The Family Gene

by Joselin Linder

  The third thing Dr. Kricket told me was that she was planning to do something amazing with my blood cells, if I were willing to sign a consent form—which I am. They are going to turn them into “induced pluripotent stem cells.” In 2012, Shinya Yamanaka of Japan and John B. Gurdon of England won a Nobel Prize for the discovery that adult cells can be reprogrammed into something like stem cells. The word “pluripotency” refers to a cell’s ability to develop into any of several types of cells. For instance, a liver cell, once it has become a liver cell, stays a liver cell. A blood cell, once it’s a blood cell, stays a blood cell. This is why the discovery of stem cells in embryos in 1981 was so exciting. They were cells that could be induced to grow into a blood cell, or a liver cell. In fact, there was a time when people thought that one day stem cells might be removed from developing fetuses and harvested for the people who grew out of those fetuses, should they ever need a liver transplant or blood transfusion. They’d actually be able to get their own blood or a new liver, whatever they needed—created outside their own body from their own stem cells.

  Yamanaka and Gurdon went one better and figured out how to turn adult cells into stem cells. At a molecular level, the cell is genetically reprogrammed to return to a stem-cell state. Dr. Kricket said, “We can actually take a blood cell from you and make it go back in time!” She said it can be turned into an early heart cell, an early liver cell . . . and on and on.

  Dr. Kricket hopes her team will be able to prove that my family members’ livers are making molecules that impact our vascular liver pressures because of our genes. She wants to use these cells to grow vessels to make proteins and see how normal proteins stick to them. This is a different way of proving what she already knows about our gene.

  In the winter of 2016, the last remaining mouse with our mutated gene successfully bred. Today our gene lives on in multiple mice in a basement enclosure of the genetics department at the Harvard University Medical School. A mouse’s life span is 1.5 to 3 years. Hopefully in the next few years, we will see a mouse model develop our vascular condition, proving that our gene is where Dr. Kricket says it is, as well as all of the theories she’s developed during twenty-five years of hard work.

  It’s more than my dad ever thought possible. It seems like his unwavering faith in medicine is being rewarded at last.

  Thirty-Five

  Aaron and I didn’t have children. It’s true that medicine has come far enough that if we decide we want to, we can. We would find a way to raise the necessary funds and hire a surrogate to carry a genetically related fetus. We could utilize a “preimplantation genetic diagnosis” before selecting an embryo that does not carry my family’s mutant gene. In this way, we might have a baby. But Aaron and I don’t feel any pressure to have children yet. We like our respective sisters’ children so well that maybe we feel like our collective gene pools might have already done their best work.

  We talk about adoption or fostering. Again, we have not begun to take the necessary steps to do either. For most people, the issue of parenting is not as fraught as it is for Aaron and me. There’s a broken condom or a night of drunken passion. There’s enough mindless sex to turn the vague notion of having kids into a very real bawling baby.

  I suspect that I would be a good mother and that Aaron would be a fantastic father. I understand that parenting deepens you and expands you. My mother regularly tells me that she feels sad for me when she considers that I may never be a mother. I am also, as I’ve said before, an incurable optimist, annoyingly so at times. I tend to like my life exactly as it is. Sometimes I think it would be great to add a child to my happy family. But then again, I haven’t done much about adding one.

  There are moments when I think I am selfish for putting Aaron in a position where he will be left alone if one of my varices bursts and I die or I become mentally deficient. Technically speaking, I am more likely to die, or grow seriously impaired quickly, because of a compromised vessel than because of a slow and debilitating lymph accumulation like my father. When I consider this, I think I would be more selfish to bring a child into a family where such a monster lurks.

  Of course, these thoughts swiftly disintegrate when I remember that love is always a gamble. Though children might make us better, we also risk the agony of their loss, whether or not your portal vein is blocked, or your genes are faulty.

  Each of us. Every day.

  My friend Elle understands this better than pretty much anyone I know. Elle, with her dark hair, feather-white skin, and doe eyes, is charmingly beautiful. She is so shy that when she speaks her cheeks redden. If Elle’s genome has anything to say about it, she is going to die young. Right now she is in her mid-thirties, and her body is poised to start breaking down at any minute. Still, she and her husband just had a baby boy.

