls were escalating to a point where their ability to deal effectively with this serious condition was being undermined.
While undernutrition sits well below the public radar, it is estimated to cost the NHS £19 billion annually, twice the cost of obesity. One in every three people admitted to a hospital or care home in the UK is found to be undernourished or at risk of the condition, but treatment can improve clinical outcomes by 70 per cent and mortality by 40 per cent.
A new way of working was clearly needed, and with the financial support of the Academic Health Science Network for North East and North Cumbria, the team at the County Durham and Darlington NHS Foundation Trust has come up with an answer that not only improves capacity and quality of care but also saves money. Known as NHS Health Call Undernutrition, it is a remote monitoring system which relies on automatic telephone dialling.
Instead of being checked every three months, patients are contacted on a weekly basis and asked if they are taking their nutrients or if there has been any change in their weight. If their answers identify a risk, an alert system ensures a follow-up. A pilot evaluation has shown savings of more than £150,000 per 1,000 patients and the scheme has already been picked up in Northern Ireland.
“It ticks the two most important NHS requirement boxes,” Catherine McShane says, “in that it improves patient care for less money.”
Help test: now it’s personal
As a GP for more than two decades in a practice in the most deprived part of an area that is already in the top 10 per cent for worst quality of life in the country, Dr Chris Duffy is understandably pleased to welcome any change for the better.
He also chairs the local clinical commissioning group working with Greater Manchester Academic Health Science Network, so is more than happy that Heywood, Middleton and Rochdale – the community in which he has spent his entire working life – has been a successful bidder for “test bed” status.
What this means is that Dr Duffy’s patch will receive help to better identify and support patients at risk of long-term conditions such as chronic obstructive pulmonary disease and chronic heart disease. This help will come courtesy of the most advanced predictive techniques and in the form of a personalised service, including access to the latest monitoring technology.
As someone whose practice deals predominantly with older people – who often “don’t like bothering the doctor until they are really ill” – Dr Duffy views this proactive approach to community health as being “a significant step forward”.
While admitting that many of the determinant factors for poor health in the area remain, Dr Duffy has witnessed an improvement in people’s approach in terms of stopping smoking and thinking about healthier eating. He is convinced that the use of predictive technology through refined risk stratification will be a major benefit, as will the provision of technology such as telephone support and hand-held monitoring devices.
Or, as he puts it in day-to-day practical terms, “When people get breathless they can check for themselves whether they need to come to me or go to A&E.”
How to look out for yourself
Retired magistrate Ian Paterson, aged 71, from Lytham, has suffered from chronic obstructive pulmonary disease for the past four years. Whenever his symptoms worsen, he is unable to breathe and has to call for medical help. Now, though, he is one of several hundred patients in a “test bed”, trying out new technology so that he can monitor and manage his condition at home.
“When I first developed this condition,” Mr Paterson says, “I did not know what signs to look out for and found myself calling for an ambulance and going to hospital on a regular basis.”
The test bed in Lancashire and South Cumbria is one of a handful of collaborations between the NHS and innovators supported by the Innovation Agency, which have won Government funding to address some of the most complex issues facing patients and the health service.
The main commercial partner is Philips, which supplies equipment to people living with long-term conditions. For patients such as Mr Paterson, this will include a set of scales and a blood pressure device, connected to a tablet computer which automatically receives information on his health and notifies him if there is a problem.
“Having access to equipment like this would have helped me a great deal,” Mr Paterson says, “as I could have identified when things were going wrong and done something about it without the need to go into hospital.”
Dr Tony Naughton, the clinical chief officer with NHS Fylde and Wyre Clinical Commissioning Group, says: “The impact has to be that we stop people going into hospital, because hospitals are being overwhelmed with elderly and sick people who perhaps live alone and don’t look after their medical conditions very well.”
Led by Lancashire Care NHS Foundation Trust, the test bed partners include Lancaster University (in the form of Lancaster Health Hub and the Centre for Ageing Research), Philips, local small businesses, social enterprises, the voluntary sector and the Innovation Agency.