Allergic, p.1
Allergic, page 1
Copyright © 2023 by Theresa MacPhail
All rights reserved.
Published in the United States by Random House, an imprint and division of Penguin Random House LLC, New York.
Random House and the House colophon are registered trademarks of Penguin Random House LLC.
Library of Congress Cataloging-in-Publication Data
Names: MacPhail, Theresa, author.
Title: Allergic: our irritated bodies in a changing world / Theresa MacPhail.
Description: First edition. | New York: Random House, [2023] | Includes index.
Identifiers: lccn 2022032275 (print) | lccn 2022032276 (ebook) | isbn 9780593229194 (hardcover) | isbn 9780593229200 (ebook)
Subjects: LCSH: Allergy—History. | Allergy—Popular woks.
Classification: lcc rc584 .m28 2023 (print) | lcc rc584 (ebook) | ddc 616.97/3—dc23/eng/20220916
LC record available at https://lccn.loc.gov/2022032275
LC ebook record available at https://lccn.loc.gov/2022032276
Ebook ISBN 9780593229200
randomhousebooks.com
Book design by Simon M. Sullivan, adapted for ebook
Cover art and design: Ben Denzer
ep_prh_6.1_143667513_c0_r0
Contents
Cover
Title Page
Copyright
Prologue: Everything That Irritates Us
Part One: Diagnosis
Chapter 1: What Allergy Is (and Isn’t)
Chapter 2: How Allergy Diagnosis Works (or Doesn’t)
Chapter 3: Our Allergic World: Measuring the Rise of Allergic Disease
Part Two: Theories
Chapter 4: Allergic Inheritance: Allergies as a “Normal” Immune Response
Chapter 5: Nature Out of Whack
Chapter 6: Are We Doing This to Ourselves? The Modern Lifestyle and Allergy
Part Three: Treatments
Chapter 7: Remedies for the Irritated: Allergy Treatments Past, Present, and Future
Chapter 8: The Booming Business of Allergy Treatments
Chapter 9: What Makes a Treatment Effective? Weighing Benefits and Risks
Chapter 10: Allergy Is a Social Problem, Too
Epilogue: Irritating Ourselves to Death: Allergy in the Time of COVID-19
Acknowledgments
Notes
Suggestions for Further Reading
Index
By Theresa MacPhail
About the Author
_143667513_
PROLOGUE
Everything That Irritates Us
On August 25, 1996, my dad was cruising down Main Street in our small New Hampshire town in the respectable, boxy four-door sedan that he used to make sales calls during the week. He and his longtime girlfriend, Patricia, were headed out to the beach to enjoy the day surfside. It was 11:20 a.m. and as the sun marched toward its apogee, the temperature slowly rose with it. The car’s windows were rolled down, which was typical for my dad. He was an enthusiastic smoker of Marlboro Lights who also eschewed the use of air-conditioning unless it was blisteringly hot. We were New Englanders, after all, and expected to tough out all but the most miserable of weather.
My dad’s hand dangled outside his car, a lit cigarette pinched between his fingers, his forearm resting on the warm metal of the car door. The radio was tuned in to an AM station covering the Boston Red Sox. My dad could never get enough baseball. He dialed in to seemingly every game and if one wasn’t being played, then he liked to listen to analysis of past matchups and predictions about future ones. As a teenager who was more into reading Dickens and obsessing over Duran Duran, I found his enthusiasm for sports exasperating, especially his addiction to sports radio. As a rule, I would sit in the back seat, trying to concentrate on reading, my eye rolls partially hidden behind a thick paperback book. Sometimes, just to annoy him, I would root for the opposing team until he threatened to pull the car over and let his only child walk home.
But in 1996, I was twenty-four years old. That Sunday in August, I wasn’t in the car with my father. I heard about what happened from three sources: the state police, who informed me as next of kin that he was dead; a local funeral director I phoned to see where my father had been taken, who remembered his colleagues discussing the unusual condition of his body; and, twenty-five years later, Patricia, during our first conversation since my father’s wake. Yet my dad was such a creature of habit that I have no trouble picturing the events as they likely unfolded. If I close my eyes, I can see him sitting in his car, a Styrofoam cup of hot coffee wedged into the cup holder, his hand loosely resting on top of the wheel.
Growing up, I had a strained relationship with my father. My parents divorced when I was just two months old, and I saw him only a few times throughout my young childhood. The tension that existed between us deepened after my mother’s death in a car crash in 1986, when, at fourteen, I moved from my hometown in rural Indiana to live with him and Patricia in suburban New Hampshire. My dad and I were what I euphemistically liked to call “estranged” whenever I tried to explain our familial situation to new acquaintances or friends. I had a father and I loved him; I just never spoke to him.
As my dad drove that day, a solitary bee was on its usual pollen-collecting rounds when its flight trajectory intersected with my father’s open car window. The bee became confused and panicked. It stung my dad in the side of his neck, close to his ear. My dad, surprised but still calm, continued to drive.
What happened next was not visible to the naked eye. Events shifted to the microscopic level, inside my father’s body. Biology took over.
