| Molecules to observe and manipulate biological systems can be devised by a variety of strategies, ranging from pure chemical design and total synthesis to genome mining and high-throughput directed evolution. Examples of both successes and failures will be chosen mainly from my own experience, including calcium and sodium indicators, caged second messengers, molecular voltmeters and photomultipliers, fluorescent proteins, genetically encoded indicators of intracellular biochemistry, and clinically applicable peptides to target human tumors. |