Human psychology and physiology are too complex for us to trust that the medical world is infallible.
—Ellen J. Langer, Counterclockwise
Normal science, the activity in which most scientists inevitably spend almost all their time, is predicated on the assumption that the scientific community knows what the world is like.
—Thomas S. Kuhn, The Structure of Scientific Revolutions
A fascinating article lands on my desk while I’m trying to understand what sorts of wedges might be able to interrupt the feedback loops of an out-of-control immune system. For decades, best-selling pop books have made big promises about how the power of positive thinking can reverse disease and make a person healthier. But the paper in my hands offers another perspective, told through the eyes of a patient known only as “Mr. A.”
It’s not clear what was going through Mr. A’s mind when he took all 29 capsules of an experimental antidepressant—other than, of course, the argument with his girlfriend. Mr. A always had trouble making decisions, but tonight he gave in to impulse. Perhaps he thought the pills would course through his bloodstream and turn off one organ system after another until he died. Perhaps he figured that if one antidepressant wasn’t enough to cure his blues, maybe a whole bottle might do the trick. Either way, a few hours later he showed up in the emergency room of a Virginia hospital. He stood at the front desk just long enough to stammer the words “Help me, I took all my pills” before collapsing on the floor.
Nurses and attendants rushed to his aid, and their notes from that evening recorded that he was drowsy and lethargic. They found an empty bottle of pills in his pocket, but the sticker didn’t reveal any medication that they’d heard of before. It was just a string of numbers and codes indicating that it had come from a nearby clinical testing facility. All they knew for sure was that Mr. A was in trouble. Sweat beaded on his brow, his heart rate spiked, and his blood pressure plummeted to 80/40. Nurses threaded a saline solution into his trembling arm as the office staff scrambled to get ahold of whoever ran the clinical trial to figure out what chemicals might be causing the reaction. When they finally made contact with the researchers running the study, the doctors on the other end of the line were puzzled. It’s true that Mr. A was part of their experiment, but he was part of the control group. The bottle contained 29 sugar capsules.
Placebos.
When the staff at the ER told Mr. A that he was taking inert chemicals, his demeanor changed almost immediately. Within 15 minutes he was fully alert, blood pressure back to normal, and probably slightly embarrassed by the whole affair. Rather than a life-threatening condition brought on by a chemical reaction, Mr. A’s story showed up in the journal of General Hospital Psychiatry as a dramatic instance of the nocebo effect—serious symptoms caused by belief alone. The nocebo effect is the evil twin of the placebo effect—or, what happens when simply believing a medicine will work ends up making someone better. A skeptic might say that Mr. A’s blood pressure, heart rate and fainting were all in his head, but that doesn’t explain the very real symptoms that hospital staff recorded when he entered the hospital.
The medical community often pillories the idea that the mind can overcome biology. But the Wedge has made me think of the division between mind and body in different ways. If we are the environment at the same time we are an environment, then what we think of as health has to take into account those different layers of perspective at the same time.
Our minds don’t have direct control over every autonomic process. We can’t just think the word “adrenaline” and trigger the hormonal release we want. But we can put ourselves in situations that trigger that same predictable hormonal release. When we choose stressors, we choose our biological reactions. The same goes for the immune system: We can’t think it into action, but we can certainly change the environment that the immune system responds and reacts to. I believe that this explains what happened to Mr. A—and that has implications for the entire medical system.
The nocebo and placebo effects are the most mysterious phenomena in medicine. Their very existence calls into question the underlying mechanics of how the body tackles illnesses, the function of the immune system and the power of the mind to control biological processes. Every clinical trial approved by the U.S. Food and Drug Administration has to control for the healing power of the placebo effect, and yet medical research almost never directly studies it. With just a few exceptions, pharmaceutical companies treat the body’s in-built healing mechanisms as an obstacle to overcome rather than a system to bolster.8 The remedies of the past half-century tend to try to circumvent the immune system with targeted chemical therapies that attack pathogens or intervene directly in biological processes that have gone haywire.
The Western approach has certainly generated a boon in life-saving therapies and radically improved human health and life expectancy. That said, when an “incurable disease” spontaneously goes into remission, most medical practitioners chalk it up to chance. However, it’s likely that the healing power of the body isn’t just dumb luck, but at least in part a physiological response to the environments that we inhabit, our sensory pathways and the mindset that we give to medical treatment. In other words: The placebo effect might actually be the Wedge in action.
