The Family Gene

by Joselin Linder

  She explained that when someone is in liver failure, for example an alcoholic, the portal vein, which is a main pathway through the liver, the thing that Dr. Kricket had said was blocked in me, sometimes became blocked.

  The vein fails, or clots with blood. Because the blood still has to find a way to pass through, alternate channels open up. They call these “varices,” like varicose veins. Imagine that a car accident blocks a five-lane highway through your town at rush hour. The cars are routed onto the smaller streets around it. Now, let’s say the city decides to expand the side streets to accommodate all the cars that usually take the five-lane highway. Instead of adding cement, they just spread out the cement already on the road and thin it out to fit the traffic. In a similar way these smaller channels expand to take on their new role as the primary supplier of blood to the liver. These expanded side streets typically run all throughout the digestive tract, through the stomach, and ultimately up into the esophagus. They are more delicate, holding more blood in unnaturally expanded, weaker channels. It turns out, Molly explained, it’s the ones in the esophagus that we need to worry about.

  “Why?” I asked, and let me just say that even after everything I’d heard up to this point in the day, I still wasn’t scared.

  Molly side-eyed me again. “Well, if an esophageal varice bursts,” my friend explained, “you could bleed out your entire blood supply through your mouth.”

  You. Could. Bleed. Out. Your. Entire. Blood. Supply. Through. Your. Mouth.

  And with that, I stopped sleeping.

  * * *

  I got married forty-five days after seeing Dr. Kricket.

  We were doing it in western Massachusetts, near Pittsfield, where both of my parents had grown up. We had chosen a beautiful ski resort called Jiminy Peak where we had stayed several times, always in the summer. Aaron and I were both from Ohio, where ski club is really something school kids just sign up for so they can make out on the bus. Mountains are in limited supply in Ohio, but this New England ski resort in the summertime had become someplace we liked to go. The resort had a small eco-friendly amusement park that included a gravity roller coaster that barreled through the trees. There was also a heated pool and a twenty-person hot tub. They had an alpine slide, and Aaron and I had joked about riding down it while holding hands as a dramatic entrance to the ceremony.

  I still didn’t have a doctor, so instead I carried a bottle of antinausea pills in my pocket and a low-grade near-constant dread in my heart. On a lighter note—or perhaps a heavier one, given that I was about to get married—I had grown accustomed to my bloated leg, but not yet to the fact that my wedding shoes no longer fit my right foot. The shoes I had purchased six months earlier, I had loved. They were comfortable off-white ankle boots.

  But the day of the wedding, when Aaron and I awoke, I still didn’t have a replacement plan beyond my yellow Walmart work boots. I had brought the ankle boots, and as I fought to stuff an extra two-inch girth of lymphedema into them, I had started swearing to myself.

  As I sat on the floor trying to wedge my right foot into the shoe, Aaron grabbed my hand and shepherded me into the car. I’m pretty sure I groaned, rolled my eyes, and stomped my foot en route. We drove past several groups of our guests. I felt surges of anger. Amy had flown in from Prague. Another best friend from high school I rarely saw had come in from California. Our wedding was a destination for almost everybody. I had been drawn to the idea of keeping my guests contained for three whole days of celebration. I deserved it. I had a blocked portal vein.

  “We’ll be quick,” my almost-husband promised me, squeezing my arm.

  Aaron guided me into a nearby mall and over to the nearest bargain shoe outlet. I became parallel-universe Cinderella as my prince Velcro’d a pair of hideous seven-dollar beige house slippers around my bulbous foot. It fit! It didn’t have a choice. It was Velcro. Aaron bought the shoes for me and drove us back to get ready.

  Later, as we walked down the aisle together at our wedding, my long dress covered my feet. My smile covered my internal vascular highway, filled with collateral, presumably poorly paved pathways. I smiled at Valerie, who had come with her husband, Michael. A year out from her stroke, she was wearing lipstick again.

  In front of everyone we loved, I read my written vows, which were characteristically long-winded. My husband began his by announcing, “I will be delivering the Gettysburg Address to Joselin’s Declaration of Independence.” Everyone laughed, and I was grateful to him for knowing how to keep things light.

