The angel and the assassin The tiny brain cell that changed the course of medicine

Donna Jackson Nakazawa

Book - 2020

"Until recently, microglia were thought to be the boring little housekeepers of the brain, helpfully pruning away dead cells. But science now understands them to have a terrifying Jekyll and Hyde control over brain health. When triggered, they morph into destroyers, causing a wide range of issues: from memory problems and anxiety to depression and Alzheimer's. Under the right circumstances, however, microglia are indeed angelic healers, making repairs in ways that reduce symptoms and, now that we understand their true role, could one day prevent disease. A fascinating behind-the-scenes account of the science that identified microglia as our neurological immune system, The Angel and the Assassin also explores the promising medical ...implications of this game-changing discovery. Award-winning journalist Jackson Nakazawa (who herself has health issues explained by microglial behavior) follows three patients as they seek to reduce their psychiatric symptoms and cognitive issues through new treatments. Giving new meaning to the mind-body connection--emotional distress alters our physical health, and our physical health impacts our mental health--the discovery of the true role of microglia in brain health could rewrite psychiatry and medical texts as we know them. The Angel and the Assassin stands to change everything we thought we knew about how to heal our bodies and our brains"--

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Subjects
Published
New York : Ballantine Books [2020]
Language
English
Main Author
Donna Jackson Nakazawa (author)
Edition
First edition
Physical Description
xii, 300 pages ; 25 cm
Bibliography
Includes bibliographical references and index.
ISBN
9781524799175
  • Prologue: When the Body Attacks the Brain
  • 1. The Accidental Neurobiologist
  • 2. "Ten Feet Out of a Forty-Foot Well"
  • 3. Friendly Fire in the Brain
  • 4. Microglia Everywhere
  • 5. A Bridge to the Brain
  • 6. "It Seems There Are No New Solutions"
  • 7. A Modern Braindemic
  • 8. Brain Hacking
  • 9. A Beleaguered Mind
  • 10. Untangling Alzheimer's
  • 11. Desperately Seeking Healthy Synapses
  • 12. Rebooting the Family Fixer
  • 13. In Search of a Fire Extinguisher for the Brain
  • 14. The Fast-er Cure?
  • 15. Future Medicine
  • 16. A Final Analysis
  • Epilogue
  • Acknowledgments
  • Notes
  • Index
Review by Kirkus Book Review

How the brain's microglial cells affect the body and the mind.From 2001 to 2006, science journalist Jackson Nakazawa (Childhood Disrupted: How Your Biography Becomes Your Biology and How You Can Heal, 2015, etc.) was stricken, for the second time, with Guillain-Barr syndrome, an autoimmune disease that attacks nerves, causing paralysis. As she recovered, she experienced cognitive and psychological changes that urged her to question the connection between physical immune dysfunction and brain-related and psychiatric illness, a connection that went against the prevailing medical belief that the brain could not be affected by immune disorders. The author's investigations led her to the work of scientists across many disciplinesneurobiology, genetics, psychology, psychiatry, medicine, and immunologyseveral of whom she profiles in lively detail: the caffeine-fueled Beth Stevens, for one, a MacArthur fellow who directs a laboratory, and Jonathan Kipnis, whose graduate school professors, decades ago, did not encourage his experiments in the immune system-brain connection. Translating scientific research into brisk, readable prose, Jackson Nakazawa reports on breakthrough discoveries regarding microglial cells, which function as the brain's white blood cells, with "enormous power to protect, repair, and repopulate the brain's billions of neurons and trillions of synapses, or to cripple and destroy them." But besides functioning as helpful "angels," they also can spin into overdrive in response to stressors such as infection, environmental toxins, trauma, physical or emotional abuse, and chronic mental stress. When these stressors appear to microglia as if they are biological pathogens, the resulting "frenzied" microglial activity can lead to depression, anxiety, cognitive impairment, forgetfulness, lethargy, and similar symptoms. The author follows three autoimmune sufferers whose psychological symptoms were significantly improved by one of the new therapies resulting from microglial research: transcranial magnetic stimulation, neurofeedback, gamma light therapy, and fasting diets. Scientists in many fields, writes the author, are looking into a microglial connection to Alzheimer's disease, with the hope that if the cells can be rebooted and reprogrammed, they can "help reverse the ravages" of the disease.A fascinating look at cutting-edge research with profound implications. Copyright Kirkus Reviews, used with permission.