The bee’s stinger introduced its venom—a mixture of water, histamine, pheromones, enzymes, and various amino acids, or proteins—underneath the thin layer of skin into the fatty tissue of my father’s neck. Packed tight with blood vessels, the neck is a great circulatory site, so the venom had a unique opportunity to spread rapidly throughout my dad’s body. Some of my father’s immune cells—his mast cells and basophils—swiftly detected certain of the venom’s components.
White blood cells like mast cells and basophils are produced in our bone marrow and circulate throughout the human body, helping to fight off infection or disease by ingesting foreign or harmful materials like viruses, bacteria, and cancer cells. Mast cells can be found in the connective tissues under our skin, lining our respiratory tract and intestines, and in the tissue around our lymph nodes, nerves, and blood vessels. Basophils are found in our bloodstream. Mast cells and basophils, then, are nearly everywhere inside the human body. Their job, to dramatically simplify it, is both to begin and to amplify the severity of our immune response. Think of them as the conductors of our immune system, modulating its response by releasing various proteins and chemicals.
Bee venom is not a natural substance that the human body responds particularly well to, even under normal circumstances in a nonallergic person. Bee venom is naturally hemorrhagic, meaning that it has the ability to blow apart our blood cells. Even so, bee and wasp venoms are relatively harmless in most humans, apart from causing a painful, localized swelling near the injection sites. Everyone’s immune cells react to venom; my father’s dramatically overreacted, sending his immune system into the deadly spiral known as anaphylaxis. Anaphylaxis is medically defined by the World Health Organization as “a severe, life-threatening systemic hypersensitivity reaction characterized by being rapid in onset with potentially life-threatening airway, breathing, or circulatory problems.” What that means in layman’s terms is that my father had an underlying allergy to the bee’s venom, a hypersensitivity that he tragically underestimated until it was too late.
Just a few weeks prior, while in the parking lot of Walmart, my father had been stung by another bee. When he returned home, he told Patricia he wasn’t feeling well and took some Benadryl—a well-known brand of antihistamine, commonly recommended for coping with milder allergic responses. Soon after, he felt better, but Patricia nagged him to see a doctor, suspecting he had an allergy to bees. My father, notoriously bad at taking care of his own physical health (he smoked too much, drank too much bourbon, and ate too many servings of prime rib), demurred.
Allergic responses can strengthen over time with repeated exposures. The first time my father was stung, he may not have had more than a small welt at the site of the sting itself. The second or third time, his body’s immune cells would have remembered the offending substances and reacted more swiftly and strongly—causing a proportionally larger reaction. My father’s body, unbeknownst to him, was already primed to betray him.
The process of anaphylaxis starts as soon as an antigen—a fancy term for any substance, like bee venom, that initiates an immune response—encounters and activates the mast cells and basophils in your body. My dad’s mast cells and basophils began the process of anaphylaxis mere seconds after he was stung in his sedan, as soon as they came into direct contact with the venom’s proteins and started emitting histamine. Histamine, an organic compound created by the body, is a key part of a normal immune response, released when cells are injured or stressed. It causes blood vessels to dilate and their walls to become more permeable—thereby making it much easier for infection-fighting white blood cells to leak out of blood vessels and move into affected areas. Histamine is also a signal to other nearby cells to release even more histamine. Think of histamine as the body’s chemical alarm system; once it goes off, it alerts your entire immune system to go into action. How does this alarm system feel within your body? Histamine acts on receptors on your organs, causing inflammation, flushing, itching, hives, and swelling.
Unfortunately for my father, everything that happened next would be accelerated simply because he was still sitting upright in his car, his body’s position partially obstructing the flow of deoxygenated blood returning back to his heart. The allergic surge of histamine circulating throughout his body caused my dad’s veins to dilate too quickly, reducing his blood pressure and the flow of blood to his heart even further, a process that can—and, in my father’s case, eventually did—culminate in cardiac arrest. The excess of histamine additionally shifted fluid from his vascular system—the network of blood vessels throughout his body—into his tissues, causing my father’s body, including his neck, to swell. In an effort to help protect the lower airways from inhaled irritants, histamine also thickens mucus, increases mucus production, and causes the smooth muscle tissue around your lungs to tighten. During an anaphylactic event, your airways begin to constrict within minutes. My father, sensing all of this beginning to happen to him, pulled over to the side of the road and asked Patricia to drive.
Panicked and miles away from the nearest hospital, Patricia decided to drive to a local pharmacy for more immediate help. Now in the passenger’s seat, my father started to gasp for air, his face changing color.
Minutes later, Patricia pulled the sedan into the tiny lot in front of the small drugstore, threw it into park, and ran for help. The pharmacist on duty that day explained that he couldn’t give my father a potentially lifesaving shot of epinephrine, also known as adrenaline, because my father didn’t have a current prescription for it. Epinephrine, a natural hormone secreted by the adrenal glands during times of stress, helps to stop the process of anaphylaxis by halting the release of histamine and constricting the blood vessels—thereby aiding blood flow. It also binds to receptors on the smooth muscles of the lungs, helping them to relax and allowing the breath to return to normal. An emergency shot delivers a much greater dose of adrenaline to the body than it can produce on its own in a short amount of time. But instead of administering the drug to my father, the pharmacist called for the paramedics.
