Exactly 5 weeks from today Festival of Genomics California will open its doors, kicking off three days of presentations, workshops, discussions and debates designed to drive forward the progress of genomic medicine. Among the multitude of speakers will be Dr Tom Fowler, Director of Public Health at Genomics England


The 100,000 Genomes Project is about a lot more than just hitting a number. It’s about getting in place the processes and infrastructure required to successfully integrate genomic technology in the national healthcare system. It is an extraordinary challenge, and one that requires an incredible joint effort from a lot of groups and individuals.

Several members of the Genomics England team have been busy engaging with the public, answering all manner of questions. They have been equally active in engaging with the global scientific community. Ahead of his presentation at the Festival of Genomics in California, Tom gave us a valuable insight into how to manage a large-scale sequencing project.

FLG: The question we get asked a lot when we speak to family members about the 100,000 Genomes Project is ‘What does it mean for me?’ What answer should we be giving to people who don’t have a genetic education?

TF: Some patients involved in the 100,000 Genomes Project may benefit because a better treatment is identified for them or their condition is diagnosed for the first time. The potential of genomics in healthcare is huge, leading to earlier diagnosis, better treatments and potentially, in time, new cures. For most who have consented to take part, the benefit will be in knowing that they will be helping people like them in the future through research on the genome data they generously allow to be studied. Everyone who takes part will be helping to develop a genomic medicine service for the NHS, available to any patient who might benefit.

FLG: You have a tremendous amount of government buy-in at the moment. How do you keep expectations realistic while keeping backers and investors excited enough to back the work you’re doing without over-hyping?

TF: Because this really is exciting there is huge international interest in this area and great potential for this to make a real difference to lots of people. However because this is at the cutting-edge of science and healthcare, you’re absolutely right that it’s important not to over-hype or give false promises to patients.

FLG: Cancer is one of the big areas of focus for the 100,000 Genomes Project, and is often cited as one of the lowest hanging fruits for genomics. That’s a misleading statement at times as we’re not exactly talking about curing cancer, but making cancer management a lot more efficient. What’s the goal when it comes to cancer for the 100,000 Genomes Project?

TF: One of our aims in the cancer programme is to optimise the quality of cancer genomes routinely collected in the NHS. Up until now, the way that cancer tissue has been processed in hospitals has meant that the DNA extracted from the samples did not produce a high enough quality for whole genome sequencing. Our goal is to establish the evidence base to define in detail the absolutely best methods or pathways for cancer tissues. We are currently conducting such experiments and we have a wide range of scientific experts across the UK working with us on these. In time, this work will contribute to transforming the NHS through the application of genomics to better inform cancer patient care.

FLG: Another big area for the 100,000 Genomes Project is rare diseases. If we’re talking about low hanging fruit, this certainly seems like an area with an exceptional amount of promise. What were the criteria against which you made the decision to include diseases in the scope of the project?

TF: When the Project was first established, rare diseases, cancers and infectious diseases were chosen because these are the areas where we anticipate genomic medicine will offer the strongest prospect of patient and scientific benefits and the ability to drive NHS transformation. 

Our current rare disease list is based on where there is unmet need. However the list will evolve throughout the life of the Project and there is a mechanism to nominate additional rare diseases via our online form. This will inform the way that healthcare in these areas will be provided in the future, which we hope will benefit many patients affected by conditions not currently covered by the programme.

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FLG: People are a little more familiar with the work that you guys are doing on cancer and rare diseases. But people forget that infectious diseases are also part of the focus of the 100, 000 genomes project. What are the areas of focus and goals for infectious diseases?

TF: The infectious disease strand is being led by Public Health England. There is significant extant infrastructure to do this within the NHS, which Public Health England will harness to undertake a number of pilots. Currently there is a focus on human immunodeficiency virus, hepatitis C virus, and tuberculosis.

FLG: At the Festival of Genomics, Craig Venter delivered one of the most retweeted quotes of the week “a genome without phenotype is almost useless”. It’s not an isolated sentiment. We’re at the point now where people recognise that limitations of understanding complex diseases through genotypic data. What kind of information are you collecting through the 100,000 Genomes Project?

TF: Alongside genome sequence data (from samples of blood, tissue, and saliva), we are collecting clinical data and healthcare records of our participants. Participants are explicitly asked to consent to us being able to link to their healthcare records for the rest of their lives. This creates a powerful resource for research. Participants can withdraw from the Project at any time.

