Back in the 1980s, the idea of locating the gene for canine narcolepsy was off-the-scale ambitious. Breeding narcoleptic Dobermans is harder than it sounds, as the afflicted tend to topple over mid-coitus, temporarily paralyzed by a cataplectic thrill (a so-called ‘orgasmolepsy’ that can occur in humans too). This impracticality aside, there was also the task of locating a gene whose sequence was not known, in a genome that was, at the time, a no man’s land. “Most people said I was crazy,” says Mignot. In a sense, they were right, because it took him more than a decade, hundreds of dogs and over $1 million. And he was nearly beaten to it.
In January 1998, after more than a decade of painstaking mapping, and just as Mignot’s team was closing in on the gene, a young neuroscientist called Luis de Lecea at the Scripps Research Institute, San Diego, and colleagues published a paper describing two novel brain peptides. They gave them the name ‘hypocretins’–an elision of hypothalamus (where they were found) and secretin (a gut hormone with a similar structure). They appeared to be chemical messengers acting exclusively inside the brain.
Just weeks later, a team led by Masashi Yanagisawa at the University of Texas independently described the exact same peptides, though called them ‘orexins’ and added the structure of their receptors into the bargain. They speculated that the interaction of these proteins with their receptors might have something to do with regulating feeding behavior. “We didn’t even think about sleep at all,” admits Yanagisawa, now director of the International Institute for Integrative Sleep Medicine at the University of Tsukuba in Japan.