The physiological hypothesis of weight regulation and hunger that then emerged in the mid-1970s evolved directly from the work of the French physiological psychologist Jacques Le Magnen, one of the more remarkable figures in the past century of science. Le Magnen was blind, the result of an attack of encephalitis when he was thirteen years old. He compensated by developing what his colleagues described as a “phenomenal” and “encyclopedic” memory, particularly for the nuances of relevant scientific research. “Jacques Le Magnen knew everything,” as his obituary in the journal Chemical Senses commented after his death in 2002. He was also “incredibly brilliant,” says the University of Cincinnati physiological psychologist Stephen Woods, which seems to be a consensus opinion among those who knew his work. Le Magnen joined the prestigious Collège de France in 1944, and he remained there for forty years, much of it spent working in the office and laboratory that had originally belonged to Claude Bernard. His Laboratory of Sensory and Behavioral Neurophysiology would eventually grow to become perhaps the largest in the world focused on issues related to hunger and weight regulation.

Le Magnen’s research on eating behavior began in the early 1950s, when he designed a device to monitor food intake in rats over entire twenty-four-hour cycles. This led him to report that rats ate discrete meals separated in time by discrete intervals. He then set out to establish what factors regulated the size of the meals and the length of the intervals between meals.

Le Magnen’s research resulted in two fundamental observations, both confirming Adolph’s observation that eating behavior in animals, and thus hunger, is driven by those “quantitative deficiencies of currently metabolized materials.”

Le Magnen learned that when rats are allowed to eat whenever they want, the size of the meal determines how long rats will go before they get hungry again. As a new supply of ingested calories is exhausted by the rat’s energy expenditure, the animal is motivated to eat again. “All increase or decrease in the two sides of this balance (calories eaten in meals versus metabolic expenditures) will lead to an immediate shortening or lengthening of the meal-to-meal interval,” Le Magnen explained. And this is “the major and direct agent of the regulation of food intake.”

The second observation was one that is obviously true for humans as well: Rats eat to excess during their waking hours, which means their intake exceeds their expenditure of energy, and so they are hyperphagic while awake, storing fat during this period. While they’re sleeping, the rats are in negative energy balance—hypophagic—and they live off the fat accumulated during the waking hours. Weight peaks as the rats are going to sleep and it ebbs as they awake. In humans, this cycle would explain, among other things, why hunger doesn’t (or at least shouldn’t) wake us from the depths of a night’s sleep so we can raid the refrigerator.