100,000 Genomes Project demonstrates the value of embedding ethics

Yesterday, everyone who’s anyone in the UK genomics scene gathered at the Royal Society in London to celebrate the achievements of the 100,000 Genomes Project. The project recently reached its goal of sequencing 100,000 genomes from 85,000 patients with a rare disease and their families, and patients with cancer.

What it has taken to achieve this milestone is certainly impressive. Prof Dame Sue Hill, Chief Scientific Officer at NHS England, led us through some major changes that have been implemented across the NHS. These include extensive workforce training, new ways of obtaining patient consent, restructuring of the UK’s genomics medicine centres and involving multiple clinical specialities, and standardisation of data collection, storage and access – a huge feat in itself. And all this in the seven years since David Cameron first announced his big idea for making the UK the world leader in genomic medicine. There was general agreement in the room, including among visitors from Australia, France and Qatar, that the 100,000 Genomes Project is indeed leading the way internationally.

Examples of the real benefits that the project has delivered for patients were heart-warming to hear. The diagnosis of a baby with a rare genetic disorder led to treatment with simple vitamin supplements and a transformation in the child’s functioning. But American geneticist Professor David Goldstein reminded us that these cases are rare. Most patients still do not receive a diagnosis from whole genome sequencing, and for most of those who do, there is no treatment. He called for more basic biological research on how gene variants cause disease and the development of much-needed therapies.

A stand-out feature of the 100,000 Genomes Project is how patient participation and consideration of ethics have been central to the project from the beginning. Ethics has not been an after-thought, or separate from the design and implementation of the project. Genomics England has an Ethics Advisory Committee and a permanent member of staff with the job title ‘Head of Ethics’. Independent expertise from the academic community and ethics bodies, such as the Nuffield Council on Bioethics, are consulted and drawn in on particular questions. There is a standing Participant Panel made up of patients and families who have had their genomes sequenced. Project participants also sit on other committees, such as the Access Review Committee, which examines requests by researchers for access to the genomic data that has been collected. By all accounts, participants receive a high level of respect within the organisation and have a strong influence on how things are done.

Mike Parker, chair of the Ethics Advisory Committee, described how ethics can support, rather than hinder, science and medical progress. The Ethics Advisory Committee has recognised how genomics is changing medicine in significant ways. The lines between research and clinical care are becoming blurred, personalised care is dependent on data sharing by others, and patients are increasingly being asked to live with uncertainty and open-endedness. The recognition of these changes is leading to new understandings of how healthcare technologies, such as genomic sequencing, can be delivered to NHS patients in ways that gain their trust and confidence. Indeed, Genomics England reports high levels of public support for its work. Participants are often willing to take part even if they are unlikely to see any personal benefit, and they don’t seem bothered about ‘free riders’ – people who reap the rewards of genomic research but don’t want to share their own data. Professor Parker contrasted the 100,000 Genomes Project with the doomed ‘care.data’ initiative, and suggested that embedding ethics can be the difference between success and failure.

Unsurprisingly, the Nuffield Council on Bioethics has long advocated placing ethics and stakeholder and public engagement at the heart of healthcare initiatives and policy making. In 2015, for example, when we considered the collection and use of biological and health data, we recommended that governance mechanisms should be allowed to evolve during the life of an initiative through deliberation with stakeholders, including participants and the public. In 2017, we recommended the UK National Screening Committee should take better consideration of the ethical and social consequences of prenatal screening programmes, and improve its stakeholder and public engagement activities.

Matt Hancock, Secretary of State for Health and Social Care, further acknowledged the importance of ethics in his speech at yesterday’s event. He mentioned issues around data sharing in relation to genomic diagnosis, but mostly he talked about the potential for genomic testing to indicate the risk of disease in healthy individuals in future. The scientific basis behind polygenic risk scores is becoming more robust, he said. This could present opportunities for encouraging people to take more responsibility for their health, but would also raise challenges in supporting people to deal with results they weren’t expecting.

A distraction from this was Mr Hancock’s revelation that his ‘life may have been saved’ by a predictive genomic test. The test, similar in nature to the health predisposition DNA tests that can be bought over the internet for around £100, suggested he had an above-average risk of developing prostate cancer. As a result, he says, he has booked a blood test on the NHS and won’t miss any screening appointments in the future. The Minister’s response to his test results has been criticised. Professor David Curtis, of University College London, for example, said it was “a perfect example of someone massively misinterpreting such tests, which are often inaccurate”, and wasting valuable NHS time. Although Mr Hancock may have simply wanted to put himself in the shoes of people who, in future, might receive information about their predisposition to disease through the NHS, it has been received as an inadvertent plug for 23andme.

Dr Julia Wilson of the Wellcome Sanger Institute rounded up yesterday’s meeting with a look to the future of genomic medicine. She outlined a range of possible uses of (hopefully accurate) health risk prediction, such as in the selection of participants for clinical trials, in public health initiatives, and in personalised treatment regimes. We could also be seeing genomic testing technology in mobile phones, the rise of epigenetic testing, increasing utilisation of genome editing techniques, and the ability to write whole human genomes. The success of the 100,000 Genomes Project suggests that consideration of ethics in relation to these and other applications of healthcare technologies ideally should be central to any initiative, drawing on independent expertise from the academic community and ethics bodies, and with patient and public involvement.