One of my first jobs was to keep a lookout for lions. There are some occupations that are not suitable for someone with untreated narcolepsy and this is probably one of them.
I was 22, a recent zoology graduate studying meerkats in the Kalahari Desert in South Africa. We worked in pairs, one of us on foot, walking with meerkats, the other in the jeep scanning the horizon for signs of leonine danger. On many occasions, I awoke with the imprint of the steering wheel on my forehead, realising that meerkats and colleague had wandered out of sight. I would look for signs of life and, as the panic grew, signs of death. I can tell this story now only because nobody got eaten.
I have not always been like this. For the first 20 years of my life, I had a healthy relationship with sleep. Shortly after my 21st birthday, though, I began to experience symptoms of narcolepsy, a rare but not-so-rare disorder thought to affect around one in 2,500 people. If people know one thing about narcolepsy, it’s that it involves frequent bouts of uncontrollable sleepiness. This is true, but the condition is so much more disabling, often accompanied by cataplexy (where a strong emotion causes loss of muscle tone and a ragdoll-like collapse), trippy dreams, sleep paralysis, frightening hallucinations and, paradoxically, fractured night-time sleep. There is no cure. Yet.
In the Kalahari, back in 1995, I was new to these symptoms. I had little sense of the incalculable toll that fighting a never-ending battle against sleep (with defeat the inevitable outcome) would take on mind, body and soul. I was not alone. Few family doctors had heard of the disorder, let alone encountered a patient. Some neurologists knew what to look for, but many did not. Not even sleep specialists could explain why this disorder would suddenly strike, with peak onset at around 15 years of age.
A lot has changed in 20 years. There is now overwhelming evidence that by far the most common cause of narcolepsy is an autoimmune attack, where the body’s immune system mishandles an upper respiratory infection and mistakenly wipes out the estimated 30,000 neurons in the centre of the brain.
In an organ of up to 100 billion cells, this might not sound like too much to worry about. But these are no ordinary cells. They are found in the hypothalamus, a small, evolutionarily ancient and unbelievably important structure that helps regulate many of the body’s basic operations, including the daily see-saw between wakefulness and sleep. The cells in question are also the only ones in the brain that express the orexins (also known as hypocretins). This pair of related peptides – short chains of amino acids – were completely unknown at the time of my diagnosis in 1995.
The story of their discovery, beginning in the 1970s, is a brilliant tale of chance and luck, imagination and foresight, risk and rivalry, and involves a colony of narcoleptic Doberman pinschers to boot. It might even be the perfect illustration of how science works.
Yet while there are drugs that can help manage the worst of the symptoms of narcolepsy, none of these comes close to repairing the underlying brain damage. It is remarkable that a lack of two chemicals results in such a bewildering constellation of symptoms. The answer to my problems appears to be simple – I just need to get the orexins (or something similar) back inside my brain. So why am I still waiting?
In April 1972, a toy poodle in Canada produced a litter of four. Eager families were quick to snap up the cute puppies, but one of them, a silver-grey female called Monique, soon developed what her owners described as “drop attacks” when she tried to play. These did not look like sleep; they were mostly partial paralyses: her hind legs would go weak, her bottom would slump to the floor and her eyes would become still and glass-like. At other times, particularly when fed, Monique would be struck by a full-blown attack.
When vets at the University of Saskatchewan observed Monique, they suspected these were bouts of cataplexy, and hence figured this might be a case of narcolepsy with accompanying cataplexy. As luck would have it, Monique’s diagnosis coincided with the arrival of a peculiar circular from William Dement, a sleep specialist at Stanford University in California. He was on the lookout for narcoleptic dogs. The Saskatchewan vets wrote back to him immediately. With Monique’s owners persuaded to relinquish their pet, all that was needed was to figure out a way to get her to California.
I met Dement, now 89, to find out what he remembers about those early years. He retired several years ago, but still lives in a leafy neighbourhood on the edge of the Stanford campus. His office is a large, shed-like structure attached to the main house and not unlike a Scout hut.
The walls are wood-clad and covered with framed posters, photographs and miscellaneous memorabilia from an illustrious career in sleep medicine. Dement’s desk is a picture of organised chaos. Among all this is a water pistol. I ask him why. “It’s for when students fall asleep in class,” he explains, referring to an incredibly popular lecture series on sleep and dreams he instigated in the early 1970s.
In 1973, Dement approached Western Airlines to see if they could fly Monique down from Saskatchewan to San Francisco. They had a strict ‘no sick dogs’ policy. “It’s not a sick dog. It’s a dog with a brain abnormality,” he told them. “It’s an animal model of an important illness.” Eventually, with some political lobbying, Dement succeeded in persuading the airline to help. Once in San Francisco, Monique quickly became something of a celebrity.
“Monique is very likely to collapse when she’s eating something she especially likes, or when she smells a new flower outside, or romps around,” Dement’s colleague Merrill Mitler told the Associated Press for a story that ran in dozens of newspapers across the USA. “We hope to discover exactly where in the brain the dysfunction occurs that causes narcolepsy,” Mitler had told the newspapers soon after Monique’s arrival at Stanford. “This could be the first step towards developing a cure.”
Mitler is now a forensic examiner based in Washington, DC, specialising in litigation arising from fatigue-related accidents. I ask him if the story of the discovery of narcolepsy is really as good as it appears. “In a word, yes,” he says. “In the 70s, we didn’t know what we didn’t know about narcolepsy.”
There is simply no way anyone could have anticipated how profitable the research into Monique and other dogs would turn out to be. The plan at that stage, he admits, was simply to use the animals to test new drugs that might improve treatment of the symptoms and to carry out autopsies in case there were some obvious physical changes to the brain.