  Molly pronounced us married, which was our cue to pile onto the ski lift, our chair bearing a “Just Married” sign amid dangling cans. Our guests followed in chairs behind us for a champagne toast by my new father-in-law at the top of the summer-green mountain. My mother remained wheelchair bound, having faced countless setbacks in her recovery from a hip fracture. She didn’t join us at the top of the mountain but she had made it through the ceremony, and would even finally make a speech at the reception later that night. The day was perfect with sunshine flooding the valley. My slippers dangled beneath me as the sloping Berkshire Hills met us on our way up to a green summit, then fell swiftly away on our way back down.

  Later, only one person, a cousin of Aaron’s who knew nothing about our gene, and who thankfully hadn’t noticed my swollen leg, pointed at my footwear.

  “Smart choice,” she commended, and we high-fived.

  Twenty-Seven

  Not every genetic illness is inherited. Conditions like dwarfism have multiple genetic lines, each one starting with a different founder—the individual with the original genetic variation. For example, the gene for dwarfism is a relatively common mutation. One might say it’s a delicate gene. Whether or not it mutates is entirely random. Once a person with that genetic variant has a child, he or she might pass the gene for dwarfism to his or her offspring.

  Hunting down founders has become easier since the advent of the Internet. During my father’s illness, the technology was still being developed. But today, when it’s used correctly, answers can be uncovered in a matter of days.

  Bo Bigelow, my friend’s cousin, has a daughter named Tess, struggling with global developmental delays (the six-and-a-half-year-old had the developmental equivalent of a one-year-old) and a form of blindness related to cortical visual impairment. Her eyes worked, but the connection between those organs and her brain made interpreting the world around her complicated. None of Tess’s doctors or specialists could figure out what was causing her problems.

  Finally, the doctors found a genetic variant in Tess that her parents didn’t have. The doctors wished the Bigelows luck and sent them on their way. Tess was, as far as they knew, “patient zero” with this condition. Not knowing what that variation meant for their child (would she live another year . . . another ten?), the Bigelows went home.

  Bo hated it. He didn’t want to just watch his daughter and wait. He wanted answers. First, he went online and continued the six-year Google search he’d started when Tess first began showing symptoms. Then he contacted a family he read about who had done a wide-reaching search for answers to similar health issues in their own child. He was instructed to build a web page and focus on making it as accessible as possible to anyone looking for answers. Instead of doing a Google search, he would become the Google result.

  That’s how I first heard about Tess. My friend forwarded me Bo’s website. The way Tess’s information had spread was—forgive the comparison—practically genetic, first through Bo’s family and then into the greater population. A friend of another of Bo’s cousins uploaded the information to reddit, where a scientist at Baylor University saw it and passed it on to a colleague.

  The genetics department at Baylor had already brought together eight cases similar to Tess’s, all with a similar genetic variant. Tess is the youngest. The oldest is thirteen. But the good news is that all the children seem healthy aside from their disabilities. None of the children in the study are biologically related, w
hich means that their genetic variation is likely to have randomly happened in the sperm or egg that made them, or was a spontaneous mutation that occurred when they were in the womb.

  Spontaneous mutations cause what is called a “mosaicism.” My great-great-grandmother Ester Bloom, whose ankles, according to family lore, swelled while she was hanging laundry on a Brooklyn rooftop, might have been the origin of our family gene. If so, it’s possible only some of Ester’s cells carried the genetic variant or mutation. Once the sperm entered the egg, it remained one cell for around thirty hours, and then it divided into two cells. If the mutation or variant happened during this first split, only 50 percent of Ester’s cells carried the gene. If it happened fifteen hours later, during the next split, only one in four of her cells carried it, and so on. We will never know for sure. Our only clue that Ester shared our genes are those swollen ankles staring out at us from photographs. But if we’re right, and the information for this bad gene that may have existed only in some of her cells passed to her daughter, Ester Bloom is the founder—or patient zero—of our gene.

