“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?

“A fascinating deep dive into the unsung heroes (and villains) inside our skulls ….Donna Jackson Nakazawa has a journalist’s eye for story, a scholar’s understanding of the research, and patient’s appreciation for high the stakes truly are.” 
—Susannah Cahalan, New York Times bestselling author of Brain on Fire

“An inspiring account…will provide a game-changing view of health for generations of researchers, clinicians and citizens for years to come. Bravo!” 
—Dan Siegel, MD, Clinical Professor, UCLA School of Medicine, author of Mindsight

 “The Angel and the Assassin is riveting, engaging. Nakazawa’s work is visionary.” 
—Terry Wahls, MD, author The Wahls Protocol

“Few non-fiction writers can tell the tale of scientific inquiry so vividly the reader can feel the excitement of discovery with every word. Donna Jackson Nakazawa is one of those writers, and this book tells the tale of one of the most intriguing and groundbreaking discoveries in all of medicine.”
—Shannon Brownlee, Senior Vice President of the Lown Institute, author of Overtreated

 “The Angel and the Assassin is one of those astonishing medical yarns that you almost can’t believe: how the power of this tiny cell was so long overlooked, how integral it has become to our understanding of neuroscience and immunology, the way it has transformed the most basic ideas of who we are as humans. It is especially essential reading for women, who face depression, Alzheimer’s and autoimmune disorders at higher rates than men.” 
—Peggy Orenstein, New York Times bestselling author of Girls & Sex

 “Colorful, page-turning, and accessible…. I have great hope for the practical application of what [Jackson Nakazawa] reveals.”
—Amy Myers, MD, New York Times bestselling author of The Autoimmune Solution

“Jackson Nakazawa puts forth a revolutionary new way of thinking about the brain’s immune system and its interactions with [the] rest of the body….Much of the information here was new to me, and has made me more optimistic about the future of medicine.”
—Andrew Weil, MD, New York Times bestselling author of Healthy Aging

“A deft, scientific story about the ‘Cinderella’ cell of the brain, microglia . . . Jackson Nakazawa explains the possible translation of the science into solutions for brain disorders, health and disease.” 
—Thomas Insel, MD, Former Director, National Institute of Mental Health 2002 – 2015 

 “A captivating, page-turning story of the scientific discoveries that overturn centuries of medical dogma. The Angel and the Assassin offers extraordinary promise and heralds new hope … paradigm shifting reading for us all.”
—Christina Bethell, PhD, MBH, MPH, Professor of Child Health, Johns Hopkins Bloomberg School of Public Health

“An impressive, inspiring, timely call to arms.” 
—Susannah Tye, PhD, Director of the Translational Neuroscience Laboratory, Mayo Clinic

“A captivating look at the new science altering our understanding of a range of conditions that especially affect women.”
—Maya Dusenbery, author of Doing Harm

“Provocative and eloquent of the cutting-edge research that proves the intimate connection between mind and body… Sets the stage for a paradigm shift for clinicians and researchers in the decades to come.”
—Ruth Lanius, MD, PhD, Professor of Psychiatry University of Western Ontario, coauthor of The Impact of Early Life Trauma on Health and Disease

“The Angel and the Assassin is a must read for everyone interested in the new science of brain health.” 
—Louann Brizendine, MD, author of The Female Brain and The Male Brain

A thrilling story of scientific detective work and medical potential that illuminates the newly understood role of microglia—an elusive type of brain cell that is vitally relevant to our everyday lives.
 
“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 brain cells. 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 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 repair the brain in ways that help alleviate symptoms and hold the promise to one day prevent disease.

A fascinating behind-the-scenes account of this cutting-edge science, The Angel and the Assassin also explores the implications of these game-changing discoveries for helping those who are suffering to find new pathways to healing. Award-winning journalist Donna Jackson Nakazawa illuminates this newly understood science, following practitioners and patients on the front lines of treatments, and witnesses patients finding significant relief from pressing symptoms, and at least one stunning recovery, offering new hope to the tens of millions who suffer from mental, cognitive, and physical health issues.

Hailed as “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.

PRODUCT DETAILS

Hardcover | $28.00
Published by Random House/Ballantine
January 21, 2020
320 Pages | 6.30(w) x 9.40(h) x 1.20(d)
ISBN 9781524799175

Paperback | $17.00
Published by Random House/Ballantine
January 19, 2021
320 Pages | 5.17(w) x 7.95(h) x 0.68(d)
ISBN 9781524799199

The Angel and the Assassin, mentioned by Dr. Christina Bethell as an important coming resource for understanding the biophysical link between trauma and mental health disorders at the July 11 Congressional Committee for Oversight and Reform at the congressional hearing on Identifying, Preventing, and Treating Childhood Trauma.

