Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes

by Moalem MD PhD, Sharon

  * Worker honeybees, at times, can lay eggs that will hatch into drones (male bees). But given the complexities of their reproductive genetics, worker bees are incapable of laying eggs that will become other female workers.

  Chapter 4

  Use It or Lose It

  How Our Lives and Genes Conspire to Make and Break Our Bones

  Doctors and drug dealers. Those are the only people who seem to carry pagers anymore—and when I check my beeper in a crowded restaurant or before heading into the theater, I often wonder what other people must be thinking.

  When it went off one recent morning, I was just approaching the front of a long line at the Starbucks in a bustling hospital atrium. From where I stood, I could have almost grabbed a cup and scribbled my own order on it, but the person in front of me was taking her time ordering a venti double shot, soy mocha something or other.

  So close, yet so far.

  I stepped away to return the page. The woman on the other end of the line was from the pediatric team that was caring for a young patient with multiple bone fractures. She asked if I could come by for a consultation involving a little girl. They were just finishing up some routine work but would be ready for me in 15 minutes or so. I jotted the room number down on a napkin and got back into a line that had grown significantly longer in the two minutes since I’d stepped away.

  I didn’t really mind—the extra few minutes in queue gave me time to collect my thoughts. I began running through an internalized algorithm for recurrent fractures in a young child—if this, then that…if that, then this—that would help me evaluate her condition.

  And as I did that, I thought about the special connection our bones give us to the rest of our body.

  From plastic Halloween yard decorations to The Pirates of the Caribbean, we’ve all had plenty of opportunities to get acquainted with skeletons. Our collective familiarity—even if you can’t name a single one of your 206 bones, you can probably draw a very basic map of your skeleton—makes them easy to visualize when it comes to talking about how our bodies respond to the ever-changing demands of our lives.

  Like most of our body’s systems, our skeleton follows the use-it-or-lose-it dictum of biological life. In response to our actions or inactions, our genes can be called upon to put into motion processes that can give us strong and malleable bones or ones that are porous and brittle as chalk. In this way, our life experiences affect our genes.

  But not all of us inherit the genetic know-how to create the types of bones that are needed for the skeletal flexibility that life requires. That’s what I surmised might be the case as, hot Earl Grey tea finally in hand, I rode up to the seventh floor and knocked on the door of the patient’s room. On the bed before me, with black locks and wearing a tiny hospital gown, was a sweet little three-year-old girl named Grace.

  There was perspiration on her brow, likely from the pain she was feeling from her fractures. I made a mental note of that as I dove into the rapid scan that takes place whenever I pull the curtain that provides patients a little extra privacy from the hospital’s busy hallways.

  Quickly, I focused on one very important feature.

  Her eyes.

  Liz and David couldn’t have a biological child of their own. And for a long time, that seemed just fine.

  Liz was a gifted graphic artist. David was an accountant with his own company. They were both quite happy to put their time into their careers and focus their attention on each other. On vacation, they traveled around the world. At home, they enjoyed the best of everything.

  They’d watched their parenting friends expend immense amounts of energy just coming up with a weekly car-pool plan. There were schools to consider. Parent-teacher conferences to attend. Music classes. Athletic practices. Summer camps. There were 2 a.m. nightmares and 6 a.m. wake-ups. It was all too much.

  Which is why they themselves were surprised to discover that one day, seemingly out of the blue, their perspective had changed.

  There were children around the world who needed parents. But as Liz studied the tragically imbalanced mortality rates for orphan girls in China, she knew what they needed to do.

  The world’s most populous nation instituted its one-child policy in 1979, at a time when the nation was about to become the first in the world to cross the one billion population threshold, even as many of its residents struggled to find shelter, food, and work. Government medical authorities issued birth control, but when it failed, abortion became the standard option.* Those who did give birth to a second or sometimes even third child, especially in urban areas, often had no option but to leave those children at the doorstep of a state-run orphanage.

  But one parent’s sorrow could be another’s joy. The Chinese system had created a glut of orphans, especially female ones, more than could be adopted by Chinese couples who couldn’t have children of their own. Within five years of implementing the controversial policy, a nation that had little history of permitting children to go overseas for adoption had become a key “sending” country.

  And by 2000, China had become the single-largest foreign provider of adoptive children to U.S. and Canadian families. Although the numbers have waned somewhat in recent years, China remains one of the most significant contributors to the adoptive pool for North American parents.

  Liz and David understood that this path would be full of challenges, too. The process has, at times, been marred by corruption. And even when done right—from the moment prospective parents begin working with an agency to the moment they bring a child home—it can take years. But couples willing to adopt children who have some type of physical problem—generally medically “correctable” issues such as a cleft lip—are sometimes treated to a bit of bureaucratic wheel-greasing.

  One such condition is called congenital hip dysplasia, a fairly common disorder in which children are born with a hip that easily dislocates. In most developed countries where children have good access to health care, hip dysplasia cases are generally treatable if corrected early in life. But in countries that lack medical resources, these children can end up having significant handicaps. That, the would-be parents were told, was Grace’s problem.

