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What are the conditions that create a ripe environment for innovation? This is a question that is hopefully entertained by all managers, whether they work at the world’s Dunder-Mifflins or the Fortune 500. For people working in creative fields, fostering innovation and discovery is not a luxury but the bottom-line. Countless business school cases and their book-length offspring have taken on this question. A popular approach, not at all unreasonable, is to analyze proven innovators and attempt to retrospectively divine the secrets of their success. In this week’s New Yorker, a special issue in the recurring “Innovators” series, one can read about the development of the mouse by Xerox and Steve Jobs, Pepsi’s new “nutritional” snack foods, and Pixar – probably the most visible innovation factory of the moment. The problem with the “learn innovation from great innovators” approach is that much of the early struggle and failures that are an intrinsic part of the process of discovery are forgotten or minimized in the hindsight of success. The more honest the account, the more likely there are to be nuggets of insight.

The May 13th issue of Science includes a lovely essay by Francois Jacob, the 1965 Nobel Laureate in Medicine or Physiology, marking the 50th anniversary of the description of a genetic switch: E. coli’s lac operon. What was the discovery? E. coli takes in glucose from the environment as its preferred energy source. In conditions where glucose is absent and lactose (a molecule made of two sugars – glucose and galactose) is present, E. coli can turn on a set of genes and ramp up the production of their encoded proteins that allow the bacteria to adapt and feed on lactose. A key gene that allows this transformation encodes an enzyme called b-galactosidase which breaks down lactose to digestible glucose and galactose. An electrical engineer (or a systems biologist) might describe the logic of the regulatory mechanism as a two-component negative feedback loop (see Uri Alon’s network motifs). Jacob, Jacques Monod, Andre Lwoff and colleagues were able to accomplish the feat of identifying the actual proteins that turn this switch on and off and how these proteins are able to sense the concentration of sugars in the bacteria’s environment.

Of course, the lac operon (Jacob and colleagues called the unit of adjacent genes for functional and regulatory proteins an operon for “to operate”, the “lac” stands in for lactose) is a simple switch used by a humble bacteria to make a basic decision – glucose or lactose? That genetic and biochemical experiments easily applicable to human cells could elucidate the physical components and the regulatory logic of biological pathways was the triumph of the discovery. It spawned “gene regulation” as a huge field of biomedical science. In some ways this field has been a victim of its own success – it is now taken for granted that gene regulation is at least a component to the answer of whatever question today’s biologists ask. I was attracted to bioscience because I thought that it was cool that through experiments one could actually understand how our bodies use proteins to make decisions.

How did Jacob, a hapless medical student who failed in his aspiration of becoming a surgeon and had little or no expertise in science, come to participate in innovation? In the essay, and in his autobiography, “The Statue Within”, Jacob describes how with a combination of charm, persistence, and sympathy for his status as a wounded war veteran, he was able to talk his way into the research group of Andre Lwoff, the best in Paris. In the Science piece he writes, “Our breakthrough was the result of ‘night science’: a stumbling, wandering exploration of the natural world that relies on intuition as much as it does on the cold, orderly logic of ‘day science’”. Mentors took a chance on Jacob, perhaps not understanding exactly who they were betting on, and immersed him in a fertile environment. Collegiality and proximity allowed people working on seemingly unrelated problems to realize that they were actually studying two case studies of the same phenomenon. Students of the lac operon story could pinpoint a number of key factors in the alchemical mix of innovation: a small team of collaborators with different perspectives and experience, new technological tools, the freedom to test ideas, fail, and try again.

Jacob closes his essay with a warning, “In today’s vastly expanded scientific enterprise, obsessed with impact factors and competition, we will need much more night science to unveil the many mysteries that remain about the workings of organisms.” Is the ideal of night science, which drew so many of us to science in the first place, still viable given the never-more-intense pressure to produce papers and win grants? People truly interested in using the process of innovation to solve important problems must find ways to bring more of the fun of night science into the light of day.