Prologue: When the Body Attacks the Brain 

My interest in the mystery surrounding the link between physical disease, the immune system, and brain-based disorders began more than a decade ago, when I developed a rare autoimmune disease that left me unable to walk. Over the course of a five-year span, between 2001 and 2006, I spent, all told, a year in bed or in a wheelchair. My doctor, a neuroscientist at Johns Hopkins, was studying my disease, Guillain-Barré syndrome. My case was unusual in that I had been felled and paralyzed not once, but twice by the disease—rare but not entirely unheard of.

My doctor, who knew I was a science journalist, and I talked at length about what was happening repeatedly to my body, and how he hoped to reverse my paralysis. He explained that in my disorder, as in all autoimmune diseases, my immune system’s white blood cells were behaving erratically, like an army gone rogue. Instead of judiciously protecting my body from invading pathogens, my white blood cells were mistakenly attacking and destroying the protective myelin sheaths that coated my body’s nerves, causing the nerve-muscle interconnections that I needed to stand and walk, or simply wriggle my feet, to go dark.

I began to think of these overactive immune cells as being like Pac- Men—those 1980s video game characters—crazily gobbling up and destroying my good nerve cells, eating away at the crucial nerve connections that made my physical body mine—strong, capable, dependable me. Regular intravenous therapies would, my neurologist hoped, reboot my immune system so that my white blood cells would stop overreacting and behave normally. If this approach worked, and we could get my overvigilant immune cells to back off from their attack, my nerves would hopefully start to regenerate on their own. The nerves that had gone dark would light up again, regrowing enough neuromuscular connections that I might even be able to walk once more.

Many months later, it would turn out that my neurologist was right. In the end, my immune system’s overexcited cells did back off. I did get much better. Not all of my nerves regenerated, but enough did so that I could walk again, and the significant gains I made have allowed me to live a good life. The human body can be miraculous that way. 

I had one question for my medical team during that time, however, that they could not answer. After losing the use of my legs, I’d also experienced what seemed to be some distinct and disquieting cognitive changes. For one thing, although I’d always been pretty even-keeled, I found myself facing a black-dog depression. The feeling was at times so oppressive that when I read Harry Potter aloud to my young children, I felt as if I’d been attacked by the “dementors”—those dark, sky-drifting ghouls who introduce a cloud of despair that steals a human being’s happy thoughts and replaces them with bad ones. It almost seemed, I told my primary care physician, whom I was also seeing at the time, “like someone has inhabited my brain.” 

I’d also always had a stellar memory and could recall conversations that had taken place weeks, months, even years earlier, word for word. Now, though, I was having to write simple things down, such as what time the physical therapist was coming the next day. No big deal, I thought. That’s new for me, but it happens to lots of people. 

But there were other, more worrisome “glitches.” It was, for instance, taking me a disturbingly long time to recall the names of people I’d lived with and loved all my life. At Thanksgiving dinner in 2005—when I’d graduated from being bedridden to getting around, albeit in a limited fashion, with a walker or cane—it became a source of good-natured amusement for my extended family to watch me struggle to come up with a person’s name. Everyone smiled patiently as I called out a string of names across our long table, one after the other, until I landed on the right one: “Sam! Christian! Zen! Don! Jay! Cody!”—the dog’s name— “Chip! Could you please pass the salt?” 

Even that could be seen, I told myself, as almost humorous; at least my brain was able to distinguish between male and female names. But some things weren’t at all funny. My six-year-old daughter would ask for help with simple first-grade math and I found my brain stuttering just to add seven and eight. Or I’d reach down to tie her shoes, something I’d done for years, and find myself staring dumbly at the laces, struggling to re- member how, exactly, it was done. I can still recall cutting up slices of watermelon, putting them in a bowl, and staring down, thinking, What is this again? I knew, but I could not remember the word. I’d cover my lapse by bringing the bowl to the table and waiting for my children to call out, “Yay! Watermelon!” And I’d think, Yes, watermelon, of course it is. 

My rife anxiety was less surprising, given that I’d been plunged, practically overnight, into almost complete physical paralysis and hospitalized for several weeks at a time, more than once. In the process, as my body’s nerves had demyelinated, I’d endured excruciating muscle spasms, and undergone repeated spinal tap and electrical conduction tests in which technicians shocked nerves in my arms and legs to see which ones were not responding. For a time, I’d lost use of the muscles needed to swallow solids. In the hospital, I’d blacked out after an allergic reaction to an IV therapy and come back to consciousness to find a team of ashen-faced doctors hovering over me with a crash cart, and a nurse uttering prayers under her breath. And then there were the endless weeks I’d spent in physical rehabilitation centers, learning to balance myself and push a walker across a room on numb legs that were nevertheless riddled with shooting pains. 

