LEXINGTON, Ky. — The man had come for a third opinion. Other doctors had told him he had amyotrophic lateral sclerosis, or ALS, a neuromuscular disease that causes progressive paralysis, but he didn’t believe them.
In his hometown of Ewing, Va. — just east of the state’s mountainous meeting point with Kentucky and Tennessee — a handful of his relations had had the same thing, and they knew it as cancer of the throat. They lost the ability to chew, swallow, and speak, they lost weight, and then they died.
Dr. Edward Kasarskis admitted him to the University of Kentucky’s clinic for testing that same day in 1984. What had seemed clear when the patient first arrived only became clearer: No matter what they called it in Ewing, this was ALS. The man went home, and within a few months he, too, was dead.
But Ewing stuck in the neurologist’s mind. He had a fondness for names and places — he can talk about tree species and Civil War battlefields with equal ease — and in 1984 his oldest son was an avid 12-year-old hiker. From Lexington, Ewing was only a few hours away, and for a small fee, some residents would keep your car on their lawn while you were out among the yellow poplars and buckeyes of Cumberland Gap.
So nine years later, when another ALS patient mentioned she was born in Ewing, the town name wasn’t just familiar: To Dr. K, as he’s often called, it was the parking place where family stories began, and it flicked on some narrative instinct within him. The woman had been married four times, acquired some new names, and moved around — but when the neurologist glanced at her intake form, he saw that her maiden name was the same as that man’s from 1984.
“I thought, ‘Holy smokes, this is like the same family kind of deal,’” he said. Then, two years later, her 33-year-old son showed up, also weakened by ALS.
At the time, the hunt for ALS-linked genes was just beginning, and Dr. K wondered what he would find in Ewing’s DNA. Unwittingly, he was about to embark on a search, one of many in medicine staked on the possibility of new treatments for genetic diseases. It would extend over thousands of cumulative miles and more than 20 years.
Before she died, the mother had whispered a clue about how Dr. K could trace her clan’s neurodegenerative inheritance. “There was some little old lady somewhere that knew the whole family history, and if I could talk with her, she would just let me know everything about it,” Dr. K said. “And this woman just refused to talk to me … like flat out, no way, Jose, was it ever going to happen.”
He tried to piece it together himself, making calls, jotting names and dates on bits of paper. Families were tight-lipped, though, and he didn’t have much luck. He turned to other things. It was only a decade later that he mentioned his desultory attempts at genealogy to a University of Kentucky research coordinator named Debby Taylor, who was just migrating from stroke studies into ALS. She’d been mapping her own family history on Ancestry.com, and she offered to try with software what hadn’t worked by hand. Within a day, she had 12 pages of names.
The Scroll, as that document is now known, resides in a former storage closet in the basement of the Kentucky Clinic. This cupboard has been Taylor’s office for years, and on a swampy evening in June, she sat at her desk, explaining how a measly, hand-tended sapling had grown into a 250-page digital family tree, with around 6,700 names, eight generations, two intertwined families, and a lot of ALS. Some of her most important tools were on her desk: Three rolls of Scotch tape in bulky black dispensers, to stitch pages of The Scroll together, and a big can of Raid, to spray around her chair when the roaches come skittering into her workspace.
A piece of her handiwork sat facedown a few feet away. In hard copy, under the glare of the fluorescent lights, it looked at once ancient and ultramodern — like a printer-paper Torah. The comparison is obvious — maybe even blasphemous — but apt. For Taylor and Dr. K, The Scroll really has become a kind of Bible. It is the foundational text of their research: an origin story and a mystery and a guide for how they should spend their days.
The next morning would be a case in point. At 8 a.m., in a red Toyota Prius, they would motor south from Lexington to visit certain people of The Scroll. Their destination was a picnic shelter in Harrogate, Tenn., where an extended family would be getting together, and where Taylor and Dr. K hoped to add new names to the family tree and to use it as a roster in collecting flesh and blood for their research.
