One feature that marks victims of FOP, one that strikes everyone who meets them, is their ability to take the unbearable in stride. The first time I spoke to Nancy on the telephone, I asked her about this, and she said perhaps it is because FOP is so slow and predictable that people who have it can see challenges coming, prepare for them, outsmart them, and delight in the triumph.
Nonetheless, the abrupt and permanent loss of some abilities can be devastating. When Nancy's jaw became rigid, she wrote a list of things she could no longer do, such as eat anything but "slurped," or pureed, meals that looked like cat food, brush the backs of her teeth or floss, stick her tongue out, yawn, cough effectively, lick envelopes and stamps, whistle, kiss, and lick her lips. She feared choking on food. Vomiting would be a nightmare. It bothered her that her young niece pretended that her dolls aspirated food and had to be suctioned.
When Nancy's body finally settled into its new shape, she went to the Mary Free Bed Rehabilitation Hospital, in Grand Rapids, to have her custom wheelchair modified. The International FOP Association had just gotten under way, and she was eager to find new members, so she asked the staff at the center to give her name and address to any other FOP patient who might pass through.
Andy Sando was an FOP patient who lived in St. Joseph, Michigan. He went to college, worked at odd jobs, tried to make it as a cartoonist, and then studied computer graphics and design. He lived independently with minimal help, and coped without a wheelchair until he injured his leg, in 1985. Even then he relied on a manual push chair only when necessary, and otherwise staunchly defied his handicap, insisting on walking even if it wore him out. In April of 1988, however, Andy conceded that he was needlessly limiting himself by refusing a power wheelchair. He went to Mary Free Bed, where the staff told him about Nancy Whitmore. He was mildly interested in the prospect of meeting someone else with FOP, he told me recently, but he was too busy with school and other things.
"Tell him the truth," Nancy piped in.
"Well," Andy confessed, "St. Joe is a small town compared with someplace like Philadelphia, but at least we have things to do. They told me there's this woman up in northern Michigan, in the north woods. I figured she was probably some frumpy old hick. Some lumberjack's daughter in a flannel shirt. All I remembered from a trip my family took up there when I was little was that the stores were full of moccasins. So I promptly forgot about Nancy."
Nancy, though, heard about Andy. She wrote, care of the rehabilitation center, inviting him to join the IFOPA. A week later, in August of 1988, Andy telephoned. They immediately realized that they shared many interests and values. They began writing and calling each other once, twice, six times a week. They decided to meet. In the second week of October, Andy and his mother drove up to northern Michigan.
Nancy and Andy met a few more times that fall. In December they were married. As they were pronounced man and wife, Andy's brother called, "Let's get him, boys!" and several of Andy's friends grabbed the rigid groom, picked him up, and tilted him sideways to kiss the bride. A photograph in the Sandos' wedding album shows Andy nearly horizontal, with a huge grin on his face.
The Sandos' house and circumstances are models of how the severely handicapped can live independently and with dignity. A legal settlement for Nancy's accident provided money to modify the house she had shared with her sister's family, now occupied by her, Andy, and their caregivers. Her complete disability justified complete medical and personal care. The insurance company offered to pay for a nursing home. Nancy successfully argued in favor of being her own health-care provider, hiring and managing round-the-clock caregivers who would tend to her needs in her own home. Health-care economics being what they are now, both the company and Nancy got a good deal.
The Sandos call their house an "interconnected duplex." The nighttime caregiver occupies the original house, while the Sandos live in a new addition. Ramps lead to the front door and the back yard. To accommodate wheelchairs, the addition has few halls, and all doors but the front one are pocket doors that can be pushed open with one foot. The nucleus of the house is the Sandos' bedroom, or "the room of many doors," with access to both sides of the house and to the back garden. Two television sets let them watch the same program while lying in bed, despite their different body positions. The bathroom features a large hot tub to help ease the aches of FOP, with an electric hoist and a sling to maneuver them into the tub. "No one but me holds the control box when I'm in that lift," Nancy says. "I've learned."
Most of the house is one large, bright room, combining kitchen, living room, and Nancy's work space. Andy has his own small office. Each of their computers—a computer is one of the greatest boons to a person with FOP—is adjusted to its user's unique position. Kitchen counters are slightly raised, to accommodate Nancy when she stands. Light switches are low, at wheelchair height. The computers are wired to the wall switchplates, with bright red switches to distinguish them from the lights. The couple debated over floor coverings, and still are not quite happy. Most of the house is tiled, to bear the weight and friction of heavy electric wheelchairs. Elsewhere carpet lends warmth and dampens the hard acoustics. But one carpet has already been ruined by a wheelchair-battery leak—a housekeeping problem that most people don't have. For someone with FOP this house is the best of all possible worlds.
FOP was always assumed to be hereditary, though this belief was based on old, uncertain, largely anecdotal reports. Proof came when Kaplan learned of two American families, a father and child in Louisiana who had the disease, and an afflicted man in Georgia whose three children also had FOP. Another family turned up overseas. There are so few of these instances, however, because FOP patients rarely marry and have children. Most cases of the disease result from a mutation in a sperm or an egg cell which causes FOP only after it has been passed on to the next generation. Modern techniques of genetic analysis are powerful tools for identifying genes that cause disease, but they require very large populations, which do not exist with FOP. So the next step in FOP research was to study the process by which bone is formed.
In the early 1960s Marshall Urist, an orthopedic surgeon and bone scientist at the University of California at Los Angeles, found that when demineralized bone—the essence of bone, without its calcium content—was implanted in a pouch of muscle, it induced that tissue to create a lump of bone. Urist was able to extract protein that retained this osteoinductive capacity, which he called "bone morphogenetic protein," or BMP, though he was unable to purify it completely using the technology available at the time.
More than twenty years later John Wozney and some colleagues at Genetics Institute, a Massachusetts biotechnology company, succeeded in purifying and sequencing four bone morphogenetic proteins from cow bone. In retrospect, Urist's difficulties were hardly surprising. BMP is a whole family of substances rather than a single entity (more than a dozen had been found by 1996), and each is present in the body in minute quantities. Wozney began with huge masses of raw cow bones, which were cleaned of their outer tissue and marrow and then pulverized. Forty kilograms of bone powder was treated with acid to dissolve away the calcium and other minerals that make up about 70 percent of bone's mass, leaving a rubbery residue of protein of various kinds. Ninety-five percent of this protein is collagen, which was discarded. The remainder was sorted according to protein size by gel electrophoresis, and each purified protein type was then laboriously tested in mice for its capacity to induce new bone growth. Wozney ended up with forty millionths of a gram, an invisible speck, of pure BMP.
When Zasloff saw Wozney's paper, in the December, 1988, issue of Science magazine, he showed it to Kaplan in great excitement. Zasloff had long suspected that Urist's elusive BMP might be implicated in FOP. No other known substance, after all, could produce new bone. But the most astonishing part of Wozney's paper was not that he'd been able to purify BMP. When a scientist identifies a new protein or gene sequence, he punches it into a computer database to learn whether it truly is new and whether it is similar, or homologous, to anything else. Homology provides important and sometimes unexpected clues to a molecule's function and evolutionary provenance. Sequences drift over time. All allow a certain amount of leeway, but crucial features cannot change without losing their function. Very important or fundamental sequences are generally held within strict bounds.