“For just at that moment the light came over the hill, and there was a mighty twitter in the branches. William never spoke for he stood turned to stone as he stooped; and Bert and Tom were stuck like rocks as they looked at him. And there they stand to this day, all alone, unless the birds perch on them; for trolls, as you probably know, must be underground before dawn, or they go back to the stuff of the mountains they are made of, and never move again.” -J.R.R. Tolkien, The Hobbit
Being turned to stone features prominently in our legends. From Medusa’s head to the White Witch’s frozen garden we seem to carry a fear of being trapped in our own bodies, unmoving and mute as the world passes us by.
It’s a fate that seems terrifying, but for approximately one person in every two million this is a fate that they have to resign themselves to. They have a disease called Fibrodysplasia Ossificans Progressiva (FOP) and it will slowly turn their body into bone.
Children born with FOP seem normal except for a strange deforming of their big toes. But sometime before they’ve even reached their tenth birthday their body starts to react to the normal wear and tear of childhood by replacing injured tissue with bone. It’s usually misdiagnosed, partially because it is so rare, and partially because the hot, spongy mass of developing bone in a “flare-up” is often mistaken for a large tumor.
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| Children appear normal except for slightly deformed big toes |
One of the worst parts about FOP, though, is that it cannot be fixed with surgery. A surgery really isn’t much more than a controlled injury, and most injuries in a FOP patient result in more flare-ups. This means that misdiagnoses are often incredibly dangerous, especially since one of the first actions taken when suspected tumors appear is to take a biopsy of the tissue. In trying to help these children, doctors who don’t know what they’re dealing with often make it worse.
The bone development on its own isn’t terribly bad, but these pieces of bone often fuse to the original skeleton and immobilize the patients. Looking at the skeleton of Harry Eastlack, an FOP sufferer who donated his body to science, it is possible to trace the injuries of a lifetime.
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| Harry Eastlack |
Bumps here, bruises there, that on anyone else would have been forgotten. But on a FOP sufferer its possible to see the slow imprisonment that develops as ribbons of bone formed and fused, sheets that encircle joints and lock them into place, ill-placed supports and weldings that make movement impossible.
Even small injuries, such as childhood vaccinations or dental injections, can cause the body to create new bone and lock up joints that will never move again. Certain tissues seem to be immune, which means that these people are fully coherent, thinking individuals slowly locked into to cumulative cage of bone.
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| FOP throughout life |
Harry passed away right before his 40th birthday, unable to move except to smack his lips. Patients barely into their twenties find themselves frozen into strange positions and confined to customized wheelchairs. Perhaps an elbow is stuck forever folded across the chest. Or the neck is always turned to the right, while the spine curves uncomfortably to the left. Some are stuck in an almost upright form, able to nap while leaning in a corner.
Monica Anderson was eight years old when a trip to the amusement park landed her in the doctor’s office. After a ride that whipped her head around her FOP flared up, causing bone to spread through that joint and immobilize her head.
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| Young sufferer with FOP |
Tiffany was ten months old when she had her first flare-up and at 17 required an oxygen machine because a bone crossing her rib cage didn’t allow her to fully expand her lungs. She explained to ABC News that one of the worst things about FOP is how fast it can change your life.
“A flare-up can happen overnight while you’re sleeping,” she explains. “Like, you’ll be walking around one day and the next day you won’t be able to move.”
Often times, though, FOP sufferers are amazingly zen about their sufferings. Nancy Sando has had a trying life, losing almost all of her remaining mobility in an accident where the driver of the specialized bus she had chartered misread the controls and launched her and her chair into its hard metal side. In her thirties she was almost completely immobile, frozen mildly bent at the waist, her jaw and ankles fused and her elbows locked at right angles.
But throughout it all she has remained active in the community, campaigning for better handicapped access and volunteering as an advocate and a speaker, all while working as a computer programmer. She’s married to a fellow patient and still active, and upbeat through it all, although she credits it to the predictable nature of the disease. “People who have it can see challenges coming, prepare for them, outsmart them, and delight in the triumph.”
Thanks to the groundbreaking work of Dr. Fred Kaplan, Dr. Michael Zasloff, and the University of Pennsylvania, we now have and idea of why this happens. Essentially what is happening in their bodies is that the cells that usually repair injury, the lymphocytes, are saturated with BMP. BMP, or bone morphogenetic proteins, was discovered when scientists removed the calcium and other minerals from bones and has been found to create bone when introduced into normal tissues.
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| Dr. Fred Kaplan with a patient |
So basically, when an injury occurs the body sends out its repair cells which, rather than repairing the muscle properly, repair it in the same way that fractures heal or bones grow longer. They make a cartilage outline of the tissue and then infiltrate and integrate it with bone material. In the process they don’t just make a dead shell of the original tissue, they make real bone, complete with living cells and marrow.
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| Bone Growth |
“It’s extraordinary that a differentiated tissue like a muscle or a tendon can turn into another differentiated tissue, like a bone,” Kaplan told the Atlantic Magazine back in 1998. “You never see the brain turn into the pancreas. You never see the kidney turn into the heart. But here you have perfectly normal muscle turn into perfectly normal bone. It’s normal in every way except one: it shouldn’t be there.”
Strangely enough, the pattern of bone development in FOP sufferers seems to be the same that occurs in developing fetuses. It changes a bit depending on the specific trauma of the patient, but in general first the neck and spine, then the shoulders, followed by the hips and elbows and then the knees, wrists and ankles, and last and most horribly, the jaw.
And, almost more importantly, developing fetuses use the same mechanism for growing the initial skeleton as FOP sufferer’s bodies do. It’s as if the body is confused and is doing its best to form an entire other skeleton in addition to the first one.
It seems that all of this is caused by a single amino acid substitution on a single gene called ACVR1. This gene is usually turned off after a fetus forms its first skeleton in the womb, but in FOP sufferers it never is properly shut down.
Researchers in the field trumpet the discovery of this gene as a potential panacea, claiming that it is relevant to every single bone related medical condition, from the development of bone spurs after hip replacement to helping sufferers of severe osteoporosis.
But really, in the end, it has the most hope for those children who are slowly being robbed of their lives by an incurable disease.
Kaplan agrees, “If this knowledge helps us to see farther to help others, that will be great, but this work is for and about the children.”
Megan! This is amazing. I've heard about FOP, but I've never had it so succinctly broken down for me.
My only question is this: You write, "This gene is usually turned off after a fetus forms its first skeleton in the womb…" What do you mean by first? Just curious.
–Angie
P.S. I'm gonna follow you!..okay that was creepy.
Thanks for reading Angie! By first I mean, for most people, the only one they have. Unfortunately for people who have FOP their body is convinced that it needs to keep building skeletons in addition to the one they already have.
And not creepy at all with the following. As long as I don't start seeing you behind me on the bus we should be fine.
It would be interesting to know more
“The road will overcome walking.” I wish you never will stop and be creative – forever!