With patient visits along the way, the Prius would also be tracing, in reverse, the path of the families’ ALS-causing genetic mutation back to one of its sources near the Cumberland Gap. The region is thick with myth — and, consequently, tourists, who come to hike and inspect dioramas of their forebears wending through an opening in the mountains to settle the Western frontier. The researchers’ interest is a little different: This corner of Appalachia runs thicker with a particular form of inherited ALS than almost anywhere else.
It’s easy to forget, with the brains of biotech huddled in their coastal labs, the far-flung, gene-finding legwork behind the latest dish-grown DNA and antisense oligonucleotide. Like many scientists obsessed with familial disease, Dr. K and Taylor had been on a number of these expeditions — blood and barbecue trips, they sometimes called them. “We ate and we drew blood; what else do you do at a picnic?” Taylor joked. As exciting as it sounds, it’s unpredictable work. Just as venture capitalists can never be sure their investments will yield approvable drugs, so these DNA-seekers can never know if they’ll find anything treatable in their vials of blood.
As The Scroll had spidered outward, the tenor of their excursions has changed. When that first patient from Ewing had arrived in 1984, neurologists were just starting to scrounge for ALS-causing genes. Dr. K would take part in a worldwide hunt for samples from affected families, sending his vials to join a collection of thousands in a freezer in Massachusetts.
Now, Taylor and Dr. K know that among the 5,000 annual diagnoses of ALS in the U.S., only around 10 percent are inherited. They know there are over 30 different major genes in which a mistake might be causing the disease. They know that the mutation they’re studying is among the rarer ones, affecting a gene called FUS. What they still don’t know is why certain family members with the mutation get the disease, and others don’t.
“This is a classic example: this guy died in his 90s,” said Taylor, pointing to a facsimile of The Scroll, which she’d printed without names to protect the families’ privacy. Each person on it was represented by a little diamond: light if you managed to escape the mutation, dark if you’d definitely gotten ALS, gray if you’d reportedly gotten ALS, and pixelated if you carried the genetic error but never got the disease. The diamond representing this guy was pixelated. “He was healthy as hell,” she said. “Healthy as a horse, yet he gave ALS to three of his children and passed the gene on to two others.”
When the team first came across someone like this, the researchers thought they had made a mistake. They ordered the tests again, sure they’d find that the FUS gene was normal after all. It wasn’t, and that reshaped their obsession with these families. If they could figure out why this mutation was killing some in early adulthood and letting others become living antiques, they might find the key to treating these families’ ALS. It was a big if — and one that depended on a lot of blood from the dark and pixelated diamonds.
“We can’t legally go doing cold calls: ‘Hey, George, how’s it going? By the way, have you developed your ALS yet?’”
Dr. Edward Kasarskis
Genealogy, to those who don’t pursue it, can seem a little fusty: a retirees’ pastime, like canasta for the historically minded. But in this game, there’s no predetermined way of winning. Start with a handful of names and you might end up at the Mayflower or the Tang dynasty, a genocide or an instance of incest. With the addition of websites and commercial genetic testing, the possibilities explode. Families find stories lost in the trauma of slavery. Children email fathers they’ve never met. Cold cases get cracked.
In April, when an investigator in California used the family trees on GEDMatch.com to pinpoint a suspect in an unsolved, decades-old suite of rapes and murders, the reaction was part true-crime fascination, part anxiety about genetic privacy online. The issue is often on Dr. K’s and Taylor’s minds. The Scroll reaches back into the 1850s, when these families lived side by side in and around Ewing, follows their 20th-century migrations, extends into the present — and sometimes, eerily, into the future as well. In some cases, when a patient first contacts the clinic for an appointment, Taylor already knows that person’s name.
Unlike those cops in California, she can’t just look up an address and show up at someone’s door. “Until they develop an illness and come to medical attention, they’re just a name on a chart, on a pedigree,” Dr. K explained. “We can’t legally go doing cold calls: ‘Hey, George, how’s it going? By the way, have you developed your ALS yet?’”
