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

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Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes Page 16

by Moalem MD PhD, Sharon


  The discovery of SCN9A and its association with pain transmission came after scientists from the Cambridge Institute for Medical Research decided to look into reports of a boy in Lahore, Pakistan, who was said to have a superhuman ability to be impervious to pain. As a human pincushion, he made a living from his apparent inability to feel pain in street performances, impaling himself with all sorts of sharp objects (none of them sterile), swallowing swords, walking on hot coals, and expressing not the slightest hint of being bothered by it all. He kept showing up at a local hospital to have wounds patched up after having stabbed himself with knives. By the time the scientists reached Lahore, tragically, the boy was dead, just shy of his fourteenth birthday, having jumped off a building in an attempt to impress his friends. Interviews with relatives in the boy’s extended family revealed several others who reported that they’d never felt pain, and a dive into their genetic pool showed that all of them had one thing in common: the same mutation in their SCN9A gene. 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. One single letter change in a series of billions of letters and you’ve got bones that break with the slightest of pressure. Another small shift in expression and you wouldn’t feel that broken bone at all.

  When it comes to pain, things have moved rather quickly since the discovery of the SCN9A gene. We now have a growing list of other genes (close to 400 already) that play an instrumental role in how our lives are impacted by pain. All of these discoveries are leading to a whole new line of research into how—in the very near future—we might hopefully be able to selectively dial down the intensity of some types of chronic pain. The selective part is key—because, as we learned from Gabby and the boy from Lahore, the protective effects of immediate pain are vital to our survival.

  Many of the small differences in our genetic inheritance play a far greater role than mediating our response to pain. Figuring out how they all link together is the next big research challenge that I’ve become involved in unlocking.

  ***

  When the human genome was first published, the rush was on to identify genes linked with specific traits—and most of the low-hanging fruit was picked clean pretty quickly. Many of the gene-linked conditions we’ve identified thus far are monogenic. As in the boy from Lahore who didn’t feel pain, these changes can result from alterations in one single gene. Far trickier is the task of untangling the complicated web of factors that give rise to conditions such as diabetes and hypertension that likely involve more than one gene.

  To get a sense of what that task is like, imagine trying to walk in a specific pattern from dormitory to classroom to courtyard to laboratory to library and back again across the unpredictably moving and shifting grand staircase at Harry Potter’s Hogwarts School of Witchcraft and Wizardry. Just the slightest misstep and you’re back where you started. That sort of complexity can be mind-boggling and frustrating, particularly when the stakes are, quite often, literally a matter of life and death.

  Today, the movement in genetics is not only to look at specific genes and what they do but rather to better appreciate what our genetic inheritance does as a network—and, of course, to understand how our life experiences impact that intricate system through mechanisms like epigenetics.

  Further complicating matters is the even more difficult challenge of understanding how the life experiences of our parents and other relatively recent predecessors are also impacting our current and varied genetic landscapes.

  Knowing what these changes mean to us personally will help us make better decisions about everything from what kinds of adventures we should undertake (no more mountain climbing for me), where we live (you won’t find me moving to Alma, Colorado, elevation 10,578 feet, any time soon), and, as we discussed in detail in chapter 5, what we eat (I still really love my semolina gnocchi, though I prefer to eat it at sea level).

  All of those things—and so much more—that we have been genetically gifted with are part and parcel of our own unique inheritance.

  Other than the Coke machine and my aching feet, I don’t remember much else from being on the peak of Mount Fuji. But I do remember seeing the sunrise. And I remember looking around, in that moment, at the faces of all of the people who were sharing that experience with me. There were people of all ages. Some looked fresh and rejuvenated as though they’d spent the night soundly asleep and had not just climbed up a mountain—appearing bright as that morning sun—while others, like me, looked as though they were ready to collapse.

  And soon after the sun broke through the clouds on the horizon, we were all on our way.

  Our guide came over with an outstretched arm, pointing toward somewhere beneath the clouds. It was time for us to make our way back down the mountain. As I collected my pack, I fumbled around, searching for a fresh pair of socks to prepare for the descent. I couldn’t help thinking that despite not having Sherpa genes, I managed to make it to the summit of Mount Fuji. Which for me was symbolic of the human capacity to surmount the supposed limitations of our genetic inheritance. After all, being a superhero has more to do with making superhero choices, day after day, irrespective of the genes we’ve inherited.

  Chapter 9

  Hacking Your Genome

  Why Big Tobacco, Insurance Companies, Your Doctor, and Even Your Lover All Want to Decode Your DNA

  Cancer is the black death of our time. And that, in and of itself, can be seen as something of a success. After all, we’ve come extremely far in taming many of the infectious diseases that were the top killers of our kin for most of human history. Today, in the developed world, one of the greatest dangers comes to us not from rats or ticks, viruses or bacteria, but rather from within us.

  About 7.6 million people die of cancer every year across the globe. Fill a room with 10 people and you’ll have four among that group who will be diagnosed with some form of cancer in their lifetime.1 Do you know anyone whose family hasn’t been touched, in some way, by this disease? I don’t. And I don’t know anyone who hasn’t considered that they or someone they love might one day get it, too.