  When Elle and John met six years ago, they didn’t fully know about Elle’s future. There had been a smattering of cases of “Huntington’s disease” (formerly known as “Huntington’s chorea”) in Elle’s family tree. No one talked about the fact that it was genetic. At the time, there wasn’t much that could be done about it. Huntington’s has an adult onset. Sufferers typically don’t fall ill until they are into or even beyond their childbearing years. At a molecular level, adult-onset illnesses typically involve a slow breakdown.

  Dr. Kricket has discovered that the bodies of my family members have too few cysteinyl-leukotriene receptor keys in their livers to match up with their cysteinyl-leukotriene locks. As we age, her theory is that the number decreases further until eventually there are not enough keys for our locks. This is why we aren’t born sick. Why we don’t grow sick until we’re past the age of childbearing.

  The gene for Huntington’s causes an abnormally long version of a protein known as the “Huntington protein” to develop. As the protein breaks into toxic fragments, it binds to neurons, affecting cell functions. This toxic buildup causes Huntington’s early symptoms, but over time, the neuron dies. Soon after, so does the person. Unfortunately, with every generation, that Huntington protein gets longer, and the life span of the sufferer is shorter.

  Perhaps the most famous victim of Huntington’s was the folk singer Woody Guthrie. The “This Land Is Your Land” writer and singer began experiencing early symptoms of the illness in his thirties. By the time he was forty, he was correctly diagnosed. However, by then he had already been labeled both alcoholic and schizophrenic. Mental health issues are common for sufferers of Huntington’s, as the disease is neurodegenerative, meaning that it leads to a loss of neuron function.

  Guthrie’s mother, Nora, had Huntington’s. During her decline, she set two coal-oil fires, one that killed Guthrie’s seven-year-old sister and another that disfigured his father. Over time, sufferers can spend years without speech, steadily losing bodily control until they die.

  Woody Guthrie had eight children, including a son, Arlo. Arlo grew up to be a famous musician like his dad. His hit “City of New Orleans” was one of my parents’ favorites. “Good morning, America. How are you?” went the chorus. “Don’t you know me? / I’m your native son. / I’m the train they call the City of New Orleans. / I’ll be gone 500 miles when the day is done.”

  During an intro-to-psychology class I took in 1994, the professor alluded to the Guthries. “Arlo Guthrie,” she said, “can’t know if he has the gene for Huntington’s disease until he gets sick with Huntington’s disease.” She pointed out that this would factor into the younger Guthrie’s reproductive choices as well as into his other life choices.

  Perhaps at the time I was hearing about him, Arlo couldn’t find out if he had the gene for Huntington’s until he did or didn’t come down with Huntington’s, but I found his story fascinating. There was something so inherently cruel in the kind of lottery his fate had caused him to play. Go ahead and live your life, Arlo Guthrie. But don’t get too comfortable, and stay away from coal oil and matches.

  About fifteen years ago, Elle’s father lost his job. Elle was away at college a
t the time, but she says he was having trouble keeping up at his new job—which the family mostly attributed to the fact that it was a new job. There were little things that caused contention, like forgetting to put the milk back in the fridge. Elle thinks her father’s failing health might have been more noticeable to her dad than to the rest of the family. His own father had gone through the same thing when he had been around Elle’s age. Pretty soon, her father got the news: he had Huntington’s disease, and his two adult daughters were potentially carriers of the gene.

  A year after Elle met John, she still hadn’t been tested for the gene. For her, the years following her father’s diagnosis, when she knew she had a fifty-fifty chance of having the gene, were the toughest. By the time she and John decided she should be tested for the sake of their future offspring, she was resigned to the idea that she had it. A positive result would simply be a confirmation. A negative result would be winning the lottery. Elle’s test results came back positive. Her twenty-nine-year-old sister hasn’t been tested yet. She might be if she ever decides to have children, but for now, she doesn’t want her life impeded by the weight of knowing.

  Elle wasn’t sure she wanted to have children until John asked her to. He told her he didn’t want to be left alone. I can imagine both the tenderness and the terror of such a conversation. Elle came to the realization that no matter who you are or what you are contending with, having a child is an act of hope. Life becomes awfully bleak in the absence of hope. She agreed to try. Henry was born in March 2016.