  * * *

  During the summer of 2016, the first Founder Population Summit met in Haifa, Israel. The action plan for the summit was simple: look back over the Ashkenazi Jewish gene pool and figure out where things had gone so genetically wrong. The Ashkenazi gene pool has a disproportionately high number of genetic mutations, largely because of geographic and political isolation as well as a religious standard placed on marrying other members of the population. The Ashkenazi gene pool owes its lot to forced homogenization—sometimes self-imposed, but also thanks to anti-Semitism and prevailing political ideologies.

  Some of the genetic variants seem to benefit the population, like a gene that is currently being hunted down and is affectionately known as “the Super Bubbe gene.” The Super Bubbe gene is believed to help the mostly women who have markers for illnesses like cancer and Alzheimer’s live deep into old age. Other genes are harmful, like those for Tay-Sachs disease and Bloom syndrome, both of which usually kill their young sufferers before they reach puberty. There are at least eleven deadly genetic conditions for which one in four Ashkenazi Jews is believed to carry the variant. When two Ashkenazi Jews prepare to have children, they are screened for all of them.

  Aaron decided he wanted to try out a new service, where you send away your DNA and find out your ethnic heritage. Just how homogenous was my DNA? We used a boutique company called 23andMe. They billed themselves as “the largest DNA ancestry service in the world,” offering basic genetic information to anyone who wants it for the low, low price of $99—at least, they did when we tried it in 2014. Regardless, when you consider that in 2007 a single sequenced genome cost $350,000, you have some perspective on just how far we’ve come.

  For now, 23andMe only allows users to see the places from which their genes originate with limited information about their health. It delivers a circle graph broken into pie wedges letting you know what percentage Scandinavian you are, if you are any percentage Scandinavian. It also connects people who share your genes—distant cousins and the like. It’s supposed to be fun.

  Much of my adult life had been spent focused on my genes. I wasn’t sure sending my DNA to 23andMe would be as much fun as Aaron thought it would be. But I supposed it wouldn’t be unfun, so I agreed.

  The tests arrived in a small white box a few days later. We spit into a small plastic container, sealed it up, and sent it back. Ten days after that, our results appeared on a website. Aaron’s revealed that he was 40.7 percent Irish and English, 13 percent German/French. There were additional bits and pieces from other places, mostly in Northern Europe.

  My results were a little different. My circle, which was supposed to be divided into a nice little assortment of pie wedges, was just one giant orange circle. Ninety-eight percent Ashkenazi Jewish ancestry. Ninety-eight percent. I have to admit I was surprised. I figured someone somewhere along the way might have had a fling with the milkman. But no. The other 2 percent of my circle had something to do with Neanderthal genetic code, which is a little joke 23andMe mixes into everyone’s results.

  One of my best friends, also of Ashkenazi Jewish descent, recently underwent genetic testing in the midst of fertility treatments. Her DNA was riddled with flagged genetic markers. She was even told she carried one gene that, if paired correctly, would yield a hermaphroditic child. Her husband, a Maine-born lumberjack type of mixed Northern European ancestry, was also tested. The doctors couldn’t believe their eyes. His genetic sequence, they told him, was that of “a superior specimen,” a funny anecdote they both—but especially he—still like to bring up at dinner parties.

  * * *

  Martin Fugate made his way to Kentucky in 1820 to lay claim to a land grant. An orphan, Fugate had grown up in French workhouses. For all intents and purposes, he was healthy and attractive enough to find himself a red-haired American wife with pale white skin. He and his bride, Sarah, settled on the banks of a place called Troublesome Creek. But there was something causing Martin Fugate trouble. Martin Fugate was blue.

  Although historically we have used words like “red,” “yellow,” “white,” and “black” to describe skin color, from kindergarten onward most of us understand that we’re talking about a subtle variation in a skin tone and not the actual color of the skin itself. But Martin Fugate wasn’t a “winter,” with blue undertones to an otherwise peachy glow. He was blue, somewhere between “periwinkle” and “Smurf.”

  Now, as the generations wore on, whispers about pockets of blue people had spread throughout the mountain communities. Then, in 1960, a blue person oddly but somehow appropriately named Luna Fugate arrived at a clinic in Hazard, Kentucky, asking for a blood test. A sixty-seven-year-old nurse named Ruth Pendergrass took one look at Luna and expected her to die of a heart attack at any minute. She described Luna as “dark blue” with indigo fingernails.