  But Liz and David were instantly in love. From the moment they first saw a picture of Grace, they knew she was the girl for them. They gathered Grace’s documents from the adoption facilitator and consulted with a pediatrician, who assured them Grace’s situation would likely be easy to treat once she arrived in North America.

  Giving Grace the medical care she needed seemed a relatively small hurdle to overcome for the honor of becoming her parents. With that, they booked their tickets to China and started childproofing their home.

  They didn’t know a lot else about their daughter-to-be. What they were told at the time was that Grace had been left at the orphanage doorstep a year earlier and was thought to be two years old. That was about it. When Liz and David arrived at the orphanage in the southwest Chinese city of Kunming to pick up their daughter, they learned there was a lot more.

  They’d known to expect a spica, the type of cast that starts at the waist and holds the legs akimbo. The only surprise was how big it was and how small she was—it seemed as though the tiny little girl, weighing just about 12 pounds, had been swallowed by a big plaster monster.

  Still, given the assurances they’d received from their doctor, they remained confident that Grace’s condition was only temporary and perfectly treatable. When an orphanage worker saw how unbothered they were by the challenges posed by the little girl’s condition, she pulled them aside to tell them how excited she was that Grace would be going home with them.

  “You are her destiny,” she said.

  And they absolutely were.

  A few days later they were back in North America and, after a quick visit and examination by the pediatrician, they were able to get Grace out of her cast and scheduled for a follow-up visit to begin addressing the hip dysplasia.

  But hidden under the cast, the l
ittle girl’s waist and legs were terribly scrawny. And less than 24 hours after the spica was removed, Grace had broken her left femur and right tibia.

  Rather than helping address the hip dysplasia, it seemed at the time that the cast had made things worse, allowing her bones to attenuate to the point of glasslike fragility. Back into a cast she went.

  A few months later and finally free of the cast, Grace was resting in her mother’s arms in a sporting goods store where they were looking to purchase a canoe for an upcoming camping trip. She shifted her body to point at a pink one that she fancied.

  The sound, the little girl’s mother would later tell me, was like a gunshot. Liz shuddered. Grace wailed. Minutes later the frantic new mother and screaming toddler were back at the hospital. Grace’s leg had broken again.

  Even before I began taking the history from her parents, it was clear to me that there was far more at play in Grace’s case than congenital hip dysplasia.

  The answer was in her eyes. Human eyes are distinct in that the sclera—the so-called “whites of our eyes”—is visible, whereas in most other species’ eyes, it’s mostly hidden behind folds of skin and the optical socket. For dysmorphologists, that presents an extra window of opportunity to understand what’s happening within a patient’s genes.

  Grace’s sclera wasn’t white but a light shade of blue—and that, along with her history of bone fractures, told me that she was likely suffering from a type of osteogenesis imperfecta, or OI, a condition in which a genetic defect inhibits the production or quality of collagen, which is essential for strong and healthy bones. The same lack of collagen that was making her bones so brittle was also giving her sclera its slightly blue hue, and a quick peek at her teeth—which were translucent at the tips for the same reason—told me I was on the right track.

  It wasn’t so long ago that OI might not have been diagnostically considered at all. In the past few years, though, the condition has been getting a lot of attention, thanks in no small part to an unquestionably adorable kid named Robby Novak—better known as Kid President—whose viral string of pep talk videos calling on the world to “stop being boring” have been watched by tens of millions of people around the world.

  But Robby, who suffered more than 70 broken bones and underwent 13 surgeries before he was 10, didn’t set out to draw attention to OI. “I want everybody to know I’m not that kid who breaks a lot,” he told CBS News in the spring of 2013. “I’m just a kid who wants to have fun.”1 Robby’s story, though, has inspired many people to take a harder look at OI and what is being done to help those who suffer from it.

  The disease has also been in the news for other reasons—mainly because it has become a factor in thousands of child abuse investigations. Take Amy Garland and Paul Crummey, for instance. The British couple was accused by social workers of abusing their young son, who was found to have eight fractures in his arms and legs shortly after he was born. After being arrested on suspicion of abuse, Amy and Paul were also banned from seeing their children without proper supervision. The courts wouldn’t take the infant away, since he was still breastfeeding, so they ordered Amy to move into a facility where they could monitor her. In a case of reality imitating reality television, the local authority had them placed in a home where it could watch the family 24 hours a day through closed-circuit cameras, as though they were contestants on the TV show Big Brother.2

  It took 18 months for social workers and others involved to realize they’d made a terrible mistake. Amy and Paul’s son wasn’t suffering from abuse but from OI.

  It’s understandable why an X-ray of a child who suffers from OI can look like evidence of child abuse, as such pictures will reveal multiple fractures in different stages of healing. But given cases in which social workers and doctors—seeking only to protect children from danger—have wrongly accused good parents of being abusers, most courts now ask that the possibility of OI be considered as part of abuse investigations.