…
I got my first canker sore back when I was a toddler—so long ago that I only have my mother’s memories of it. She tells me that it made my whole tongue swell up and that I wouldn’t stop crying. For those fortunate enough to never have had one, let me explain. A canker is a white raised disc of an ulcer on the inside of your mouth. Cankers start after one of a hundred strains of herpes that humans have toted with them since prehistory enters the body. But the virus doesn’t cause the sore; the immune system does. The immune system sniffs out something that reminds it of the virus and then wages a scorched-earth campaign to get rid of it. The sores are painful, horrible, and pretty much ruin everything for a week.
For roughly thirty years, I’d get one sore a month, and it would take a week to go away. I tried everything to get rid of them—different toothpastes, supplements, ice, salt (really bad idea), steroids, goops, gels and herbal coverings. Nothing worked. Some things made them worse. I started to consider myself a canker survivor. I figured that when I die, I’d have a canker in my mouth.
And then I started practicing the Wim Hof Method and learned how to manipulate my own reactions to the environment. I practiced the breathing regularly and felt myself getting stronger. It wasn’t until about five months after coming home from Poland for the first time that I realized I wasn’t getting cankers anymore. Sometimes I would feel them starting—a rough spot on the inside of my mouth that I learned to associate with impending pain—but redoubling my efforts with the Wim Hof breathing makes them go away before they progress. While this is by far the least interesting immune-system remission story in the annals of medicine, I’ve only had one canker in the last decade.
Now, here’s the question: Was the Wim Hof Method medicine, the placebo effect or something else?
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Until the invention of antibiotics in 1928, Western medicine couldn’t deliver much better results than indigenous medicine anywhere else in the world. In many cases, going to a shaman or witch doctor offered just about the same likelihood of recovery as seeing a Western doctor. As for hospital stays, the general lack of hygiene often meant that the risk was actually higher.
Antibiotics were miracles because they reliably took care of the root cause of infections—the bacterial growth in the body. Later, anesthesia helped our surgical prowess to achieve a similar level of success. Now we are masters at repairing physical injuries. Break a leg or show up in the emergency room with a gunshot wound, and you’re pretty likely to survive. Yet for all those achievements, Western medicine is pretty darn bad at managing chronic illness.
The majority of drugs that appear on the market today—to manage autoimmune illnesses, psychiatric conditions, hormonal deficiencies and even cancer—have rather dubious records. Most drugs tested for chronic conditions barely perform two or three percentile points better than the healing power of the mind. While placebo response rates vary drastically, it’s common to find drugs where placebos account for between 20% and 85% of the healing power of any given medicine. This is particularly true for drugs targeting pain, anxiety, depression, coughs, erectile dysfunction, irritable bowel syndrome, Parkinson’s and epilepsy. While that 2% or 3% is statistically significant across millions of patients, more often than not, when we think a pill is curing our ills, we’re actually healing ourselves. This open secret has huge financial implications for the pharmaceutical business. Clinical trials for a successful drug can cost billions of dollars to run, but no patient is going to want to pay for a therapy that their body already provides naturally. And since it’s impossible to separate economics from modern medicine, it’s also important to note that Western treatment for chronic illnesses often requires that patients continue to take expensive medicine their whole lives. In these cases, the disease is much more profitable than a cure.
One way to think about the placebo effect is the basic principle of statistics known as regression to the mean, where any sort of complex system will return to its baseline over time. To illustrate this concept, think about the weather in Los Angeles, a city typically bathed in sunshine and pleasant marine breezes. On any given day, you can bet that L.A. will be pretty nice. Sometimes the heat can spike to insufferable peaks, and other times it can even rain. But wait a few days, and L.A. will likely regress to the mean and be nice again.
Your body is a little like L.A. Illness tends to go away over time whether there’s a medical intervention or not. Think back to the last time you had a cold. Your eyes might have itched. Your bones ached, and you might not have been able to stop from sneezing.
When you reached for standard-issue cold medicine, the directions on the package probably stated that once you started on the medicine, your condition would go away in a few days. But guess what? It was going to do that anyway. Cold medicine will help you feel better in the short-term—stopping the mucus, helping you breathe—but even without it, your body should eventually fight off the viral infection and leave you right as rain. Like L.A., you’ll regress to the mean—in this case, back to being healthy.