When the ambulance finally arrived, emergency medical technicians (EMTs) intubated my father, who could no longer breathe due to the swelling in his neck tissue coupled with the constriction of his lungs. The ambulance did not have any adrenaline on hand, and the pharmacist continued to adamantly, if regretfully, refuse to give the EMTs access to the drug my father now so desperately needed. Despite how cruel his decision may appear to us now, the pharmacist’s hands were legally tied. In the 1990s, pharmacists were not allowed to administer adrenaline, even in the case of an emergency. As precious minutes ticked by, my father’s body went into shock, the final stage of what is referred to as an inflammatory cascade.
As my father was being loaded into the back of the ambulance, Patricia, hovering over him, asked him to blink if he could still hear her. He softly closed and opened his eyes. She squeezed his hand, still terrified, yet relieved and hopeful. As she climbed back into my father’s sedan to drive herself to the emergency room, she listened to the sound of his ambulance’s siren as it faded into the distance.
On the way to the hospital, despite all efforts to save him, my father’s heart stopped.
James MacPhail—die-hard Boston sports fan, computer chip salesman, Vietnam veteran, Jackie Gleason look-alike, the life of every party, loving son, stand-up comedy aficionado, musical lover, and my father—was gone.
* * *
—
As I was researching this book, I turned forty-seven, the same age my father was when he died, and I often found myself thinking about his unusual death as I talked to experts across the country about the puzzle of allergies. Deadly anaphylactic reactions to bee stings remain incredibly rare. Each year, around 3 percent of adults will experience a life-threatening reaction to an insect sting (bees, wasps, or hornets), yet most will survive.[1] In the two decades since my father’s death, an average of just sixty-two Americans, or 0.00000002 percent of the general population, have died annually from an insect sting.[2] My dad’s death was an outlier, an unfortunate accident, and a life-changing event for all of his friends and family.
But the more I learned about allergy, the more I kept wondering, Why him? Was it something about his genetic makeup (and thus also part of my own) that primed his immune system to overreact in the first place? Or was it something about his environment growing up in Boston or the way he had lived his life? In theory, my dad could have become more sensitized to bee venom after being repeatedly stung—either in childhood or during his two tours of duty in Vietnam. Or, he could have just been very, very unlucky to die from his second encounter with venom in just under a month. Yet as I write this—having finished my research and now three years older than him—I know that there is no way to know for certain what caused my father’s allergy because allergies themselves are complicated.
From a biological perspective, I can explain exactly what happened during my father’s last moments on earth. The underlying biology is, in many ways, the easiest part of the story to understand and to tell: My father’s immune system response was too effective for his own good. In Greek, anaphylaxis literally means “backward defense.” My dad’s immune system—built to protect him—was completely functional but overly sensitive, misrecognizing a naturally occurring, relatively innocuous substance as a direct threat. Once a heightened immune system reaction begins, it can be nearly impossible to stop. For the people who live with a severe allergy, the paradox of having such a strong, active immune system is that, in addition to protecting you from germs and parasites, it can kill you. And that’s exactly what happened to my dad.
The thing that I continue to struggle with—that I simply cannot grasp—is what my dad must have been thinking and feeling as he helplessly watched his own body fail him. How frightened he must have been in those first few seconds as he felt his throat begin to swell shut and his lung muscles contract, cutting off his ability to breathe. How terrified he must have been as his heart began to slow inside his rib cage. What is it like to incrementally, and yet swiftly, die as your immune system goes into overdrive? Would he even have understood what was happening to him? At the very end, as his heart stopped, did he have time to think once more of me, or my grandmother, or his girlfriend? Did he know how much we would miss him?
* * *
—
Strange as it may seem, I didn’t originally set out to research the topic of allergies because of my father. Over time, I had normalized his death and ruminated on it less and less. For years, the only time I thought about my dad’s final moments was when I was sitting outside at a picnic table or walking through a garden and heard a familiar buzzing sound. The mere sight of a bee could send my heart pounding and freeze me in my tracks. But outside of these random encounters with wasps, hornets, or bees, I didn’t think all that much about allergies. Until, that is, I was diagnosed with them myself.
In 2015, I was a busy new assistant professor teaching a full course load and trying to write a book about influenza. Ironically, I kept getting sick. Very sick. After being diagnosed with my fourth respiratory infection in less than a year, my doctor shipped me off to see an otolaryngologist—an ear, nose, and throat specialist—proclaiming that something must be wrong with my nasal “plumbing.” The otolaryngologist listened to my complaints, examined my doctor’s notes, and then looked inside my nasal cavities and down my throat with a scope.
“You’ve got some serious irritation,” he said, still peering into the deep recesses of my nose. “Much more than would occur with just an infection. I’d say that you have allergies. That’s your real problem.”
