As a mattress review site and a wellness platform, one of our areas of interest is obviously the importance of sleep and how it affects our biology and how it impacts our everyday lives.
We know that sleep is a fundamental requirement that our body and brain requires for normal function, that it is essential for building cells, hormones, repairing our bodies, rebooting our brains, and removing toxins.
Every once in a while, all of us experience sleep deprivation, and we can pretty much agree that it is an uncomfortable experience that ultimately ends in emotional and physical turmoil if we can’t get the rest we need. But just how long can a human body last without literally zero sleep, I mean, being in a perpetual state of wakefulness?
Consider the story of Randy Gardner and his science experiment, which was to determine just exactly how long he could stay awake. Today, Randy is 68 years old and in great shape, despite staying awake non-stop for 264 hours at age 17. Thats 15.6 days, so one day beyond a full two weeks. Pretty remarkable, right?
Randy not only set a record for sleep deprivation, but he also showed that you can miss out on shut-eye for more than a week and still not risk death. But before brewing a pot of coffee and seeing how you would fare in such a contest against yourself, there are a few things you should know first.
There is zero evidence that shows you can die from a lack of sleep, unless you possess a certain gene that prevents you from sleeping, a condition called FFI, or Fatal Familial Insomnia, which we will get to later.
While longer episodes of sleep deprivation have been noted in individuals, even for as long as 449 hours, Gardner’s intrepid almost 15 day journey without sleep has remained notable because of its level of scientific scrutiny. On learning about the school science experiment, Stanford University psychiatrist William C. Dement arranged to observe and record Gardner’s brain waves throughout the experiment.
As you might expect, things soon went awry once the effects of sleep deprivation kicked, almost immediately. After three days, Gardner was moody and began stumbling, quickly losing his sense of balance. Slowly, his senses were being affected, including his sense of smell.
By day five he was hallucinating, his brain slipping in and out of dream-like states. Analysis of Gardner’s brain activity found he wasn’t actually fully awake much of the time, and was actively experiencing “micro-sleep”, where certain parts of the brain actually shut down and run on auto-pilot, allowing the brain to get some rest.
Micro-sleep is a fairly newly discovered phenomenon that most of us experience from time to time. It’s an automated response that we actually might not even be aware of, and it can occur anywhere, at a traffic light, sitting at your desk, even while in the middle of a conversation.
While Randy would not describe his experiment as horribly unpleasant, the sheer span of time without shuteye just seems inherently dangerous. However, there is nothing to suggest that the young mans long-term health was in danger.
Where this gets particularly interesting is the fact that those findings are in stark contrast with experiments that had earlier been conducted on sleep-deprived animals.
In 1898 two Italian physiologists kept dogs awake by constantly walking them over a period of several weeks, when they suddenly died from what appeared to be deterioration of various nerves in the brain and spinal cord. Experiments on rats have also shown that a lack of sleep can be deadly.
Interestingly though, humans appear to have evolved neurological tricks similar to those of some birds and aquatic mammals – an ability to shut down parts of the brain for maintenance while sort-of staying awake.
An experiment with seafaring frigatebirds found that they could sleep with both eyes closed at the same time, and engaged in bihemispheric sleep, in which both hemispheres of the brain are asleep at the same time. Frigatebirds are able to fly with both of their eyes closed.
The monitored birds even experienced brief bouts of rapid eye movement (REM) sleep, although they lasted only a few seconds. During REM sleep, muscle tone is reduced, causing birds’ heads to droop. Despite this muscle tone reduction, REM sleep was not found to affect the birds’ flight patterns.
Other mammals can sleep standing up, with certain components of the brain still running in the background while other areas that are typically engaged in higher order processes can shut down, reboot, re-energize, and repair themselves.
Our ability to slip into microsleep when we push past our limits might have helped us stay alive in the past, possibly in line with other endurance-enhancing adaptations that let us stay on the move for long periods. we likely evolved complex systems which allowed us to engage fight or flight responses when approached by predators while sleeping for example.
But in today’s busy world, we might be taking too much of an advantage of our flexible sleeping routine. And self imposed sleep deprivation comes at a heavy cost.
Karyn O’Keefe from the Sleep/Wake Research Centre at Massey University in New Zealand reported that lack of sleep dramatically raises the risk of injury or accident while carrying out safety-sensitive tasks. “For example, lack of sleep has been shown to substantially increase our risk of having a motor vehicle accident,” she explains.
