Yes, I farted my way up Mount Fuji.
I’d heard of hypobaric hypoxia, a lack of available oxygen due to a decrease in atmospheric pressure. But I never experienced it before that night, and my mind was in no condition to realize that flatulence, light-headedness, confusion, and exhaustion were all just part of the joy of altitude sickness.
But why was this specifically happening to me and not to my sweet, elderly climbing partner? Why was she able to keep chatting away, carrying my pack along with hers, and occasionally looking back to flash toothy smiles of reassurance as I fought desperately to keep up?
Well, it turns out that my genes apparently leave me a bit more susceptible than most to altitude sickness. Instead of helping me with my climb up Mount Fuji, my genetic inheritance was weighing me down.
If only I was a little more Sherpa.
***
Almost every civilization has a story about how its people came to be where they are today. Quite often these stories of origin have to do with a physical journey. A trip across a raging sea, a flight across a barren desert, a crossing through a rugged mountain range.
There’s good reason for that. Although today we might feel separated by language, culture, or politics, our collective human story is one of movement—a search for greener pastures, a quest for giving seas. And as people travel, so do their genes. Indeed, we are all genetic migrants.
These days, with the help of widespread genetic mapping, we’re increasingly able to scientifically explore stories of origin, but there are still many holes to be filled and stories yet to be discovered.1
To me, one of the most fascinating stories to emerge is that of the Sherpas, who are thought to have arrived about 500 years ago from other regions of the Tibetan Plateau to a particular place in the Himalayan Mountains. That was the nearest they could get to a sacred peak they called Chomolungma.2
You might know it as Mount Everest.
The biggest problem with being so close to the Mother of the World, as the peak is known to the Sherpas, is that the great matriarch exists amid a scarcity of the very substance that makes human life possible on this planet. At more than 13,000 feet in altitude, the Tibetan village of Pangboche, the oldest Sherpa village in the world, is nestled nearly a full mile above the altitude where many people begin to feel the effects of hypobaric hypoxia.
I, for one, am not planning a visit anytime soon.
So, what happens to most people at that altitude? Well, for those who ascend very gradually, perhaps just a little headache, fatigue, nausea, or even euphoria.3
But as we’re about to see, those who haven’t inherited specific genes for high altitude living can suffer the consequences, as I did. Even if you don’t have the genetic makeup that makes high-altitude living comfortable, there are a few things you can do. You can take the time to try to acclimatize as you ascend and let your genome, through genetic expression, help you adjust.
Or there are some drugs you can take—some with a prescription and others not. Some South American indigenous groups are said to chew coca leaves to deal with the symptoms associated with altitude sickness. There are also anecdotal cases that suggest that caffeine at high altitudes might be helpful.4 Maybe that’s why the can of Coke I had on top of Mount Fuji tasted so good. Back then I thought it was because I paid ten dollars for the honor of acquiring “a passport to refreshment.”5
In most circumstances when we spend a lengthy amount of time at higher elevations our genes begin to subtly adjust their expression, which prompts cells in our kidneys to make and secrete more erythropoietin, or EPO for short. This hormone stimulates cells in our bone marrow to increase the production of red blood cells, as well as keep the ones already in circulation around past their typical expiration date.
Our red blood cells normally make up a little less than half the content of our blood, with men having a little more than women. The more we have, the better we are at absorbing and shuttling about the vital oxygen our bodies need to survive. Because red blood cells are like little oxygen sponges. And the higher up you are, the less oxygen there is, so the more red blood cells you need. Our bodies’ physiology recognizes these changes and signals our genes to shift their expression to accommodate them.
When you need to make more EPO, your body increases the expression of a similarly named gene. That serves as the genetic template for the production of more EPO. However, nothing in your biological life is free. So EPO needs to work a bit like a Washington, D.C., lobbyist, convincing members of Congress to spend a little more capital on the production of red blood cells when your oxygen availability decreases. And, just as in Washington, increased funding for one pet project often comes at the expense of another. Biological currency, after all, is not much different than greenbacks—and like all forms of capital expenditures, there are always some unforeseen costs.
In the case of increased genetic spending on EPO—which causes you to have more red blood cells—another biological cost is that blood becomes thicker. Like high-viscosity motor oil, your blood moves a little more slowly through your system. And that, of course, makes clotting more likely.
As long as things don’t get too thick for too long, though, a little extra genetic production of EPO can be just what your body needs to increase oxygen flow. Just as a lack of oxygen can leave you feeling lethargic, a surplus can provide your body the ability to utilize and burn more energy. That’s why synthetic EPO has been such a gift for people who can’t make enough of their own due to kidney failure, and who suffer from anemia as a consequence.
But that’s also what made synthetic EPO a darling of quite a few people in the professional endurance sports community. That is at least until tests were developed to detect it. Among those who have admitted or otherwise been caught “doping” with synthetic EPO are Lance Armstrong, fellow cycling champion David Millar, and triathlete Nina Kraft.
