Mondays are vodka days. For the members of Dr. Kristina Simonyan’s lab, this is not a feeling but a fact — not a result of the workday but a necessary part of it. Everything takes place strictly according to protocol. When Karen Feeley arrived one Monday in April 2019, they gave her scrubs, flimsy blue slipper-socks, and a crinkled white lab coat, and after some initial testing, led her into what they call a “behavioral room” — a joyless place with the air of an unused office.
Pharmacists had prepared the therapy specifically for her, in little reddish bottles that reminded her of liquid penicillin. A research assistant gave her careful instructions. But Feeley already knew exactly what do to do. “What do you do with a shot of vodka? Basically, you pour it down your neck. So I drank it and then banged the bottle on the table,” Feeley said.
Usually, she’s more of a wine or daiquiri sort of person, but she’d put aside her taste — and a few days of her time — to help answer a question that had been rattling around Simonyan’s mind. It had first appeared about 15 years ago, when Simonyan was doing neuroscience research in New York City, trying to understand exactly how the brain choreographs the intricate dance of muscle and air that gives rise to speech.
Betting that she could learn about language production by examining cases in which it’s slightly out of whack, she recruited patients like Feeley with laryngeal dystonia — also called spasmodic dysphonia — a mysterious condition that causes involuntary moving of the vocal cords. It creates breaks in words, strangled syllables, frustrating speech delays. Your voice vanishes and reappears, like a radio signal flickering in from far away. But some of Simonyan’s study participants kept telling her it happened less when they drank alcohol.
“What do you do with a shot of vodka? Basically, you pour it down your neck. So I drank it and then banged the bottle on the table.”
Simonyan didn’t pay much attention at first. She figured they probably just felt more relaxed. People overestimate all sorts of their own abilities when they’ve had a few. But in patient questionnaires, it became a kind of refrain, so much so that Simonyan started asking about that specifically. When she surveyed 531 patients, more than half said their symptoms improved with drink — and a significant number had sometimes hit the bottle to help ease them through the torment of social and professional interactions.
It seemed almost too simple. Leads for new therapies often emerge from endless libraries of chemicals or the molecular Rube Goldberg of genes — stories so long and statistical that you forget they’re stories at all. In the anecdotal exceptions, pharmaceuticals tend to beget pharmaceuticals. An angina medication with a side effect of erections became Viagra. Glaucoma patients noticed that treatment enhanced their appearance; their medicated eye-drops soon gave rise to a lash-lengthener called Latisse.
Could the liquor cabinet yield that sort of breakthrough? The proposition was risky. Drinking is the third leading preventable cause of death in the United States, and if the trends of the last two decades continue, the number of us killing ourselves glass by glass is only going up. Still, Simonyan hoped to transmute this anecdote into a laryngeal dystonia drug, and to do that, she needed to prove it was true.
To doctors, patients’ descriptions can seem like a fickle source of evidence. We’re at once the foremost experts in our own experience and the least reliable of narrators. Our stories are unscientific — suspect, even — but physicians ask us to self-report our darkest moods, to rate our aches and pains on a scale from 1 to 10. Even as we’re being irrational, there’s a chance that we’re onto something. We notice patterns in a wash of everyday events. We try medicating ourselves with unprescribed oddities from both the kitchen cupboard and the furthest reaches of the internet.
In dystonia cases, both laryngeal and otherwise, that mix of reliance and distrust is especially fraught. When Feeley was around 30, she started having trouble saying her own name. The vowels were hardest: The short “a” in Karen, the long “e” in Feeley. It was as if her mind and vocal cords were out of sync. She was a consultant, accustomed to pressure: schedules stacked with meetings and presentations, crunch-times with 20-hour workdays. As soon as thoughts formed, they were out of her mouth. But now, suddenly, shaking hands with a client, she could hardly introduce herself. “I felt like — ‘Oh, my God, my career is coming to an end,’” said Feeley, 53, who lives in Arlington, Va.
She went from doctor to doctor to doctor. Allergies, one said. Anxiety, said another. One told her she simply didn’t know how to project — a verdict that struck her as especially questionable for a patient whose professional reputation was partly built on public speaking.