O’Keefe cites an American study that demonstrates reducing sleep time to four or five hours made you four times more likely to have a motor vehicle accident, compared to those who got around 8-9 hours of deep, REM type sleep.
“With respect to risk of work-related injury, a large US study has shown that workers who got less than 5 hours sleep per day were almost 3 times more likely to have a work-related injury than those who got 7 to 8 hours’ sleep,” says O’Keefe.
If you’re fortunate enough to avoid an accident, a consistent lack of sleep plays havoc with other aspects of your health.
“In the long-term, lack of sleep has been shown to lead to problems with physical health, such as increased risk for obesity, type 2 diabetes, cardiovascular disease, and stroke, as well as increased risk for depression and anxiety,” says O’Keefe.
Given most of us aren’t getting enough sleep, this is a significant problem that might only worsen in the future.
The Strange Phenomenon Of Fatal Familial Insomnia
Silvano was on a cruise ship when the family curse struck. An elegant 53-year-old with auburn hair who enjoyed wearing a tuxedo at every possible occasion, he tried to present himself with the poise of the film stars he admired. But while on the ship’s dance floor one evening, he was embarrassed to find that his shirt had become drenched in sweat.
Concerned, he examined himself in a mirror, only to find that his pupils had shrunk to two tiny black pinpricks. It was the same glassy-eyed stare that had afflicted his father and two sisters at the beginning of their mysterious illnesses.
He knew this was just the beginning. Tremors, impotence and constipation could follow. But the most terrifying symptom would be the disappearance of sleep – almost total insomnia for months; a kind of zombie like coma that ultimately would end in death.
Silvano eventually referred himself to the University of Bologna’s sleep unit for further study, but he was under no illusions about the course of the disease. “He said, ‘I’ll stop sleeping, and within eight or nine months, I’ll be dead,’” one of his doctors, Pietro Cortelli, told me in a phone interview.
“I said ‘how can you be sure?’ He then drew me his genealogical tree from the 18th Century, all from memory.” In each generation, Silvano could name family members who had succumbed to the same fate.
As Silvano had predicted, he died less than a couple of years later, but his brain was harvested for research so that it might shed some light on the strange disorder that had tormented his family.
The first known case of fatal insomnia can be traced to a Venetian doctor. Local records describe a paralyzed stupor lasting for months. What’s going on inside the brains and bodies of people with this strange disease? It’s a mystery that researchers are only now starting to fully understand, and possibly treat with a promising new drug. However, since “Fatal Familial Insomnia” (FFI) involves a genetic legacy that is passed through generations, this research is also raising a difficult and ethically fraught question: if your family’s genes meant you could one day be struck down by the inability to sleep, would you want to be told your fate?
Finding Patient Zero
Silvano’s family have mostly remained silent about their struggle with FFI, but about 15 years ago they opened up about their history to the writer DT Max, whose book The Family Who Couldn’t Sleep offers an engrossing portrait of a family living in fear of their own genes. Hunting for “patient zero”, Max found the disease could be traced as far back as a Venetian doctor who fell into a continuous, paralyzed stupor during the late 1800’s. Soon after, a nephew named Giuseppe succumbed to a similar fate, and from there, the illness passed through his sons Angelo and Vincenzo to their children and great grandchildren, until it reached Silvano’s father Pietro, who died during World War Two.
Despite this chain of losses, the family tried not to talk about the illness for fear of tempting fate, but that suddenly changed in the 1980s when the disease reared its ugly head and Silvano started developing his symptoms. His niece had married a doctor named Ignazio Roiter, and as a man of science, he persuaded his wife’s uncle to visit Elio Lugaresi’s famous sleep clinic at the University of Bologna, where Cortelli was working.
Together, they set about solving the mystery of the illness. Although their efforts could do nothing to save Silvano or two other family members who would succumb shortly afterwards, extensive testing eventually found the culprit: a misshapen protein in the brain called a prion, caused by a tiny genetic mutation. For some reason it is only at middle age that the prions begin to proliferate wildly, collecting in pockets that poison the neurons.
This made it a relative of something called Creutzfeldt–Jakob disease (CJD) and Mad Cow Disease – two other prion diseases that were garnering serious scientific interest at the time. But whereas CJD leaves the surface of the brain looking like Swiss cheese, Silvano’s condition seems to target parts of the thalamus, at the very centre of the skull. Normally the size and shape of a walnut, the thalamus in Silvano’s brain appeared to have been riddled with boring worms.