But this omnipresent anxiety felt like a separate disease in and of itself. My memory, clarity of mind, word recall were different—my brain did not feel like my own.

I sometimes commiserated on the phone with a friend of mine, Lila, who had Crohn’s disease and was having similar cognitive concerns. She told me that one day when she’d dropped off her older son at kindergarten, she’d left her two-year-old son (he’d clambered down out of her arms to play at the sand table while she chatted with the teacher) in the class- room too, by mistake. The teacher had followed her out of the class, with the toddler shrieking in her arms. “I forgot my own son!” Lila said, sobbing. Her doctor had sent her to a psychiatrist, who was prescribing anti- depressants for anxiety and obsessive-compulsive disorder and Ritalin for ADD. But, she wept, “I never needed Zoloft or Ritalin before I had Crohn’s.” 

I empathized with Lila; her concerns mirrored my own. The next time I saw my primary care physician, I confided to her, “It’s like a part of my brain has gone dark too, along with my legs and feet.” It reminded me of people I’d known who’d had a mini stroke. “What’s going on with that?” I asked, hoping to learn more about my own situation. 

I had not had a mini stroke, my internist assured me. She reminded me that my life had been much changed, and what had happened to me had been traumatic. It made sense that my mental state would be deeply affected. My neurologist, meanwhile, encouraged me, cheered me on in my recovery, and reassured me that as time went by I would continue to heal. 

And so I did. Still, a number of my cognitive symptoms lingered. And I could not shake the feeling that just as my body had been altered, something physical had also shifted in my brain. 

I began to wonder whether any immunologists, who studied the immune system’s effect on all the other systems and organs of the body, suspected there might be biological links between physical immune dysfunction and brain-related or psychiatric illness. I began to dig a little deeper. 

During this same time, between 2007 and 2010, I was also enormously busy writing books, lecturing, managing my illness, and raising a young family. But I kept doing sideline research on the topic. And it turned out that a handful of researchers in labs around the world were setting forth to examine this precise link. I collected every peer-reviewed study that documented patients whose immune systems were overactive— thus causing inflammation and disease in their body—who also reported considerable cognitive and mood issues. 

In 2008, research revealed that patients with MS also experienced changes in their ability to remember things and were several times more likely to suffer from depression and bipolar disorder than individuals without MS. 

In 2010, an analysis of seventeen different studies showed that having lupus, which often manifests in systemic inflammation in the organs of the body, was associated with a much greater likelihood of suffering from depression, and even psychosis. Shockingly, as many as 56 percent of patients with lupus reported cognitive or psychiatric symptoms, including trouble concentrating, mood disorders, depression, generalized anxiety, and learning issues. Having lupus is also associated with early dementia. 

And, that same year, researchers found, after looking at thirty years of health data on three million people, that individuals who’d recently been hospitalized with bacterial infections were 62 percent more likely to develop depression, bipolar disorder, and memory issues. 

Several case studies in the scientific literature showed a link between disorders in the bone marrow—where most of our body’s immune cells are “born”—and schizophrenia. In one case study, a patient who received a bone marrow transplant from his brother, who suffered from schizophrenia, also developed schizophrenia just a few weeks after receiving the bone marrow. In another case study, a young man with schizophrenia and acute myeloid leukemia received a bone marrow transplant from a healthy donor, and both his cancer and his schizophrenia were cured. 

Yet, as compelling as all this research was, at the time that many of these studies were coming to light, it just did not make any scientific sense that being sick in the body could be connected to, much less cause, physical sickness in the brain. In 2009, the majority of the scientific community believed (as one research review put it) that it was “an undisputed anatomical fact” that the brain was the only major organ lacking a direct connection to the body’s immune system.

Let’s take a minute and step back to remember high school biology basics about how your immune system functions. Your white blood cells— the army of the immune system—constantly circulate in your body, scanning for invaders, germs, pathogens, and environmental toxins you can’t see or smell. In the time it will take you to read just this sentence, your immune system will respond to thousands of unseen threats to your well-being. The germ cloud from the person sitting next to you on the bus who just sneezed. The minute bacteria in the dirt still clinging to the organic salad you had for lunch. The fungus that’s growing in your office building’s HVAC system. The chemicals coming off the new plastic bins you bought to file away this year’s tax receipts. Your white blood cells are there to snuff out an endless parade of invaders, 24-7. 

If you cut your thumb while slicing onions, your immune system’s white blood cells rush in like a SWAT team to battle any infiltrating bacteria while also mending damaged tissue. Your thumb swells up and becomes inflamed—red, hot, swollen, and painful—while your white blood cells congregate to do the necessary repair work. While red, hot, swollen, and painful might seem problematic, this is actually your immune system doing its job, and doing it well. 

