A necessary hero.

Choice of a career, like the origin of a species, is remarkably contingent. Random variations in our genes combine with pulls and pushes from each person's unique mix of experience, opportunity, heroes and villains. In my case, the key push came from meeting a hero in a book.I applied to medical school because doctors made a good living, not because doctors (or scientists) were my heroes. The first two years of medical school provided my first encounters with biology as a science. My delight in ‘discovering’ ATP production in mitochondria and the molecular defect of sickle cell disease led me to think it might be fun to tackle other biological puzzles. I wondered, in an unfocused way, how insulin works, and how Listeria makes macrophages ‘angry’. Research was beginning to emerge as a possible career but I wasn't yet fully convinced. It seemed that I needed a hero, and I found one in the pages of Charles Darwin's The Voyage of the Beagle[1xDarwin, C. See all References[1].Unlike the Origin of Species, with its finely honed arguments and daunting mass of detail, Beagle tells the fast-moving story of a 23-year-old youth's sailing voyage around the world. Darwin's discoveries on this voyage, including the theory of evolution, changed his life and all our lives. Like generations of readers before me, I was enthralled not only by Darwin's passion to understand the natural world but also by the immensely appealing, larger-than-life character of the man himself.The Beagle's Darwin is not the reclusive, white-bearded patriarch we know from portraits. He is a dashing, gregarious young fellow, brimming with wondering delight and curiosity at the world's infinite variety. He climbs every mountain he comes across. His passion for geology lures him into dangerous expeditions over deserts and mountain ranges. He never fails to make a human connection — with a farmer in the Chilean mountains, with a mule driver, anyone who can tell him where to find birds, animals, unusual rocks, or old bones. Gauchos teach him how to throw the bolas on horseback, riding pellmell after an ostrich; Darwin is game, but manages to bring down only his own horse.Everywhere, Darwin is having the time of his life. After crossing the Atlantic: “Delight… is a weak term to express the feelings of a naturalist who, for the first time, has wandered by himself in a Brazilian forest.” In Valparaiso, Chile: “… everything appeared delightful… [T]he climate felt quite delicious — the atmosphere so dry, and the heavens so clear and blue with the sun shining brightly, that all nature seemed sparkling with life.”Wavering on the brink of a career in biology, I found Darwin's dash and zest exciting, but the real thrills came from watching him in the nitty-gritty practice of science, pitting observations and ideas against one another. His gourmand's appetite for carefully observed detail ranged across virtually every aspect of the natural world and his fertile imagination churned out explanations of what he saw. Never content with facts or ideas alone, Darwin constantly juggled induction and deduction, asking whether facts fitted theory and harnessing theory to direct a deeper search for facts.Today, the powerful tools of molecular biology make it easy to ask detailed questions about precisely defined molecules, but the details can seduce us away from asking larger questions. In contrast, Darwin juggled myriad observations every day, without losing sight of the big picture. The Voyage of the Beagle gives us these observations in all their amazing variety, and painted in almost cinematic detail: a Pacific atoll glitters in the bright Pacific sun; low-lying clouds curl up the valleys of the Andes, forming coves and inlets like those of a rocky coast; in Concepcion, Chile, an earthquake destroys walls that run north by northwest but leaves standing walls built at right angles to them; shapes of finches’ beaks (see FigFig) and tortoises’ shells differ on different Galapagos islands.Figure 1Original woodcut showing some of the finches whose distinctive beaks caught Darwin's eye.View Large Image | View Hi-Res Image | Download PowerPoint SlideAlmost every page reveals Darwin's passion for drawing inferences, large and small. From the pattern of destruction in Concepcion, he deduces the direction of the earthquake's undulations (from the southwest). Cloud patterns bolster his account of how the Andes were formed. The theory of evolution would not appear for almost 20 years; in Beagle Darwin offers only alluring hints: “Seeing this gradation of structure in one small, intimately related group of birds [Galapagos finches], one might really fancy that from an original paucity of birds in this archipelago, one species had been taken and modified for different ends.” It is astonishing that his short sojourn in the Galapagos — less than a month of Beagle's five-year voyage — generated the theory that ties together almost everything we do and think as biologists.For a master class in how to confront complexity with imagination, and for sheer exhilarating intellectual adventure, every young scientist should read Darwin's account (see [1xDarwin, C. See all References[1], chapter XX) of how coral atolls and reefs originate and grow. He first shows how prevailing theories got it wrong, and then constructs a new 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.”