Disease Detectives: How do we solve the Cluedo of human disease?

This Dining with Dinosaurs talk was about solving the mysterious of human disease. It was a big topic but I was sure the speaker Prof Mark Coles (Theme Lead of Cellular Life and Professor of Immunology at the Kennedy Institute of Rheumatology) would carry it with an optimal balance as he always does.

The talk centred on the ultimate question in medical research – “Is it possible to manage, eradicate or cure all human disease (by 2100)?”. This is a triple-barrelled question, but even the least ambitious part to manage all human disease (properly) seems unattainable – and that was what Mark thought few years back when the Chan Zuckerberg Initiative proposed such a blue-sky mission. Since then, however, there have been major technological breakthroughs in understanding the mechanisms driving human disease, in rapidly generating new therapeutics, and in rapid and low-risk drug development approaches. These advances persuaded Mark to change his mind.

One of the monumental breakthroughs was the establishment of The Human Cell Atlas; essentially a map of the human body at a “single cell” resolution. The vast amount of data, representing the complexity of every bit of the human body down to the single level, has revolutionised our approach and efficiency in understanding pathogenic mechanisms and identifying therapeutic targets. For example, it became possible to quantify inflammation across tissues and time, and the effect of perturbation with therapeutic interventions. These also enable in silico (i.e. computer-based) simulations of virtual patients and analysis of incredibly rich cross-tissue data.

Another major advancement, in many ways, was amplified by the COVID-19 pandemic. During the global crisis, the world witnessed how close collaboration between academics, pharmaceuticals, governments, and international agencies can produce reliable therapeutics saving millions of lives within a fraction of the usual development timeline (10+ years). With the explosion of data on human cells and an enhanced understanding of mechanistic biology, we can now apply machine learning and simulation approaches to conduct virtual clinical trials, facilitating adaptive trial designs and personalised medicine.

Before coming to the talk, all I knew about “single cell” technologies was that they are fancy cutting-edge stuff. I still don’t know what they really are, but with Mark’s CLUEDO framework I began to appreciate the great promise of this field of research: “if we know the map of cells in a disease pathology (where?), we can identify which cell is pathogenic (who?) and how it is mediating the pathology (how?) and thus we can develop therapeutics to target it”.

The talk was followed by an engaging discussion with Dr Calliope Dendrou and Prof Tom Freeman about the distinctive roles of academics and pharmaceutical industry, and their partnership in therapeutics development (via the Oxford-Janssen Cartography Collaboration), and the unique challenges and excitement for academics to run spinout companies for drug development.

Then it was game time with the Reuben version of CLUEDO – which I sadly missed for returning home to feed my two always-hungry house rabbits… And I went to sleep pondering about the secret passage between the President’s office and the college bar. I hope they have retained the carefully crafted Reuben CLUEDO in the common room!

Was Mark Coles the guilty party in the Reuben Cluedo game?