Dedication
This Book is Dedicated to:
Addison and Billy
Robert, Bailey, Zackary, Tova, Chelsey, Riley, Emilia, Casey, Jacob, Sam, Henry, Gavin, Ethan, Max, Ian, Colin, Vincent, RJ, and Aviva:
The Sixth Generation
–—
And to my father, Dr. William I. Linder, D.O.,
Who never stopped believing in medicine and its power to heal.
“Harvest” (Lyrics)
What can you say
About one who has gone away?
You may curse
You may frown
You may ask
Hey man—why don’t you come on back?
What can one do
About he who has left you?
One can cry
One can pray
One can ask
Hey man—why don’t you come on back?
Dream on I am told
The cards have been folded
The movie’s over
The ship has passed
The day is gone
It’s night at last
You can relive what has
Already passed
Don’t you feel it?
Have you seen
Though he has gone
He will always have been
Bill Linder
1947–1996
Contents
Cover
Title Page
Frontispiece
Dedication
“Harvest” (Lyrics)
Family Tree
Introduction
One
Two
Three
Four
Five
Six
Seven
Eight
Nine
Ten
Eleven
Twelve
Thirteen
Fourteen
Fifteen
Sixteen
Seventeen
Eighteen
Nineteen
Twenty
Twenty-One
Twenty-Two
Twenty-Three
Twenty-Four
Twenty-Five
Twenty-Six
Twenty-Seven
Twenty-Eight
Twenty-Nine
Thirty
Thirty-One
Thirty-Two
Thirty-Three
Thirty-Four
Thirty-Five
Thirty-Six
Acknowledgments
References
About the Author
Copyright
About the Publisher
Family Tree
Introduction
When I was sixteen years old, my dad sat me down in the living room and told me he was very sick. My mom was away and my sister had recently left our home in Columbus, Ohio, for college in Connecticut.
“What do you have?” I asked.
“I don’t know,” he answered. He looked terrified.
“Then how do you know it’s bad?” I asked sincerely. My dad had been complaining of fatigue. I remembered him fainting the summer after a family vacation, but he chalked it up to “getting up too fast.” Otherwise, he was a tall, healthy-seeming, forty-four-year-old man. He didn’t look pale. He wasn’t running a fever.
“I want your mother,” he said.
I didn’t know what else I could do, so I called my mother and told her to come home.
* * *
Five years later, on September 24, 1996, my father succumbed to his illness. After he died, the surgeon who assisted with the autopsy described his organs as “practically fused together.” They had been pressed so tightly against one another by countless liters of fatty lymph fluid that they had basically congealed. Doctors had only ever encountered this illness twice before—in my dad’s fifty-five-year-old grandmother (who’d passed away in 1955) and in his thirty-four-year-old uncle (who followed her in 1961). No one drew a connection between the three illnesses until two years into my father’s decline.
In the years that followed, several of my family members experienced similarly strange symptoms. After tests revealed a complex system of swollen veins throughout her digestive tract, my thirtysomething sister was told by her doctors that she was “a ticking time bomb.” The same year, my father’s first cousin lay in a coma after a vein burst in her brain. It took three years before she could walk and talk again. At a routine checkup, another cousin was told that she needed a liver transplant as soon as possible.
I wasn’t spared. When I was in my twenties, my legs started to swell. Every time I went to the doctor, I received ominous news—from reports of extreme liver blockage to increased quantities of wayward fluid much like my father’s, deposited where it should not be deposited within my body. In my thirties, I was plagued with questions about my reproductive capabilities. Not a single medical professional could explain what was causing such terrible complications in an otherwise healthy family.
My father’s illness was unique in the medical field, and it attracted the attention of a Harvard geneticist who has spent the last twenty-one years trying to find out what was killing him, and if it was killing us. Together, we discovered that my father’s body was reacting to the expression of a genetic mutation, now more commonly called a genetic variant, that seemed to have occurred only a few generations earlier—a private mutation. Private mutations are genetic variants found in a group of related individuals. For one of the first times in human medical history, my family is allowing medical science to witness a “founder effect”—a new mutation passing to subsequent generations during its fifth generation, instead of hundreds or even thousands of generations after the initial mutation of the gene.
Medical genetics has given my family a way of addressing our illness. We now understand the gene and its impact on our bodies. For us, this means hope, and the chance to change our fate. Medical mysteries like these are rarely solved. The fact that we’ve made so much progress in seventeen years has a profound significance that is not lost on any of us. My family has an opportunity to weed a deadly gene out of existence, to use the power of medicine to do something that humanity has never before been presented with the opportunity to do. But nothing is certain.
Our story is the story of science, its shortcomings, and its miraculous capabilities to change the world. It’s the story of doctors on a quest to map a gene and understand it. It’s the story of our gene—the lives it claimed, the lives it has changed, and the future of genetics.
