Phenotypic Drug Discovery with High Content Screening

Drug discovery in its early history used to be conducted mainly in a target-agnostic fashion, focusing on qualitative readouts from a living system -cells, tissue, or organisms -and asking the question, ‘Did this entity affect the phenotype?’. With the rise of molecular biology in the early 1980s and an ever more powerful genomics toolkit from the 1990s, there was a marked shift away from phenotype-driven approaches towards screening techniques that looked to discover molecules affecting a defined disease target in an efficacious way. Initial assays were often performed using isolated, purified proteins rather than cells with the assumption that a target-based approach was the most streamlined path to finding the next marketable drug.