Instead, they wait for patients to come to them. They don’t ask about participating in research right away; there is no cure for ALS, and the diagnosis can be devastating. It’s only later, when there has been time to take stock, that they begin to probe a bit farther. Would their family members be willing to give Taylor a little history, too? What about little bits of skin and blood? If they say yes, then Taylor and Dr. K get in the car.
So the next morning, they headed out of Lexington along Nicholasville Road. “If you want to get your chest pain looked at, now’s the time to do it,” said Dr. K as he sped past a glittering glass-and-brick façade. “We’ll be out of sight of hospitals pretty soon.”
Taylor had been driven to genealogy by loss. In 1999, her mother and brother died about a month apart. It landed her in the hospital — and sent her scrolling through ancestry message boards. “When you lose your family members, then you want to know where you came from,” she said.
She grew up about 12 miles north of Lexington, in Georgetown, where she would sled through the cemetery as a child, growing familiar with the graves. She thinks of herself as a Kentuckian — “clean to the core,” as she put it. But her mom’s history was not that straightforward. Her mother’s mother had died two weeks after giving birth, and she didn’t know much about her mother’s father. It was only a card from a family funeral that gave her some names to work with online.
From her sleuthing, she saw how rich digitized records could be — pages of births, deaths, and marriages. She became a census connoisseur, intimately familiar with its quirks and frustrations. “I learned it’s not all that worthwhile to go back past 1850 because there’s only men, and there are women in my family just like everybody else’s,” she said.
Taylor’s work was mostly unrelated. She’d worked as a teacher. She’d worked as a chemist, testing thoroughbred urine for performance-enhancing drugs and analyzing human blood for signs of disease. She’d worked as a clinical research coordinator, following up with stroke patients for data, finding them even when their phone numbers went dead.
But it was her job as an assistant on a horse farm that influenced her most. Incidentally, the business was built on pedigrees — equine family lines carefully plotted for stamina and speed. Taylor wasn’t involved in any of that. Instead, she was booking mares for servicing in springtime, arranging transport to the breeding shed and back. A session with a stallion could be astronomical. “They breed three times a day, and you hope you don’t get the third,” she said. “That one he’s just doing for fun.”
“If you tell your fiancé that there’s ALS in your family, do you think he or she is really going to marry you? So this is not anything that people want to talk about.”
Such high-stakes scheduling was, oddly, good preparation for the gargantuan task of building The Scroll. “I learned more there than I did in all my degrees in pharmacology,” she said. Tracking a disease through a pedigree presented its own kind of puzzle. Archives had burned and records had disappeared. Birth and death dates were imprecise at best, fictional at worst. Couples took in nieces and nephews, who became their children on the census.
Taylor did everything she could to make sense of this piecemeal history. She drove down to the Ewing area to spend a week leafing through courthouse documents. She called keepers of family lore. She chatted with folks at funeral parlors.
Traces of ALS were hard to find, though. The disease’s discovery dates back to 1869, but even now it’s a diagnosis by elimination: You rule out all the other possibilities until you’re left with ALS. In 1984, families in Ewing believed they had cancer of the throat. Before that, an ALS death in a rural town could have been attributed to anything: consumption, respiratory failure, heart attack, suicide.
To Taylor, the erasure of the illness wasn’t always accidental. “This disease is not desirable,” she said. “If you tell your fiancé that there’s ALS in your family, do you think he or she is really going to marry you? So this is not anything that people want to talk about.”
Even so, she was able to piece together a story. Once, in the middle of the 19th century, there lived two families cheek by jowl in Ewing and the surrounding towns. Family 1 and Family 2 weren’t technically related, according to the census, but when you looked up one, you tended to find the other. The names seemed so inseparable that Taylor suspected they were more than just neighbors. “Way back then,” Taylor said, “you married what was convenient.” Members of Family 1 generally stayed around the Cumberland Gap; members of Family 2 scattered, moving into other parts of Kentucky and then away — to Indiana or Ohio or beyond.