The disorder has a long history of diagnoses that ring with overtones of accusation. Nineteenth-century doctors, encountering symptoms they didn’t quite understand, imbued the bearers with a whiff of insanity; the condition was considered “of emotional origin” well into the twentieth. No coincidence, Simonyan points out, that laryngeal dystonia is much more prevalent in women than in men. “The assumption was that women are hysterical,” she said.
Slowly, the scientific literature began to change. In 1968, some New Mexican neurologists examined a distraught cattle auctioneer who’d been hospitalized after three years spent trying to recover his knack for rapid-fire bid calling. The disorder, they wrote, didn’t seem to respond to psychotherapy, and bore a remarkable likeness to writer’s cramp, in which the muscles of the hand suddenly lose their ability to grip a pen.
Their hunch was prescient. Now, this condition is just one specimen in an entire genus known as focal dystonia, characterized by muscles misbehaving only during very specific tasks. One manifestation affects pianists’ fingers, another horn players’ mouths. As journalist David Owen writes, similar issues have historically interrupted work for everyone from telegraph operators to seamstresses, enamellers to cigarette makers, knitters to masons, while golfers know the dreaded damage it can do to your putting as “the waggles” or “the yips.”
If the auctioneer’s neurologists were ahead of their time, Feeley’s initial doctors were lagging far behind. Getting the correct diagnosis took her six years. “I started going into a depression, started getting much more introverted, thinking, ‘What’s wrong with me?’” Feeley said. “It was such a relief to know that my problem was in my brain, but it wasn’t all in my head. I wasn’t crazy.”
Now, as a researcher at Mass Eye and Ear in Boston, Simonyan hears such stories all the time: On average, patients go 4 1/2 years without an answer. They feel isolated. Their speaking trouble erodes their professional confidence and their mental health. They worry they have cancer. They worry they have some terrible, inexplicable contagious disease. One patient’s symptoms appeared just as she was becoming a first-time grandmother, Simonyan recalled. “She said, ‘My son lives a few houses away from me, and I was not allowed to go see my grandchild.’”
The root cause isn’t clear. Counterintuitively, the problem doesn’t lie in the vocal cords themselves. They can be as elastic as ever, ready to vibrate in the gusts pushed up by the diaphragm and lungs. What’s gone haywire are the instructions coming from the brain.
For now, the best treatment is often to disrupt their delivery, paralyzing the muscle’s nerve input with a little jolt of Botox. But that lasts only a few months, and depends on the injector’s hands: The stuff doesn’t work as well if it’s a millimeter off. It’s painful either way. “Imagine a toothpick going into your Adam’s apple,” Feeley said.
“I passed out the first time. It was a horrific procedure. They started giving me Valium, but there was not enough Valium in the universe that made it OK,” said Dorothy Tannahill-Moran, 68, who leads a laryngeal dystonia support group in Kansas. “It’s a shot in the front of your throat, and once it’s there, they kind of drive it around like a stick-shift and squirt stuff. Oh, and by the way, don’t move or swallow while this is going on. I mean, holy smokes.”
So just about any science on laryngeal dystonia seemed worth volunteering for. And, as Feeley put it, if the experimenters wanted to give her free vodka — well, she wouldn’t say no.
When Simonyan first hit on it, the idea of alcohol as medicine for movement disorders wasn’t new. It was just new to laryngeal dystonia. The effect was most famous in essential tremor, another neurological condition that’s often of unexplained cause, this one characterized by involuntary rhythmic shaking. “Some patients find that a heavy dose of spirits will temporarily check the tremor and this factor has appeared only too often to have served as an excuse for habits of intemperance,” noted the British neurologist Dr. MacDonald Critchley, in 1949.
Later physicians were less judgmental and more practical. In the 1970s, Massachusetts General Hospital specialists gave tremor patients either alcohol injections or swigs of screwdrivers, and then compared the therapeutic effects. When, a few years ago, a 29-year-old came into a Buenos Aires clinic with generalized dystonia so bad he could neither stand nor walk, neurologists tried treating him with a glass of red. Not long before that, at the National Institutes of Health, movement-disorder researchers were strapping accelerometers onto volunteers’ quivering hands and serving them mixed drinks.
But Simonyan is nothing if not prudent. Her hobbies, no matter how tame, are firmly off the record. The stories she’s most comfortable telling are the ones adapted from journal article statistics. During her training as an otolaryngologist, she spent hours in the operating room, slicing out tumors and tonsils, correcting architectural issues of the aerodigestive tract. Though she’s no longer in clinical practice, she still thinks of her research in surgical terms — “dissecting the brain virtually” — and she hoped her inquiry might prove at once illuminating and therapeutic.