But inflammation occurs in ways that can be harmful too. If your body happens to be overtaxed by too many environmental triggers, your army of white blood cells can become overwhelmed and go into over- drive, mistakenly attacking your own tissues, joints, organs, and nerves, leading to autoimmune diseases such as rheumatoid arthritis, lupus, MS, and type 1 diabetes.

Inflammation and autoimmune disease can both arise in virtually any organ or system in the body. White blood cells have to get it just right. If they don’t battle hard enough, infection and pathogens can spread and shut down organs, and you can die of sepsis. If white blood cells overdo it, they may protect you from outside invaders, but in the process mistakenly launch an inflammatory hyperattack on your body too, giving you a new illness you didn’t previously have. (In my case, when I fell ill, I’d originally had stomach virus. My white blood cells knocked out the infection—but went too far and knocked out the myelin sheaths around my nerves too, which resulted in Guillain-Barré syndrome.) 

There is only one organ in the human body that scientists have categorically believed for over a century was not affected by the body’s immune system. 

That organ is your brain. 

And, it follows, if your immune system can’t reach—and doesn’t rule—your brain, then your brain cannot be touched by inflammation or become inflamed. 

When my internist and I talked about the cognitive changes that occurred during flare-ups of my physical disease, we assumed these symptoms had to be purely emotional in nature because for decades, textbooks had declared that when a disease was attacking the human body, the brain was off limits. The prevailing idea in neuroscience, long taught in medical schools, was that the brain was “immune-privileged.” Scientists unilaterally believed that, for better or for worse, the immune system had access to every single organ in your body except your brain. Inflammation in the brain could occur only if there was an external event—head trauma, or an infection known to directly target brain tissue, such as meningitis. Other than that, the brain simply could not generate inflammation. 

This theory made sense for anatomical reasons. After all, if your inflamed thumb swells up—even to twice its normal size—your skin can expand (albeit painfully) to accommodate the internal swelling. But if your brain expands, it has nowhere to go—it’s trapped inside your skull. If too much pressure builds up, the brain—and you—can’t survive. In extreme instances, when there is a major head trauma such as in a car crash, brain tissue can swell—and pressure has to be relieved by surgeons drilling into the skull. So early anatomists had very good reason for assuming the brain was simply not an immune organ.*

But by 2011, an increasing number of researchers were starting to doubt that dogma. Neuroscientists and immunologists were beginning to wonder: Could the brain be affected by inflammatory processes—and if so, how? 

But these questions had no answers. 

Occasionally, I’d mention what I called my “Brain Flame project” to my literary agent. She’d play devil’s advocate, asking, “But if we don’t know how or why the brain could be affected by the body’s physical immune system, how can you say that having an overactive immune system can result in brain-based illness?” 

To be honest, at that time—around 2011 and 2012, prior to the groundbreaking discoveries I’ll detail in the following pages—I could not prove that the brain was affected by disorders of the body. No one understood the exact way in which immune dysfunction in the body could lead to brain-related psychiatric or neurodegenerative disorders, or cognitive decline. The brain was immune-privileged, and that was that. 

And yet, even as my agent and I had that conversation, the scientific community was on the verge of exploding with surprising answers to the questions that had haunted me for more than five years. Newly under- stood scientific links between physical immune health and brain health were emerging at a rapid pace. 

And all of these discoveries revolved around one type of tiny cell that had, for over a century, been largely overlooked in human health. These deceptively minuscule cells, called microglia, had never been seen as significant in determining mental and cognitive health. Then, in 2012, groundbreaking research showed that, contrary to scientific dogma, these microglial cells held enormous power to protect, repair, and repopulate the brain’s billions of neurons and trillions of synapses, or to cripple and destroy them, leaving wildfire-like devastation in their wake.* Unbeknownst to researchers, microglial cells had long been functioning as the white blood cells of the brain, governing the brain’s health. 

In fact, the five-year span between 2012 and 2017 was a watershed time for neuroscience and immunology, during which the discovery of microglia’s true role in brain health would cause the two fields to be- come one. 

During these same years, scientists also unveiled that these microglia cells in the brain were chatting with the body’s immune cells in direct and indirect ways: If there was inflammation in the body, there would almost inevitably be immune changes within the brain. Moreover, these immune changes in the brain could manifest themselves as cognitive or neuropsychiatric disorders. 

These immune changes could affect the brain’s synapses and neural connections even when there were no signs of physical illness in the body itself. 