Both branches carried this mutation with them like a secret. Taylor’s job was not just to track it through history, but also, as descendants came out of the woodwork, to help Dr. K ask them for genetic samples.
“Genealogy is a contact sport,” Curtis Rogers, one of the co-founders of GEDMatch.com, said, months before his website made headlines for helping to nab the suspected serial killer-rapist. That’s a fair description of Taylor’s approach. She refers to the people of The Scroll as “our family.” She often knows more about their forebears and distant cousins than they do. When she arrives at a family gathering, she doesn’t just ask about names, birthdates, who begat whom; she also swaps stories as if they were about her own grandparents.
So when Dr. K says that this research couldn’t happen without Taylor, he means it. They make for strange travel companions: the jovial neurologist from elsewhere and the straight-talking genealogist from here. He likes hotels with local character. Her idea of charm is a Holiday Inn. He points out hollows he’s hiked through. Her idea of a hike is walking next door. What they share is an almost ferocious obsession with The Scroll and its possibilities. If they come home empty-handed, that makes it even more important to drive out again.
Some family members haven’t been as enthusiastic about the project. As Jennifer Mundy, who provides care services for the ALS Association in southwestern Virginia, put it, “In the culture here, there’s very much an insider versus outsider dynamic.” Some people don’t trust Taylor and Dr. K. Others don’t see how this research could possibly help them. Yet others simply refuse to accept the diagnosis.
“Remember the guy in the trailer? He resisted it until the day he died,” Taylor said, as they drove toward their first patient visit of the day. “He’s the sixth patient we drew blood on, but he wanted to be 007.”
Dr. K laughed behind the wheel. “We have no patient with the number 006.”
“When we went to see his wife, she said, ‘He had ALS? I had no idea!’”
“That was 007?”
“Yeah, he was denying it.” She paused. “Some people say, ‘Oh, I can fight this disease — like cancer.’ You can’t fight ALS.”
When Jackie Sutton had turned 30, she thought she was finally safe. She was only 4 when her father died of ALS at 29, and she doesn’t remember much about his final months, but it left a vague threat at the back of her mind. Every year, on Dec. 10, her mother made her a confetti birthday cake, the batter and icing flecked with rainbow sprinkles, and with every cake she was creeping closer to the age when her father got diagnosed.
Her grandfather, her great-grandfather, and three of her great-uncles had also died of ALS. So when she hit 30, she felt a muted sense of relief. “Because my dad died when he was so young, I always thought, ‘Well, I’ve lived this long, I’ll be all right,’” she said.
By the time Dr. K and Taylor pulled up at her house in Somerset, Ky., on their way to the family reunion, a lot had changed. She’d reconnected with Ryan Sutton, a high school acquaintance, at the education tech company where they were both working. They’d laughed over the idea that the coat hook on his office door looked like an angry drunk octopus, two tentacles raised to fight, and Jackie drew him a picture of it — a visual inside joke. A week later, he had a tattoo artist friend ink it in orange on his leg.
They were married in 2014, had a daughter named Fern in November 2015. Jackie felt the first symptoms six months after that. “At the age of 31,” she wrote, “I suddenly had to start thinking about not growing old with my husband … leaving my daughter to be raised without me, planning my funeral instead of my future.”
The research team had already collected Jackie’s blood and skin. They were just here to check in. As part of another study they were running, she’d been getting two injections weekly: a steroid that had seemed, at least in the lab, to help with the neuronal damage caused by the mutation in the FUS gene. Other neurologists had seen similar drugs fail, but Jackie liked it, because it increased her appetite enough to eat. Breads could be tough, and she avoided rice: The machine pushing air into her nostrils could blow the tiny grains down her throat. But her church family brought over other foods — chicken and dumplings, casseroles, meatloaf — that could still provide the daily pleasure of meals.