“I cannot envision a laryngologist prescribing alcohol,” she joked. Rather, she imagined alcohol responsiveness as a kind of test: The subset of patients whose voices improved with vodka might be good candidates for other, less inebriating treatments.
Those drink-mixing NIH neurologists had found a good alcohol substitute — a fruity food additive and dietary supplement called octanoic acid, so strong it smelled almost rancid. With pharmaceutical industry funding, they showed it to be a potentially promising treatment for tremor. But when they realized it wasn’t patentable, the commercial backers lost interest. As Dr. Khalaf Bushara, now at the University of Minnesota, explained, “On the market, in natural stores … it’s widely available.”
The alcohol replacement Simonyan eventually settled on had the opposite problem. It’s a drug called sodium oxybate, and she first heard about it from Dr. Steven Frucht, now at New York University’s Grossman School of Medicine, who would become her collaborator.
“It was such a relief to know that my problem was in my brain, but it wasn’t all in my head. I wasn’t crazy.”
Originally, the idea had come from Italy, where sodium oxybate is used both to treat the delirium tremens of alcohol withdrawal and to wean those with addiction off drinking. Seeing that the chemical could act as an alcohol substitute, Italian neurologists tried it as a treatment for one rare, hereditary movement disorder, in which muscles jerk involuntarily: Some reports of the illness noted not only the affected family’s reliance on self-treatment, but also their history of drunk-driving charges.
The sodium oxybate data were encouraging, and Frucht wanted to see if the drug would work for his own hard-to-treat patients. There was a catch, though. Sodium oxybate was simply a more stable version of gamma-hydroxybutyrate, or GHB. In Italy, it was the stuff of therapy; in the U.S., it was feared as a lubricant for raves and a sedative for date rapes. Just as Frucht was reading about the Italian trial in 2000, the Drug Enforcement Administration was making the molecule as illegal as heroin.
Only after a few years, once the Food and Drug Administration had approved sodium oxybate as a treatment for narcolepsy, could Frucht get his hands on some. GHB was still banned, and the sodium oxybate that Jazz Pharmaceuticals sold under the brand name Xyrem was tightly controlled. But Frucht thought the bureaucratic headache was worth it for his patients who had post-hypoxic myoclonus — a disorder brought on, whether through drug overdose or surgery gone wrong, by a cutoff of oxygen flow to the brain. “Every time they try to move or hold a cup or pour or stand, they generate these very violent movements,” Frucht said. “Yet their mental status can be remarkably preserved. So in a sense they’re trapped within their body.”
With one patient, he was so desperate that he finally turned to alcohol — white wine, to be exact. “I gave it to her in a plastic cup with a straw, which I had to hold because she couldn’t hold anything or bring a cup to her mouth,” he remembered. The results, he said, were surreal. Within 20 minutes, the daily motions she’d lost came flooding back. She could suddenly talk and hold a cup; instead of her hands waving against her will, she could sit still if she wanted to sit still. Alcohol gave her access to those tiny gestures we take for granted: She could motion for someone’s attention, could lift a hand to her face to brush away an itch at the tip of her nose.
So he began a trial of sodium oxybate in which she was the only participant. The before-and-after video seems almost like a testimonial for a television faith healer. Without the drug, she can’t help but slop water all over the desk; with it, her arm quivers but the liquid lands safely in the cup. Before, when she tries to stand up from her wheelchair, her every move is precarious. After, her gait is tentative but steady.
She stayed on the drug until her death, around eight years later. Frucht still has a photograph album her husband sent him, documenting all the events that the wine-inspired treatment made possible. In one, she’s celebrating the holidays. In another, she’s maneuvering chopsticks to eat Korean noodles. In another, she’s brushing her teeth.
To test patients’ laryngeal dystonia is to put them through paces at once comical and frustrating: They have to repeat a series of Dadaist-sounding mini-poems expressly composed to emphasize the sounds they have trouble saying. “It can be a vulnerable place,” said Alexis Worthley, one of Simonyan’s research assistants.
