A global approach to studying health and disease

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Professor Nick Thomson joined the Wellcome Sanger Institute in 1999. At that time, the Institute was already creating open access resources and leading the way in sequencing at scale to provide solutions that benefit human health.

But, disease is not something that just involves humans. Scientists at the Sanger Institute were also tackling new microbiological data from bacteria, viruses, and parasites, and sequencing these at scales never seen before. The scale at which the Institute was producing data was what first attracted Nick to campus.

Fast-forward to today and Nick has recently returned from visiting key collaborators at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) to launch the long-term Climate and Health research hub. As a faculty member at the Institute, Nick leads research projects and international collaborations in infectious diseases, tracking and predicting the spread of diseases that impact the health of people around the world. In 2024, Nick was appointed Head of the Parasites and Microbes Programme at the Sanger Institute, setting out an ambitious vision and strategy for the next decade.

I like taking things apart. When I was young, I was not so good at putting them back together. I suppose that process of being a reductionist, trying to break problems down into pieces but then having the discipline of putting them back to a narrative that has impact, always attracted me.

I was adrift pre-A levels. Thankfully, at A-levels in school I was properly introduced to science.

In the history of science there are fundamental changes that happen that result in a massive leap of knowledge. The genomics revolution is one of these, and this is what drew me to the Sanger Institute.

At the time, genomics was the most exciting thing happening in biology full stop – and the Sanger Institute was and still is one of the best places in the world to do genomics. Genomics was sort of the lure, but the scale at which science is done at the Sanger Institute is what has kept me here.

The tools created at the time I was applying to the Institute were so multi-dimensional – not only were the tools created here algorithmically cool, but they also allowed researchers to look at biology in new ways. We could suddenly ask and answer questions that were impossible before genomics. The Sanger Institute developed tools, like Artemis, a genome browser and sequence visualisation software, that really had that wow factor. I just had to be a part of it!

I have many, but perhaps one of the most important was when I travelled for fieldwork to South America to study disease caused by the bacterium Bartonella bacilliformis that was more or less thought to be eradicated. This disease, spread by sand flies, is sometimes called Oroya fever or Carrions disease. It impacts indigenous communities in remote, rural areas but could be cured with antibiotics.

The challenge was getting the diagnosis and the antibiotics to the patients. While my colleagues and I were working in these rural communities, we realised there were other diseases people were suffering from, such as Leishmania, which could not be ignored.

This has taught me to think more broadly – not just selecting one pathogen to focus on, but to consider the vectors, the parasites, respiratory viruses, and to partner with local experts such as clinicians and health workers to study health from local and global perspectives.

In my group, we use genomics to ask basic scientific questions about the evolution and spread of bacterial pathogens.

My group is really great at establishing collaborative networks across the world to create genomic datasets that help us all understand how pathogens migrate over space and time through populations and across continents. Using large-scale genomic datasets provides us with high-resolution insights that can help track diseases and limit their spread. It also provides the evidence needed to inform rational policies and direct control strategies.

With genomics we can design tests that can detect microbial isolates all over the world, not just in high resource settings. We can use genomics to understand how microbes become resistant to treatments and study how they adapt to human-induced climate change.

My team focuses on diseases such as cholera and dysentery that cause significant morbidity and mortality in low-income countries, as well as a number of sexually transmitted infections, such as syphilis. These diseases individually and collectively have a major impact on human health worldwide. There are up to four million cases of cholera alone per year. A major theme in our work is the understanding of antimicrobial resistance and the impact this has on the evolution of these bacteria.

My team also develops new ways to track disease. For example, we are creating tools that enable direct sequencing of genomes from swabs used to collect a clinical sample, which is particularly important for bacteria that are difficult to grow in the lab. This allows for new possibilities to do genomics in countries with less support and infrastructure.

I am excited to be a part of collaborative studies that encompass health and disease at a population-wide scale. We are interested in not just people who are sick, but the health of entire communities. Going forward, our research questions must attempt to model the complex relationships we have with microbial life, such as how is a person’s gut microbiome and overall health affected by climate change, and how does the salt-water encroachment of drinking water impact a person’s overall health?

We work closely with collaborators in the countries where the diseases we study, like cholera, are endemic, allowing us to gain a better understanding of the bacterium and its host, as well as assess the impact these diseases have on people and their communities. We recently launched a really exciting collaboration led by icddr,b in Chakaria, Bangladesh, which is a leading global health research institute that offers a wealth of local expertise. At the icddr,b, the long-term health studies can be combined with the Sanger Institute’s genomics expertise.

This collaboration will allow us to really understand health in all its forms, as well as delve into the interplay between human health and our environment. Along with researchers at icddr,b we will expand on our previous studies looking at gut health and climate change to include more health factors, such as respiratory health and parasitic worm transmission. We want to work closely with researchers at icddr,b and apply our scientific knowledge to improve public health for communities impacted by climate change.

It is a testament to the great work already being done by our collaborators at icddr,b that Wellcome has invested in growing the research space at the Institute and I am excited to see what comes from this collaboration. Working closely with icddr,b will establish the first of our many planned sentinel sites, where sample collection and data analysis workflows will be standardised and rolled out to additional research sites worldwide.

Back in the early days, if you sequenced one Escherichia coli it was suggested you can then understand all E. coli strains. That now seems absurd. Genomic landscapes can vary greatly from one bacterium sequenced from soil to the same type of bacterium sequenced from a hospital patient. We’ve moved on from thinking at a single-species level. We now look at variation across genera and phyla. Currently, we are really good at mapping global diversity of bacterial strains. We’ve learned how major pathogens like Vibrio cholerae, which causes cholera, have spread across the world in our lifetimes.

So, looking ahead, we want to dig even deeper, something that is now possible to do because we understand more complex principles and mechanisms about how bacteria, parasites, and viruses are evolving. In the next decade, we must harness our collective expertise both at the Sanger Institute and around the world, to look further ahead. We will work towards studying what’s driving microbial and parasite evolution, their interactions with each other and us and our immune system - all at the scale of whole populations.

Now is the time for the Sanger Institute’s Parasites and Microbes programme to be more ambitious to derive new insights to unlocking infectious disease patterns. We can do this by sequencing whole genomes at the population, rather than single bacterium, level.

If I had to put my strategy for the future of the programme into three key points, I would say that we want to:

1. Study pathogens and disease at a global scale
2. Align our research with key health priorities relevant worldwide
3. Approach infectious disease in context

We are interested in answering the question how climate change and the environment influencing health status? How does prior exposure to a pathogen contribute to immune priming? These questions, and many more, remain unanswered – but our collaborative research can address them.

It takes tireless large-scale effort and collaboration to tackle lofty goals but we are ticking off incremental wins towards disease treatment, intervention, prevention, and the improved understanding of human health every day. For many reasons, technological or otherwise, there has never been a better time to be involved in research that uncovers new biology or impacts on human health. So, my advice would be: think big, be brave and be bold.