One
It began the summer after I turned fifteen in 1990, just after our parents took Hilary and me on a two-week trip to Israel. Our great-aunt, who had joined us on the trip, suffered a minor heart attack. Our mother stayed behind to care for her while Hilary and I flew home to Columbus with our dad.
While my father was napping away his jet lag upstairs, Hilary and I set ourselves up in the basement to watch Dirty Dancing for the millionth time on our new VCR. As Johnny lifted a dripping white-tank-top-wearing Baby powerfully over his head in the lake, a loud series of thuds echoed down the basement stairs.
Hilary jumped up first. She was a year and a half older than me and nearly seventeen. She took the stairs two at a time out of the basement, her long athletic legs confident as she raced around the corner to a second set of stairs up to the second floor. I tiptoed behind. Hilary landed next to our father’s head at the top of the stairway. His eyes blinked, glazed with confusion. Blood dripped from above his forehead to his cheek, forming a rivulet through his dark hair.
“Come here and stay with him,” my sister ordered.
“Where are you going?” I called up from where I stood at the bottom of the stairs.
“I’m calling an ambulance,” sh
e answered. “Get up here.”
My father was on his stomach at the top of the stairway with his head near-tangled in the metal bars of the banister. That banister had kept him from falling headfirst onto the stone-tile floor below, but also gashed open his scalp. I approached him carefully, winding my way up around the curve in the steps.
“Get him a towel,” Hilary called while explaining the situation to 911. “Daddy! Are you okay?” she shouted.
He was sitting up now. I fumbled a towel off the rack in the nearby bathroom I shared with my sister.
“Yes,” he answered quietly. I watched awareness settle over him. He suddenly focused on my face, no longer gazing out vaguely at nothing in the distance. Slowly he knitted his brow in an expression of absolute confusion, or was it disgust? At first I wasn’t sure what was going through his head. For all I knew, he was having a stroke.
Then it dawned on me. I was hysterical. My now-sober father was trying to assess not just his own medical state, but mine too. I hadn’t noticed earlier since all I could hear was the thumping silence of residual panic born solely from the possibility that my father had been in mortal danger.
My dad rolled his eyes and tossed the towel I’d given him back at me, presumably so I could wipe the tears that were pouring down my own face. Hilary returned and helped our father to his feet. He was composed enough to put himself back to bed, order us to cancel the ambulance, and request a glass of water. Meanwhile, I went to the bathroom and took several deep breaths.
An alarm had been sounded, but right then it was unclear what it foretold—or that it even had anything to foretell. We were not a family who routinely dealt with catastrophe. We lived in Ohio.
My dad always liked watching thunderstorms. Once we had all been sitting on our front porch watching a particularly wild storm when lightning struck our neighbors’ house across the street. I remember the electricity tickling the tiny hairs on my face as sparks flew off their roof. We went inside and called them in time for a fire truck to come and contain the fire to the attic. We were heroes that day, but really it’s just what we were good at. It’s where we excelled: watching lightning strike other people’s houses.
* * *
We called our dad’s nearby office, where he worked as a physician. Hilary drove when we accompanied him to get seven stitches in his head.
As the nurse cleaned the wound, he explained that he had gotten up too fast from his nap. He explained that when we arrived home from the airport, he had taken a diuretic, or a water pill, designed to help reduce swelling from water weight. He was jet-lagged and otherwise tired from our two-week trip. As he stood up too quickly from his nap, he became disoriented and then finally fell at the top of the stairs.
My dad left out several important items that didn’t come to light until much later: two months before our trip to Israel, in April of 1990, he went to see Dr. Keith Pattison, a cardiologist, because of minor swelling in his ankles. Ankle edema, as it is known, is often linked to heart disease. My father had undergone open-heart surgery as an adolescent in the 1950s. Dr. Pattison offered no definite medical reasons for the swelling that day. His findings simply maintained that “the patient is not functionally impaired . . . and he retains superb exercise capacity.” In other words, my dad’s ankles might be swollen, but they didn’t seem to affect his heart or health.
Dr. Pattison more or less chalked up those puffy ankles to a familial trait. My dad’s mother and maternal aunt both experienced similar swelling and they were healthy. To my father’s mind, that was probably explanation enough. He seemed to have felt pretty good otherwise. He’d videotaped our whole trip and danced to klezmer music at least once.
Pressures on board the aircraft during the flight home from Israel likely impacted the pressures in his body, causing his ankle swelling to expand upward into his legs. Those cabin pressures are why plastic water bottles crinkle up in flight.
At the time I don’t recall knowing about that doctor’s visit or the swelling in my dad’s legs at least in part because I was a teenager. It certainly wasn’t of any concern in my day-to-day life. Instead, I went with the story my dad, his head wound now stitched, told us that day. He’d taken a water pill for swelling he’d gotten on the plane, which, at the time, sounded like something people sometimes got on planes, like summer colds and tomato juice. My dad seemed healthy. He was active and even athletic. From my perspective, after the stitches had been stitched, it truly seemed the worst was over. There was absolutely no reason to think otherwise.
