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

by Moalem MD PhD, Sharon

  Even something as seemingly positive as a short, relaxing vacation abroad can be surprisingly bad for you. And your rap sheet would probably look something like this:

  Air travel between the United States and the Caribbean—check.

  Stayed out in the sun too long working on your tan—check.

  Consumption of two poolside daiquiris—check.

  Secondhand tobacco smoke—check.

  Exposure to insecticides, used for bedbug control—check.

  Nonoxynol-9, found in contraceptive lubricant—check.

  I’m sorry to have to ruin your recent fictitious holiday vacation in this way. But the Department of Genetic Protective Services is leveling these charges against you to try to make you appreciate just how much you take your genome for granted.

  Everything on that list can damage your DNA. Without the ability to continuously and properly repair all of the negative changes we cause to our genome, we would run into some serious trouble. How good we are at repairing genetic damage has a lot to do with the “repair” genes we’ve inherited. If you happened to have inherited one of the more than a thousand known mutations in the BRCA1 gene that can predispose you to cancer, then you need to be extra careful with the way you treat your genes. And yet interestingly, not all of these inherited mutations are equally worrisome.

  Which brings us back to Angelina Jolie. When they tested her BRCA1 gene, her doctors told her that her particular genetic variant or mutation was not reassuring at all.21 There was, they said, an 87 percent chance that she would develop breast cancer and a 50 percent risk that she would get ovarian cancer.

  Over a three-month period in the winter and spring of 2013, one of the most closely watched women in the world emulated some of her on-screen espionage-savvy characters, managing to elude the paparazzi as she underwent a series of procedures at the Pink Lotus Breast Center in Beverly Hills, California, including a double mastectomy.22

  “You wake up with drain tubes and expanders in your breasts,” Jolie wrote in the New York Times shortly after the procedure was completed. “It does feel like a scene out of a science-fiction film.”

  And not too long ago, it would have been.

  Doctors have been performing mastectomies for a long time, but until quite recently it was a surgery intended to remove disease, not to prevent it.

  That all changed, though, as our understanding of the molecular underpinnings of cancer matured and genetic screening and testing became more available and subsequently more women (and even some men) began getting the terrifying news that Jolie received. Faced with the decision to undergo a significant but imperfect screening regimen, about a third of these women are now opting for a preventative mastectomy. Having their breasts preemptively removed before cancer could strike. In doing so, they’ve created an entire new class of patient: the previvor.

  The previvors are already thousands strong—almost entirely women who have had to face the same decisions as Jolie. As we come to better understand the genetic factors at play in other diseases—colon, thyroid, stomach, and pancreatic cancers are among the likely contenders—it’s almost certain that this group of people will get bigger still.

  “Cancer is still a word that strikes fear into people’s hearts, producing a deep sense of powerlessness,” Jolie wrote. But today, she noted, a simple test can help people understand if they are highly susceptible, “and then take action.”

  All of that is creating a whole new set of ethical complications for physicians, who foremost practice by the dictum primum non nocere.*

  When it comes to action, we’re not just talking about radical surgeries like mastectomies, colectomies, and gastrectomies. Because, of course, some things you just cannot remove. So other preemptive actions that people could employ will include increased surveillance or screening, preventative drug regimens, and, where it’s possible, avoiding potentially damaging genetic triggers.

  Which is why that rap sheet may turn out to be an important reminder of all the things you can do to take care of your genetic inheritance. If you don’t take care of your genes, you may inadvertently change them.

  Exposure to radiation during routine air travel, ultraviolet radiation while working on your tan, ethanol in your cocktail, chemical residues in tobacco smoke, insecticides, and chemicals in your personal care products, are all examples of general factors that can damage your DNA. How you choose to live will determine how well you treat your genome.

  This means we all need to be better educated, not just by uncovering our family’s medical history and by decoding our own genetic inheritance but by investigating what proactive and positive changes we can make in our life with that information. These proactive changes will require different actions from each of us. For some of us that means avoiding fruit, while for others it could mean a mastectomy.

  At the same time we also need to appreciate how others might use this information in an accelerated genetic future. And “others,” as we’ve already seen, will include your doctors, insurance companies, corporations, government agencies, and very likely your loved ones as well. Even though we might have expectations of confidentiality, we also need to keep in mind the real lack of protection against discrimination for life and disability insurance before considering hacking our own genome.

  We’re not just standing at the precipice of a tremendous paradigm shift; a lot of us have already gone over the edge. And because we are so connected, technologically and genetically, a lot more of us will be going over as well, whether we like it or not.

  * Latin, meaning “First do no harm.”

