Silvano was on a cruise ship when the family curse struck. An elegant 53-year-old with striking red 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 waking coma that ultimately would end in death. 
 
 He said, ‘I’ll stop sleeping, and within eight or nine months, I’ll be dead 
 
 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 by heart.” 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 he left his brain to science in the hope that it might shed some light on the strange disorder that had plagued his family. 
 
 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? 
 
 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, paralysed torpor during the late 18th Century. 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 changed in the 1980s when 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. 
 
 The size and shape of a walnut, in Silvano’s brain the thalamus appeared to have been riddled with boring worms 
 
 This made it a relative of 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. 
 
 The closest they get to normal sleep is a kind of mindless stupor – not quite asleep, but not quite aware 
 
 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. 
 
 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. 
 
 Slowed 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.) 
 
 Daniel’s response was to buy a motorhome and travel across the US - he wasn’t just going to sit there and die 
 
 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. 
 
 Floating in the egg-like shell, he found the rest that had proven so elusive, enjoying a blissful four and a half hours of sleep 
 
 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. 
 
 He even tried electroconvulsive therapy to see if the sharp electric shock could knock him out 
 
 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. 
 
 Clearing the debris 
 
 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. Last year, they announced a clinical trial of a new drug, which, they hope, may prevent (or at least decelerate) the formation of the poisonous prions. 
 
 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. 
 
 The problem was that many family members did not want to know the results of the test: the fear would cloud the rest of their lives 
 
 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 sceptical 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. 
 
 David Robson is BBC Future’s feature writer. He is @d_a_robson on twitter. 
 
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 If you liked this story, sign up for the weekly bbc.com features newsletter, called “If You Only Read 6 Things This Week”. A handpicked selection of stories from BBC Future, Earth, Culture, Capital, Travel and Autos, delivered to your inbox every Friday. ||||| (CNN) "Look, I'm so sorry to do this to you on your birthday," Hayley Webb, a television reporter in Australia, recalled her mom saying in 2012. "I have six months to live." 
 
 A month later, her mother, Narelle, was calling her by the wrong name, hallucinating and falling over. She could hear the cries of a baby she lost when he was 6 months old. 
 
 "Initially, we would try and reason with her, but we ended up playing into her reality to make it easier for her," said Hayley's brother, Lachlan, co-founder of an urban development startup. 
 
 Hayley and Lachlan Webb learned that their mom's illness could be inherited. 
 
 But perhaps most strikingly, their mother couldn't fall into a deep sleep. 
 
 "You're in this gray area, in this limbo land between being awake and being asleep," Webb said. "You get into a perpetual stage of a dream." 
 
 She died in July 2012 at 61 years old. 
 
 The same thing happened to their grandmother -- and they learned it could be passed down to them. 
 
 'It's about mom' 
 
 Sonia Vallabh was in her second year at Harvard Law School in 2010 when her mother got sick. 
 
 Just months before, her mother had been healthy and vibrant, planning Vallabh's wedding to Eric Minikel. 
 
 "It was a small Indian wedding, by which I mean 300 people," Minikel said. 
 
 Vallabh's mother began having trouble with her eyesight, and her strange symptoms progressed to the point where she couldn't recognize her daughter. Her muscles would jerk and spasm. She spoke in tongues. 
 
 "She was fitful and couldn't really tell you if she'd been awake or asleep," Vallabh said. 
 
 Kamni Vallabh, left, was planning her daughter Sonia's wedding less than a year before she came down with a mysterious, debilitating illness. 
 
 By fall 2010, she was on life support, with needles, tubes and wires coming out of her. 
 
 "She looked like she was being tortured," Vallabh said. "How could we ask this person to keep going?" 
 
 Her mother died in December 2010 at age 52. 
 
 Shortly thereafter, Vallabh's father, a doctor, pulled her aside during a visit home. 
 
 "I need to talk to you about something. It's about mom," he said. 
 
 "We got her autopsy report. Her disease was genetic." 
 
 A major discovery 
 
 In 1986, this disease was given a name : fatal familial insomnia, or FFI. 
 
 Much of what doctors first learned about the disease comes from a family in Venice, Italy, who have suffered from it for over 200 years. 
 
