Partnering up to develop genomic medicine for the next generation

The Generation Study aims to sequence the genomes of up to 100,000 newborns and screen them for over 200 rare and actionable genetic conditions to improve early diagnosis and treatment. This pioneering study, run by Genomics England in partnership with the NHS, reflects years of public consultation, drawing insights from families affected by rare conditions, members of the public, healthcare professionals, policymakers, and scientists. With recruitment underway in multiple NHS Trusts, Barts Health NHS Trust has recently gone live in the study. Here, we speak with Alice Tuff-Lacey, Programme Lead for the Generation Study, about the significance of the programme.

 Note the views expressed herein are those solely of the author.

What are the current trends nationally and internationally in genomics research and how does this fit into what is happening here in North East London?

In my nearly 10 years with Genomics England, I’ve seen tremendous growth – from the 100,000 Genomes Project to the establishment of whole genome sequencing (WGS) as a clinical service for diagnosing cancer and rare diseases. We’re now on the cusp of a significant shift: exploring how we can use genomics as a preventative tool, not just for diagnosis.

The Generation Study is a critical part of this evolution, where we’re examining how WGS can be used to help diagnose and treat rare conditions by screening newborns for genetic changes associated with more than 200 treatable rare genetic conditions.

Since I started working on the Generation Study three years ago, there were only about six international projects focused on genomics and newborn screening. Today, that number has grown to nearly 30. Globally, there’s also rising interest in areas like pharmacogenomics, and we’re beginning to see a shift internationally toward using genomics in a more preventive capacity.

We are really excited that the Generation Study has now opened for recruitment in three Barts Health NHS Trust hospitals – Whipps Cross, the Royal London, and Newham. Working with multiple Trusts is key to us understanding how this could work across the NHS, which is why having trusts like Barts Health join us is so important.

We also know that genomic datasets that are used for research disproportionately consist of individuals of Northern European ancestry – Barts Health covers an area that is very diverse, and encouraging equitable participation in genomic research can help make genomic medicine work better for all.

What makes the Generations Study unique and how does the programme showcase the UK’s leadership in genomics research and innovation?

Around nine children are born every day with a rare genetic condition that could be treated, and it typically takes about five years to get a diagnosis. However, if we can identify these conditions early and start treatment before symptoms cause irreversible harm, we can often achieve much better outcomes.

A really good example of this is spinal muscular atrophy (SMA) which causes progressive muscle weakness and can be life-limiting in childhood. Often, parents only find out their baby has SMA after the child starts to show serious symptoms, by which point the options for treatment are limited. But if they have another child and genetic testing shows SMA early, that baby can receive treatment right away. This early intervention can be life-changing, turning what might have been a future of limited mobility and severe challenges into one where the child can run, talk and thrive. It’s a powerful reminder of how crucial timing can be in genetic screening.

The Generation Study is crucial because it shifts our approach from diagnosing conditions after symptoms appear to screening at birth, using whole genome sequencing to identify potential issues before symptoms even start. But we can’t simply assume this is the right thing to do, which is why research like this is so important. It helps us gather the evidence to determine if this method is clinically useful and how it could work within the NHS. We need to fully understand its potential impact on the system and on families before moving forward.

I think what makes this study unique, especially when you look internationally at other projects, is that while many are looking at the clinical utility of whole genome sequencing in newborns, few are doing it on a national scale. Our partnership with the NHS is crucial because it lets us take a broader, more holistic approach.

The study is being run across around 30 NHS trusts, and it’s exciting that Barts Health is one of the sites that has now gone live. Recruitment is already underway in the national study – we’ve signed up over 2,000 participants and collected over 1,000 samples. Things are starting to really take shape, and it’s great to see results coming through.

What role does the UK government play in supporting genomic research and implementation, and how has this benefited projects in North East London?

The study is fully government-funded, with financial support from the Department of Health and Social Care. In my experience, I’ve seen how government funding can really accelerate research, driving further investments and partnerships. A great example of this is the 100,000 Genomes Project, which, like this study, was fully government-funded and focused on understanding how diagnostic genome sequencing could be implemented within the NHS.

From there, we saw significant further investments through collaborations with industry partners and ongoing research partnerships. These have helped us explore the use of new technologies and how we can utilise the data generated by the 100,000 Genomes Project to help further diagnosis and treatment across rare conditions and cancer.

For the Generation Study, while the primary goal is to understand if whole genome sequencing can help detect rare conditions, but we also ask mothers for consent to retain their baby’s genome data and link it to health information over time – approved researchers can then access this data without knowing the babies’ identities.