Now, it’s true, we feel better when the innate immune system is dormant, but it’s important to realize that “feeling sick” often isn’t the sensation of a pathogen, but the sensation of our body fighting back. All of those cold symptoms are actually evolutionary in-built actions of the innate immune system to help kill cold viruses. Mucus membranes make it hard for viruses to propagate, while fevers raise the body temperature to a degree that makes it harder for them to survive.
It’s fair to assume that much of what we call the placebo effect is in reality the work of the immune system acting behind the scenes. The body returns to its normal homeostatic state because the immune system rooted out the cause of the illness all on its own. Evolution has gifted humans (and vertebrates in general) two immune systems: the innate immune system and the adaptive one. The innate immune system is the front line of defense and has a standard set of responses—fevers, inflammation, mucus generation, attack cells—to biological threats that are quick and easy to deploy. The innate immune system is a blunt instrument that has a pretty dramatic effect on how you feel. It alters your internal environment to make it hostile to invaders. The adaptive immune system is more selective (this is the Special Forces rather than the regular Army); it identifies the specific threat to the body, learns its weaknesses, then deploys a very targeted response. The adaptive immune system remembers the weaknesses of what attacked you so it can deal with the invader more efficiently in the future. In contrast to the innate immune system, you almost never feel the adaptive immune system doing its work.
In terms of your cold, the first time you encounter it, your body responds with mucus, fever and achy joints—the innate immune response. Meanwhile, your adaptive immune system starts learning the virus’s weaknesses and storing that information for later use. The next time you meet that same virus, your adaptive immune system responds without you ever even knowing there was a threat.
We like to think that most medicine works like a substitute for the adaptive immune system—that scientists in a laboratory have discovered the root cause of an illness and developed a chemical that can eradicate the pathogen with a surgical strike. While a few classes of medicine do work like that, most of our go-to therapies actually suppress the activities of the innate immune system in order to buy time for the adaptive immune system to learn about the threat, ramp up against the invaders and neutralize the infection.
Our immune system is the best weapon we have to root out the source of most illness. While not perfect, it’s been successful enough to allow our species to survive in a world of things that want to kill us. While I would never discount the great achievements that Western medicine has given overall to human health, if we spent half as much money and time trying to invent a better placebo—or, maybe more accurately, better ways to train our immune system to protect our bodies—we’d likely discover entirely new ways to treat disease. This is, of course, where it’s beneficial to consider the relationship between the environment and human physiology as a wedge to help control and strengthen the immune system itself.
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A few years ago, I took a fellowship at the University of Colorado Boulder that gave me the opportunity to audit any class in the institution. I sat in on courses on astronomy, abnormal psychology, creative writing and an immunology class designed for medical students. Over the course of the semester, two things stuck with me.
First was the discussion of autoimmune diseases—the sorts of conditions where the immune system turns against the body that it’s supposed to protect. Such conditions are some of the hardest for the medical community to treat, and are growing faster in the first world than they are in the third. The professor stood at his lectern and noted that all autoimmune illnesses conform to a similar pattern. They all start with an insult to the body’s sense of homeostasis. That insult could be a virus, bacterial infection, splinter, transplant organ, whole-body hypothermia, fever or allergen that triggers an immune response, and, for reasons we barely understand, that immune response never turns off. The insult is a negative wedge—an environmental intrusion that interrupts our homeostatic feedback loops. Long after the insult is over, various immune cells continue their fight and, instead of going dormant, start attacking the body—apparently confused into thinking that the threat isn’t around anymore. In rheumatoid arthritis, the immune system eats the connective tissue in joints. In Crohn’s disease, it’s the lining of the intestines, while multiple sclerosis consumes the mylar sheath along our nerves. Lupus triggers inflammation throughout the body. The list goes on, but the concept remains the same: The immune system is out of control.
There’s a parallel here to anxiety. Think back to Feinstein’s lab, where he explains anxiety as a feedback loop that interprets every environmental signal as a reason to go into fight or flight. Chronic anxiety redefines what “normal” means, so that everything is a threat. The new normal was called allostasis.
In this way, auto-immune illnesses share a trait with cancer. Cancer is essentially the uncontrolled growth and replication of cells until it overwhelms the host.9 In both cases, the body fails to issue an off-signal to a process that is usually beneficial.