  Chapter 10

  Mail-Order Child

  The Unintended Consequences of Submarines, Sonar, and Duplicated Genes

  It started out as a quiet morning in the Caribbean. It was Thursday, May 13, 1943, and the SS Nickeliner, an American merchant ship uniquely configured to carry large quantities of ammonia, was carrying a 3,400-ton stockpile of the volatile cargo that was ultimately destined for England. Ammonia was an essential ingredient to make munitions that was in short supply during the war, and to get it to England necessitated a perilous journey across the ocean during the climaxing months of the Battle of the Atlantic during World War II.1

  As for the Nickeliner’s 31-man crew, the day ahead would be anything but routine. That’s because a German submarine, captained by a 35-year-old naval officer named Reiner Dierksen, had been tracking the ship from the moment she’d left port.

  Six miles north of Manati, Cuba, a steel periscope belonging to the German submarine quietly broke the surface of the water. Slowly, deliberately, Dierksen’s torpedo men lined up their shot. With his target confirmed, the veteran captain—who already had been responsible for sinking 10 Allied ships—gave the order to fire. Two German torpedoes entered the water, propellers whirling, gaining speed. There was a tremendous explosion—water and fire shooting a hundred feet into the sky. Soon the Nickeliner was at the bottom of the sea, her crew left to their fate in life rafts.

  For the Allies, the problem was both simple and maddeningly complex: They needed a way to locate the submarines once they were submerged.

  They found their answer in sonar. At the time, it was all in caps—SONAR—an acronym for sound navigation and ranging. A large amplifier would produce an underwater ping, and a receiver would “listen” for the sounds to bounce back, which could then be used to roughly derive the distance to their target.

  Seventy years later, navies around the world still use sonar technology as a key part of their countersubmarine and antimining efforts. But over the years we’ve found that’s not all sonar is good for. Today, a technology that was originally designed to take life from this world has become a mainstay of those who help bring it in.

  As thousands of sonar men returned home from the war in the late 1940s, they began experimenting with other uses for the technology. Some of the earliest adopters were gynecologists, who quickly learned that medical sonar, as it was originally called, could b
e used to detect gynecological tumors and other growths without invasive exploratory surgeries.2

  Where sonar really came into vogue, though, was when obstetricians learned they could use it to see images of a fetus and its placenta, starting just a few weeks after implantation. Giving them what must, at the time, have seemed like a magical ability to watch firsthand as the baby’s developmental stages unfolded. What most people don’t realize even today is that these images also convey the very delicate genetic interplay between the expression and repression of genes during fetal life that play a significantly important role in our development.

  Fetal ultrasounds, as they are known today, allowed physicians for the very first time to catch an early glimpse of any genetic missteps or abnormalities that previously lay hidden until delivery.

  Before we move on to learn about the influence of genetics in our development, let’s go back in time for a moment to answer the question: Whatever happened to the German submarine in WWII that attacked and sank the Nickeliner?

  Two days after the sinking, a U.S. patrol plane spotted what appeared to be a surfacing U-boat. The plane released a marker into the water to indicate its position. As the German crew worked desperately to dive their sub back into the relative safety of the deep, an Allied ship sped out to the location where the sub had been spotted and, using its newly minted sonar device, was able to locate the submarine under the water.

  Using the depth and direction information provided by the sonar device, the patrol plane’s crew dropped three depth charges into the water. And with that, like a shredded aluminum can, the Nazi sub joined the Nickeliner on the bottom of the ocean.3

  What started out as SONAR technology to find hidden submarines has today, without a doubt, become inestimably important in helping bring babies into the world. The one thing that no one could have ever imagined was that a technology that was initially developed to take life could return, so quickly after its reprieve, to once again selectively take it.

  A technology that we’ve developed for one purpose often becomes repurposed in surprising ways. As you can imagine, in countries where more cultural currency is given to male children than female ones, the use of ultrasounds has become extremely problematic. When the value of gender is asymmetrical, the ability to tell a baby’s sex before delivery allows parents to choose their child’s gender.

  Which is exactly what has happened in China. For many years, China has enforced strict and sometimes obligatory population control policies that limit most parents to having one child. The cultural importance of having a son in China, combined with the one child policy, has created an even greater pressure for pregnant parents to have a boy. The results—an excess of 30 million Chinese males, an imbalance created by the use of ultrasounds to systematically find and abort female pregnancies—speak for themselves.4 And the practice is thought to be spreading.

  Indeed, researchers have shown that when ultrasound technology has made its way to areas of China where it hasn’t been before, the imbalance between male and female births increases.5

  Ultrasounds also helped spark another trend, rather benign in comparison, which is still raging today. One it’s likely you’re guilty of participating in and supporting as well.

  The advent of gender-specific clothing for babies and toddlers in the United States really began to take shape in the postwar period, and calcified as prenatal ultrasounds became more widely available across the U.S.—friends, family members, and colleagues simply had more time to go shopping, and the gender-specific baby shower was born.6

  But where some see pink and blue, trucks and kittens, camouflage and lace, I see the cultural effects of what was, in effect, the world’s first widely available prenatal genetic test. After all, for the greater part of the past century we generally agreed that, on a chromosomal level, the major difference between females and males is that the latter has a Y chromosome while the former does not. More than a fuzzy picture of our babies-to-be, the advent of prenatal ultrasounds provides us with a snapshot of the DNA they’ve inherited.