Copyright (c) Kirkus Reviews, used with permission.

One The Accidental Neurobiologist As you enter Beth Stevens's lab office in Boston, Massachusetts, where she serves as associate professor of neurology at Boston Children's Hospital and Harvard, you're greeted by a giant whiteboard. At its center sits an elaborate hand drawing of a microglial cell, rendered in bright green fluorescent marker. Tentacle-­like arms extend probingly out from the cell's blob-­like center, each delicate arm pointing toward a different handwritten list of the primary research projects currently under­way in Stevens's lab, along with important deadlines. It's clever. It's nearly five o'clock in the afternoon. Stevens's ten-­year-­old daughter, Riley, is finishing homework at her own child-­sized desk not far from her mom's. Riley's hair--­the same towheaded white-­blond as her mother's--­hangs in neat pigtails. Riley pushes her glasses up on her nose, heads over to the majestic whiteboard, and picks up a marker and dry-­eraser. Her blue eyes--­also her mom's--­sparkle mischievously. "Riley, don't erase that board!" Beth calls out. Her voice conveys pretend mom sternness. "All kinds of crazy things are going to start happening around here if that board gets erased!" Stevens's husband, Rob, walks in just then to pick Riley up after school. He offers me a warm hello, then smiles playfully as he points out a silver espresso cup sitting on Stevens's desk. The cup is still steaming. "Yup, I just had another cup of espresso," she says, exchanging a smile with her husband. A large mug with the words Death Wish Coffee also sits on her desk. She looks at me and gives a minuscule shrug. "These mugs are gifts from my lab. I guess that should tell you something?" She kisses her daughter and husband goodbye before showing me around the lab. Stevens is stylish and crisp in an olive-­green summer dress, her wavy blond hair neatly pinned back with a silver clip. She gestures under her desk, where research papers rise in foot-­high stacks. "My reading pile!" she laughs. Above her desk, photos of her daughters, Riley and Zoe, are pinned to a bulletin board, interspersed with favorite pieces of their preschool artwork. There's a photo of the beach house where she and Rob vacation every summer on Cape Cod. Stevens points fondly to a photo of herself embracing a young woman in a graduation cap and gown. They're both smiling widely. "This is my first grad student." There are several collages made up of the faces of dozens of the students and colleagues she's worked with over the past twenty years. "Looking at all these faces makes me really happy when I'm feeling stressed," she says. In the area outside her office sits an espresso machine, which Stevens gifted to her lab. She points out the "dual heads so two people can fill up at the same time." (A fellow neuroscientist once described Beth Stevens as being a lot like "a four-­shot espresso." It's an apt description.) A plate of cookies awaits kids who--­like Riley--­might come to the lab for a few hours after school to do homework while they wait for their mothers. (Yes, much of Stevens's team is female.) Intermingled with the microscopes and computer screens there is one apparatus I've never seen before in a biology lab: a miniature brewery. "My postdocs and students brew our own beer," Stevens explains, with a laugh. "We call it microgliale." It's a busy, cozy, happening, caffeine-­fueled, fun place, Stevens's lab. Today, there are fifteen postdocs and students working on different projects. Stevens runs a smaller second research group at the Broad Institute, a biomedical and genomic research center, and she is in high demand at neuroscience conferences all over the world to share her game-­changing discoveries about the tiny cells that science almost forgot--­microglia. But it didn't start out that way. In many ways, Beth Stevens is an accidental neurobiologist. Student of Nature Beth Stevens grew up in the small industrial city of Brockton, Massachusetts, known for its history of shoe manufacturing. Her father was an elementary school principal in downtown Brockton, and her mother taught at another local elementary school, closer to their home. Reading books and kitchen table arithmetic were both encouraged and supported. Stevens was bookish, like her family, but she also had a more hands-­on brand of curiosity. She spent hours in her backyard turning over rocks, sitting in trees, looking at the undersides of leaves, smearing sap between her fingers, and watching insects, in an effort to discern the unseen workings of the natural world. Later, in middle school, when it came time to participate in the frog dissection that most students dreaded in biology, Stevens felt none of the squirmy hesitation of her classmates. "I couldn't imagine anything more intriguing than seeing how the inside of a frog's body worked," she says, taking a sip of her espresso as we sit at her desk. After that day, "I know it might sound gross, but if I saw a dead squirrel or opossum on the side of the road--­yes, road kill, it's awful!