And so, in a very real sense, we are all one letter away from having a life-altering genetic condition. But just as we saw with Grace, that doesn’t mean we’re completely helpless, either. As we’ll see in a lot more detail, getting off the couch does a lot more than just get your body moving.
What we don’t use, we lose. And rather quickly, too.
Just as the most efficient businesses have employed just in time strategies that match industrial production to demand in near real time, our species has evolved genetically to keep the cost of living down, reducing inventory when we don’t need it and hyperproducing it when we do.
That’s one possible reason why older obese people are less likely than their thinner peers to suffer many kinds of common fractures. They resemble ancient archers carrying around extra weight. The added wear and tear on their skeletons throws their osteoclasts and osteoblasts into a furious break-it-fix-it cycle that can result in stronger bones.
By way of contrast, we also know that swimmers, whose athletic endeavors take place in reduced gravity environments, have lower femoral-neck bone mineral density than athletes who engage in weight-bearing activities,16 likely because swimmers (though they get an incredibly beneficial cardiovascular workout) just don’t take the same kind of skeletal pounding as athletes in other environments, such as runners and weight lifters.
We get another example of this whenever space travelers return from the International Space Station after long voyages. When a Soyuz space capsule carrying U.S. astronaut Don Pettit, Russian Oleg Kononenko, and Dutchman André Kuipers landed in southern Kazakhstan in July of 2012, ending a six-month sojourn in space, the three men had to be gently hoisted into special recliners for postmission press photographs.17 During 193 days of swimming through the weightlessness of space, their bodies had begun to chip away at their skeletal solidity.
In this way, astronauts are a lot like osteoporotic old women. And, as it turns out, their medical care is a bit similar. Bisphosphonates such as zoledronate and alendronate (drugs that essentially convince osteoclasts to kill themselves instead of breaking down our bones) are a mainstay of treatment for older individuals with osteoporosis. And we’ve recently learned that these same drugs can also help both astronauts and people with OI keep their bones in better shape.18 With the news that some private companies are looking for volunteers to make the first human mission to Mars—a journey that will likely take a minimum of 17 months in a zero-gravity environment—those drugs will be vital.
But before you volunteer to step onto that spacecraft, a little warning. Although people who are taking bisphosphonates do become less susceptible to fractures where they usually happen in the elderly, at the femoral neck, they conversely become more susceptible to fractures in the shaft of the bone.
Why? Because the drugs are actually working too well—stopping bone turnover and remodeling, leaving users with something called “frozen bone,” which is thought to increase susceptibility to certain types of fractures, just like the statue David’s ankles.
I’m always left awestruck by the incredible range of effects that emanate from the subtlest of changes in our genetic code and its expression. As we’ve now seen, one single letter change in a series of billions of letters, and you’ve got bones that break with the slightest bit of pressure. A small shift in any of our genes can completely change the course of our life.
And if you have inherited a faulty gene, or stay in bed long enough, don’t exercise, eat poorly, escape gravity, or simply get older, you’ll be setting yourself up for similar detrimental skeletal consequences. With a growing list of options that include an arsenal of medications, weight-bearing exercises, and maybe even vibrational therapy, we are far from helpless skeletal custodians. Whether the vulnerability is related to genes, lifestyle, or both, there are many preventative and therapeutic modalities available that we can employ to make our bones less susceptible to fractures.
Understanding the basic biology of how we lose our bones can also play an important role in shaping how we learn to keep them. Such knowledge can be used to inform our own life choices, guiding us onward to pursue activities and lifestyles that will build us the strongest of skeletons.
To do that we need to discover the entire genetic underpinnings of how our bones work. By studying Grace and other people whose DNA leads to brittle bones, we can arrive much more quickly at newer treatments for far more common conditions such as osteoporosis.
When it comes to genetics, the rare informs the common.
And in so doing, millions of unsung heroes like Grace are gifting the entire world with an incredibly precious genetic gift.
* We’ll discuss the unexpected history behind this phenomenon further in chapter 10.
* In the example given, the single nucleotide change turned out to be deadly, causing a lethal form of osteogenesis imperfecta.
Chapter 5
Feed Your Genes
What Our Ancestors, Vegans, and Our Microbiomes Teach Us about Nutrition
I fell asleep in my day clothes. Sometimes, after a particularly long shift at the hospital, that’s just the way it goes. It takes every bit of energy I have just to get home, walk up the stairs, and fall into my bed—and pajamas feel like a luxury I simply can’t afford.
It was a little past midnight when I crashed atop the covers. I could have sworn that only a few minutes had gone by when my pager began buzzing against the bedside table.
With my face still buried into my pillow, I reached for the cursed little black box. When I couldn’t immediately find it, I reluctantly craned my neck and opened my eyes. The glowing blue numerals on my alarm clock flickered from 3:36 to 3:37 a.m.
Three and a half hours, I thought to myself, already trying to calculate how much wakefulness I’d secured with a half-night’s deposit of sleep. That’s not so bad.
It doesn’t take many wee-hour pages before you begin to recognize the numbers: 175075 is the emergency department, 177368 is the inpatient ward. And 0000 means there’s an outside caller, on hold, waiting to speak with you.
