No one needs more skeleton than they need.
When Jeannie Peeper was born in 1958, there was only one thing amiss: her big toes were short and crooked. Doctors fitted her with toe braces and sent her home. Two months later, a bulbous swelling appeared on the back of Peeper’s head. Her parents didn’t know why: she hadn’t hit her head on the side of her crib; she didn’t have an infected scratch. After a few days, the swelling vanished as quickly as it had arrived.
When Peeper’s mother noticed that the baby couldn’t open her mouth as wide as her sisters and brothers, she took her to the first of various doctors, seeking an explanation for her seemingly random assortment of symptoms. Peeper was 4 when the Mayo Clinic confirmed a diagnosis: she had a disorder known as fibrodysplasia ossificans progressiva (FOP).
The name meant nothing to Peeper’s parents—unsurprising, given that it is one of the rarest diseases in the world. One in 2 million people have it.
Peeper’s diagnosis meant that, over her lifetime, she would essentially develop a second skeleton. Within a few years, she would begin to grow new bones that would stretch across her body, some fusing to her original skeleton. Bone by bone, the disease would lock her into stillness. The Mayo doctors didn’t tell Peeper’s parents that. All they did say was that Peeper would not live long.
“Basically, my parents were told there was nothing that could be done,” Peeper told me in October. “They should just take me home and enjoy their time with me, because I would probably not live to be a teenager.” We were in Oviedo, Florida, in an office with a long, narrow sign that read The International Fibrodysplasia Ossificans Progressiva Association. Peeper founded the association 25 years ago, and remains its president. She was dressed in a narrow-waisted black skirt and a black-and-white striped blouse. A large ring in the shape of a black flower encircled one of her fingers. Her hair was peach-colored.
Peeper sat in a hulking electric wheelchair tilted back at a 30-degree angle. Her arms were folded, like those of a teacher who has run out of patience. Her left hand was locked next to her right biceps. I could make out some of the bones under the skin of her left arm: long, curved, extraneous.
“It’s good to finally meet you,” she said when I walked in. Her face was almost entirely frozen; she spoke by drawing her lower lip down and out to the sides. Bones had immobilized her neck, so she had to look at me with a sidelong gaze. Her right hand, resting on her wheelchair’s joystick, contained the only free-moving joint in her body. It rose and swung toward me. We shook hands.
Peeper’s condition is extremely rare—but in that respect, she actually has a lot of company. A rare disease is defined as any condition affecting fewer than 200,000 patients in the United States. More than 7,000 such diseases exist, afflicting a total of 25 million to 30 million Americans.
The symptoms of these diseases may differ, but the people who suffer from them share many experiences. Rare diseases frequently go undiagnosed, or misdiagnosed, for years. Once people do find out that they suffer from a rare disease, many discover that medicine cannot help them. Not only is there no drug to prescribe, but in many cases, scientists have little idea of the underlying cause of the disease. And until recently, people with rare diseases had little reason to hope this would change. The medical-research establishment treated them as a lost cause, funneling resources to more-common ailments like cancer and heart disease.
In 1998, this magazine ran a story recounting the early attempts by scientists to understand fibrodysplasia ossificans progressiva. Since then, their progress has shot forward. The advances have come thanks in part to new ways of studying cells and DNA, and in part to Jeannie Peeper.
Starting in the 1980s, Peeper built a network of people with FOP. She is now connected to more than 500 people with her condition—a sizable fraction of all the people on Earth who suffer from it. Together, members of this community did what the medical establishment could not: they bankrolled a laboratory dedicated solely to FOP and have kept its doors open for more than two decades. They have donated their blood, their DNA, and even their teeth for study.
Meanwhile, the medical establishment itself has shifted its approach to rare diseases, figuring out ways to fund research despite the inherently limited audience. Combined with Peeper’s dedication, this sea change has enabled scientists to pinpoint the genetic mutation that causes her disease and to begin developing drugs that could treat, and possibly even cure, it.
Although rare diseases are still among the worst diagnoses to receive, it would not be a stretch to say there’s never been a better time to have one.
When Peeper’s parents received their daughter’s diagnosis, they didn’t tell her. She enjoyed a kickball-and-bicycles childhood in Ypsilanti, Michigan, and only became aware of her disorder when she was 8.