This will allow us to evaluate the study over time to understand whether and how this approach works, as well as enable further research questions to be asked of the data. This has the potential to significantly advance our understanding of how to diagnose and treat rare conditions more effectively and both academia and industry play a pivotal role in this. It also means that data collected in North East London may not only improve diagnosis and treatment for our local population, but across England and beyond.

Parents can withdraw their babies’ data if they choose, and our engagement and user research with parents and the public has indicated that people see the potential benefits of contributing to research that could help others in the future, so long as this is done with transparency and the right safeguards are in place.

How does the partnership between local healthcare providers and academic institutions in North East London contribute to advancements in genomic medicine?

Throughout my career, I’ve seen firsthand the value of collaboration between healthcare providers, academic institutions and industry. Clinical applications of research can’t be developed in isolation – doing so makes it much harder to bring those solutions into real-world healthcare settings. The Generation Study is a great example. While we could have simply assessed the impact of whole genome sequencing on families, which is vitally important, we also recognised early on that we needed to understand how this could work within the NHS.

Our partnership with the NHS is so crucial because it allows us to understand what it would take for the healthcare system to adopt this kind of technology. If the evidence shows this is the right approach and it’s decided this should become a clinically commissioned service, our work with the NHS should help speed up clinical adoption, as we’ll have already navigated some of the challenges and learned from them.

If we were to focus purely on research, we’d run the risk of facing major hurdles when trying to scale up to a national health system, which could slow down progress. Take the Baby and Mums Sample Study we ran with Barts Health as an example. It was a feasibility study to explore which sample type would be most suitable for whole genome sequencing, balancing the need for high-quality results with the practicalities of what was feasible to collect within hospitals.

The experience helped us choose the right sample type for the main study, which not only improved the quality of the results but also made the rollout smoother and faster, with fewer implementation challenges.

How do you engage with families and communities around concerns about privacy and consent, and the potential wider use of genomic data, particularly with newborns who cannot advocate for themselves?

Public trust is absolutely crucial for projects like this, and Genomics England has always valued the importance of engaging with the public to ensure that trust is earned and maintained.

From the very beginning of the Generation Study in 2020, we made it a priority to understand public sentiment about using whole genome sequencing for newborns. We held a public dialogue where we asked people whether they thought we should use this technology in this way, and, overall, there was broad support. However, the public also raised important concerns, such as the need to focus only on conditions that appear in early childhood, not those that manifest later in life. This feedback became a guiding principle for the study.

As part of our ongoing commitment to transparency, we also conducted a follow-up dialogue to explore how people felt about the potential use of genomic data for further research. We brought together members of the public really to understand how they felt about the data being used in that way, how they would feel about different data sets being accessed and, again, where their red lines were.

Looking ahead, one of the more complex ethical issues we face is the possibility of using newborns’ genomic data throughout their lives for future healthcare purposes. We’re currently working with the same groups from our earlier dialogues to explore the risks and benefits of this potential approach. This ongoing conversation is vital. It’s not a one-off discussion, as people’s views on data use will evolve over time.

As the children in the study grow up, we will need to think carefully about how we engage them in the research. How will we seek their consent as they become adults, and what information will they want to receive? We can’t predict what their lives will look like in 10 to 15 years, so it’s essential that we continue these conversations and remain responsive to their evolving expectations.

As society changes, so too will expectations about how genomic data is used, who accesses it, and how people want to be informed. It’s about building a foundation of trust that lasts and adapts as new questions arise.

While the Generation Study aims to improve health outcomes, how do you ensure that these genomic advancements benefit all communities equally, especially in diverse regions like North East London?

Ensuring that genomic advancements benefit all communities equally, especially in diverse regions like North East London, is crucial. It’s a complex challenge, and there’s no one-size-fits-all solution, so we approach it from multiple angles to ensure accessibility for everyone, regardless of their background.

From the early stages of the study, we made sure to include diverse perspectives in our research. We conducted user research to develop recruitment materials that would resonate with a broad range of communities. For example, we specifically consulted with groups like the Black Motherhood Group and worked with organisations to understand the concerns of different communities, particularly those from various faith backgrounds, to ensure the study was accessible and sensitive to their needs.

One key takeaway from a feasibility project we conducted with Barts Health, which focused on understanding sample types for whole genome sequencing, was the need for multi-language approaches. During that study, we translated a video for the Bengali community, and for the main study, we’ve worked to ensure our materials are translated into multiple languages to make them more accessible. We are also currently exploring how people from different linguistic backgrounds might interact with our website, and we’re continuously working on improving accessibility.