FLG: We can’t talk 100,000 Genomes Project without mentioning GeCIP (Genomics England Clinical Interpretation Partnership). The temptation is to focus on the sequencing effort, but GeCIP is what is going to be putting all of that data to use. We saw the GeCIP domain lead researchers announced earlier this summer. It’s like reading a list of ‘who’s who’ of UK researchers! What are you hoping that they’ll deliver through their work?

TF: We never could have imagined how positive the response to GeCIP would be from researchers, clinicians and trainees when we called for applications last year. Within their domains, the GeCIP community will constantly refine the clinical interpretation of the 100,000 genomes dataset. A core aim of GeCIP is to optimise clinical reporting to inform diagnostics and treatment decisions for patients. The GeCIP programme provides a research platform to enhance our understanding of genomics and its application within a healthcare setting.

FLG: It’s not just disease specific research either is it? You have groups looking at Electronic Records, Education and Training, Ethics, and Health Economics as well. How big of a transformational impact are you hoping GeCIP will have?

TF: While at the heart of GeCIP we’re looking at how to bring benefits to patients, it isn’t just about disease-specific research. The cross-cutting domains are going to play an important role in bringing research and clinical practice closer together, realising the hybrid approach of the 100,000 Genomes Project as an NHS transformation and clinical research programme.

FLG: Genomics England recently announced the winners of their own ‘bake off’ for Clinical Interpretation Systems. That kind of head-to-head evaluation is a huge vote of confidence for the four companies who made it through: WuXi NextCODE, Nanthealth, Omicia and Congenica. How receptive was the field to going through that kind of competition?

TF: The field was very receptive to taking part and we’ve had feedback that this was often as useful for the companies that took part as it was for us. Going through the bake-off was informative of which companies had a robust service and understood the diagnostic space. In terms of our evaluation process of these service providers, it boiled down to understanding the difference between clinical diagnosis and gene discovery and how they complement each other. Do they bring algorithms from the research space that can help prioritise variants?

Do they understand what constitutes a diagnostic test and the rigour around it? Do their systems support a wide range of genetic presentation, do they have solid software platforms and can they provide a reliable service?

FLG: The work you’re doing today is really driving at increasing our understanding of the diseases that fall under the scope of the project. At what point does that data and understanding start to lead to new therapies and potential cures?

TF: At this early stage of the Project, we’ve started working with industry (i.e. GENE Consortium) to make the most of companies’ expertise in developing new diagnostics and treatments. The requirement on all members of the consortium to share their learning and results in a collaborative environment will ensure that the 100,000 Genomes Project and its partners can turn research findings into treatments, diagnostics and benefits for patients as soon as possible. While new therapies and cures will take longer to realise, the first rare disease diagnoses have already been returned to two families through the pilot phase of the project.

FLG: Commercial partnerships have the potential to help make Genomics England financially self-sustaining to a certain extent. How important is it to try to generate funds through leveraging the database?

TF: A key aim of the project is to kick-start a UK genomics industry and bring benefits to patients through the development of new medicines and treatments. It has always been the case that medicines and diagnostics are developed outside the NHS and government by the private sector. However as we are wholly-owned by the Department of Health any surplus income generated by Genomics England will be returned to the UK taxpayer.

FLG: You’re also being very protective around not just who get’s access to the database, but how they access it as well. What approach did you take to data security?

TF: Patient confidentiality and protection is a cornerstone of the 100,000 Genomes Project. When dealing with highly sensitive patient data Genomics England has an obligation to use information responsibly. We have developed comprehensive information governance policies to ensure maximum medical benefit whilst always respecting and safeguarding patient privacy. This is why researchers will only be allowed access to de-identified subsets of the data for approved research purposes, within a secure, monitored data environment.

FLG: What’s next for Genomics England? There’s still a lot of work to go to reach the 100,000 number, and integrate genomics into healthcare. Are there plans to include other research domains further down the line?

TF: We are due to open a call for additional GeCIP domains shortly.

FLG: What advice would you give to other countries looking to set up their own large scale sequencing projects?

TF: Come and talk to us!

FLG: We’re very excited to hear you speak at the Festival of Genomics in California in November. What are you hoping to learn from the US genomics crowd?

TF: Genomics is such a fast-paced area so it’s absolutely essential to keep up-to-date with experts in this field. By engaging with colleagues from the around the world – that’s the only way that we’re going to fully transform healthcare in the UK.

FLG: Thank you so much for your time. Is there anything else you’d like to let people know?

TF: We are keen to harness the expertise of international researchers and companies in the genomics arena. This is why GeCIP is open to international collaborators so please visit our website to find out how you can engage with us.

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