 "You'd have 14 kids in a generation. Six or seven of them would die from the disease," said D.T. Max , a writer for the New Yorker and author of the book "The Family That Couldn't Sleep." 
 
 The family, who prefer not to use their surnames, had kept the disease a family secret for generations, Max said. Doctors listed their causes of death as "nervous exhaustion," encephalitis and even schizophrenia, he said. 
 
 "It's been a disaster. A brutal suffering," said Lucia, 63, one member of the Italian family. She has lost many relatives to the disease, including her father, brother and sister. 
 
 But when another family member, Silvano, started showing signs of the disease -- he began sweating profusely, with pinpoint pupils -- he decided it was time for his family to stop suffering in silence. It was 1984, and he was 53 years old. 
 
 Silvano went to the University of Bologna, where researchers filmed his final months. In some of the videos, his eyes are half-open, staring into space. Just as it appears he's dozing off, he jerks to a half-wakefulness. 
 
 "Exactly what you can feel if you get a sleep attack when you are driving," said Dr. Pietro Cortelli , one of the researchers Silvano approached at the University of Bologna. "You are falling asleep, and then you wake up." 
 
 In other videos, he is lying in bed, pretending to comb his hair or button an imaginary shirt. 
 
 Sleeping pills didn't work. No matter what, his brain didn't allow him to reach the deeper, restorative stages of sleep. 
 
 "In few months, I'm going to die," Silvano told Cortelli. "This is one of the few (chances) you have to discover what is the cause of the curse of my family." 
 
 Silvano died that year, in July 1984. Cortelli and his mentor, Dr. Elio Lugaresi , shipped his brain tissue to Lugaresi's former student -- a pathologist in the United States who could take a much closer look at what was going on. 
 
 Dr. Pierluigi Gambetti , the pathologist and a professor at Case Western Reserve University, found that most of the brain tissue appeared normal. But one small structure, near the center of the brain, looked "like a sponge," he said. 
 
 "At that moment, I knew what FFI probably was," he said. 
 
 A deadly typo 
 
 Gambetti had seen the spongelike pattern before -- just not like this. His mind instantly shifted to a group of diseases caused by a protein known as a prion. 
 
 "There's this one protein that's sort of at the heart of this disease, the prion protein," Vallabh explained. "This is a protein that we all have. We're all producing it all the time, and it's part of normal biology, but it's capable of undergoing ... a change in shape." 
 
 When that change happens, it begins a domino effect. The abnormal prion converts a healthy one, creating two abnormal ones. They go off and convert two more. And so on. 
 
 "As these prions spread, they're killing brain cells in their wake," Vallabh said. 
 
 In the case of FFI, these proteins mostly home in on two locations within a central brain structure: the thalamus. 
 
 The thalamus is often described as the brain's switchboard, relaying signals from one region to the next. It plays a crucial role in movement, sight and many other processes. 
 
 The spongy tissue that Gambetti found in Silvano's thalamus was full of tiny holes: the aftermath of prions that left dead cells in their path. And the two spots in the thalamus where he found those holes turned out to be crucial to the sleep-wake cycle. Damaging them can lead to a persistent, deadly insomnia. 
 
 Lachlan Webb is taking part in a study of human prion diseases, hoping that researchers will find a cure for his own. 
 
 "We don't know why that specific mutation ... causes that particular part of the brain to be affected," said Dr. Michael Geschwind , a neurologist at University of California, San Francisco who runs a clinical study of prion diseases. "That's a big mystery." 
 
 Perhaps the best-known prion disease is mad cow disease, which destroys the brains and spinal cords of infected cattle. But there are other infectious forms: scrapie in sheep, kuru and Creutzfeldt-Jakob disease in humans. There are several genetic forms too, including FFI. 
 
 FFI is caused by a single, dominant gene mutation, meaning the Webbs and Vallabh had a 50-50 chance of inheriting the gene themselves. There is no cure. 
 
 "It was a typo that has unfortunately been passed on to the future generations," Hayley Webb said. "A deadly typo." 
 
 People with the gene have no symptoms until later in life, when the disease suddenly hits. Before that, the only way to know is to get tested for the gene. 
 
