Yes. We started by deep sequencing of very small pieces of tissue first. This led to the discovery that normal tissues such as skin or oesophagus of healthy individuals have a high frequency of somatic mutations in them, including an unexpectedly high number of cancer-causing mutations. We found that, as we age, our tissues become progressively colonised by clones (copies) of cells carrying mutations that enable them to outgrow their neighbours. It was clear to us that understanding this phenomenon better, across tissues and diseases, would likely shed light on the development of cancer, ageing and other diseases.
However, to be able to study this in other tissues, we had to develop more sensitive methods. Working closely with the Research and Development (R&D) team at Sanger, we first developed a laser microdissection method that allowed us to detect mutations present in tiny clones of cells under the microscope. This new technology has allowed us to first study somatic mutations in many different tissues in the last few years. We then developed an even more sensitive method, called Nanoseq, which allowed us for the first time to detect somatic mutations in highly diverse, or heterogeneous groups of cells, by detecting mutations down to single molecules of DNA. This technology is now enabling us to do faster and more sensitive studies of somatic mutations in many tissues and diseases.