Physically, there wasn’t much else she could do. She could still talk. She had a screen with software that would let her type with her eyes, her cursor following her gaze and clicking if she lingered on a letter. She wrote emails and text messages, scrolled through Facebook, made grocery lists. If she wasn’t too tired, Ryan would help her into a van for church on Sundays, but otherwise she was home in a hospital bed in the living room. The blanket covering her was printed with a picture of her, Ryan, and Fern silhouetted against the ocean in North Carolina, a wave glittering behind them as it broke.
Dr. K now lifted up a corner, revealing her feet, the toenails painted cardinal red. “OK, kiddo,” he said, “can you lift this one?”
“No,” Jackie said, her voice made nasal by the oxygen machine.
He placed her heel in his palm, asked her to push down, testing how much strength, if any, was left in her leg.
Fern was padding barefoot over the carpet, making motor sounds with her lips. Taylor had brought a copy of her favorite genealogy software and handed it to Ryan. She’d already given them 60 pages of The Scroll, and Jackie loved tracing the path of Family 2 back across the region, seeing names and stories she’d never known. There was even one death that looked like a murder, long before they’d settled in Somerset. “I just like to know where I come from,” she said.
But it was Ryan who’d really clamored for these pages. He’d had troubles of his own — “From about 18 to 20, I was bad off on drugs,” he said — but he was sober now, working from home, caring for Jackie with help from her mom. Last year, he’d taken that piece of The Scroll to congressmen’s offices in Washington, advocating for more ALS research funding. He installed Taylor’s program immediately.
“We’re going to work together on filling in some of the gaps,” he said, his voice getting quiet. “Because, obviously, I’ve got a daughter to worry about. This is my life now.”
Later, over lunch, the conversation kept coming back to the Suttons. “She’s worried about her daughter — something that none of us have ever experienced,” said Dr. K. “She’s only 34.”
“Her baby wasn’t 1 year old when she got the diagnosis,” said Meghann Bruno Svec, the team’s research nurse.
“It’s not right,” Dr. K said, stabbing a French fry into his plate for emphasis. “See something like this and you think, ‘We’ve got to figure this out.’”
He and Taylor had now spent more than a decade doing exactly that. They’d logged thousands of miles, hopping in the car if they heard a new branch of the families might see them, or that a daughter might give them blood or skin while home on spring break.
They’d been on so many of these trips that the stops had become rituals. That day’s lunch was in their favorite highway-side steakhouse not far from Somerset; that night’s dinner would be at their usual Italian comfort-food joint in Cumberland Gap. They pointed out overgrown country roads they’d once driven down to collect an ounce of family history. They passed a sagging, blue-trimmed trailer in Ewing, where they’d once worried their patient’s wheelchair might fall through the floor. Every time they were nearby, they drove up the twisting road to the Pinnacle Overlook to peer out over the forested hills and hollowed-out towns in three different states. “You’ve got to remind yourself that, yes, beauty still remains,” Taylor said.
While they’ve been drawing blood on picnic tables and pianos, biotech firms on the coasts have begun tinkering with potential treatments for other, more common forms of inherited ALS.
These subsets of the disease involve mutant genes giving faulty instructions, turning everyday proteins into poison. To try to correct that, both Ionis Pharma, in Carlsbad, Calif., and Wave Life Sciences, in Cambridge, Mass., are trying to kill the messenger — the RNA that transmits those toxic blueprints. They’re sending in tiny chains of nucleic acid — the stuff of DNA, but grown in a lab — to glom onto those specific strands of abnormal RNA and disable them. Voyager Therapeutics, also in Cambridge, is trying to do something similar, but by delivering genetic material into these cells with a virus acting as a Trojan horse.
Those treatments are still far from the pharmacy. Ionis is testing one such drug in patients now, Wave promises a clinical trial before the end of the year, and Voyager says it will file paperwork in 2019 to be able to inject a gene therapy into humans. But they’re part of an upswing in attempts to treat inherited disease that has gotten Dr. K even more excited about his own work.