And this meant that we could begin to understand the interior health of the brain in ways that had been unimaginable just a few years earlier. The discovery of microglia’s ability to both build and break down the brain provided researchers with an entirely new organizing principle for deciphering brain health and brain illnesses. 

Still, it was clear that even as this research rocked the scientific world, patients were not learning about what scientists now knew, or why this information was so vital to their well-being. 

As a science journalist, I had often seen that it took many years for research to trickle down to the patients who needed answers most. My goal as a writer was simple: report on findings that could ease suffering, in order to close the gap between what science knew and what patients needed to know in order to live their best, healthiest lives. 

And so I set out to do a journalistic investigation, delving into, analyzing, synthesizing, and connecting the dots between the stunning new stories of research emerging on microglia and their role in helping to cause, but also to reverse, brain-based illness. This book tells the story of the birth, exploration, and promise of one of the most paradigm-shifting and powerful stories in the history of medicine—the story of these tiny microglial cells in brain health. In the pages that follow, we’ll see how these cells hold the potential to trans- form human health by helping us to repair the brain in ways that we have previously only dreamed of. I’ll take you on a journey of discovery, detailing the most exciting promise for healing that I’ve ever reported on in my thirty-some-year career as a science journalist. 

I believe that you will come to see, as I have, how and why this ground- breaking revelation about microglia has forever overturned many of the longstanding and powerful assumptions we have made about the mind- body-brain connection—including why it tells us, categorically, that the brain is indeed an immune organ, ruled by these powerful, enigmatic immune cells. Along the way, we’ll follow the progress of a few patients whose lives have been transformed by our new understanding that this cell serves as both the angel and the assassin of the mind. 

Perhaps most important, we’ll learn about cutting-edge new approaches that help reboot and redirect the activity of microglia so that these little immune cells stop their attack, thus allowing the brain’s neurons and synapses to regrow and heal. 

We’ll peer too inside top research labs across the country and see how the work of a small band of fearless and dedicated neurobiologists, who discovered the extraordinary power of microglia, have changed the future of human health forever. 

Including, quite possibly, yours. 

* This longstanding belief that the brain was immune-privileged also had to do with scientists’ understanding of the blood-brain barrier, a dense, complex constellation of cells that congregate around the blood vessels that lead to the brain. These vessels are so tightly packed together that they block particles from the bloodstream and the body, including immune cells, from reaching the brain. The inviolate nature of the blood- brain barrier has long been seen as proof that the brain is off limits to the body’s immune system—and therefore immune-privileged. 

* Synapses are the small gaps between neurons that allow electrical and chemical signals to pass from one neuron to the next.

Copyright © Donna Jackson. All rights reserved.

People often ask me why I wrote my new book, The Angel and the Assassin: The Tiny Brain Cell That Changed the Course of Medicine. Here’s why:

Over the past several years, a series of revelations about a long-overlooked brain cell, called microglia, have changed our understanding of mental illness and human suffering, including how brain disorders develop, and how we might better prevent and treat them.

For most of the past century, scientists believed the workings of the mind were separate from the body – and that the brain was our only organ that was not ruled by our body’s immune system. But new findings about the true role that microglia play in orchestrating brain health have overturned this centuries-old assumption.

Microglia, long assumed to be boring cells that simply carted away dead cells, were recently found to be powerful, swift-moving immune cells that constantly monitor the brain. And just as detecting something off kilter – emotional stressors, infections, toxins – can trigger our body’s immune system to rev into overdrive, sparking inflammation and disease, these same stressors can trigger microglia to over-prune the brain’s synapses, setting the stage for depression, anxiety, mood disorders, and Alzheimer’s. Other recent discoveries show that microglia are able to “communicate” with our body’s immune system via the vagus nerve, as well as through a network of immune vessels that travel up from the body to the brain – vessels we never knew existed before 2016. All of these developments give new meaning to the mind-body connection.

This extraordinary research wasn’t being covered, or when it was, no one was standing on the mountaintop, connecting the dots between emerging research and synthesizing what this meant for our understanding of the brain, brain-related disorders, patient well-being, and the extraordinary hope that this entirely new understanding of the brain provides for the future of medicine and psychiatry.

So I set out to follow the tale of this little cell, microglia, and bring it to life, and connect the dots between different researchers’ work and different patients’ experiences to tell  one of the most paradigm-shifting and powerful stories in the history of medicine—the tale of these tiny, powerful, enigmatic microglial cells in determining brain health, and their potential to transform human health by helping us to repair the brain in ways that we have previously only dreamed of.

As I am out on book tour, from Harvard to Indy bookstores up and down the East Coast, talking about The Angel and the Assassin, a lot of folks want to know, how did all of science miss the true role of this tiny cell—microglia, which links our physical and mental health—for so long?