“I remember vividly, because I was getting dressed for Sunday school,” she told me. She realized that she could no longer fit her left hand through her sleeve. “My left wrist had locked in a backwards position”—the result of a new bone that had grown in her arm.
Peeper’s doctors took a muscle biopsy from her left forearm. Afterward, she wore a cast for six weeks. When it came off, she couldn’t flex her elbow. A new bone had frozen the joint.
Over the next decade, as Peeper grew more bones—rigid sheets stretching across her back, her right elbow locking, her left hip freezing—she became accustomed to pain.
But, like most kids, she adapted. When she could no longer write with her left hand, she learned to use her right. When her left leg locked, she put a crutch under her arm and tipped her body forward to walk. She even learned how to drive. After graduating from high school, Peeper lived on her own in an apartment, taking classes at a local college.
When pain from a fall kept her in bed for three days, her parents, who had recently retired to Florida, begged her to move in with them. She caved, enrolling at the University of Central Florida. There she earned a bachelor’s degree in social work, interning at nursing homes and rehabilitation centers. In 1985, three weeks after graduating, Peeper tripped over a blanket in her parents’ home. “My hip hit the corner of an end table,” she said, “and that changed my life.”
Her body responded to the fall by growing another bone. She could feel her right hip freezing in place. She knew that if she couldn’t stop it, she would probably never be able to walk again. Before the fall, Peeper had been planning on getting a job as a social worker. Now she couldn’t even get dressed by herself. On top of it all, she was lonely. She assumed that, of the 6 billion–odd people in the world, she was the only one with a second skeleton.
“I don’t know how to explain it,” she told me. “I never dwelled on it—Is there someone else? Could there be someone else?—in my thinking. I thought I was the only one with this condition. That’s all I had ever known.”
Peeper asked her doctors back in Michigan about getting one of her locked hips replaced with an implant. They referred her to a National Institutes of Health physician named Michael Zasloff. Zasloff had been trained as a geneticist, and sometimes he would encounter patients with rare genetic disorders; in 1978, he met a young girl with FOP. “I’d never seen anything quite like it,” Zasloff told me. “I had no idea what it was.”
When Zasloff asked his adviser, Victor McKusick—at the time the world’s greatest clinical geneticist—what caused fibrodysplasia ossificans progressiva, McKusick told him he didn’t have a clue. So Zasloff headed to the medical library.
The first detailed report of the disease dates back to 1736. A London physician named John Freke sent a letter to the Royal Society about a patient he had just seen:
There came a Boy of a healthy Look, and about Fourteen Years old, to ask of us at the Hospital, what should be done to cure him of many large Swellings on his Back, which began about Three Years since, and have continued to grow as large on many Parts as a Penny-loaf, particularly on the Left Side.
Freke noted how superfluous bones arose from the boy’s every neck vertebra and rib: “Joining together in all Parts of his Back, as the Ramifications of Coral do, they make, as it were, a fixed bony Pair of Bodice.”
In the generations that followed, doctors recorded almost nothing more about the disease. Zasloff found only two papers from the 20th century. He was in the worst position a doctor can be in: he didn’t know how to help a young patient in pain, and he had nothing to tell her distressed parents. He decided to adopt FOP as part of his research.
As a geneticist at the National Institutes of Health, Zasloff had the greatest medical resources he could desire at his disposal. But he still struggled to get his hands on information about FOP—largely because he was hard-pressed to find anyone who had it. Zasloff took over the care of a few patients who had been referred to McKusick, and he began accepting new referrals. But many doctors didn’t even know what the disease was, let alone how to diagnose it. Over a decade, Zasloff managed to examine 18 people with FOP. That made him the world’s expert on the disease.
When Peeper visited Zasloff in 1987, he told her that a hip implant would be impossible. He had learned this lesson the hard way. Years earlier, he’d taken a biopsy from a patient’s thigh, and the trauma had triggered the growth of a new bone. He suspected that the biopsy Peeper’s doctors had taken from her arm years earlier had caused it to freeze.
The whole article is worth it. Another gem by Carl Zimmer.
