“The rarest of books: a combination of page-turning discovery and remarkably readable science journalism.”—Mark Hyman, MD, #1 New York Times bestselling author of Food: What the Heck Should I Eat?
NAMED ONE OF THE BEST BOOKS OF THE YEAR BY WIRED
Until recently, microglia were thought to be helpful but rather boring: housekeeper cells in the brain. But a recent groundbreaking discovery has revealed that they connect our physical and mental health in surprising ways. When triggered—and anything that stirs up the immune system in the body can activate microglia, including chronic stressors, trauma, and viral infections—they can contribute to memory problems, anxiety, depression, and Alzheimer’s. Under the right circumstances, however, microglia can be coaxed back into being angelic healers, able to make brain repairs in ways that help alleviate symptoms and hold the promise to one day prevent disease.
With the compassion born of her own experience, award-winning journalist Donna Jackson Nakazawa illuminates this newly understood science, following practitioners and patients on the front lines of treatments that help to “reboot” microglia. In at least one case, she witnesses a stunning recovery—and in others, significant relief from pressing symptoms, offering new hope to the tens of millions who suffer from mental, cognitive, and physical health issues.
Hailed as a “riveting,” “stunning,” and “visionary,” The Angel and the Assassin offers us a radically reconceived picture of human health and promises to change everything we thought we knew about how to heal ourselves.
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About the Author
Read an Excerpt
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, roadkill, 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!”
Table of Contents
Prologue When the Body Attacks the Brain 3
1 The Accidental Neurobiologist 15
2 "Ten Feet Out of a Forty-Foot Well" 29
3 Friendly Fire in the Brain 41
4 Microglia Everywhere 53
5 A Bridge to the Brain 66
6 "It Seems There Are No New Solutions" 76
7 A Modern Braindemic 86
8 Brain Hacking 103
9 A Beleaguered Mind 118
10 Untangling Alzheimer's 137
11 Desperately Seeking Healthy Synapses 156
12 Rebooting the Family Fixer 170
13 In Search of a Fire Extinguisher for the Brain 182
14 The Fast-er Cure? 192
15 Future Medicine 210
16 A Final Analysis 230