--­I'd poke gently at it with a stick, just trying to peer inside. I wanted to understand how its body functioned, and why it died." To young Beth, it seemed as if looking inside things was the most important and interesting thing you could do in the world. But there were no scientists in her family. When she did read about a biologist having discovered something exciting, it was invariably a man. She had the sense, growing up in her town, that she was a bit odd--­one of those things that is not like the others, as the saying goes."It certainly never occurred to me that my interests could lead to a career," she recalls, looking back. That began to change when Stevens took an Advanced Placement biology course in high school. Her teacher, sensing her interest, told her stories about past female students who had gone on to become researchers. He held down a second job working in a medical lab, and he sometimes brought projects into class. "We'd be pouring different mediums into petri dishes and turning on Bunsen burners and I'd think, Wow, can you really do this as a job?" Beth says. When she graduated from high school in 1988, Stevens went on to study biology and medical laboratory science at Northeastern University in Boston, sure she'd later go to medical school. One term, she interned in a hospital lab, where she assisted researchers in identifying a food poisoning outbreak: Listeria monocytogenes bacteria lurking in store-­bought sausages. After Stevens graduated, she wanted to find work that would help build her résumé while allowing her time to study for the MCATs. Her husband, Rob Graham, then her boyfriend, had landed a job working on Capitol Hill in Washington, D.C. Stevens was seeking lab experience--­and one of the best and biggest labs in the world was situated on D.C.'s outskirts: the National Institutes of Health. It was 1993. "We moved to D.C. and I thought I'd wait tables at a Chili's restaurant near NIH for a few months until I landed something," Beth recalls. "On breaks I'd pull off my apron and run over to NIH to search the job board and drop off my résumé." Stevens liked to read science journals in her spare time, and she'd recently read "the very odd and fascinating case of a woman with a parasitic infection inside her eye," she tells me. "So I thought I'd really like to work in infectious disease." Among the dozens of applications she put in, she submitted one to work for a Nobel laureate who was studying infectious disease and HIV. Ten months into her job search, Stevens got a call from the HIV lab offering her the position of lab tech. She was twenty-­two years old and had, she thought, landed her dream job. But "I got another call around that time too--­from a scientist whose lab I hadn't applied to," she says, with some bemusement. Doug Fields was, at that time, a young neurobiologist who was setting up his first lab at NIH. He'd called Stevens out of the blue. "He told me he'd thumbed through the rejected résumé pile in NIH's personnel office, where mine had landed." He explained that he was studying the firing patterns of neurons, and how that affected brain development. "Going into neuroscience simply was not on my radar at the time," says Stevens. Besides, to someone fascinated with viruses and infectious diseases, it seemed less interesting than studying HIV. So Stevens turned Doug Fields's offer down. Then life took a circuitous turn. "I showed up for my first day of work at the Nobel laureate's HIV lab, and the lab manager told me there was a hiring freeze; they'd forgotten to tell me I no longer had the job," Beth says. "I went home feeling more dejected than I'd ever felt in my life. The next day I put my waitress's apron back on and went back to serving burritos at Chili's. After almost a year of looking, I'd only had two job offers." She laughs. "And I'd turned one of them down!" Excerpted from The Angel and the Assassin: The Tiny Brain Cell That Changed the Course of Medicine by Donna Jackson Nakazawa All rights reserved by the original copyright owners. Excerpts are provided for display purposes only and may not be reproduced, reprinted or distributed without the written permission of the publisher.