The challenge with calls like that is you never know what to expect. Sometimes it’s concerned parents who already know their child suffers from a rare genetic disorder but who aren’t sure whether a new set of symptoms they are seeing is something to be worried about. Other times it’s a physician from another hospital who has just seen a patient they’re having trouble figuring out how to treat, and so it’s a call for advice. In some cases the call is one no physician wishes to get at any time—a patient has taken a turn for the worse.
I grabbed my phone and tried to sneak out of bed without waking my wife, who was sleeping softly beside me. Tiptoeing out of the bedroom, I gently closed the door, peeking back through the crack as I exited. No mumbles. No restless thrashing. She was still out.
Success! I am a nighttime ninja.
I pressed the recall button on the pager. The dreaded 0000 stared back at me like two tiny sets of owl eyes. The bright blue numbers lit up the dark hallway. I dialed the number and waited.
“Hospital locating…”
“It’s Dr. Moalem. I’m on call for—”
“Thank you for returning the page. Connecting…”
There was a soft beep, then a torrent of words.
“Dr. Moalem? I’m sorry, I know it’s late…or is it early? Either way, I’m sorry to bother you. It’s just that—my daughter Cindy. She’s had a fever the last few hours and I’m worried because she hasn’t been eating very much today.”
To some people, this might sound like an overanxious parent. But I knew the hospital wouldn’t have patched her through to me if there hadn’t been more to it.
She paused for a moment. Instead of breaking in, I let the silence hang over the line.
“Oh—I should have mentioned,” the woman said. “My daughter has OTC deficiency.”
There it was. In ornithine transcarbamylase deficiency, or OTC, a rare genetic condition affecting about one in every 80,00
0 people, the body struggles to work its way through the process of turning ammonia* into urea, which under normal circumstances is quickly expelled from our bodies when we urinate.
This process, called the urea cycle, takes place mostly in the liver and, to a lesser extent, in the kidneys—it’s a barometer of sorts for our overall metabolic health. When it’s working right, we’re doing what needs to be done to metabolize protein. When it’s not working right, our bodies become loaded with ammonia—which is every bit as nasty as it sounds.
And like a factory pumping out toxic waste, the greater the metabolic demand, the greater the level of waste ammonia produced. Which is exactly what normally happens when we have a fever. For every two extra degrees Fahrenheit of increased body temperature, our systems burn through about 20 percent more calories than normal. Most of us can handle that extra demand for a time. In fact, for most people a little fever when ill does some good, raising the body’s temperature just enough to make life quite difficult for some illness-causing microbes, thus slowing their growth and giving the body a chance to fight back.
But for people like Cindy, whose systems are more precariously balanced to begin with, just a slight low-grade fever and things can go very badly, very quickly. The nervous system is, after all, quite sensitive to rising levels of ammonia and falling levels of glucose, which we use for energy. And if left unchecked, this metabolic situation can cause seizures and organ failure, which in turn can lead to coma.
In other words, Cindy’s mother had good reason to be concerned about her daughter. And I had good reason to get out of bed.
I grabbed my laptop and tapped in the pass code that lets me log in remotely to the hospital’s system. Given Cindy’s previous history—over the past few years she had been hospitalized multiple times—it was clear she needed to come to the emergency department.
Thankfully, her family lived nearby.
I’m close, too—doctors on call who choose to live more than a few minutes from the hospital often come to regret that decision. I packed a few things into a knapsack and counted myself fortunate that I didn’t have to sneak back into my bedroom to change my clothes—because the truth is that I’m not actually a ninja. When it’s dark, I’m pretty clumsy—and noisy. In the wee hours of that morning, at least, my wife could stay warm, snug, and undisturbed in our bed.
I grabbed a banana from the kitchen counter and headed out the door. It wasn’t yet 4 a.m., but I was wide awake.
***
As I drove to the hospital and snacked on my banana, I considered how privileged I was not to have to fret too much about the food I eat. Like most people, I try to keep my sugar and fat intake down. On rare occasions, when I’m feeling gastronomically bold and mathematically capable, I try to balance a breakfast, lunch, and dinner that will help me hit 100 percent on all 21 vitamins and minerals recommended by the Food and Nutrition Board. Try it sometime—it’s harder than it seems.
Truth is, though, that a diet based on those recommendations alone is hardly perfect for most people. In fact, it’s extremely unlikely (as in you’ve got a better chance at winning the lottery) that the portion recommendations and percentages you’ve been studying on the sides of prepackaged foods are anywhere close to exactly right for your individual needs. That’s because those numbers are based on a sweeping estimation of the necessary intake of calories, vitamins, and essential minerals for a majority of the healthy people in the United States over the age of four. (And for the Food and Nutrition Board, “majority” means 50 percent plus one person; which leaves a tremendously big minority for whom the guidelines are simply a nonstarter.)