Since the Enlightenment, scientists, clinicians, and patients have operated under the age-old assumption that the workings of the brain are physically divorced from mechanisms of the body. The philosopher Descartes first put forth this concept, known as mind-body dualism, in the seventeenth century, and the medical dogma that brain and body function as separate church-and-state entities has permeated the way in which we’ve viewed mental health disorders ever since.

Throughout the twentieth century, scientists categorically ruled out the idea that there might be biophysical pathways between the body’s immune system and the development of psychiatric or cognitive disorders, largely because of what’s known as the blood-brain barrier, a dense constellation of cells that surround the blood vessels that lead to the brain. These vessels are so tightly packed, they block particles from the bloodstream and the peripheral body, including immune cells, from reaching the brain. The inviolate nature of the blood-brain barrier has long been accepted as proof that the brain is off-limits to the body’s immune system, or what we call “immune-privileged.”

So, really, it was unthinkable that these tiny microglial brain cells could be functioning as the white blood cells of the brain. From the time they were first noted by neuroscientists in the 1920s, they didn’t generate much interest among the scientific community. But all that changed when Beth Stevens’ lab at Harvard revealed in 2012 (a millisecond ago in terms of scientific literature!) that microglia are capable of terrifying Jekyll-and-Hyde behavior. We now know that, when triggered (and anything that activates the immune system in the body can activate microglia) these tiny cells can morph into big Pac-Men like destroyers and take out healthy brain synapses, and stir up inflammation, in the same way that immune cells in the body can attack tissue or organs.

We also know that a loss of synapses is associated in brain scans with anxiety, depression, bipolar, schizophrenia, and Alzheimer’s Disease – often years before symptoms set in.

This gives us an entirely new understanding of mental health and cognitive disorders and offers a new picture of hope and possibility for patients.

One question I’m getting a lot as I do news interviews, podcasts, and live on-stage events talking about The Angel and the Assassin is this: how is this science a game-changer in terms of our understanding of the brain and brain-related disorders?

Our new understanding of the power of microglia sheds new light on hundreds of different disorders and diseases that have long remained the black box of psychiatry and neurology, and provide researchers with an entirely new organizing principle for approaching brain health and treating brain illnesses. I call this the Microglial Universal Theory of Disease.

Many of the big, bad, and difficult to treat brain-related diseases of our century, most of which are on the rise, share one common denominator: triggered microglia are wreaking havoc with the brain. And we missed it.

This discovery stands to rewrite psychiatric and medical texts as we know them. For decades, scientists thought that mental illness was all about chemical imbalances in the brain, but now, we’re beginning to understand that disorders of the mind are first and foremost immune disorders that reflect alterations in the brain’s immune health and in the health of the brain’s synaptic connections. Already, researchers and clinicians are developing treatments that address brain illnesses at the source, by rebooting microglia so that they return to their good role – protecting and healing the brain. This science has given us a promising new window into better understanding an array of intractable disorders of the mind, and the field in moving fast – this is science in motion. Today, in both clinical research labs and therapeutic settings, scientists are uncovering extraordinary approaches to help calm overreactive microglia so that they behave as nature intended: as the angels of the brain, rather than as blind assassins.

One of the most important questions I get from people while I’m on book tour for The Angel and the Assassin (whether I’m at Harvard or a local independent bookstore) is also the most moving for me: how does this groundbreaking science offer new hope for patients who are suffering right now? Often, people ask me this with tears in their eyes. Here’s what I try to convey to them:

Microglia act like a “light switch” in the brain. Their behavior for good or ill can help prevent, or lead to, or worsen a wide range of issues, including: depression, anxiety, OCD, bipolar disorder, cognitive decline, glaucoma, Parkinson’s, autism, schizophrenia, post-concussion syndrome, neurological autoimmune disease, and Alzheimer’s.

This research tells us that the brain is even more plastic than we previously imagined, and constantly changing. Our brain’s immune system is physically connected to, and engaged in, a constant dialogue with the body’s immune system; it’s all one system, connected by a brain-immune super highway. The long-held line in the sand between mental and physical health simply does not exist. Our brain, like our body, is always engaged in a complicated, interactive dance with our environment. The promise and the peril of this science tells us that our emotional and physical capacities cannot be separated: the emotional gradually becomes physical and the physical gradually becomes emotional.

With this new understanding that microglia are the white blood cells of the brain, and that brain-body crosstalk is constant, it makes sense that chronic inflammation in the body is correlated with cognitive decline, depression, mood disorders, and a loss of synaptic connectivity in the brain. Microglia hold enormous power to protect and repair the brain’s trillions of synapses or to cripple them, leaving wildfire-like devastation in their wake.