Two
Two years later, during my senior year of high school, when I was arguably at the zenith of my adolescent narcissism, my father’s health concerns—if there were any—existed only at the far corners of familial conversation. He sometimes mentioned feeling tired and had grown fascinated with a trendy illness called chronic fatigue syndrome. But he seemed okay. After all, he’d recently started a band that met in our basement that was appropriately embarrassing to high schoolers, and he’d purchased a rowing machine.
When a beloved ice cream chain from Cincinnati called Graeter’s opened up near our house in Columbus, my father wanted us all to go there for our first time together during Hilary’s semester break at the University of Hartford, where she was a sophomore. My parents’ best friends, Jackie and Jimmy, joined us, as they often did for family outings.
When we arrived at the counter we called out our orders one at a time. When the ice cream server got to our mother, his expression changed.
“Oh, hey, Rhoda!” he said informally.
“Hey,” our mother muttered under her breath.
“Can I get you your usual?”
We were all stunned. To be fair, Graeter’s is the undisputed producer of the world’s greatest mint-chocolate-chip ice cream. But the place had literally just opened: it was at most a month old. How could this person know my mother’s name, much less her usual? My mom’s love of sweets wasn’t a secret, but even for her, this was fast work. She sheepishly admitted she had been going to Graeter’s every day, sometimes twice a day, since it had opened. And although that day we all laughed about it, the incident remained troubling to my father. My mother wasn’t overweight, but she agreed she couldn’t always control her intense sugar cravings.
My dad was pathologically weight conscious. The product of a family who prized a healthy, skinny body, he immediately began asking my mother to go for treatment. She later told me that this pressure became a point of real contention in their marriage. It’s possible my dad was fat-phobic, not that he had a problem with overweight people, per se. But over the years, more than one close female friend of his admitted to me, unprompted, that he was always fairly casual about mentioning it when he thought they were putting on weight. While it might have been related to my dad’s lifelong commitment to medicine and health, some part of it was certainly linked to his upbringing and a subsequent mind-set that mirrored his parents’ that people, especially women, should be thin. After a year of fighting, my mom finally agreed to sign herself up for a reputable Texas wellness spa—that we had gleefully taken to calling “fat camp”—to fight any future weight gain.
The day she left, two years since my father’s fall at the top of the stairs after our family trip to Israel, she couldn’t have known that my father’s body was ready to deliver its next harsh blow.
* * *
I don’t remember when I first noticed my father’s swelling. I once watched as he pulled off a pair of black stockings after a long day at the clinic. His lower legs appeared chickenlike beneath a hovering swollen knee. I had asked him about it and he told me it was normal for his legs to swell after a long day at work. He said the stockings he wore used pressure to help push the fluid toward his heart. I don’t remember delving any more deeply into it than that.
Twenty years later, when I began researching the early days of my father’s illness for a National Public Radio program that never aired, one of the first people I called was Kim Kneuven. Kimmy, as
I always called her, had worked alongside my dad as a nurse since his first job out of medical school. Kim’s shiny straight black hair and fair, peachy complexion went well with her warm laugh and Ohio twang.
Kim and my father were fast friends from the day they met, bonding over a heart procedure they had both undergone as adolescents that left them with long matching scars running down their chests. They were almost five years apart in age to the day, often sharing an office birthday party. Kim said that my dad always tried to get out of the standard doctor-nurse rotation so that he could continue to work with her. One day he made the suggestion that every doctor at the clinic pair off with one specific nurse. When he had everyone on board, since it was his idea, he chose first. He chose Kim.
Kim told me she’d noticed in her career that a lot of doctors didn’t act like healers the way my father did. He was the kind of doctor who gave his patients our home phone number and never minded that they used it. As a doctor, he was hardworking and honest, and it helped that he was the kind of person who could get away with calling strangers “buddy.” More than one of his patients’ children was named after him.
When my dad left his first job to start up his own practice, Kim naturally went with him. Fifteen years into growing it, the clinic was thriving and my father had just opened up second and third locations.
On Fridays, Kim said they often stayed after the clinic closed to talk about the business over a beer. On one of these Fridays, Kim found my father sitting alone in an exam room. His breathing was shallow.
“I can’t catch my breath,” he told her. “I need you to take me to the ER.”
“Shit, let’s go!” Kim replied. With my mother away, Kim called my parents’ best friends, Jackie and Jimmy, to meet them at the ER. Then she helped my dad, struggling to breathe, to her car.
Jackie left Jimmy at their house. The call from Kim sounded like my dad simply needed a lift back to his car. Jackie and Jimmy lived down the street from us and my father’s office was only five minutes away. While Jackie was being seated in the ER waiting room, my dad was already being seen.
The Family Gene Page 1