Editorial Assistant, European Medical Journal
As innovation catalyses the potential for personalised medical diagnosis and treatment the English National Health Service (NHS) moves to embrace these notions in order to transform healthcare delivery for the benefit of the patients, society, and the economy. Amongst areas of innovation such as biotechnology, informatics, and machine learning, genetic research stands as a strong pillar of personalised medicine concept. The 100,000 Genomes Project has emerged from a partnership between NHS England, Genomics England, Public Health England, and Health Education England as one in a long line of initiatives geared toward the expansion of trailblazing areas of scientific research. Genomics England shared their progress and plans for the 100,000 Genomes Project and beyond at the NHS Innovation Expo held in Manchester, UK, from 7th–8th September 2016.
With genes representing <5% of the genome, the remaining DNA was once considered the computational ‘trash can’ of human genetic coding; now this long-neglected section of genomic data is moving to the forefront of medical interest. The project seeks to sequence the whole genomes of 70,000 NHS patients with rare diseases and certain cancers along with their families, providing 100,000 whole genome datasets with which to drive the implementation of tailored medical care and obtain fresh insights into the causes of disease. Informed by genomics, targeted treatment represents a shift from symptom-driven diagnosis to defining underlying causes through individual profiling of genomic and clinical data.
Typically, patient care begins with the characterisation of symptoms and the efforts of clinicians with organ-specific expertise. Subverting the classical paradigm of a single complex disease entity, genetic research has informed the finding that complex diseases manifest both variable phenotypic symptoms across individuals, and changes in pathogenic mechanisms within the individual as a product of senescence. Genome-wide sequencing (GWS) has enabled the characterisation of the often nuanced genetic differences or mutations that factor into these multiple iterations of complex diseases thus facilitating the development of personalised treatment plans, which have the benefits of greater efficacy and reduced side effects.
Speaking of this change in attitude, Prof Bill Newman, Clinical Director and Overall Programme and Project Lead, Greater Manchester NHS Genomic Medical Centre, Manchester, UK, stated that: “It is completely humbling frankly. The more that we do this, the more that we realise that our preconceived ideas about certain conditions are not as they should be, that we need to be more flexible, that we need to embrace this new information. We have to balance that to make sure that we are matching up the clinical features of the individuals with the genomic data that we are getting and therefore accurately being able to make full appropriate clinical assessments and marry that up with the genomic sequence data that we are able to access is really the key.”
The advantages of genetically tailored care include a quicker diagnosis and a reduction of invasive screening procedures. The technique and its implications are expected to be life-changing for certain patient groups, notably those with familial cancers, paediatric neurological diseases such as severe early onset epilepsy, and rare diseases. The pathogenesis of cancer begins with a genetic mutation and thus oncological medicine has been an early adopter of genetic stratification for more targeted treatments. Nonetheless Vivienne Parry, Head of Engagement, Genomics England, London, UK explained: “Rare disease is the area of the programme that has gone on ahead most successfully, but we are in a difficult place still with cancer which is extraordinarily difficult to do.”
Indeed, while GWS can provide a wealth of data, without a myriad of policies, training, and communication procedures in place, the full potential of GWS will not be reached. Ms Parry conceded that: “This is at the edge of science. This is a problem that has not been solved anywhere on the globe. And it is a problem that we do not want to be solved in an academic setting, by which I mean the answers may come from academia but it has got to work in Bridgend Hospital on a Saturday afternoon.” The speakers went on to emphasise that the project is not just about applying GWS to cancer profiling but more importantly, about ensuring that the NHS is equipped with the right processes and training to ensure that clinicians and administrators are able to get patients the right test at the right time.
A crucial element in this regard is the issue of consent. Within the NHS Five Year Forward View and the wider reality of personalised and integrated healthcare, the sequenced patient is consenting not only to the access of their medical records at the time of treatment but also to the access of their genomic and medical data by clinicians for future learning and the treatment of others. Dr James Fisher, Implementation Unit Director, 100,000 Genomes Project, Genomics England, London, UK, posed a question on the latter to the panellists and audience: “Is this a model that we should be using potentially outside of this project in the future?” The response was unanimous agreement. On the other hand, these procedures remain in their infancy, and as Dr Caroline Benjamin, Patient Public Involvement Lead, North West Coast NHS Genomic Medicine Centre, Liverpool, UK, explained: “As the project has gone along, the consent materials have been changed, they have adapted, and it has been a dynamic process as clinicians are learning how to use them, as patients are giving their feedback as to how to use them as well.”
How will the NHS ensure that those involved in these processes are sufficiently trained to understand and advise on the subject of genetic counselling? The discussion centred around a genomic education programme spearheaded by Health Education England that will target both specialist staff and the wider healthcare workforce to increase this understanding; plans to incorporate such training into graduate curriculums were also alluded to. Although much of these initiatives remain in the early stages of development and the reach of the 100,000 Genomes Project is constrained by the current healthcare economy resulting in a discordance between the desires of the patient and the abilities of clinicians, Dr Benjamin reflected that: “It is a journey of opening up that debate and involving [the patients] as equal partners in that debate.”