Structural genomics

theory, based on the shape and location of coral formations, on coral’s inability to grow at depths greater than 30 fathoms, and most of all on a scenario for which he had no evidence: that each reef or atoll represents the outer limit of an island that has slowly subsided into the ocean. Read this chapter, if only to be struck by its masterly fusion of acute observation and trenchant imagination, capped by Darwin’s challenge: “... I venture to defy any one to explain in any other manner how it is possible that numerous islands should be distributed throughout vast areas — all the islands being low — all being built of corals, absolutely requiring a foundation within a limited depth from the surface.” Although no more than the product of Darwin’s imagination in 1839, the theory is now known to be correct. Three decades ago, Darwin’s heroic image helped push me into a career in cell and molecular biology. For biologists of the 21st century, Beagle’s message has become even more critical. We are inundated with floods of information about genomes, regulatory mechanisms, molecular machines, protein folds, developmental programs, neural networks and social behaviors. Overwhelmed by the challenge of trying to understand life in all its complexity, we may turn to easier tasks, such as mutating an active site, knocking out a gene, tagging another protein with GFP — like 19th century naturalists naming yet another beetle or, even, another finch. Real imagination is hard work, and it’s tempting to avoid dealing with complexity. Darwin’s example can help us resist this natural temptation. We cannot hope to match his limitless energy and penetrating intelligence but we can try to emulate his spirit. This means being open to new experience and ideas. It means trying always to focus on the truly big questions, realizing that the problem at hand is never more than an example. Perhaps most important, we must learn to take delight in using our imagination, especially at the edge of what we know. As Darwin wrote: “The limit of man’s knowledge in any subject possesses a high interest, which is perhaps increased by its close neighborhood to the realms of imagination.”