Twenty-five million Americans struggle with rare, debilitating diseases. One pioneering doctor is crowdfunding their hope.
The geneticist called it a one-in-three-billion chance.
Just one. Out of three billion. Take a plane to Asia—absolutely anywhere in Asia—and randomly point to the first person you see. Is it Kim Jong-un, the fade-hairdoed leader of North Korea? Yes? Well, you’ve just beaten the odds we’re talking about here.
But that’s all the likelihood it took for Robert Stone—the only never-in-a-million-years, statistical screw-you that Robert’s body needed to land him in a wheelchair and cause legions of medical know-it-alls to scratch their heads in wonder for thirteen long and painful years.
* * *
The outdoor terrace at the 2012 TED Conference in Long Beach, California, is spilling over with Sauvignon blanc and swagger. The crowd is thick with TED Fellows, the “young world-changers and trailblazers,” as the organization calls them, behind geopolitical ventures, like one that creates fuel from Africa’s agricultural waste, and highly lucrative ones, like a 3D-printing operation called MakerBot, which fifteen months later would announce a merger worth north of $600 million.
Jimmy Lin appears to float above the crowd, a boyish energy about him, a perpetual smile that just won’t go away. And that says a lot, because Lin has seen things. He’s studied patients, kids mainly, whose hopeless conditions would make any optimist wince.
Lin, 34, has mid-length black hair that parts just left of center; he wouldn’t look out of place in an undergraduate science lab, or waiting in the pizza line at the dining hall. He becomes easily excited and animated, not necessarily qualities one would expect in someone who got his start in cancer research, as the lead computational biologist on a team that pioneered the genetic mapping of the disease in 2006.
“There were many, many inspiring stories of people fighting cancer, for sure,” Lin would later say of his time at Johns Hopkins, where he received a dual MD-PhD in 2012. But despite his groundbreaking work, the young researcher had become increasingly haunted by an uncomfortable medical disparity: cancer claims nearly eight million lives a year, and attracts billions in federal research dollars, but multitudes more people—25 million in the U.S. alone, and 300 million globally, by some estimates—suffer from rare diseases or disorders for which there are often no clues, let alone cancer-esque coffers of funding.
The universe of rare diseases is a fascinating and troubling place. It brims with maladies that have names like arthrogryposis, derived from the Greek term for “curving of the joints,” and transverse myelitis, which can lead to a sudden loss of spinal cord function. Its patients are comprised almost entirely of children, since, as Lin gravely puts it, most people with such diseases “don’t survive to become adults.” It’s a world in which mothers and fathers blog and pray, long after giving up hope for a diagnosis. You can forget about treatment.
Lin likens these parents to grossly underpaid and disturbingly hands-on Chief Medical Officers. “They’re literally on-call 24/7 fighting for their kids’ lives,” he says. But in an era of medical marvels and untapped scientific talent, Lin saw an opportunity. So in the spring of 2011 he decided to donate his free time to the business of “trying to dissolve rare diseases”—all 7,000 of them.
It’s a lonely business, with little in the manner of active research, since only a basketball team’s-worth of people on earth might sport the same symptoms. So Lin’s volunteer foray from cancer—where his career in academia is still focused—was tantamount to LeBron James’s leaving the NBA’s twice-reigning Miami Heat to moonlight on the practice squad of a youth team in Burundi: no face-painted fans, no private masseuse, no sports car; just endless work, veiled in obscurity—the windowless-basement type—with rarely a breakthrough in sight.
“If someone else is working on a disease we’ll let that person attack it,” Lin says. “We literally draw our area where there’s no one else.”
* * *
Jeneva Stone keeps coming back to the video camera analogy. That’s the only way she can make sense of what started happening to her baby, Robert, back in 1997, shortly after he was born.
“Something would happen,” Stone, now 49, recalls, “and it would happen for thirty or sixty seconds, and he would be absolutely fine. And you would think to yourself, ‘What did I just see?’ Because your brain’s not really a video camera, you don’t really know how to replay what you saw.”
