Next-generation sequencing (NGS) has transformed genome sequencing, but Clive Brown, former CTO of Oxford Nanopore Technologies (ONT), believes the next frontier in diagnostics lies in directly sensing the biochemical consequences of disease. Brown, who helped drive two decades of innovation in NGS, says that sequencing genomes ever faster may have a diminishing return beyond a few hours.
Shifting Focus from Sequencing to Sensing
Brown’s reaction reflects a broader shift in thinking, where the focus is moving from reading DNA to detecting molecular signals that reveal disease in real time. This framework comes into focus in the context of cancer, where liquid biopsy approaches attempt to detect circulating tumor DNA (ctDNA) in blood. However, these signals can be sparse, unstable, and difficult to interpret.
Tumors also release proteins, metabolites, and immune-modulating signals that may reflect disease activity more directly. Brown suggests that measuring the full complement of blood proteins might be easier and more informative than trying to find little bits of tumor DNA. Michael Snyder, PhD, professor of genetics at Stanford University, stands by ctDNA as the most mature molecular approach for early cancer detection, but acknowledges that protein signatures are emerging and may ultimately take over, similar to how cancer treatment is evolving.
The Challenge of Molecular Recognition
The bottleneck in moving from sequencing to sensing is not measurement but molecular recognition. Brown argues that the challenge lies in developing molecules that can reliably bind specific biological targets at scale. If that capability matures, diagnostics could shift from reading genetic fragments to simultaneously detecting thousands of proteins that directly reflect physiological states.
Advances in protein modeling and molecular design are enabling researchers to computationally create highly specific binding molecules.
Brown is optimistic but cautious about clinical translation, saying that while people are able to design binders to proteins, there’s no evidence yet that they’re any good.
A New Model of Medicine
The shift towards molecular sensing and continuous monitoring could transform the way medicine is practiced, with disease detection becoming a routine surveillance tool rather than a reactive response to symptoms. Snyder sees continuous monitoring as an extension of the digital health revolution, where wearable technologies and molecular sensing technologies converge to enable early detection and prevention of disease.
They see reimbursement as the principal obstacle to widespread adoption, as the current healthcare system is not designed to pay for preventive measures. However, if monitoring becomes routine and widely adopted, the economics could dramatically improve through scale, enabling healthcare systems to manage patient care more efficiently and reduce costs in the long run.
Sequencing remains foundational for discovering genes, mapping regulatory networks, and identifying disease mechanisms, but its role may shift from a clinical endpoint to an upstream discovery engine. In this model, sequencing generates hypotheses, while sensing enables real-time interpretation, allowing for a more dynamic and responsive approach to disease diagnosis and treatment.
It is a significant change.
Researchers like Brown and Snyder are working towards this new model of medicine, where continuous monitoring and molecular sensing enable early detection and prevention of disease. They believe that this approach could transform the way medicine is practiced, making it more proactive and preventive. The development of artificial sweeteners and other technologies has also led to a greater understanding of the importance of molecular sensing in disease detection.
Furthermore, the connection between the gut and the brain is being studied, with some researchers suggesting that SIBO is often mistaken for IBS, highlighting the need for more accurate diagnostic tools. As the field of molecular sensing continues to evolve, it is likely that new technologies and approaches will emerge, enabling earlier and more accurate detection of disease.
Leave a Reply