After years of further research, the scientists can now explain why damage to this small nub of neural tissue unleashes such a puzzling constellation of symptoms. We know, for instance, that this hub orchestrates all our “autonomic” responses to the environment – things like temperature control, blood pressure, heart rate, and the release of hormones to keep the body ticking over comfortably. When it breaks down, it is as if your central heating is going haywire, your water pipes have sprung a leak, your windows are wide open and your loudspeakers are blaring at full volume – everything is in chaos. Hence the profuse sweating and shrunken pupils, the impotence and the constipation.
Turning Off Consciousness
This erratic autonomic control could also contribute to the patients’ insomnia: their bodies can’t prepare for a night’s sleep. Where blood pressure typically drops before sleep, theirs would be abnormally high, for instance, giving the sensation that their body is still on high alert. “If the sympathetic nervous system is unbalanced, of course you’ve got insomnia,” says Cortelli, who presented his ideas in a recent issue of Sleep Medicine Reviews.
Compounding these issues, the brain’s rhythms are now in complete disarray. During the night, we normally experience periodic cycles of “rapid eye movement” punctuated by a deeper “slow wave” sleep. During this stage, low-frequency oscillations of electrical activity ripple across the cortex – the gnarled, bark-like tissue on the surface of the brain.
This appears to calm down the buzz of coordinated conscious activity you’d normally see when we are awake, while also performing important maintenance work, such as consolidating our memories. And what nub of neural tissue deep in the brain orchestrates those delicate rhythms? The thalamus.
Lacking this dimmer switch, the FFI patients are always switched on and can never descend into deep, restorative sleep, says Angelo Gemignani at the University of Pisa, who has demonstrated that people with FFI are missing this important pattern of brain activity.
At periodic points in the night, people with FFI may enter a kind of trance in which they mindlessly act out daily activities (Credit: Carmen Jost/Flickr/CC BY-NC-ND 2.0)
Without those slow waves, the closest they get to normal sleep is a kind of mindless stupor – not quite asleep, but not quite aware, in which they mindlessly mime their routine daily activities. Cortelli thinks this is a pale remnant of the REM stage that punctuates the deeper stages of sleep; in some ways, it looks like they are acting out dreams. He remembers a woman, Teresa, who would mindlessly mimic the action of combing someone’s hair; she had been a hairdresser before the disease struck.
Slowing The Decline
One remarkable patient, however, has hinted that there may be some unusual ways to alleviate the misery. A psychologist at Touro College in New York, Joyce Schenkein first came across Daniel not through her work, but through a radio chat line (a precursor to internet forums in the 1990s). “His profile was very clever – he was a brilliant guy, extremely funny,” she says; they ended up having a long-distance friendship. (Daniel’s name has been changed to preserve his family’s privacy.)
In a conversation a few years later, he started to sound confused and vague. “At some point, he said ‘pardon me if I sound incoherent but I haven’t slept for five days,’” says Schenkein. Medical tests revealed he was carrying the FFI mutation. (His mother had apparently known there was some illness in his father’s family, but had decided not to worry her son with the details.) Worse still, it was the form that should progress most rapidly.
Rather than crumbling into despair, his response was to buy a motorhome and travel across the US. “He was an adventurous spirit – he wasn’t just going to sit there and die,” Schenkein says. As the symptoms became more extreme, he employed a driver, and then a nurse, to take over the steering wheel when he was too unwell, she says.
Meanwhile (and sometimes with Schenkein’s advice) Daniel was determined to try as many potential treatments as possible, ranging from vitamin supplements and exercise to improve his general fitness to anaesthetics such as ketamine and nitrous oxide, and sleep medicines like diazepam – anything that would give him a few winks of sleep, even for as short as 15 minutes at a time.
He even bought a sensory deprivation tank, having found that even under an anaesthetic, his fragile slumbers could be interrupted by the slightest sound or movement.
Floating in the egg-shaped cocoon while bathed in warm salt water, he found the rest that had proven so elusive, enjoying a blissful four-and-a half hours of solid sleep. Once he awoke, however, he had to face terrifying hallucinations – including a strange uncertainty as to whether he was alive or dead.
