First Actin-binding Protein, circa 1975

It was 1975, and Thomas Stossel and John Hartwig were baffled by the "ugly precipitate" in the bottom of their test tube. Eager young biologists, the Harvard friends had set out to solve the mystery of how cells crawl. The field of cell movement was abuzz with the revelation that non-muscle cells contained actin and myosin, but no one understood the mechanism regulating those cytoskeleton proteins. Many researchers believed the protein contractions were controlled by calcium, similar to muscle cells. Stossel and Hartwig decided to purify myosin from white blood cells as a way to find the "magic calcium stuff," recalls Stossel. Instead, their test tube was filled with some "contaminant": A high molecular weight polymer they would soon identify as the first actin-binding protein, later called filamin A.