  Meanwhile, around the same time, Dr. Charles Behlen II was working an afternoon shift in the emergency room of a hospital at the University of Kentucky when a man named Luke Combs came in with his ailing wife. From minute one, Dr. Behlen couldn’t have cared less about what ailed Combs’s wife.

  “Luke was just about as blue as Lake Louise on a cool summer day,” he poetically explained to Bryce Nelson of the L.A. Times in an article published on November 6, 1974.

  Soon Nurse Pendergrass and a hematologist named Dr. Madison Cawein found themselves trudging on foot through the mountains looking for the people the locals called “the Blue People of Troublesome Creek.” Eventually, they found a brother and sister named Patrick and Rachel Ritchie.

  Dr. Cawein is reported to have said, “They were bluer than hell!”

  First, he and Nurse Pendergrass sat down and wrote out their family tree. It quickly became clear that the blue skin of the Ritchie siblings had been passed through their genes. Due to their relative geographical seclusion, along with a lack of adequate roads, blue people had been cropping up in pockets all over the region since the arrival of Martin Fugate. Cawein noticed that four families—the Fugates, the Combses, the Ritchies, and the Stacys—had, over six generations, frequently intermarried, most typically among cousins, but also, in one instance, an aunt and a nephew.

  Dr. Cawein and Nurse Pendergrass drew the Ritchie siblings’ blood. Upon doing so, they discovered that they both lacked a specific enzyme, diaphorase. Their findings revealed a rare condition called “methemoglobinemia,” or met-H. Specifically, diaphorase repairs the protein molecule that carries oxygen in the blood. Without it, the damaged protein carries less oxygen, turning it blue, finally turning the skin of the sufferer blue. Otherwise, its impact is virtually nonexistent. Luna Fugate lived to be eighty-four years old and gave birth to thirteen not-blue children. People with met-H live healthy lives, even if they are not always so happy.

  You’ve heard that it’s not easy being green, but being blue is no picnic either. The clinicians who studied Rachel and Patrick Ritchie described two
people visibly ashamed of their skin hunched over and avoiding eye contact with their doctors. Luna’s own husband, who outlived her by twenty years, happily talked about many of his wife’s blue-skinned kin, but shied away from admitting that his own wife was blue, even if everyone who ever knew her was quick to state otherwise.

  Luckily for Rachel and Patrick, they learned that met-H can be treated with a daily injection of methylene blue—a literally blue substance that restores iron to the blood, turning it red.

  Today, almost all of the blue people of Troublesome Creek have passed away. Benjy Stacy, forty-five years old, has skin that turns blue when he’s cold or under stress. But the mutation that leads to met-H is recessive and exceedingly rare. Both parents must carry the mutation that causes it.

  Small gene pools have been shown to lead to an increase of rare genetic conditions, largely thanks to the heightened possibility of two parents passing along the same gene. The fact that for every single gene in our DNA, there is a second gene coded to do the very same thing—one from each parent—actually makes us stronger. Our bodies, in a “survival of the fittest” spirit, often opt for the stronger, more successful of the two genes, also called “alleles.” Richard Dawkins, in his book The Selfish Gene, suggests that alleles are in fact competitors—“rivals,” he calls them—for the same job. When those two genes from each parent are exactly the same, by default the body must choose that gene, for better or worse, whether or not it contains less good or even bad genetic information.

  Perhaps the most remarkable story about the detrimental impact of “inbreeding” (a mostly negative word indicating that two mates are closely related over multiple generations) concerns the Spanish monarchy. The Hapsburg line famously died out when King Charles II passed on without an heir as a result of his well-documented infertility. Severely mentally challenged, the thirty-eight-year-old king likely suffered from a multitude of recessive genetic conditions and a weakened immune system resulting from rampant intermarriage between siblings, cousins, and other family members throughout the Hapsburg line, a common occurrence among aristocrats of the time. King Charles’s father was his mother’s uncle.