Despite these (relative) successes, Daniel still faced regular relapses that became more intense as the disease progressed. “When the symptoms reared themselves, he couldn’t do anything,” says Schenkein. “There were times when he lost the whole day – it takes over your consciousness. He could sit there without the initiative to move; he’d be frozen in time.”
Once, he tried electroconvulsive therapy to see if the sharp electric shock could knock him out; it did, but he suffered such bad amnesia afterwards that it seemed a far from ideal solution. After a few years of this struggle, he too finally passed away.
Although none of the treatments provided long-term relief, Daniel lived years longer than his diagnosis might have predicted. Schenkein points to recent evidence showing that slow-wave sleep triggers currents of cerebrospinal fluid to wash through the channels between brain cells, carrying away the debris and detritus from the day’s activity, and leaving it clean like the beach after high tide.
Perhaps, by alleviating the insomnia, you can encourage this clean-up and forestall the brain’s further disintegration. Together with the Italian neurologist Pasquale Montagna (who had worked on those other cases of fatal familial insomnia), Schenkein wrote up the case study for a medical journal in the hope it may inspire others to look for measures to extend the life of patients with FFI.
“It at least opens the possibility to say that there is something we can do,” says Cortelli – though he emphasises that we can only learn so much from a single case report; it is unclear if similar measures would help any other sufferers.
The Venetian family’s hopes lie in a different direction. Lugaresi passed away at the end of December last year after decades of working with people with FFI, but Roiter and his colleagues at Milan and Treviso believe they may finally be close to the cure they had all dreamed of. Finally, a new drug had finally been found, a drug which has been around for decades.
The drug in question, doxycycline, had previously shown some promise in experiments investigating CJD; originally an antibiotic, it seemed to stop the prions sticking together in clumps and encouraged their breakup through the brain’s natural enzymes. Indeed, in a small clinical trial on people showing early signs of the disease, the 21 people taking the drug lived about twice as long (an average of 13 months) as the 78 control subjects.
Disappointingly, a later study that tested the drug on patients already showing more aggressive symptoms of CJD failed to find a benefit. Roiter and his colleagues wonder if by that point, it might simply be too late to be of use. For this reason, they want to see if doxycycline may still function as a preventative treatment in people at risk of FFI, before the prions have started to amass.
“It might delay or completely disrupt the development of the disease,” says Gianluigi Forloni at the Mario Negri Institute for Pharmacological Research in Milan, who is helping to lead the project.
Setting up a reliable trial, while remaining sensitive to the family’s anxieties, involved some knotty considerations. First, the scientists had to genetically test each member to see who was carrying the mutation, and so should be given the active drug. From these, they selected 10 members aged 42 to 52 who might be expected to decline within the next decade.
Fear Of Knowledge
The problem was that many of the family members did not want to know the results of the test: even with the hope of the drug, the fear would cloud every waking minute of their lives. For this reason, a further 15 members who are not at risk of the disease will also receive a sham treatment.
This means that each member should have no way of figuring out the results of their test: as far as they can tell, there is less than a 50:50 chance of proving positive or not.
Without treatment, Forloni predicts that at least four of the 10 subjects carrying the mutation would be expected to succumb within the next decade. So if the team find that more than six have escaped the disease by the end of that period, they will consider the trial a success – perhaps justifying more widespread use.
Despite the glimmer of hope it offers, the trial remains controversial among some of the doctors who have been following this family closely. Cortelli, for one, has decided not to be involved in the project because he is concerned about its ethics. Some of the side effects of the antibiotics may still give away the subjects’ diagnosis, causing unnecessary distress, he thinks. (In their defence, Roiter and Forloni’s team will be providing psychological support throughout the experiment.)
In any case, he is skeptical that the evidence for the drug’s potential is not strong enough to justify such an extended period of treatment.
And even if the family members have escaped the disease at the end of the trial, Cortelli says we can’t rule out the possibility that these few individuals were simply lucky; some people with the mutation have still lived into their 80s, although no one knows why their gene remained dormant.
But with anxiety and uncertainty plaguing them whatever they decide, it’s not hard to see why the family is willing to take a gamble on the treatment: here is a chance to absolve the death sentence that has been written in their DNA for centuries.
Silvano’s niece once spoke of creeping into her mother’s room each night to check that she was really asleep and not hiding the first signs of insomnia. She was, she said, a “spy in her own home”. If the drug really does work, it would be the end of this living nightmare – the start of a future in which the solace of a night’s sleep can be embraced without fearing it could soon be the last.