Not everyone has to dose up on synthetic EPO to get a bit of a competitive advantage, though. Take Eero Antero Mäntyranta, for example. The legendary cross-country skier who won seven Olympic medals for Finland in the 1960s is affected by a genetic condition called primary familial and congenital polycythemia, or PFCP, which means he has naturally higher levels of circulating red blood cells pulsing through his arteries and veins. And that means he has a natural genetic advantage when it comes to aerobic competition.
So here’s a question: If some people have a natural genetic advantage—extra oxygen-carrying capacity in their blood, for instance—is it truly unfair for others to try to bring themselves up to that level? To be clear, I’m not advocating doping. But as we learn more about how our genetic inheritance impacts our lives, we’re likely to be confronted with the reality that some of us are genetically doped to begin with.
It would be ridiculous to singularly reduce Mäntyranta’s Olympic successes to the genes he happened to have inherited. Even for a biologically advantaged athlete, the level of training required to compete at the international level is extreme. But as with Shaquille O’Neal’s imposing 7-foot-1-inch frame and Olympic champion swimmer Michael Phelps’ unusually long arm span and oversized feet, it would be a little naive to pretend that Mäntyranta’s unique genetic inheritance wasn’t a factor in his path to success.
Owing to the vast diversity of human body sizes, wrestlers and boxers have long fought in weight classes. Stock car racers compete in a system in which all cars are built to roughly the same specifications. And, of course, men and women almost always compete separately in professional sports, since adult men tend to have a natural height, weight, and power advantage over adult women. All of that is a sometimes arbitrary way to keep the competition as fair as possible.
So is it inconceivable that we might one day compete in genetic classes, too?
Mäntyranta’s turbocharged cardiovascular genetic inheritance, by the way, results from just a single letter change in his DNA. The change was in a gene that serves as the template for a protein that is the receptor for EPO.
Instead of a G (for guanine) in nucleotide position 6002, Mäntyranta and about 30 members of his family have an A (for adenine) in a gene known as EPOR. This 0.00000003 percent change in Mäntyranta’s genome was enough to cause the EPOR gene to make a protein that was really sensitive to EPO and that resulted in many more red blood cells being made. Yes, one letter in a field of billions is all it took for the corresponding protein made from the EPOR gene to give him a 50 percent increase in oxygen carrying capacity in his blood.6
We all carry these minor single letter or nucleotide changes in our genomes. The more related we are, the more similar our genomes. As we now know, since our genomes encode for templates that direct how our body is put together, the more similar your genome—think monozygotic or “identical” twins—the more you may physically look alike. Now, if you don’t look at all like your siblings, that doesn’t mean that you’re not related. What’s at work there is that you likely each inherited a different and unique combination of genes from your parents.
And what you’ve inherited has also been shaped by what all your ancestors have experienced. As we saw previously with lactose intolerance, if your ancestors didn’t raise animals to consume their milk, then you’re likely genetically out of luck when it comes to being able to enjoy ice cream into adulthood. And many of our adaptations don’t end there.
Which brings us back to the Sherpas, who, given their unique genetic inheritance, have taken on—as a matter of cultural pride and economic necessity—the brunt of the dangerous burden of helping mountaineers from around the world reach the summit of the world’s tallest mountain (which, at 29,029 feet, peaks just below the altitude at which most large commercial airliners fly). Among these amazing people is an unassuming man named Apa Sherpa, who as of 2013 jointly shared the world record for the most ascents of Everest, including four in which he climbed without the aid of supplemental oxygen. As a boy, Apa never intended to climb the mountain even once, but when he learned he was good at it, he discovered a way to help his family.7
How is it that he is so good at climbing to the top of a mountain that, until 1953, had never been touched by human feet? Indeed, how is it that Sherpas appear to be so well adapted to living in this high-altitude environment at all?
Well, as you may have guessed, some members of this ethnic community have inherited a very small genetic change that has led to profound differences in their lives. In their case, the change is in a gene called EPAS1. Rather than producing more red blood cells, this special Sherpa gene produces fewer, seemingly blunting Sherpas’ biological response to EPO.
After everything I told you about the mighty Mäntyranta and his genetic inheritance, this might not seem to make sense, at first. After all, wouldn’t Sherpas be better suited for their atmospheric existence if they were born with blood thick as honey that’s brimming with red blood cells and thus loaded with oxygen?
Well, sure—for a while. But remember: While thick blood can be good for short periods of time, it can also be dangerous, increasing the odds of devastating strokes if allowed to endure for too long. The Sherpas don’t just visit the Himalayan highlands, they live there. And so they don’t need well-oxygenated blood just for skiing and cycling races, they need it all the time.
Instead of ever-rising levels of red blood cells under situations of decreased availability of oxygen, what the Sherpa’s unique EPAS1 genetic configuration provides them is stability over time—the ability to transmit adequate oxygen throughout the body even in conditions in which it’s harder to come by in the surrounding atmosphere.
As unique genetic groups go, the Sherpas are really quite young. By way of context, their move toward Chomolungma is likely to have happened right around the time that Christopher Columbus was getting ready to sail to a place we’d ultimately come to call North America.
The Sherpa-specific EPAS1 mutation might, in fact, be an example of natural selection at play—and some researchers believe it may be the fastest case of human evolution that has been documented so far.