He was born in Chicago, and has an infectious gee-whiz enthusiasm for everything from rhododendrons and centipedes to the molecular wizardry of gene editing. His voice rises when describing recent discoveries. Spinraza, the drug for spinal muscular atrophy. Gene therapy, gone from an elusive goal to a regulator-approved reality.
He hopes that his Scroll-guided road trips might yield a treatable target, something to take advantage of these advances. After every expedition, he and Taylor drive whatever blood they’ve managed to collect — if any — back to Lexington, to biochemist Haining Zhu’s lab at the University of Kentucky, where it gets spun in a centrifuge, doused with DNA-extracting solvent, and spun again. Add some alcohol, and soon the sequencing can begin.
First, they’re looking at the FUS gene, which can, in concert with each person’s clinical history, tell the team what kind of diamond should represent that individual on The Scroll. Later, Zhu plans to widen his scope. He’s hoping to find other snippets of DNA that modify how the body deals with that genetic error in FUS, determining whether or not someone gets the disease.
“If it’s environmental, then it’s a totally different ballgame,” said Zhu. “That’s much more difficult to figure out. So we’re operating under the hypothesis that there is a genetic factor.”
That search for modifier genes can be as much of an undertaking as building a 250-page family tree — a series of molecular road trips through billions of nucleotides, with no clear destination.
As for the tiny discs of skin, many get sliced up, their cells isolated and then frozen with liquid nitrogen. They’ll be packed away in case the team finds some modifier genes to work with and a possible medicine to influence them. Then, Zhu said, these fibroblasts will be thawed and chemically converted into stem cells, which in turn will be transfigured into motor neurons, so that the researchers have at least one microscopic piece of these families on which to try their potential treatment.
This approach of looking for modifier genes is one that biotech companies are interested in. “In pretty much every genetic disease, like Huntington’s, like ALS, there is a similar story,” said Frank Bennett, Ionis’ vice president for research. “We’re looking for modifier genes, trying to figure out whether they’re suitable drug targets or not.”
The huge, worldwide library of familial ALS blood samples is now kept in Dr. Robert Brown Jr.’s lab at the University of Massachusetts Medical School. He was instrumental in identifying some of the more common ALS-causing mutations, as well as the error in the FUS gene, and he’s now working on both Wave’s experiments and a gene therapy that his team has begun testing in patients. He hopes that these projects will help elucidate non-hereditary forms of the disease, too.
“Where do the falling dominoes converge? At what stage do the molecular … roads find a common pathway?” he said. “You’re going to have to treat at that level, otherwise you’re in highly personalized medicine where you’re treating each gene as its own disease.”
Dr. K knows that these projects — both others’ and his own — will extend longer than he has left in him, and he’s started quietly looking for a young neurologist who might inherit his obsession with these families. He’s 71, no longer the hiker he once was. He’s had some back surgery, has quit his second job, as chief of neurology at Lexington’s VA Medical Center.
Even so, his drive for more samples has become a kind of instinct. When he popped in to see another patient who happened to live in the Cumberland Gap area but had non-inherited ALS, and the family mentioned someone nearby who’d recently been diagnosed, Dr. K’s body stiffened, like a dog catching a scent. The same thing happened that evening, when the team was sitting having coffee, and a passerby — who was visiting his childhood home from Kansas — mentioned that his folks were originally from Ewing.
The team had laughed about it over dinner: Everyone could see Dr. K restraining himself, trying not to ask the man about any relatives with ALS. But later, as the clock inched toward midnight, he stood under a streetlamp outside the hotel, thinking about the family reunion that would take place the next day.
“We just don’t know,” he said. A moth, drawn by the light, was fluttering around his feet. “There could be 10 people. There could be three. It could just be us, eating our sandwiches.”