  This isn’t a new curse. Some anthropological archaeologists believe Egypt’s longest-reigning female pharaoh, Hatshepsut, may have died from complications related to cancer.2 Going back even deeper into our evolutionary history, paleontologists have found fossilized skeletal evidence that dinosaurs—in particular the duck-billed hadrosaurs (Late Cretaceous herbivores who were known to eat the leaves and cones of what we think of as carcinogenic conifer trees)—suffered this fate as well.3

  Among our own species these days, the most prolific of these malignant killers is lung cancer.4 But while we know that 80 to 90 percent of lung cancer cases involve people who smoke, we also know that not everyone who smokes is equally likely to develop lung cancer.5

  Take George Burns. In one of his final interviews the then 98-year-old comedian told Cigar Aficionado magazine, “If I’d taken my doctor’s advice and quit smoking when he advised me to, I wouldn’t have lived to go to his funeral.”6 Did Burns’ penchant for cigars—10 to 15 of them a day over the course of 70 years—contribute to his longevity? Unlikely. But as far as we can tell, all those El Productos don’t seem to have shortened his life, either.

  Some people wrongly mistake cases like this as evidence against the prevailing wisdom that tobacco is bad for you. It’s not evidence of that at all. But it is fair to say that just because a habit—be it compulsive smoking, drinking, or binge eating—makes adverse health effects more likely (people who smoke are 15 to 30 times more likely to get lung cancer than nonsmokers, according to the Centers for Disease Control and Prevention), that’s not the same thing as making it likely (only about one in 10 smokers will actually get lung cancer).

  To be clear, though, smoking is Russian roulette. Not to mention expensive. And secondhand and thirdhand smoke puts other people—generally the ones we are closest to—at greater risk.

  So why
can some people smoke their entire lives and not get lung cancer? We haven’t yet found the magic combination of genetic, epigenetic, behavioral, and environmental factors that can accurately predict who is at greatest risk. Pulling apart that tangled web is not going to be an easy task. But it’s probable that a certain mix of genetic and environmental factors, might in fact play a role in decreasing your chances of developing lung cancer as a result of smoking. There hasn’t been a lot of serious scientific work done in this area of human health. Not too many scientists out there are pining for an opportunity to do research that might have the perverse effect of telling certain groups of people that they don’t have as much to worry about when they stick a cigarette between their lips.

  There is one industry, though, that is keenly interested in this line of scientific exploration. And that’s Big Tobacco.

  ***

  Honest scientists have known since the 1920s about a probable link between smoking and lung cancer. And really, anyone who thought about it much at all could have reasonably concluded that sticking a burning piece of paper soaked with chemicals and stuffed with tobacco leaves, accelerants, insecticides, and who knows what else into your mouth isn’t likely to be the panacea that cigarette companies sometimes claimed it was.

  Yet, the health dangers went largely ignored by the public for the next three decades.

  Then along came Roy Norr. When the veteran New York writer first published his medical exposé on the dangers of smoking in the October 1952 edition of the relatively obscure Christian Herald magazine, it didn’t get much attention. But when Reader’s Digest, then the most widely circulated magazine in the world, ran a condensed version of the same article a few months later, it was as though the floodgates had been sprung open.7 Over the next few years, American newspapers and magazines published a barrage of damning articles linking tobacco use to “bronchiogenic carcinoma,” as lung cancer was called back then.8

  The reports were boosted by the increasingly sophisticated and quantifiable nature of scientific investigation that was being applied to medicine and that we take for granted today but which, in the 1950s, was still a relative rarity. We can consider this kind of research to be a success of science, but it was really born of a failure of humanity: A half century of world war, including the first uses of nuclear weapons, carpet bombings, and modern chemical and biological warfare, had made us experts at meting out and analyzing death. The sudden salvo against smoking was one of the first instances in which we really began beating all those quantitative swords into medical plowshares. It also came at a perfect time historically, as there was a concurrent wave of unprecedented funding for medical research following World War II.

  But Big Tobacco was quick to strike back. At the time, more than 40 percent of American adults were regular smokers, and the average American smoker was lighting up 10,500 sticks a year. That was roughly a whopping 500 billion cigarettes annually.9

  Big Tobacco was making a killing. And it wasn’t alone. Back then, every time a pack of cigarettes was sold, the U.S. government picked up a cool seven cents.10 Over a year, that amounted to $1.5 billion—the equivalent of about $13 billion today. That’s not to mention all the jobs smokers were supporting in tobacco legacy states like Virginia, Kentucky, and North Carolina.11

  Against the flood of bad press, Big Tobacco had to look like it was doing something. So, in what they called “A Frank Statement to Cigarette Smokers,” the heads of 14 tobacco companies came together to publish a full-page advertisement in more than 400 newspapers nationwide. In it, they made the audacious argument that recent studies linking smoking to disease were “not regarded as conclusive in the field of cancer research.”