Additionally, we are working with the existing regional network of NHS Genomic Medicine Alliances to develop community partnerships in their areas and understand what other ways we could make the study more accessible.

It’s an ongoing process, and there’s no single solution, but by considering all these different angles, we can try to make sure the study is as accessible and inclusive as possible.

What are the potential implications for parents receiving genomic information about their newborns, particularly regarding choices around health interventions or family planning?

Genetic information can have wide-ranging impacts not just on an individual, but on their wider family as well. When parents receive genomic information about their newborns, particularly in relation to rare conditions, this can bring about a range of emotions and questions about potential health interventions or family planning.

To address this, we’ve established clear principles about which conditions we’ll screen for in the study, ensuring that the conditions we focus on are those that present in early childhood and are treatable in the NHS. Equity of treatment is a core principle of the study – no matter where in the country a baby is born with a condition, there must be a clear treatment pathway and confirmation process.

We’ve worked with the NHS to develop these pathways including timely access to study-funded genetic counselling, to ensure that clinical teams across different regions are ready to support these babies and their families during this challenging period.

Beyond this, we’ve also engaged with the rare disease community to understand how best to support parents once a condition is identified. We’ve worked with relevant charities to create specific content materials for families, ensuring they are well-informed about the study and what it means for their child. This collaboration also helps to ensure that the necessary support structures are in place to guide parents through the process, offering them the right tools to make informed decisions.

Some argue that genomic research can get ahead of practical applications. How do you ensure that findings from the Generations Study translate effectively into real-world clinical benefits?

Our partnership with the NHS has been key. From the very beginning, we worked closely with NHS trusts and other stakeholders to test the feasibility of the study, including the baby and mum sample study with Barts Health, which helped us assess whether different sample types could be used effectively for whole genome sequencing.

A crucial aspect of the study has been co-designing the process with the key stakeholders involved, including midwives and paediatricians, to ensure that the study works smoothly in real-world settings. As we deliver the study, we will continue to engage with various NHS trusts, ensuring the practical elements are well-tested on the ground.

In addition to the design, a key focus has been developing a robust evaluation framework that allows us to assess the study’s impact on both the parents and the NHS. This framework will help us understand how the study fits within the NHS, the challenges we might face, and provide evidence to inform future decisions about whether genomic sequencing should be adopted as a clinical service.

By addressing these practical considerations early on, we’re laying the groundwork for the effective translation of this research into clinical practice.

Could you give us some examples where genomic testing has led to earlier intervention and better outcomes for babies and young children?

A great example is the 100,000 Genomes Project. A paper in New England Journal of Medicine in 2021 showed an increase in yield of genomic diagnoses made in patients with the use of genome sequencing across a broad spectrum of rare diseases as a result of the project. The NHS Genomic Medicine Service, which has been established as a result of the success of the Project, now plays a crucial role in diagnosing rare conditions on a daily basis.

Another great example is the rapid whole genome sequencing service for critically ill children. This service allows clinicians to quickly analyse a child’s genome based on their symptoms to enable more timely, accurate interventions.

Looking ahead, the Generation Study builds on this foundation by exploring how we can use whole genome sequencing to diagnose rare conditions even before a baby shows symptoms. By identifying these conditions early, we can help babies receive treatment as soon as possible, improving their chances of better health outcomes.

What is the long-term vision for genomics in the UK, and how do you see North East London continuing to lead in this field over the coming years?

I think we’re on the edge of something really exciting – the potential to use genomics in a more preventative way. Could we, for example, reach a point where every baby in the UK has their whole genome sequenced at birth? And if so, could we then use that information throughout their life for ongoing screening, checking for conditions that might emerge later in childhood or even adulthood? Could it even help us identify adverse reactions to drugs? There are lots of exciting potential for how the genomics landscape could change in the next 20 years.

But as we look to these possibilities, it’s as crucial that we do so with the public’s support. We can’t assume that all of these advancements are automatically the right direction for society. We need to keep having that ongoing conversation about what people are comfortable with, where their red lines are, and how those boundaries might evolve over time. That’s why it’s so important to collaborate with diverse communities, trusts such as Barts Health and organisations nationwide to ensure these innovations are both beneficial and aligned with the values of society.

About the author

Alice has worked in complex research and healthcare programme in genomics for the last 12 years. She has worked for Genomics England since 2015 across its programmes in rare disease and cancer with a particular focus on helping define programmes of work and working closely with NHSE and other groups to help deliver them. Prior to that she worked at Cancer Research UK on the set up and delivery of their Stratified Medicine Programme. Her current role in Genomics England is leading the Generation Study.