David Julius, at the University of California, San Francisco, identifies in 1997 the molecular receptor TRPV1 using capsaicin — the chemical compound responsible for chili peppers' spicy sensation — as a search tool: Julius reasons that if he could identify the gene producing the protein capsaicin binds to, he would have found a real sensory receptor, and indeed discovers a membrane ion channel activated both by capsaicin and by physically painful heat, providing the first molecular identification of how nerve cells detect high temperatures. Ardem Patapoutian, at Scripps Research, identifies in 2010 a completely distinct family of proteins, called Piezo, responsible for mechanosensation: the sense of touch and the ability to detect direct physical pressure on the skin or other tissues, using an ingenious experimental method that systematically presses individual cells with a micropipette until identifying which ones stop responding when candidate genes are selectively removed. Together, these discoveries resolve fundamental questions of sensory physiology that had remained without a molecular answer for more than a century since the first systematic studies of the senses: how the nervous system converts physical stimuli — heat, cold, mechanical pressure — into electrical signals interpretable by the brain, knowledge fundamental to developing new analgesics specifically targeting these receptors without the side effects of conventional opioids.