On the morning of the Keyes family reunion, Taylor sat in the passenger seat of the Prius, making a wish list for that afternoon. Like much of the trip, this day would be suffused with a sense of déjà vu: They had been here years before, for the same event. Now, she was trying to remember who’d been missing then, whose samples she was hoping to collect this time around. “Tinsley didn’t come,” she said. “And Deborah has never come. We could always hope she comes. And I need to get a birthdate on one of the grandsons.”
“We might not get very much,” Dr. K said, as if reminding himself.
“It’s nice to make a connection,” Taylor said.
The melancholy was audible in her voice. What makes her work pleasurable is also what makes it hard: Tracking familial disease meant tracking families, and every branch is complicated in its own way. There were spats and scheduling problems, divorces and custody battles, siblings scattered across state lines. Even when you did get invited to a family reunion, it was hard to know what you would find.
Harrogate City Park sits a few miles south of Cumberland Gap. Besides the green hint of mountains on the horizon, when Taylor and Dr. K arrived, it might have been a city park in any corner of America on any Sunday afternoon. Toddlers padded through a fountain, splashing, shrieking. Kids wriggled their way over climbing frames. Families celebrated birthdays with sheet cake and balloons.
The Keyes clan fit right in. They’d chosen a picnic shelter with an abandoned bird’s nest in the rafters, laying out pulled pork and fried chicken, potato salad and beans, a glistening tray of deviled eggs. Carloads of relations kept pulling up, from Maynardville and Cumberland Gap in Tennessee, and from Georgetown, Louisville, Glasgow, and Middlesboro, in Kentucky. They had come, in a sense, to restore something that had been lost. Some of the eight siblings had spent their early years in Michigan, where their dad had worked at a Ford plant, but the area near Cumberland Gap always felt like home. Once they were grown, this was the place they returned to once a year, to eat off paper plates and horse around and catch up.
That petered out after their brother David died, in 2009, of ALS — the same year the genetic mutation that affected their family was identified. The disease wasn’t new to the siblings: Their mother had had it, and their cousin, and their cousin’s mother — enough to make you paranoid any time you felt a twinge in your arm or leg. But with David’s death, something changed, and the yearly reunions ended. “It just got stopped,” Darrell Keyes said. “Nobody wanted to.”
Now, a few years later — and not long after Darrell’s son had been diagnosed — they were trying to revive the tradition. They needed to get together, Darrell explained, so it didn’t just happen at funerals. The picnic itself had nothing funereal about it. Granduncles doused kids with cups of ice water. Grandmothers ribbed their granddaughters. A group split off to play with a drone: It buzzed lazily above the athletic fields like some giant, sun-addled wasp.
Still, even with the exchange of hugs and plates piled high with meat, even with kids meeting some relatives for the first time, the research felt like the event of the day, the feature presentation. Dr. K was happy to oblige. He leaned one leg up on a picnic table, like a mayoral candidate stumping at a church supper, and began to speak.
He told them about the discovery of the mutation that affected some members of their family. He told them that there were now fruit flies and zebrafish and worms implanted with this kind of genetic mistake. He told them about “this CRISPR thing,” a tool that allows you to give a mouse the exact same form of the disease. He told them why he hoped they’d give him tiny hole-punches of arm skin.
“It all begins with the drawing of blood, or a skin biopsy. That’s how it all gets started,” he said. “I always tell people that if you donate a sample to science, it does not go into your medical record, you don’t have any insurance companies that know anything about it. This is just you and science.”
He said he couldn’t even tell them whether they had the mutation; for that, they would have to get a clinical test. Then, the team laid out a blue and white absorbent pad on a picnic table in the corner, to catch any stray blood — “Is that a diaper?” Debbie Young said, cackling — and started collecting, just as Darrell’s son arrived, leaning on the back of a wheelchair.
“I would never have let y’all come near me before,” Young said, her eyes sparkling with mischief. She was full of mirth, affectionately whacking her grandkids with paper plates, then kissing them on the cheek. But beneath all of that was an undercurrent of fear. That was why she’d always avoided the researchers. “We’re scared of this disease,” she explained. “I didn’t want to know if I had it.”