At first, the symptoms were subtle flashes of decreased motor skill, like a spastic smear of food on Robert’s cheek just as his spoon hit his mouth. Occasionally, there was nothing to even see—just a thud heard from the other room, an infant suddenly lying on the floor, motionless for a few horrifying seconds, a vacant look on his face, his muscles unnaturally relaxed.
“It was just like he’d been paused on a video, and you hit play, and the video just starts again. And he was fine, and he just started crawling again,” Stone says.
The doctors simply chalked it up to colic—a healthy baby boy prone to occasional fits in which he’d grow fussy, start crying and lose his balance.
Stone is a fast talker, but there’s a soothing cadence to her voice. She’s prone to bursts of laughter, like someone who hasn’t been through what she has; like she’s merely the matriarch of a typical suburban Maryland family with a devoted husband and two young kids. Maybe she’s like this because of the hand she’s been dealt, or maybe she’s been dealt this hand because of who she is. How else could she cope with the years of tests, the inconclusive results, the accusations that “extreme parental anxiety” had led her to “invent” Robert’s symptoms?
At one point, a group of mystified doctors decided that Robert had some sort of genetic disease that would end his life within three years. But Robert kept on living, and by the time the family took him to a neurological specialist at Johns Hopkins, he was experiencing periods of being “locked in” for hours. He had stopped talking and lost most of his motor function. A good day meant that Robert could sit up in bed for a minute or two at a time. The neurologist eventually exhausted all possibilities.
“I don’t have anything more to add,” he admitted to the family. “You should go see someone else.”
There was no one else, no miracle answer—only more doctors, more drugs, more tests.
“My husband and I are both competitive, driven people,” Stone says of herself and Robert’s father, Roger, who runs his own direct marketing and data company. “We would be consumed with anxiety during tests for these horrible diseases and when they came back negative you’d feel like you won a prize.”
A writer with a PhD and an MFA, Stone laughs as she recites a line from a blog post she once wrote, a string of words that form the basis of a memoir in progress:
“We are winning! If there are no answers, surely, we must be winning.”
Except, there was no prize, no consolation. Every test that came back negative was a relief that Robert didn’t have Tay-Sachs or muscular dystrophy, but also a reminder of the family’s helplessness.
Robert, now sixteen, has been tube-fed since he was two because he can’t swallow food without choking. He’s been confined to a wheelchair since the age of four. Through it all, and even when things got really bad, Stone and Roger insisted that Robert was cognizant, that he understood where he was, and who his parents were, and what they were trying to tell him.
“He still seemed like our child,” Stone says. “Our kid was in there. The question was, how were we going to get him out?”
* * *
Jimmy Lin calls it an “Amazon-slash-Kickstarter for science.” The idea is rather simple: a parent or guardian, like Zsuzsanna Darvai, uploads a photo to a dedicated online platform and creates a profile for a very sick child—Darvai’s son, Balazs, in her case. She describes his personality and details his mysterious and devastating symptoms, like the Internet-enabled version of a fundraiser printed on the back of a milk carton or taped to the side of a tomato can in a local pizzeria:
“Balazs is a 6 year old, very cute, mischievous little boy. Around the age of 9 months he started to have really bad seizures. His lips turned purple and he was not breathing!…His immune system is compromised, he has low muscle tone, and he is having age-related mental developmental delays…Despite all of his issues he is a smart and happy little boy. All the doctors we have taken him to so far said that his medical condition is a puzzle.”
The similarities between old-school fundraising and Lin’s two-year-old Rare Genomics Institute (RGI), of which he is founder and president, end there. Parents like Darvai and her husband use the nonprofit RGI’s online fundraising platform to raise $7,500—from family, friends, and often strangers—to cover the cost of a medical evaluation, blood test and DNA analysis for each of them and their sick child. (Costs increase to $10,000 in the ideal scenario that a healthy sibling is available to serve as a baseline comparison, or can decrease depending on the equipment used.) Blood is drawn at one of eighteen RGI-affiliated sites across the U.S. or at a facility with which the family has an existing relationship. Over the next few months, a team of analysts at Washington University, where Lin is a research instructor, or a number of other labs across the country, scrutinizes every twist and turn in the family’s genetic makeup in hopes of identifying a culprit among the twelve- to fifteen-thousand gene sequences in all human beings—a microscopic abnormality that might announce itself in seizures in a little boy like Balazs, contribute to Robert Stone’s frozen-in video effect, or otherwise wreak havoc on the limbs, organs or nervous system as manifested in any of the one hundred patients RGI has worked with so far. Ninety percent of them have been children.