My professor’s interest in immunology probably stemmed in part from his own condition. A victim of alopecia areata, his immune system took issue with the tiny cells in his skin that sprout hair and destroyed them. Without follicles, he has no body hair at all. As the class proceeded through the semester, he delved into the mechanics of the myriad of ways that the body attacks itself. He dissected the role of cellular receptors, hormone releases and transcription factors until the class had a molecular map of the immune system. The details were fascinating—all these cascading effects in the body that kept it attacking itself—but one day when I asked him what caused autoimmune illnesses in the first place, he just stared blankly at the class for a second.
Then he shrugged.
“It’s got to be some sort of environmental factor,” he said. Then he returned to examining the specific role of a chemical that facilitates how two cells locked together and exchanged information.
The response was troubling to me. Almost myopic. Locating the cause of a condition seems at least as important as understanding the chemical process that perpetuates the illness. It’s as if immunology is so focused on looking inward to the body that it forgot that the body lives in an environment. Why not try to treat autoimmune illnesses in the same way that we do anxiety—by interrupting external feedback loops and allowing the body to return to its original baseline? Just because autoimmune illness takes place in the body doesn’t mean that’s where the conditions start. If we can find the right way to interrupt the cycle, then we will have found our wedge. In a perfect world, we might even discover ways to treat some autoimmune illnesses just by manipulating the environment around us and eschew drugs altogether.
My second realization came a few weeks later, when the projector above my professor’s head illuminated the amorphous image of one specific immune cell called a macrophage. The macrophage derives its name from ancient Greek and translates, literally, as “big eater.” It’s a special type of white blood cell that wanders through the bloodstream, seeking out harmful bacteria and then gobbling them up. The professor screened a video of a live macrophage under a microscope. It oozed along the glass slide poking and prodding the other cells in its vicinity. It touched one red blood cell, paused, and then examined a platelet, both to no great effect. Then it came across a tiny bean-shaped bacteria, and something about the blob changed. Once it sensed the foreign intruder, it sprang into action and brought its elastic walls around the bean, absorbing it in a matter of seconds.
To my eyes, it looked like the macrophage was hunting. It sensed the environment around it and then decided what was dinner and what wasn’t. The professor looked up at the giant killer cell above him and noted that macrophages and amoeba look almost identical. He went on to note that the only obvious difference between them from a morphological perspective is that the macrophage comes from our own DNA while amoeba live out in the world on their own.10 This statement stunned me. Why would a part of our body look and act like something that evolved outside of it? When I dug into that question in the secondary literature, it got even weirder; some evolutionary biologists argue that the amoeba and the macrophage share a common ancestor. Several articles from across the research spectrum note that bacteria that interact with amoeba in the wild learn ways to effectively combat macrophages in the human body. Other papers suggest that macrophages came into existence in the first place through ancient gene transfers. Indeed, this isn’t as strange as it sounds: lots of other life forms have participated in building our immune systems. A 2016 paper in Science magazine by computational biologist Edward Chuong showed that ancient viral DNA makes up about 8% of our total DNA, and several genes we inherited from viruses actually regulate our innate immune system. Whatever the mechanism, macrophages and amoeba are eerily similar.
If you hold these two thoughts in your head at the same time—first, that the environment triggers autoimmune illnesses, and second, the physical resemblance between our immune cells and ones in the wild—it’s reasonable to conceive of the immune system not as a component of our bodies, but rather as an independent entity for which our bodies are just environments. That is to say, when attempting to understand the healing power of the placebo effect, it’s important to understand the subjective world of the immune system. If we treat autoimmune conditions as a type of bodily anxiety instead of a broken link in a chemical chain, we might have more success with our treatments—or at least another avenue to explore.
By this point, I’ve written a lot about how humans are part of a great superorganism of life on the planet and that our actions contribute to an immeasurably larger whole of the biosphere. The sum total of all human actions creates larger patterns of which we are only dimly aware. In other words, the whole is greater than the sum of the parts.
The same perspective holds when we look downward into the smallest parts of our physiology. The macrophage has no idea what is happening to the human it’s part of, but it has the ability to sense and interact with its immediate environment. When a bacterium enters into its territory, the macrophage knows how to neutralize the threat. In this way, even though it doesn’t know what’s happening to you as a person, it still interacts with the outside world. When the macrophage neutralizes the bacterium, it fulfills its evolutionary and ecological role.