The reality, of course, is that everyone’s needs are quite different. The majority of four-year-old boys (for whom 275 micrograms of vitamin A each day will generally suffice) are very different from the majority of 32-year-old pregnant women (who generally need at least three times as much vitamin A). Even two people of the same sex, age, ethnicity, height, weight, and general health are likely to have very different needs when it comes to calcium, iron, folate, and a host of other nutrients. The study of the ways in which our genetic inheritance impacts our dietary needs is called nutrigenomics.
In chapter 1, you met Jeff the Chef, who suffers from hereditary fructose intolerance (HFI). That’s a relatively rare disease, but to some extent all of us could benefit from getting to know the genes within our genomes. And for the millions of people who have some type of unique nutritional requirement that is impacted by their genes, it’s not rare at all to feel as though food isn’t your friend. That is why there are a lot of people out there with similar conditions that make minefields out of restaurant menus and gauntlets out of grocery lists.
Now, you might recall that HFI requires people like Jeff to craft personal menus devoid of fruits and veggies (and also fructose, sucrose, and sorbitol, which are often added to processed foods). Cindy’s OTC deficiency is a sort of dietary contrapositive to that. People who are mildly affected by OTC can often go undiagnosed. They will frequently say they just don’t feel good when they eat meat, and they’ve thus avoided heavy protein meals their whole lives. Genetically speaking, they’re actually much better off as vegetarians or vegans because it can be easier to manage a lower protein intake.
Not unlike our political beliefs, which can run the gamut from anarchism to totalitarianism but generally fall somewhere in between, our diets exist on a wide and diverse spectrum. Just as most of us can tolerate many political ideas that we mildly disagree with, our bodies are generally good at stomaching most types of food. And just as there are some ideas that you probably cannot abide—the repeal of universal suffrage, for instance—there may be a few foods that are simply incompatible with your genetic makeup.
Many of us may not have spent a great deal of time reflecting on the inner workings of our political views, let alone examining how we adopted those beliefs. In the same way, chances are good that there are foods that your body just doesn’t like—and chances are also good that you don’t know why.
That’s starting to change, though. In recent years, people who are concerned that they might have health problems tied to the foods they eat have found initial help in elimination diets in which they reduce their food intake to a small number of foods and build slowly back from there. The educational equivalent might be an introduction to political philosophy class that exposes students to the evaluation and history of a wide array of social and governmental ideas.
There’s just one problem: The solution is not that simple.
***
For now, a lot of us have simply resigned ourselves to eating the way our doctors have long told us to: Eat lots of this and none of that; eat this occasionally and that rarely. And for most people that advice is at least a good starting point.
Just as our politics are often a reflection of our regional and cultural heritage, so too originally our diets were a reflection of our genetic inheritance.*
For most people of Asian descent, for example, milk and dairy products aren’t just an unpalatable proposition—they can be digestively hostile. You see, if your ancestors kept animals for milk** there’s a high likelihood that their genes sustained mutations that now make your genes excellent manufacturers of the enzymes necessary to break down lactose, one of the sugars naturally found in milk, long into your adulthood. But in most other parts of the world, where dairy livestock are not as historically common, lactose intolerance in adulthood is much more prevalent.
In spite of this, China has seen a tremendous rise in dairy product consumption over the past decade. Not surprisingly, though, the Chinese tend to prefer types of hard cheeses, or local varieties such as rubing (a delicious goat milk cheese from Yunnan Province similar to the Mediterranean halloumi). That’s because, unlike softer cheeses like ricotta, hard cheeses are generally easier on the lactose.1
In a way, eating how your recent ancestors did is akin to the way today’s patients’ medical family histories are useful tools to assess
patients’ current health risks. If you come from an ethnically diverse heritage and use this approach to assess your dietary needs you can end up with some pretty interesting genetic and culinary fusions. Which can sometimes lead to confusion and frustration, especially given the ethnic genetic melting pots so many of us now come from. For example, many Hispanic individuals are a mix of a myriad of genetic fabrics. If you’re Hispanic, whether you’re lactose intolerant depends upon which part of the genetic ancestral quilt you’ve inherited.
Then again, regardless of whether we come from one ethnic and cultural background or 16, these days almost all of us have palates that have become somewhat globally oriented, which has the potential to overtake what we may actually nutritionally need. In the developed world, even the smallest of grocery stores in the sleepiest of towns offers a selection of meats, fruits, and grains that our not-too-distant ancestors, even if they were royalty, couldn’t have dreamed of accessing.
Following my own advice and looking for dietary guidance from my recent ancestors means heartily consuming a bowl of semolina gnocchi stuffed with walnuts and dates, and knowing that all will go well digestively as a result. Of course, your personal definition of palate exploration may look quite different. And if you haven’t tried recently changing what you eat, now may be a great time to grab a plate and take a seat at your ancestors’ table. Given our comparatively sedentary lifestyle today, though, we’re going to have to use a much smaller plate as well.
Even with persistent dietary experimentation, we’re still going to have to contend with the fact that changing attitudes and habits about food is a lot of work. To help you on that journey it’s useful to know that some studies have found that when we combine theoretical education with experiential “cook and eat” teaching sessions (not only bringing the horse to water but showing it that the water can taste refreshingly good, too), the chance for successful integration becomes better.2
Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes Page 9