In other words, the Sherpas’ low-oxygen living conditions have quickly changed the genes they’ve inherited, which are now being passed down through generations.
And you’ve probably inherited such changes, too. Maybe not in your EPOR or your EPAS1 genes, but likely in genes that helped your particular ancestors survive. As we map more genomes and become more and more familiar with the single nucleotide polymorphisms (changes in just one letter of a person’s genetic code that we call SNPs) that are both subtly and magnificently diverse between groups of people around the world, the more light we’ll shed on our ancestors’ history—and the more, in turn, we’ll discover about ourselves.
As I sat atop the peak of Mount Fuji and watched the sun slowly begin to crest over the early dawn sky, I couldn’t believe how much my feet were killing me. Being so busy with the nausea and flatulence that accompanied my own ascent up the mountain, I had failed to notice that my feet had been left badly blistered and sore. After sitting quietly for a few minutes sipping my can of Coke, I slipped out of my boots to assess the damage. I imagined they didn’t look as bad as they felt until I peeled back my socks all the way. My toes seemed to have borne the brunt of the climb. With all the rain my boots had become waterlogged, and this turned my toes into swollen and incredibly painful minisausages. And I knew what was coming: an hours-long descent down the mountain. As I thought about what to do next, I started fantasizing that besides being a little more genetically Sherpa so as to avoid altitude sickness, wouldn’t it be nice to live a life completely free of pain?
***
At some point in our lives we all become acquainted with some type of pain. It may be one of your earliest childhood memories. You may be feeling some right now. One thing’s for sure: Pain, especially when it’s of the chronic persuasion, is serious business. You may be surprised to learn that it’s been estimated to cost up to $635 billion a year in the United States alone,8 a figure greater than the costs associated with conditions like heart disease and cancer.
Staring at my toes atop Mount Fuji, I knew that the pain I was feeling was not serious and likely only temporary (at least I hoped so). Yet, unfortunately that’s not the reality for millions of people whose lives are chronically debilitated by pain at a cost to which no dollar figure can be attributed.
While I contemplated putting my wet socks back onto my blistered feet, there was nothing I wanted more at that moment than at least a short reprieve from the throbbing ache. I imagined what it would be like to morph into some comic book character figure with superhuman abilities. And I knew I wasn’t alone in my wishful fantasizing. Indeed, what most people wouldn’t give to be impervious to pain. But before that wish gets granted, we need to meet a 12-year-old girl named Gabby Gingras.
Very quickly after she was born in 2001, Gabby’s parents noticed that their infant girl was a bit unusual. She would scratch at her face. She jabbed her fingers in her eyes. She banged her head against her crib without crying. And when her teeth began to come in—an extremely painful experience for most children—Gabby didn’t really seem to mind.9
Then there was the biting. Lots of children bite their parents and siblings. And teeth are, of course, a common reason why mothers stop nursing. But Gabby wasn’t just biting other people. She was biting herself. She gnawed on her own tongue until it looked like raw hamburger. She chewed on her fingers until they were bloody.
It took months of doctors’ visits to find the answer to why this beautiful baby girl was hurting herself: Gabby is one of a very small number of people around the world who suffers from a genetic condition called congenital insensitivity to pain with partial anhidrosis. This condition causes them to feel no pain in parts or in all of their body.
It’s possible that more people are born with this very rare condition, but they don’t survive very long—because, as it turns out, a life without pain is a life that is really hard to keep living.
Even after Gabby’s parents understood why thei
r daughter was injuring herself, there was little they could do to completely protect her. It would be years before Gabby was old enough to reason with. In the meantime, all they could do was try their best to protect her from herself. They made the difficult decision to preemptively pull all of her baby teeth from her mouth. That, however, led her adult teeth to grow in early—and those were promptly gone, too.
Though it was badly damaged by all of the poking she had done to it, doctors were able to save Gabby’s right eye by sewing it shut for a time. Once it had healed as much as possible, Gabby was forced to wear swim goggles almost all the time. Her left eye, though, couldn’t be saved; it was removed when she was three years old.
As much as we’d like not to think about it when it’s there, pain actually protects us. It helps move us from infancy to maturity, and it provides the basic binary feedback we need to develop more advanced decision-making abilities. It hurts when I touch this? Okay, I won’t touch it anymore.
For all of that to happen, though, your body must be able to transmit pain signals from one place to the next. Handing the message of pain from cell to cell and up to your brain like a microscopic Pony Express moving at electric speed is a process dependent on specific proteins.
This became apparent when mutations in a gene called SCN9A were discovered in a rare and related condition to that of Gabby’s called congenital insensitivity to pain.10 The difference between people who are insensitive to pain and others on this planet is just a small variation in the version of the SCN9A gene that we’ve inherited.
Changes in SCN9A and other related genes can lead to a family of diseases called channelopathies. The term simply refers to different conditions that are thought to result from nonfunctioning gates that sit on the surface of our cells and mediate, or determine, what goes in and what comes out. In the case of some people who feel no pain, the protein that is made from the SCN9A gene stops the signal from being sent. The message is dropped off, but instead of setting forth on a swift and wild adventure, the pony and its rider just dawdle at the corral.
Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes Page 15