Categories: Sanger Life28 February 20225.9 min read

The power of sharing

This Rare Disease Day, Professor Matt Hurles, Head of Human Genetics at the Wellcome Sanger Institute, shares his thoughts on what needs to be done to progress rare disease research

There are an estimated 7,000 rare diseases, which are defined as conditions affecting less than one in 2,000 people. Globally, over 300 million people have a rare disease – collectively they are far from rare. Often genetic, rare diseases can have profound and debilitating consequences. Most do not have treatments.

Matt has led some of the most important rare disease research projects over the last 20 years, leading to advances in diagnosing and understanding these conditions, bringing answers to thousands of families.

From applying research technologies to multiple diseases, to combining data across international borders, he reflects on the challenges, and huge potential of sharing to make research quicker, cheaper, more powerful and more representative.

Research has the power to change things for rare disease patients, starting with understanding the causes of disease. Pinpointing the genes responsible for a condition not only advances understanding and brings the potential for developing new treatments, it also gives people a diagnosis, ending the ‘odyssey’ faced by so many families. It can enable people to connect.

Three opportunities and challenges in rare disease research

The major challenge of rare disease research is that there is a fundamental mismatch between the large number of rare diseases and the comparatively small number of researchers working on them in academia and in industry. We need to find ways of working that we can generalise and scale across diseases. While this is relatively straightforward for genetic diagnostics, where the same test can be applied across all genetic diseases, as soon as we start investigating the biological mechanisms underpinning disease, researchers fragment into groups working on different genes, proteins, pathways, cell types and disease models. To some degree, this is inevitable due to the complexity and richness of human biology and the myriad of ways in which it can go wrong.

However, the research community can do more to work across diseases by applying similar technologies to diseases that involve similar areas of biology. Sometimes researchers can get fixated on applying the latest, coolest, most expensive technology to a single disease. I would anticipate that applying the same experimental technologies across even a small number of diseases will catalyse important insights from comparing across these diseases. It will give us a much better understanding of the strengths and weaknesses of the cutting edge technologies that we use, which will render the science more reproducible and higher quality.

Facilitating research use of excess clinical samples should make research quicker, cheaper, more powerful and more representative.

Second, there is strong alignment between patients (and their families) and researchers in terms of data and samples. Patients are typically willing to donate both samples and data for research, and this matches what researchers need to progress the scientific understanding of their diseases. However, there is a fundamental mismatch between what patients are willing to donate, and what our national infrastructure that supports and governs trustworthy research is capable of delivering.

While great strides have been made in making routine clinical data on patients who have consented for research available to researchers in secure ways, all too often parts of our national health service fail to respect the consent that research participants have given for their data to be used for research. For example, while a researcher can study hospital data on participants in the 100,000 genomes project, they cannot analyse data from GPs, even though people have consented to share these data. A similar situation is true for English participants in UK Biobank (which includes my parents). This leads to a partial and biased view of the clinical features of rare disease patients. This is a separate issue to the use of health data on patients that have not necessarily consented for research (e.g. the debacle around This issue is more about respecting the desires of people to participate in research and their wishes for their clinical data to be used securely and confidentially to further understanding of their condition.

Rare disease patients are also typically very willing to provide biological samples for research. They often provide many biological samples for their clinical care over the course of a year, and often consent for any remaining material to be used for research purposes. However, very few of the biological samples managed by the NHS ever make it into researchers hands. The logistical and governance barriers are currently too onerous, although other healthcare systems have managed to overcome these. The consequences of this challenge are that researchers often have to set up parallel systems for obtaining biological samples from rare disease patients for research, which makes the research much more expensive and slower than it needs to be. It also potentially leads to certain groups being underrepresented in research studies, especially those living in the most challenging circumstances. Facilitating research use of excess clinical samples should make research quicker, cheaper, more powerful and more representative.

Thirdly, secure global data sharing has been hugely powerful in identifying new rare diseases and enabling more accurate diagnoses. Rare disease patients have the most to gain from their data being shared in proportionate ways that maximise potential benefits while minimising risk. For example, the DECIPHER initiative, which I co-lead with Dr Helen Firth at the University of Cambridge, has been going for 18 years and has shared data on over 40,000 rare disease patients, resulting in over 2,500 publications, hundreds of new collaborations and thousands of new diagnoses.

As national genomic medicine initiatives take off and roll out advanced genetic diagnostic testing to more and more patients, we need to make sure that rare disease patients are still able to share their data internationally. There is a risk that as national genomic medicine initiatives establish secure and trustworthy data infrastructure, which often involves making the data accessible only through ‘Trusted Research Environments’, that rare disease patients lose the ability to share their data internationally. Clinical trials in rare diseases are often international in nature, simply to identify sufficient numbers of suitable patients. With genetic testing in healthcare systems increasingly being centralised, there is an opportunity to make it much easier for patients to identify and participate in clinical trials and other research studies. The Global Alliance for Genomes and Health (GA4GH), of which the Wellcome Sanger Institute is member, is providing leadership, tools and standards for responsible international sharing of genomic data. However, healthcare systems tend to be very nationally-focused, and we will need to work internationally to bring this vision to reality. systems tend to be very nationally-focused, and we will need to work internationally to bring this vision to reality.

I’d really welcome thoughts and ideas about how to address these challenges and make the most of the opportunities.

I’d like to take the opportunity to thank rare disease patients and their families for engaging in scientific research.