When microglia are overactivated – by the same triggers that can overtax or confuse our immune system – they start to target and attack healthy, needed, and necessary synapses, eating away at the synapses that give us mental stamina, hope, joy, clarity of mind. Over time, many small changes in neurocircuitry wrought by inflammation-led microglia can cause individuals to feel and behave very differently.

But because these microglia-led inflammatory changes appear differently in the brain from one person to another, we give it 100 different names: ADHD, OCD, anxiety, depression, bipolar, schizophrenia, memory loss.

But there is so much good news here, too: under the right circumstances these cells can be coaxed back into being the brain’s healers and hold promise to one day prevent or halt disease.

This science sheds new light on the link between brain function and immune function, or the mind-body connection, and rewrites our understanding of the origin story for disorders of the mind, ushering in a new era of hope for patients and families. This is really nothing less than a new window into the making and unmaking of the self.

With this past decade of brain research, we are revisiting everything that we thought that we knew about brain and immune health. The Microglial Universal Theory of Disease helps us to recognize that we are all dependent on the health of our brain’s immune system, just as we are all dependent upon the immune health of our bodies.

We’ve long known that we have five established senses—smell, touch, taste, sight, and hearing. Our sense of proprioception, or where our body is in space, is often called our sixth sense. Together, these senses constantly send our brain messages telling us whether we are safe or not. One of the defining roles of the immune system is to detect when there are threats in our environment and inform the brain about them—and our new understanding that the brain is an immune organ, ruled by microglia, tells us that – as Jony Kipnis, a leading glial researcher and professor of neuroscience at the University of Virginia once put it, “this immune response is hardwired into the brain” as well as the body. That, says Kipnis, makes our immune system’s back-and-forth dialogue with our brain our “seventh sense.” Everything that happens to us – in terms of our minute-by-minute exposures to environmental factors including relationships, infections, and chronic stressors – matters more than we might ever have imagined to our brain health and well-being, our mental stamina, our mood state, our sense of hope and joy, our clarity of mind.

It has always been a conundrum for those suffering from mental health disorders to explain the depth of their pain to those who’ve never been afflicted. And the difficulty that the medical community has had in understanding mental suffering from a biological perspective has done little to ease that burden. The Microglial Universal Theory of Disease offers patients a new understanding of their conditions, while simultaneously offering physicians and practitioners a new playbook on how to intervene and help those suffering to reclaim wellbeing. Of course as with all new therapies, we much proceed with an abundance of caution.

This science is giving birth to new treatment options and also lending new credence to a range of already existing interventions that, it turns out, help patients by helping to calm the behavior of overexcited microglia. Transcranial magnetic stimulation, neurofeedback, gamma light flicker therapy, novel concussion protocols, anti-inflammatory medications, ketamine, and fasting diets are just a few of the ways that scientists hope to restore microglia to their good, angelic function: keeping synapses healthy and thus improving the quality of patients’ lives. These treatments work by addressing symptoms at their source: helping to reboot microglia to a healthy state, and bring them into homeostasis, to keep neuroinflammation in check and nurture robust synaptic health.

A lot of people are asking me how I hope my new book, The Angel and the Assassin, will make a difference in the world.  

Over the past thirty years, we’ve seen progress in almost every area of medicine—heart disease, cancer, etc.—but we’ve made very little headway, comparatively, in psychiatry. In fact, rates of treatment-resistant mental health disorders are rising. My hope in writing The Angel and the Assassin is to catalyze the emerging science around microglia and our understanding that the brain is an immune organ, involved in an intricate and intimate dance with our environment, and to underscore that just as our body’s immune system is affected by so many factors in our environment, so is our brain health. I would love to see the book help to forward this conversation in the fields of medicine and psychiatry, so that the fields can evolve with this research, and more patients can benefit from new treatment options to find the healing they long for and deserve.

Time is obviously of the essence: While survival and recovery rates for serious medical conditions, including heart disease and cancer, have improved greatly in the past fifty years, recovery rates for mental illness have barely budged. More than a third of the 300 million people around the world with major depressive disorder don’t respond to any antidepressant treatments, and some who do respond find that medications stop working for them over time.