That the next person to be diagnosed might be in the next generation had never occurred to her. “It never entered my mind, that my kids, or any of our children …” her sentence trailed off. “When it hit one of the nephews, it makes you realize it could be anyone.” Now, she let Dr. K peruse her forearm for a usable vein.
Others who’d been reluctant also came forward. Young’s oldest brother, Tinsley Keyes, just hadn’t seen the point. Healing was the province of the Lord, and there was no cure for ALS. He sat down next.
His nephew Kermit Sowders was hardly enthusiastic about the outsiders at the reunion — “I came just to show the family I do care, but the others, I don’t give a f— about,” he said. But he allowed them to swab a few cells from his cheek.
After a few others had sat down, their information logged by Taylor, their bits of skin shaken off the tips of the tweezers into a pink liquid that would keep the cells alive, the samples were packed into a cooler. Meha Joshi, the research coordinator, took a group photo. Dr. K pretended to balance a cup of water on someone’s head. By then another family had settled at a table uncomfortably close to the Keyes’ picnic shelter and lit the barbecue, blurring the surrounding air with heat. It was time to go. In dribs and drabs, they packed up, and steered their cars toward Glasgow, Louisville, Maynardville, Cumberland Gap, Georgetown, Middlesboro.
They’d left bits of themselves behind, though, to be driven back to Lexington, where they’d be dissolved, used for sequencing and tests and new branches on The Scroll. This was the bargain they’d made: Flesh and blood in exchange for lab dishes cultured in their image, birthdates and grandchildren’s names for a sliver of possibility.
Fascinating article, combining genealogy & science.
My great aunt, my aunt, and my first cousins son died from ALS. We were told it was not familial, but I believe there is a connection. Aunts from middle Tennessee, cousin from Louisville. Thanks so sharing this research.
This is an excellent and fascinating article. My sister was diagnosed in 2016 and died this past June. She had been age 70 for 12 days when she died. No family history and the doctors discouraged even looking as they say it will affect insurance coverage.
I just finished reading your article “An Appalachian odyssey” in STAT and I wanted to compliment you on a terrific piece of reportage. Beautifully written and it held my interest till the end. Of course, I have a special interest in that my father died of ALS in 1988. While I’ve mde it to 75 years old, its always in the back of my mind that I may be in the 10% that have a familial form.
Quiet a few years ago I remember Dr. Robert Brown, Jr. was Scientific Advisor to a company called Knopp Neurosciences that was purchased by Biogen. “Know” was working on a test and therapeutic based on Dr. Brown’s work. I’ve never seen any follow-up by Biogen on this project. You might inquire at Biogen.
In any event, congratulations on a beautifully written and fascinating story. Thank you,
i want to thank you for you story about Dr K. and the work they do. My family wants to say great job. Thank you
Amazing pioneer, Dr K and Taylor… always wish I could have done something like this for my ALS patients.
Great article. Heartbreaking.
Yes cried my way through and I dont think my family is affected. Hugs to everyone who is.
My youngest brother, John Andrew Spiro died of ALS in 2010 in Maryland. He was 56. No other family member on either side of our family had any encounter with ALS. My mother’s father, however, came originally from the Kingsport TN area about 50 miles from Ewing VA. My mother’s name was Doris Ophelia Spiro (nee Odum/Odom, d.2008). Her father’s name was Daniel Lake Odum (b.1874,d.1947). Family names through Daniel , besides Odum, include Bridgeman, Mullens, Gill. Any info would be helpful. The Drs./clinical research specialists at Johns Hopkins were not very helpful.
Appalachian Oydessey a very good read! Would be interested in a list of your other articles? Anything on the uninsured???
You can see all STAT articles at https://www.statnews.com/latest/ and all of Eric Boodman’s articles at https://www.statnews.com/staff/eric-boodman/
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