 "Being in limbo was the hardest time," Vallabh said of being tested. "It was really hard to think about anything else." 
 
 Searching for a cure 
 
 When the results came in, the Webb siblings and Vallabh all tested positive for the FFI gene. 
 
 "I think I was more devastated about Lachlan's diagnosis than my own, because I just wasn't expecting it," said Hayley Webb, now 31. 
 
 "You know, I'm the big sister," she said of her 29-year-old brother. "I want to protect him. He's my little brother." 
 
 "You know when you get fuzzy-brained when you're really exhausted?" Webb says in a video diary. "I think, Crap! Is that a symptom? Subconsciously, you can't help but be scared." 
 
 But all of them have turned a dire test result into motivation, mirroring Silvano's determination to get to the bottom of his "family curse." 
 
 Hayley and Lachlan Webb are participating in Geschwind's study at UCSF. Soon after learning that she had the FFI gene, Vallabh, 33, quit her job in consulting, began sitting in on classes at MIT and took biology courses at Harvard Extension School. 
 
 "My thought was, 'I'll take a sabbatical from my normal life, because this is something that's going to be important to us from now until the end,' " she said. 
 
 She and her husband, Minikel, switched career paths; they are now getting their Ph.D.s in biology at Harvard Medical School, where they are working to find a cure for FFI before it's too late. They founded the Prion Alliance to advance the science of this rare disease, which is known to affect only a handful of families worldwide. 
 
 Sonia Vallabh and Eric Minikel became scientists after learning that Vallabh carried the gene for fatal familial insomnia. 
 
 Because they see human prion diseases under the same umbrella, they hope their research leads to treatments for more than just FFI. 
 
 "It's virtually unprecedented that two people with zero scientific background would parachute into science and start working in the laboratory to think up four or five completely different strategies for taking on a complex neurological disorder," said Eric S. Lander , president of the Broad Institute, where Vallabh and Minikel conduct their research. 
 
 "Then again, you know, unprecedented things happen all the time in science," Lander said. 
 
 Vallabh and Minikel remain optimistic and see FFI's rareness as an asset. It's genetically well-defined -- more so than many more common diseases. They know their prion target; they just have to find a way to remove it. 
 
 Join the conversation See the latest news and share your comments with CNN Health on Facebook and Twitter. 
 
 They remain hopeful that their new daughter, whom they welcomed to the world in July, will watch her mother grow old. 
 
 Thanks to genetic testing and in vitro fertilization, their daughter does not have the FFI gene. 
 
 "The hope has to be always that you find a cure," pathologist Gambetti said. "And therefore, maybe there will be a time in which we will cross out this adjective -- 'fatal' -- from the name of the disease."
– In 2010, Sonia Vallabh noticed her mother acting oddly. "She was fitful and couldn't really tell you if she'd been awake or asleep," Vallabh tells CNN. Soon, the 52-year-old couldn't recognize her daughter and would spasm and speak in tongues. Upon her death months later, Vallabh recalls her father, a doctor, warning, "Her disease was genetic." Those words would change the course of Vallabh's life. Vallabh and her husband both quit their jobs and are now getting their PhDs in biology at Harvard Medical School in the hope that they can find a cure for fatal familial insomnia before it takes her life. FFI is caused by a gene mutation that Vallabh has inherited as a member of one of the few affected families in the world. Says a member of another such family: "It's been a disaster. A brutal suffering." Research on FFI began in 1984 when an Italian man named Silvano urged sleep scientists at the University of Bologna to discover "the cause of the curse of my family." Researchers watched as Silvano, 53, struggled to sleep while his body jerked him awake, preventing the restorative stage of sleep. A brain analysis later revealed two sections of his brain's switchboard, or thalamus, had been destroyed by abnormal prion proteins, affecting the sleep-wake cycle. For now, relatives can only undergo a genetic test and wait for the disease to hit, usually in their 50s. But Vallabh wants a different outcome. "The hope has to be always that you find a cure," says a pathologist, who imagines a time when "fatal" will be erased from FFI's name. The BBC reported last year on a drug that may keep abnormal prions from forming. (More on Vallabh and her husband here.)