  Elle has said to me over dinner that knowing she has Huntington’s feels surreal. She keeps wondering what she should be doing differently. “I guess,” she finally said, “it’s enough to just like your life.”

  I agree. It has to be enough.

  * * *

  Sometimes, it comes to me as a tightening in my chest. Other times, it is a rapid expansion with the simultaneous sensation of being flooded, like a dam has opened up over a giant hole where water and air have come to merge.

  I will never reproduce.

  It doesn’t arrive as an emotion . . . it is neither happy nor sad. It is a physical truth. It exists in my cells—in fact, it is cellular. From a one-celled organism to the thirty-seven trillion cells of the human body . . . reproduction is their yearning, not ours. Whether or not my quiet mind wants children, wants motherhood, wants my heart to exist outside of my body, is not a choice.

  Desire is sometimes a quiet crusader, unable even to name the thing that sits between our lives and our cellular quest for reproduction. To say we desire to reproduce is sometimes as good as our language can get. Mostly, I would say that I do not want to reproduce; it’s just that sometimes the urge comes to me, unbidden. It awakens in my cells, where it lives all the time—until I contract into oblivion, or expand beyond the boundaries of our universe—and I flood.

  I will never reproduce.

  It is neither sad nor happy. It is a physical truth. It lives in my cells. I have learned to let the physical truth overtake me and then I get on with my life.

  Thirty-Six

  A recent newspaper article written by a well-intentioned reporter referred to me as a person who “carries a genetic mutation in her heart that will eventually cause her a long and painful death.”

  As a writer, I love the sentence. “A genetic mutation in her heart” is simply stunning in its poetry. That this heart mutation will cause a long and painful death, well . . . it’s grim even if it’s possible. I mean, death is death, but to have one that is long and painful . . . that’s another story. As the person referred to in the article, however, I have a different set of feelings.

  The good news here is that the article is wrong, and I’m not just saying this because who the hell wants a sentence about them to predict a long and painful demise? The truth is that like everyone else, I have as much of a chance of getting hit by a car and dying swiftly as I do of developing a cancer that has nothing to do with my variant gene—in my heart or otherwise. Even if I live out my life without being stricken by any other malady or having an accident, I have as much chance of not having a long and painful death as I do of having one. It’s true my father’s death was the opposite of short and painless, but my ninety-one-year-old grandmother rarely had pain in her life.

  Then there is the simple truth that there is no such thing as a “mutation in a heart,” mine or anyone else’s. Hearts don’t mutate.

  Genes do.

  My family’s mutation, or variant, which is a nicer word, is too new to have given rise to a body of knowledge about it. Medicine is and has always been based on study and observation over time. We just haven’t had enough time or study to observe or understand how this variant works.

  We have found a way to “cure” the world of our scourge. For the first time in human medical history, we don’t have to wait for evolution to run with our variant, or quietly select it into oblivion. We can use the mind-blowing powers of science. Seven people have died of this gene. Seven people continue to live with it. So far, no one in the sixth generation has been passed my family’s gene.

  Our work isn’t done. Mistakes can still be made. There are four people in my generation with the gene, and all of them can still have children. My cousin Denise doesn’t plan to have any more, but if she were to accidentally become pregnant, her Jehovah’s Witness faith would preclude abortion. If Hilary or I became pregnant, we might decide that our drive to give birth trumps our need to weed out the gene. We have an even younger cousin with the gene who has not yet found a partner, but who may or may not be interested in IVF with preimplantation genetic selection. In other words, life happens. Nothing is certain until it is.

  But it is a plan, and so far, the plan is holding steady.

  As for us, the ones who carry the family gene, how might we continue to survive? Right now we all take a pill every day that helps to keep our abdominal blood pressures low, reducing the risk of a serious bleed. Valerie was never on these pills, which might have kept her from suffering a stroke. We are all taking the allergy pill that contains a chemical that Dr. Kricket found had some impact on people with asthma, an illness with a different variant on the same gene. Perhaps it will keep our good cysteinyl-leukotriene receptor keys in our livers matching up with those cysteinyl-leukotriene locks for longer.

  Meanwhile, at my last doctor’s visit after my stroke-turned-post-panic-attack, I learned that my latest MRI showed that my spleen is shrinking. Dr. Sigal, that preeminent liver specialist, looked at me with bewilderment and said, “I’ve only ever seen this in people who have undergone successful liver transplants.”