  Although such screening is becoming more widespread, the problem for those involved in cases of suspected abuse is that it can take a while to rule out OI. Despite what you might have been led to believe from police dramas on television, understanding what someone’s DNA is telling us is not always as easy as walking into a hospital lab and looking under a microscope. Since there are many ways in which a person can have brittle bones, finding the cause, through biochemical and genetic investigations, can take weeks or even months to resolve. Given increased awareness of the possibility of OI, the relative rarity of the disease (some 400 cases a year in the United States alone), and the apparent epidemic of child abuse (more than 100,000 substantiated cases of physical abuse and some 1,500 deaths each year),3 many social service and law enforcement agencies still make the heartrending decision to be safe instead of sorry.

  Thankfully, Grace’s history in no way suggested that abuse should be near the top of the list of possible causes for her multiple fractures. That meant we could immediately focus on what was going wrong, with her new parents as full partners on our quest for answers and interventions that would give Grace the healthy, happy life she deserved.

  Not so long ago, there wasn’t much we could do for the so-called nonlethal types of OI. Today the condition is still a challenge, but one look at Grace will tell you it’s not an insurmountable one.

  Of course, no single kind of therapy is usually enough to address the complex issues that emanate from deep inside our genes. But when we begin to piece together the right combination of drugs, physical therapy, and technomedical interventions, we can have a real impact. With those tools—and her own bravery, persistence, and dedicated parents—Grace has grown from a tiny, fragile toddler to a tough and adventurous little girl. With every new step she takes, her life experiences shape and defy her very genetic code. Grace is a powerful example of how the environment that Liz and David created for her allowed her to build a stronger skeleton.

  And if she can surmount her genetic destiny, so can we. Because, though you probably don’t know it, just like Grace’s, your bones are also breaking all the time. A little crack here, a little fissure there—our bones are in a constant state of deconstruction and reconstruction. In this way, we’re all growing more perfect skeletons.

  To understand how DNA is involved in making and breaking our bones, we first need to understand how our bones work. Far from being composed of the dense, dead, and rocklike material many people imagine when they think of bone, our skeletons are quite alive—and are being constantly redeveloped to meet the changing demands of our lives. This remodeling and reshaping comes as the result of a microscopic battle between two types of cells, osteoclasts and osteoblasts, that resembles the relationship between two key characters in Disney’s videogame-inspired movie Wreck-It Ralph.

  Osteoclasts are the Wreck-It Ralphs of the skeletal body, breaking down and dissolving bone piece by piece because they’ve been programmed to do so. Osteoblasts are the Fix-It Felixes—they have the onerous task of putting your bones back together again. Now, you might think that simply removing Ralph from the equation would result in stronger bones. But that’s not how it works. As the characters found out in that charming movie, one can’t well exist without the other.

  The wreck-it/fix-it partnership results in a complete renewal of our skeletal structure every decade or so. Like a bladesmith folding layer after layer of steel to forge a resilient sword, the break-and-repair-break-and-repeat cycle of bone regeneration leaves us with utterly personalized skeletons that can, in most cases, withstand a lifetime of running, jumping, hiking, biking, twisting, and dancing.

  Of course, a little added dietary calcium is usually helpful. And if you’re like many people who love breakfast cereal, you get a helping of that almost every morning.

  If you eat Froot Loops, Frosted Flakes, or Rice Krispies, you’re familiar with the products made by the company founded by William K. Kellogg, brother of the better-known Dr. John Harvey Kellogg. But Dr. Kellogg did a lot more than lend
his name to a brand. In his time, he was known as a health guru, though today we’d probably call him a little eccentric. (Among other things, he believed that sex, even the monogamous sort, was dangerous.)

  He was also a pioneer in the field of whole body vibration therapy. In his notorious sanatorium, Kellogg subjected his patients to vibrating chairs and stools in the hopes of improving their health. More or less, Kellogg’s idea was that he could shake the sickness out of his patients.

  More than a hundred years later, vibration therapy is still often viewed with skepticism. Some medical experts have specifically warned against long-term exposure to vibration for most people. But for specific patient groups, researchers are now exploring the possibility that vibrations might trigger osteoclasts and osteoblasts to work together to break down and repair bone. Which is why a therapy long ago rejected as outlandish is now being investigated for use with patients with OI. That, in turn, has prompted another look at vibration therapy for patients suffering from osteoporosis—something that impacts millions of people—by triggering the right genetic expression to make stronger bones.

  Even for those who have a perfect genetic inheritance, disuse, old age, poor diets, and hormonal changes can all wreak havoc on the exquisite balance that shapes our hidden structure. What we’re learning is that our skeletal system can be quite unforgiving toward our behavioral indiscretions.

  As we’re discovering, so too can genetic mutations. Take young Ali McKean, for instance. She suffers from a rare genetic condition that turns her endothelial cells (those that line the interior surface of blood vessels) into osteoblasts (the Fix-It Felix bone-production cells). In other words, her cells are turning her muscles into bones. And yes, that’s as terrible as it sounds.