Systems biology did not rise without skepticism. The great geneticist and Nobel-prize winning biologist Sydney Brenner once defined the field as “low input, high throughput, no output science.” Brenner, a contemporary of Chomsky who also participated in the same symposium on AI, was equally skeptical about new systems approaches to understanding the brain. When describing an up-and-coming systems approach to mapping brain circuits called Connectomics, which seeks to map the wiring of all neurons in the brain (i.e. diagramming which nerve cells are connected to others), Brenner called it as a “form of insanity.”Brenner’s catch-phrase bite at systems biology and related techniques in neuroscience is not far off from Chomsky’s criticism of AI. An unlikely pair, systems biology and artificial intelligence both face the same fundamental task of reverse-engineering a highly complex system whose inner workings are largely a mystery. Yet, ever-improving technologies yield massive data related to the system, only a fraction of which might be relevant. Do we rely on powerful computing and statistical approaches to tease apart signal from noise, or do we look for the more basic principles that underlie the system and explain its essence? The urge to gather more data is irresistible, though it’s not always clear what theoretical framework these data might fit into. These debates raise an old and general question in the philosophy of science: What makes a satisfying scientific theory or explanation, and how ought success be defined for science?