  While ultrasounds can give us quite precise anatomical information, such as gender, generally by the fourth month of pregnancy, in the modern world of in vitro fertilization and preimplantation sex selection, we don’t have to wait to find out. Which is why, if emerging and increasingly available medical technologies are not coupled with social and educational initiatives aimed at honoring girls in the same way as boys, things could get even worse.

  And, of course, the amount of information we can now derive from basic genetic tests before pregnancy, or quite early into gestation, can tell us far more than simply gender.

  Which, I suppose, might suggest that gender is a simple thing.

  It’s not.

  ***

  A boy or a girl? That’s usually your first question when you learn that someone has had a baby, isn’t it? And most of the time, that question appears to have a simple binary answer.

  Gender identity is dependent upon a veritable rainbow of influencers, but when a baby first emerges from its mother’s womb all that’s really visible is the external plumbing. As one precocious five-year-old explained to Arnold Schwarzenegger’s character in Kindergarten Cop, “Boys have a penis. Girls have a vagina.”

  The thing is, though, that’s not always the case. Today we use the term disorders of sex development, or DSD, to refer to children and adults whose bodies have taken an alternative route along the pathways involved in the development of their reproductive organs.

  Some of these paths can result in a significant amount of ambiguity in their outer genitalia—for instance, an unusually enlarged clitoris that appears to be a penis and labial lips that are fused and look somewhat like a scrotum. For physicians, it can be hard enough to keep up with the ever-changing spectrum of psychosocial understandings of sexuality. Likewise, we are now learning that the development of our physical sex mirrors that wide spectrum. This has left the classically basic and narrow “XY-means-male and XX-means-female” model of sex largely out of date.

  In a world in which gender is still tied to everything from given names, pronouns, clothing styles, and public washroom segregation, ambiguity can cause a significant amount of embarrassment and consternation, particularly when there’s uncertainty surrounding a baby’s sex.

  That’s why, rather than just being a slight parental concern, gender ambiguity is often treated as a medical emergency—one for which doctors like me are called upon for consultations at all hours of the day and night.

  So let me walk you through what happens when a child is born who is thought to have a DSD. Given the depth of the psychosocial issues at hand, we usually drop whatever nonemergency work we’re doing and head over to meet with the family and medical team caring for these precious little patients.

  Immediately thereafter, we try to get as much information as possible from the parents about their newborn child’s family tree, including siblings, nieces, nephews, aunts, uncles, grandparents, and as many people up and down the line as possible. During this process we ask lots of questions. Are living relatives healthy? Is there a history of recurrent miscarriages or children with severe learning disabilities? Are the parents or grandparents or great-grandparents related in some way?

  These questions don’t just give us valuable genetic information, they also help remind everyone involved that the young baby is rooted in and part of a larger family—and most importantly, is not just a medical problem that needs solving.

  We then move on to a physical examination that begins with the same sort of dysmorphology assessment we went through together in chapter 1, but in a lot more detail. With a hospital-issued measuring tape dangling from our necks and darting between our fingers, we check the circumference of the baby’s head, the distance between the eyes, the distance between the pupils, the length of the philtrum, and so forth. We measure the arms, legs, hands, and feet. We also measure the length of the clitoris and penis and check to see that the anus is properly
placed. Even something like the distance between a baby’s nipples can occasionally give us valuable information about what’s going on inside the infant’s genome. Most importantly, when assessing for a DSD, we try to determine whether a baby appears to be dysmorphic overall.

  It’s not uncommon for people who are watching us perform these examinations to joke that we look more like tailors taking measurements for custom-made baby clothing than doctors looking for the slightest irregularity.

  And we’re all irregular in some way. What’s important from a clinical perspective is how these incredibly small and sometimes large irregularities fit together.

  The slightest feature can lead you into a completely new diagnostic direction. And, as you’re about to see, the smallest detail can end up completely changing the way we view the world.

  ***

  He was beautiful in every way. And sleeping quietly in his Bugaboo stroller, Ethan looked pretty much like any other adorable baby.7

  We all have a unique journey of development, but most of us share a common course of travel. This journey is paved and shaped by our environmental and genetic circumstances. And it always begins with the breathtaking beauty of an infant—small and vulnerable, yet full of so much potential.

  The child sleeping before me had all of that. And although I didn’t know it at the time, he was also unlike any baby I’d ever seen. Actually, he was unlike every other baby that’s ever been born.

  It’s important to note that all of Ethan’s fetal ultrasounds had been normal. Several months back, when his mother asked whether she would have a boy or a girl, her obstetrician had glided a wand through the blue ultrasound goo spread across her swollen belly and taken a peek between the unborn child’s legs.

  “It’s a boy,” she’d said.