Michael Zasloff saw his first FOP patient at Johns Hopkins, in 1977, while he had a fellowship in medical genetics under Victor McKusick, the father of the field. Zasloff was a pediatrician with a Ph.D. in biochemistry. He worked at the National Institutes of Health pursuing research on basic genetic mechanisms, but he liked to keep one foot in the clinic.
"I saw a young lady sitting in the waiting room with her neck and head stiffly posed quite askew. The left side of her neck was terribly swollen, and she was clearly in significant pain." Monica Anderson was eight years old. McKusick had diagnosed her FOP when she was three. The disease had been quiescent until a few days earlier, when she whipped her head around while on an amusement-park ride, inflicting just enough trauma to trigger a flare-up. Monica was fortunate that McKusick had already identified her disease. Few other physicians in the world had even heard of FOP. Too often, when terrified parents rushed their children to the hospital at the first flare-up, doctors mistook the alarming tissue growth for aggressive malignant tumors and ordered emergency surgery or chemotherapy. A prominent surgeon amputated the entire right arm and shoulder of one little girl whose condition he tragically misjudged.
Zasloff's residency at Children's Hospital in Boston had familiarized him with many esoteric pediatric diseases, he told me, but nothing at all like this. "So I began to ask questions of Victor McKusick, who was probably the world expert on FOP at the time: 'Dr. McKusick, what do these lesions mean?' He said, 'I don't really know.' 'What do you think is causing it?' He said, 'I don't know.' I asked, 'What are we going to do about it?' He said, 'Well, I can tell you what doesn't work.'"
McKusick's classic textbook, Heritable Disorders of Connective Tissue, discusses FOP at great length within a chapter on other disorders. A few hundred cases had been reported since Guy Patin's single sentence in 1692, yet the level of understanding had barely increased. The disease was so strange and rare that not only weren't there any answers but no one was even asking questions.
Zasloff, a man irresistibly drawn to unexplained anomalies, studied records of past NIH and Johns Hopkins cases, pored over histology slides, and asked McKusick to refer new FOP patients to him. Zasloff began to formulate theories, but the time, sometimes the scientific techniques, and above all the patient population he needed simply were not there. He began a small clinical study to see whether he could pharmacologically inhibit the formation of heterotopic bone—work that yielded modest yet discernible results.
"My senior staff at NIH weren't against this project," he says, "but basically they couldn't have cared less. It was regarded by a lot of people as a waste of time and money." With his small and varied patient population, a statistically valid study was virtually impossible to construct. "So a lot of people asked, 'Even if you do this clinical trial, what does it mean?' Well, to the FOP patients it could mean a lot."
In 1986 Zasloff serendipitously discovered a new family of potent antibiotics in the skin of the African clawed frog. Work on "magainins," as he called them, from the Hebrew word for "shield," quickly commandeered his attention and the full resources of his lab. Zasloff's efforts to develop magainins as therapeutically useful drugs were frustrated within the bureaucracy of the NIH, and he ultimately left to continue his work at the University of Pennsylvania. A company was founded to commercialize his discovery.
Unfortunately, Zasloff's departure meant the demise of his FOP program. A colleague notified all FOP patients that they need not bother to return. Being turned away from the NIH, often the last resort for people with rare or "orphan" diseases, was a devastating blow. "It's like going to Mecca," Fred Kaplan says, "and being told that there is no hope."
One of the abandoned victims was a woman in her late twenties named Jeannie Peeper. Her disease had been diagnosed by an astute University of Michigan physician when she was four, and she'd had a normally active childhood until ninth grade, when her left hip and shoulder suddenly seized up. Still, she finished high school, moved to Florida, and earned a degree in social work while living on her own. Two weeks after graduation she fell and injured her right hip, an accident that cost her all mobility in that joint. Peeper was referred to Zasloff in 1985 (she was told he was the only doctor in the world who cared about FOP) to ask whether a hip replacement could help her. He said it could not.
Medically, Zasloff could do little for Jeannie Peeper except explain what was going wrong with her body. But during their periodic conversations his understanding and sympathy and the mere fact that he knew others like her made her feel less isolated in her disease. When, during a visit in October of 1987, he told her of his impending move, she asked if he could introduce her to another FOP patient. Zasloff put her in touch with Monica Anderson, by then a college student, and each young woman spoke to a fellow sufferer for the first time in her life.
As a parting gift, Zasloff gave Jeannie Peeper the complete list of living FOP patients known to the NIH—a scant eighteen names. He suggested that she might want to form a pen-pal club. Instead, her curiosity whetted by her conversation with Monica Anderson, Peeper mailed out letters and questionnaires asking for date of diagnosis, hobbies, interests, and a few other medical and personal details. Eleven people promptly replied, among them Nancy Whitmore, in Michigan, who was already active as an advocate for the handicapped. Rather than a pen-pal club they started a newsletter, the FOP Connection; the first issue was published in early 1988, funded by Peeper's Social Security checks. In June they incorporated the International FOP Association, with Peeper as president and Nancy Whitmore as vice-president. An FOP community had been born.