Simonyan had already heard these sorts of sentences spoken by alcohol-responsive patients under the influence of sodium oxybate. When she tested it a few years ago, it produced noticeable improvements for 37 out of 45. But she hadn’t also given them a sodium oxybate look-alike, so she couldn’t be sure how much might be attributed to the placebo effect. Nor could she be absolutely certain that everyone was in fact alcohol-responsive; she hadn’t served them drinks as part of the study, so she was relying on patients’ and their family members’ reports. In comparison with the new protocol, that one was a kind of Clinical Trial Lite.
Even after nearly 25 years with the disorder, Feeley still hates to hear her own voice. She feels a pinprick of embarrassment at the sound of every break. It’s like stubbing her toe in public, again and again. Now, in the “behavioral room,” she slipped on a telemarketer-style headset and began.
“Who says a mahogany highboy isn’t heavy?” she said. That would’ve been torture for someone who has trouble with the percussive breath it takes to say the letter “H.” For her, consonants were easy. Same with the hissing alliteration of “Does your sister like to sew?”
Her nemeses were a subset of vowels. Simonyan’s sentences to challenge patients like her had a kind of devilish simplicity to them, as if Dick and Jane had gone off script. “We eat eels every day.” “Jack sat on a tack.” Altogether, there were 20 phrases, and she would have to speak them over and over again — in and out of brain scanners, before and after downing two shots of vodka, after taking sodium oxybate on one day and a placebo on another. It was going to be a long three days.
Feeley couldn’t help feeling annoyed as she spoke. Like a call with a bad connection, her voice kept cutting out. She’d taken part in studies before, and could explain laryngeal dystonia as well as any laryngologist. Still, there remained a niggling part of her that wondered if maybe she was the problem, maybe she was doing something wrong. The feeling was strong at first. Then, as the study inched forward, second by second, scan by scan, the lines became a kind of ritual, each syllable well-worn and tedious. She knew when her speech would give way. She listened as if her voice belonged to someone else. The predictability became a kind of proof. “It’s a definite problem, a repeatable pattern,” she said. “It’s not me consciously choosing to do this.”
The proof Simonyan was after wouldn’t come for a while. Only after she’d recruited the last patient and served up the last shots of vodka and sodium oxybate and placebo — only after she’d picked apart the recordings and transformed those wavering voices into statistics — only then would she know what worked.
Even if her hypothesis proved correct, there would be plenty of convincing to do. Dr. Mark Hallett, chief of the human motor control section at the National Institute of Neurological Disorders and Stroke, and a leader on the octanoic acid studies, knows the existing results on sodium oxybate. “It can be effective in a number of alcohol-responsive situations,” he said. But the warnings about its side effects gave him pause: “I’m a little reluctant to use it myself.”
Dr. Charles Adler, a neurologist at Mayo Clinic in Scottsdale, Ariz., wondered what might happen if patients took it for years. “One-time treatment — that’s not going to help a patient in the long run,” he said.
Yet that was true of other, more established therapies as well. Many were hand-me-downs from other diseases, retrofitted for laryngeal dystonia and temporary at best. For Frucht, this trial might be a small step toward showing insurers that, for certain patients whose vocal breaks respond to alcohol and nothing else, sodium oxybate could help. He knows that a single bottle of it can cost thousands of dollars. “It can allow them to speak,” he said, “but if their insurance then changes, or the rules of their insurance change, then I don’t know many people who could afford to spend that — even if a bottle lasted three months.”
Already, though, he has prescribed sodium oxybate for a few patients. Kevin Hancock is one of them. He’d tried enrolling in the vodka trial, only to be turned away for being left-handed. What goes on in which hemisphere of his brain could make it hard to compare his scans to others’, Simonyan explained. As the CEO of a lumber company in Maine, he’d made peace with the disorder, responding to questions with other questions, letting other people do the talking. Still, he said, “It feels like, when you go to talk to someone, you put a belt around your neck and tightened it.”
So he gave sodium oxybate a try under Frucht’s careful observation. Sure enough, his sentences came out noticeably smoother. Now, at 53, after a few months of negotiating with insurance, Hancock keeps a little stash in his backpack and sometimes takes a measured swallow.
It seems to be working. He feels like he can breathe better during phone calls, as though the drug were loosening the bind around his neck. For now, though, as Simonyan might say, that’s still just an anecdote.