I’d like to travel forward twenty-ish years, to a time when patients with mental health and brain-related disorders can enjoy the promise that I lay forth The Angel and The Assassin. I’d like to see patients benefiting—in their local psychiatrist or physician’s office—from this revelatory science in their daily lives. For instance, we will soon have early, non-invasive blood tests that allow doctors to see if early synapse loss is occurring, by measuring factors released by microglia when they are over-pruning synapses. These tests can be done in the early teens years, before mood disorders develop in adolescence or young adulthood and derail a life, a future, a family. Imagine if a teenager who is facing trauma and who has a family history of a mood disorder were given a simple blood test at the age of eleven, and a pediatrician were to say, “Hey, there are signs of some early microglial over-activation and synapse loss, let’s start some neurofeedback and other therapies prophylactically.” A similar scenario applies to Alzheimer’s Disease. Over time, a physician or psychiatrist will be able to scan the brain and do blood tests to see what emerging microglia-based treatments—gamma light flicker therapy, TMS, anti-inflammatories, special diets, neurofeedback, vagal stimulation—are working or not working in almost real time. Of course we have to proceed carefully and first do no harm. But a sea change is coming in psychiatry. I want to witness this new era of medicine, and see lives restored by the promise of this science.

Some folks are asking me whether I have any personal connection to the science in my new book, The Angel and the Assassin. The answer is yes.

I myself face a neurological autoimmune disease, and there are several women in my extended family who face genetic mental health disorders, women I love and admire deeply. Many of my readers, over the years, have reached out to tell me that they suffer from mental health or autoimmune concerns, or both. In my writing, I am always trying to close the gap between the latest neuroscience emerging from the world’s most innovative research labs and what patients need to know in order to find healing and relief. I often thought of all of these women as I wrote this book.

But more broadly, I often approach my writing from a female perspective. We know that statistically, women are struck by most of these illnesses—depression, bipolar, Alzheimer’s, autoimmune disease—at three times the rate of men. (This has to do with complex aspects of the female immune response. In one chapter of The Angel and the Assassin, I write about how the female immune system functions slightly differently in response to our environment, leading to higher rates of depression in girls.) So, I also see this book from a feminist perspective. I’m on a mission to sound a clarion call to change how we view and approach mental health disorders as a society and in medicine, and I’m conscious that many of those who are suffering are women.

Sometimes I get a curveball question while I’m on book tour for The Angel and the Assassin – and this is one of my favorites: Why did I become a writer? The question has caused me to think about that…

I suppose I ended up being a science writer for two reasons. The first is that it’s in my DNA—my grandfather was an early founder of the National Institutes of Medicine (NIH) and an award-winning researcher. We had many scientists on my mother’s side of the family. My father’s side of the family were in the newspaper business and ran a small chain of newspapers in Maryland. I grew up running around the editorial offices of my dad’s newspaper in Annapolis, the Capital Gazette. A bit of both the science-gene and the writing-gene landed in my DNA.

But the other reason, I suspect, is that many members of my family have suffered from rare autoimmune disorders, several of them genetic. My father died when I was twelve from a combination of genetic autoimmune disorders and a physician’s error on an operating table, and later, I was diagnosed with a similar set of disorders. I know what it means to be a revolving-door patient, with your heart in your mouth, hoping for a seemingly impossible recovery. My children have also faced some of these issues. Perhaps on some unconscious level, the child within me wishes I could have helped my father avoid an unnecessary death, and that, I think, has also led me to want to help have the science they need to help achieve the best possible outcome.

I’m getting this question a lot from younger writers – what advice would I give to those starting out, as I look back over a 30 year career as a science journalist (six books, hundreds of magazines and news articles…)

There’s an old saying, “Writing is easy, all you have to do is lean over the typewriter and wait for drops of blood to form on your forehead.” Sometimes it feels like that; at other times, ideas pour forth and it can feel as if you can’t get your fingers to move fast enough to type all the thoughts in your mind (such days are as magical as they are rare). Either way, you will throw away or re-write most of what you write many times before it appears in print. Just keep going. Focus on bringing meaning to areas of our shared human experience that are hard to give words to. By so doing, perhaps you heal something in yourself, too. But more than anything, it’s all about putting your butt in the chair, day after day. Writing long-form means building on each day’s work; it’s not unlike building a house. You achieve your goal little by little, until your vision for what you set out to build slowly, painstakingly, emerges in front of you. Keep reading everything that interests you. After writing six books, I’ve learned that writing is less about raw talent and more about the desire to say the unsaid, and approaching the process with curiosity, discipline, and endurance. In terms of how one’s writing is received your words will be both criticized and appreciated. (Social media takes this dichotomy to a whole new level.) Some articles will get millions of “hits” and others will go unnoticed. It’s not about how things are received; it’s about setting out to say what you have to say with an open-mindedness toward the ideas of others, a realistic sense of the hard work that is entailed, while staying rooted in intellectual humility, and motivated by our shared humanity.

Hardcover
January 21, 2020 | ISBN 9781524799175 | $28.00
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Paperback
January 19, 2021 | ISBN 9780593233078 | $17.00
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Ebook
January 21, 2020 | 9781524799182
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Audio
9780593148235 | ISBN 9780593148235
10.1 hours
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