  Dr. Kricket continues to maintain that Hilary and I, as women, have great potential to live long and healthy lives.

  “It is still true,” she insists, that “men have one X chromosome, women have two. You have one that is normal, one that is abnormal. This is why I’ve always told you and why I still believe women have the disease less severely.”

  I didn’t know then that the answer was that my pressures are improving. Maybe it’s the asthma pill. Maybe it’s the blood pressure meds. Maybe it’s genetic—but things, for now at least, are looking up.

  * * *

  My grandmother Shirley died in December 2015. She was ninety-one years old. The causes of her death included lymphedema, but as my aunt Kathy pointed out, she was ninety-one and her heart stopped. My grandma spent her whole life telling Hilary and me that we would live to be old ladies like her. She never had a blockage in her liver, but who knows? Maybe she’ll be right.

  Meanwhile, the Seidman lab remains poised to publish their findings. Once they do, a much larger dialogue with the medical and medical genetics communities can take place. We are hopeful that by sharing this information, we will not only find help ourselves, but we will also help others with rare vascular and lymphatic conditions.

  Our bodies are wondrous. Perhaps that’s all we ever need to know.

  Acknowledgments

  Ten years ago, my fr
iend, writer Caroline Palmer told me that a story I’d told her about my dad would make a good book. For that and all the reading and discussing she’s done on and about this project ever since, I am grateful. In the capable hands of the outstanding agent and amazing human Mollie Glick, it finally became a reality. I also want to thank its early champions, Sean Gannet, Molly Lyons, and Joelle Delbourgo.

  Endless thanks goes to Hilary Redmond for seeing something in my story. To Denise Oswald for stepping in and captaining a boat she’d never seen before with all the skill and ability of a lifelong pilot. To everyone at Ecco, including Emma Janaskie, Dan Halpern, Beth Parker, Miriam Parker, Ashley Garland, and Meghan Deans, for their invaluable input.

  I have to thank the many brilliant writers with whom I share a writing group who have basically been this book’s first, second, and eightieth editors including Sam Ritchie, Mary Atkins, Christine Clarke, Kate Tellers, Nicole Solomon, Joanne Solomon, TJ Wells, Jorge Novoa, Jessica Mannion, Sivan Butler-Rotholz, Amit Wehle, Alia Phibes, Ilise Carter, Alina Simone, Philip Willcox, Aaron Wolfe, and Elizabeth Tannen. Also thank you to its early readers, Ann Fischer, Ellen Doyle, Christine O’Malley, Erica Barth, Allison Deutermann, Sarah Willcox, Marge Bender, Keith Newland, Jacob White, Jen Spitzer, with special thanks going out to Susan Fuhrman, Abby Sher, Boomer Pinches, and Susannah Cahalan.

  An enormous and raucous THANK YOU goes to Dr. Peter Sabatini for translating all of that science. To Nadine Thorson for bringing me to Peter, and to Susan Faulkner for bringing me to Nadine. To Molly Anderson, R.N., Dr. Jennifer Robbins, and Michelle Gilats for your time, edits, and brilliance. To Dr. Keith Pattison, Dr. Steven Delaveris, Dr. Marlys Witte, Dr. Larry Lynn, Kim Kneuvin, Terry Silverman, Dr. Michael Landzberg, Margaret Vild, Dr. Anita Steinberg, Dominique Sartain, Evelyn Garbowit, Rabbi Harold Berman, Rabbi Harold Salzmann, Audrey Salzmann, Lucas Elijovich, and Ryan Miller for your memories of my family and your important impact on our lives. To Bo Bigelow, and Glenn and Cara O’Neill—thank you for all you do for rare genetic diseases. Thank you to Zack O’Malley Greenburg, Frank Deford, Alisa Kermisch, Elijah Saintonge, Joy Larsen Haidle, Todd Toler, Jen Difiglia, Suzanne Arnold, Nina Frenkel, Libby Batten, Sharon Cohen, Jill Barnett, Connie and Darrell Luikart, and Kerry Luikart. Thank you to Dr. Samuel Sigal, Dr. Hearns Charles, Dr. Ziv Haskel and Dr. Mitchell Spinnell for all you do for my family and your contribution to our lives and stories.