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In computer science, we can theoretically neatly separate transmission and processing of information, hardware and software, and programs and their inputs. This is much more intricate in biology, Nevertheless, I argue that Shannon’s concept of information is useful in biology, although its application is not as straightforward as many people think. In fact, the recently developed theory of information decomposition can shed much light on the complementarity between coding and regulatory, or internal and environmental information. The key challenge that we formulate in this contribution is to understand how genetic information and external factors combine to create an organism, and conversely, how the genome has learned in the course of evolution how to harness the environment, and analogously, how coding, regulation and spatial organization interact in cellular processes.