Balazs is now seven years old, but Darvai says he’s developmentally closer to two or three. He can count to twenty and he knows the alphabet but it’s impossible to engage him in conversation. His seizures are uniquely terrifying, in that he stops breathing when he has them. Balazs has become medication-resistant. He’s been subjected to cranial-sacral therapy, hyperbaric chamber therapy, and a medical-encyclopedia’s-worth of other therapies that should never be uttered in the context of a seven-year-old kid.
“He’s dangerous to himself,” Darvai, 44, says, noting that it took little convincing for her to upload Balazs’s story to RGI’s website in a last-ditch effort to help him. His childhood so far, she laments, “was a nightmare because every minute you never knew when you had to jump. There was always gas in your car because you never knew when you had to run to the emergency room.”
The Darvai family lives in Panama City Beach, in northwest Florida. In February, they packed up their car and kids—Balazs has a healthy eight-year-old brother—and traveled to the University of Florida, in Gainesville, to have their blood drawn. Now they must wait—something the family is all too accustomed to—as Washington University’s Dr. Todd Druley examines their DNA and attempts to finally form a conclusion.
Druley was a dream recruit for Lin. An assistant professor of pediatrics and genetics, he runs a lab devoted to genomic technology and is a rare breed of medical professional who spans the traditionally disparate arenas of research and patient care. Druley, like Lin and every other researcher on the forty-person RGI team, takes no salary. What little funding they receive comes from small grants and family foundations and is used to supplement patient sequencing and pay for support staff.
Still, Lin contends that despite their rather bootstrapped existence, the technology and equipment that RGI brings to bear on rare genetic diseases is “just as cutting edge as in cancer.”
Until recently, genomics, or the study of genes, was seldom utilized in clinical care, largely because of prohibitive costs. But via its unique crowdfunded and crowdsourced operation, RGI ostensibly erases that expense, democratizing the field of highbrow scientific discovery. Of course, $7,500 or even $10,000 is not a massive amount in the medical world, but beyond the initial DNA analysis that RGI offers patients, Lin stresses that the “the main thing” his team provides “is access;” RGI, he says, is able to create research projects “in a small size that would otherwise not exist.”
Druley, Lin and their peers see this as a glimpse toward a future that cannot come quickly enough.
The initial medical evaluation, and the following DNA sequencing and analysis by those like Druley, are merely the first steps. Druley says he’ll typically identify five to fifteen genes whose unusual changes might potentially be the underlying cause of a patient’s adverse symptoms. His findings are then further examined by a team of fifty pro-bono RGI scientists across the globe who aim to develop a diagnosis and secure funding for relevant research on mice and other living organisms.
Lin hopes to eventually integrate a crowd-voting system into RGI’s platform, “kind of like Digg,” so that medical specialists can “up-vote or down-vote a diagnosis,” he says. Such a feature would fundamentally expand the pool of talent from a few dozen volunteer genetic analysts to anyone with a credible point of view. (Lin points to an organization called CrowdMed that offers patients something similar.)
“The biggest thing we talk about with our team is, ‘If this was our child who was sick, what extent would we go to to help them?’” Lin says of RGI’s efforts. “If this was our kid that was sick, this is exactly what we’d do.”
* * *
Jeneva Stone was back in New England for her thirtieth high school reunion. She’d just pulled off to the side of the road for ice cream with her daughter, Edith, Robert’s sister, when her phone rang.
“I’m sitting there in a car at a Creemee stand in Grand Isle, Vermont,” Stone remembers, “and they tell me they’ve got a finding and they’re reasonably sure it’s the cause.”
By that point, in August 2012, Robert was fifteen years old. The Stone family had been through a decade-and-a-half of hospitalizations. They’d learned to never think more than six months ahead—the future was far too uncertain.