  “We believe that the products we make are not injurious to health,” the tobacco chiefs’ statement continued. “For more than 300 years tobacco has given solace, relaxation, and enjoyment to mankind. At one time or another during those years critics have held it responsible for practically every disease of the human body. One by one these charges have been abandoned for lack of evidence.”

  But in the same ad—and in spite of their public stance of incredulity—the collective heads of Big Tobacco pledged to do something rather remarkable. They would create the Tobacco Institute Research Committee, an independent scientific body of inquiry that would be responsible for reviewing the latest studies and conducting research of its own to best understand the health implications of smoking.

  Perhaps not surprisingly, though, the committee (later renamed the Council for Tobacco Research) wasn’t really independent at all—and its real mission was downright diabolical. Over the next few decades, the organization’s researchers collected thousands of scientific papers and press clippings, looking for inconsistencies and instances of contrary results. It then used that information to formulate carefully crafted marketing messages, fight legal actions and regulation, and continue to sow doubt as to the real dangers of smoking.

  Leading this mission of misinformation was Clarence Cook Little, a geneticist whose academic work on Mendelian inheritance had been extremely influential in the years before World War I and whose wide-ranging curriculum vitae included stints as president of the University of Maine and University of Michigan as well as more controversial roles as president of both the American Birth Control League and the American Eugenics Society.

  But the line on Little’s résumé that the tobacco companies really coveted was his tenure as managing director of the American Society for the Control of Cancer, the forerunner of today’s American Cancer Society.

  Appearing as a guest on Edward R. Murrow’s television show See It Now in 1955, Little was asked if any cancer-causing agents had been identified in cigarettes.

  “No,” he answered. He then said, in a thick New England accent, “None whatever, either in cigarettes or any products of smoking, as such.”12

  It wasn’t supposed to be a punch line, but over the past half century that TV segment (which includes Little chewing on the end of what appears to be an unlit pipe) has been played over and over to great comedic effect.

  To Little’s Teflon credit, though, his full answer was a little more nuanced. “This is interesting in a way,” he continued, “because there are many known cancer-forming substances in tar, and I’m sure that research in this field will continue. People are bound to look for cancer-causing agents in all kinds of material.”

  So cigarettes don’t cause cancer, but tar from smoking them—which invariably builds up in the lungs—does? If Little wasn’t already sitting so comfortably in the pocket of the tobacco companies, he might have had a second career as a politician. As George Orwell said, such artful dodges are “designed to make lies sound truthful and murder respectable.”

  While Little might have danced around the truth, though, he wasn’t lying. Not strictly speaking, anyway. Because, after all, most of the research being done at the time was looking for a direct and specific association between the immediate act of smoking and lung cancer, and the sophisticated tools for homing in on what was actually causing cells to turn from friendly to malignant was still many years away.

  But for our purposes, something else that Little said on that evening is even more interesting—something that may be a clue to what’s to come, not just from the tobacco industry but from anyone who has produced a product that can make people sick.

  “We’re very interested,” he went on to say, “in finding out what kind of people are heavy smokers and what kind are not. Not everybody is a smoker. Not everybody who smokes is an equally heavy smoker. What determines these selections on the part of people? Is it a different nervous type of person who smokes a great deal? Is it a person who is reacting differently to strain or stress? Because it is very clear that certain people just can’t take it as well as others.”

  Very interested? Of course Big Tobacco would be. And of course it still is. If the tobacco industry can establish why certain people are more likely to be heavy smokers—and thus more likely to beco
me sick—then it can shift the blame, arguing that it’s an inherited and possibly genetic susceptibility to heavy smoking that is the problem and not the cigarettes themselves.

  If you haven’t already heard the same type of talk from soft drink and junk food manufacturers, just keep your ears open. It’s coming. And the next time someone sues a fast food chain for making them fat (as one McDonald’s manager did in Brazil a few years back) you can be certain that the plaintiff’s genome (and bacterial microbiome, too) will likely be on the defendant’s expert witness list.

  Because when it comes to absolution from responsibility, big business has a history of, as The Godfather’s Sonny Corleone might say, “We go to the mattresses…”

  Want proof? Look no further than BNSF, the Burlington Northern Santa Fe railroad.

  ***

  Our bodies weren’t meant to behave in this way.

  We’re active animals. Or we once were. Our prehistoric days used to be just a little more physically lively. Pouncing on small game, climbing over rocks, swimming across rivers, and running from saber-toothed cats.13

  But ever since the Industrial Revolution—and especially since the Digital one—two big changes have happened: We’ve become sedentary, and our lives exceedingly repetitive.

  Only in the past few centuries have we subjected our bodies to the types of physical beatings that come with doing the same things thousands, even millions, of times over. And from carpal tunnel syndrome to lower back pain, our joints and bodies are paying the price.

  We owe our understanding of repetitive strain injuries to the father of occupational therapy, an Italian physician by the name of Bernardino Ramazzini. His book De Morbis Artificum Diatriba or Diseases of Workers was published in Modena, Italy, in 1700 and is still quoted by those who work in public health.

 

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