“At some point, you just get tired of being on an emotional roller coaster. And for the first time in my life I was tired,” Stone says.
Earlier that year she had agreed to a phone call with a young researcher named Jimmy Lin who thought he might be able to help. Stone heard him out and reluctantly agreed to upload Robert’s story to RGI’s website. “This will be it,” she remembers telling herself. “This will be the last thing I put my family through.”
In just eleven days, the Stones raised $7,500 from two hundred people through RGI, including $1,100 from complete strangers, to cover the cost of their blood work and analysis.
And so here sat Stone, months later, her phone pressed tightly to her ear, listening like she’d never listened before, her ice cream melting, her healthy thirteen-year-old daughter by her side; listening to the news that had escaped her and her family since long before “genome-mapping” had entered their lexicon.
For the uninitiated—those who haven’t had rare genetic diseases to cope with, or, say, those who slept through middle-school science—a genome is an organism’s complete set of DNA, the genetic blueprint for everything it is and does. DNA molecules, of iconic computer screensaver fame, are made of twisting, paired strands called nucleotides—three billion of them. And there was a problem on one of Robert’s.
“The geneticist called it a one-in-three-billion chance,” Stone says, rattling off a seemingly obscure collection of letters, PRKRA, that represent the defected gene that created a universe of difficulty for the family. Stone learned through RGI’s testing that she happens to carry an unexpressed version of the genetic defect. But in a cruel twist of fate, Robert would have been fine had his father’s RNA—the sous chef, or personal secretary, to everyone’s DNA—not made a transcription error on that very same gene. The result was a mind-numbingly rare disorder called Dystonia 16 that claimed Robert as only the ninth reported case in the world. Talk about Kim Jong-un odds. Of the other eight, one lives in Germany and seven come from the same family in Brazil.
Robert’s case is far more severe than the others and there are no proven therapies—only more drugs that may or may not work. Stone, though, says the diagnosis helped to “tweak [Robert’s treatment] around the edges” and prove to the local school board that her son had more cognitive functionality than they had previously been willing to admit. “It’s a long, slow, detailed and nuanced thing,” she says.
For Stone and legions of other parents, like Darvai, hope equals knowledge equals power, which, in the rare-disease business often translates into merely more hope.
“It might be frightening to get an answer,” Stone says of genetic testing. “I mean, you get answers you don’t want. But I’m happy to have an answer.”
Lin, too, knows that RGI offers just another “micro-step” in an agonizing process that might not bear any real improvements by the time Robert or Balazs or other suffering children have left this earth.
“The biggest thing we’re developing is hope,” he says, which can at times be difficult for an around-the-clock caregiver to accept.
* * *
The past few months have been especially challenging for Robert, who battled a series of viral infections last winter and, as a result of his feeding tube, continues to struggle with acid reflux—“our nemesis,” as Stone refers to it.
“I go through some periods of intense sadness,” she admitted by phone recently, following a prolonged hospital stay for Robert. “But I always return to the feeling that when you look back on all this, there’s nothing that I could have changed.”
Stone says she could let herself grow depressed over the “bad gene” she handed down to her son. But, ever the pragmatist, she counters, “I could have just as easily given him the good copy.”
What about Robert, though? What about the teenage boy whose mother gushes about his bright eyes and “wicked sense of humor?” What about Robert, the “very happy kid,” the “very social kid,” the kid who will eventually become a man but won’t know until he gets there if he’ll ever have a shot at feeling normal? What would Robert say about all this?
Stone pauses to ponder an answer, a rare break for a woman who has had none throughout most of her adult life. “You probably can’t print this, but he’d probably say, ‘Well, this sucks.’” And at that Stone erupts into laughter, because that’s how she keeps going, keeps caring, keeps hoping. That’s how she keeps living.
* * *
Noah Rosenberg is Narratively’s founder, CEO and editor-in-chief. He is a regular contributor to The New York Times, and his writing, photography and documentary film work has also been published by The Wall Street Journal, GQ and New York magazine, among other outlets.