Throughout our evolution, humans have always been exposed to a certain number of pathogens, and the macrophage always had a certain amount of work to do. Let’s use a metaphor: Think of the macrophage—and, for that matter, the entire diverse assembly of immune cells—as a pack of friendly wolves patrolling the area inside our skin, attacking the things that might hurt us. What happens when those wolves no longer have regular prey? They go stir-crazy. They get bored. And they might turn on themselves. While macrophages pull nutrients from the bloodstream for survival, their entire evolutionary purpose is to hunt and kill invaders. They don’t have secondary jobs. Once they run out of prey, the macrophages (and for that matter, other immune cells) sometimes continue the fight, and the immune system turns on itself.
This is the clutch of what evolutionary biologists call the hygiene hypothesis. According to this hypothesis, the reason autoimmune illnesses are more common in the first world than in the third is because our efforts to clean every surface and eradicate germs from the environment have altered our internal microbial environments. But when we sterilized the places we lived, we never took into account how our own bodies might react. We never considered how the ecology we influence outside of our bodies reflects on what happens inside us. Our immune systems don’t face the constant battle that they evolved to fight and don’t respond to the body’s signals to end their watch.
The immune system isn’t a mindless machine. It has a sort of intelligence all its own. Macrophages and other immune cells don’t just respond to bacterial and viral threats; they also bathe in the wash of chemicals—hormones, neurotransmitters and everything else—that courses through the various channels of our body. Just like a human, they need to monitor their environment to survive. And just like a human brain, the immune system uses a similar set of neurotransmitters to reinforce their behavior.
Take, for example, dopamine. It’s one of the most important neurotransmitters for human cognition, and the foundation of any feelings that we have for joy or reward. When you feel excited and euphoric, dopamine is the reason for the buzz. The bliss that comes with cocaine and gambling comes back to dopamine. So does any sense of accomplishment that you might feel from learning a new skill. Dopamine is such a powerful reinforcer that not only can it change your personality, but high levels of it can actually hijack your behavior.
For example, patients with Parkinson’s almost always have critically low levels of dopamine in their system, which results in their muscles no longer working correctly. In order to counter those deleterious effects, doctors prescribe drug cocktails that ramp up dopamine production to keep their systems working. However, the practice comes with important risks. In 2006, a research team in Scotland discovered that these dopamine-enhanced patients had a radically increased likelihood of developing pathological gambling problems. The emotional and neurological rewards they received when they hit jackpots reinforced addictive tendencies and altered their consciousness.
And it turns out that immune cells also need dopamine.
Generations of immunologists already knew that the immune system could learn to defeat different infections and then store that information as a blueprint to combat future infections. But the addition of neurotransmitters into the picture gives insight into the reward system that motivated immune cells to learn and evolve. In 2017, the journal Nature published groundbreaking research that showed B-cells, the immune cells responsible for producing antibodies, take up, release and respond to most neurotransmitters, including adrenaline, noradrenaline and dopamine. T-cells (specialized killers of the immune system) produce dopamine in part to assist and teach other immune cells to select targets once they’ve learned to kill them. These are all the same neurotransmitters that neuroscientists identify in the brain that underpin human cognition and behavior. You wouldn’t be conscious without them.
So if the immune system uses the same chemical hardware that creates feelings in our brains and influences our behavior in the world, then how much of a stretch is it to say that our immune system is conscious? What if instead of assuming that the immune system is just a machine, we give it a chance to have a semblance of cognition? Obviously the immune system can’t have the sort of complex emotions or thoughts that you or I experience, but even a shard of that subjectivity is powerful.
It doesn’t stop with dopamine. Immune cells also take up and respond to adrenaline—the signpost of the sympathetic nervous system and the very hormone that gets a person ready to fight or run from an external threat. When we bathe our insides with adrenaline, we also bathe the immune system, making a pretty clear chemical connection between the mammalian stress response and how some immune systems go haywire in the modern world. Threats in the ancient past almost always required some sort of physical exertion—fighting or fleeing—that provided a physical outlet for the energy boost. But when we release copious amounts of adrenaline into our bodies today and just sit and try to think our way out of a problem, that extra energy boost has nowhere to go. Stress needs a physical counterpart.
Together, this all at least partially explains how people who learn to control their stress response in ice water and hold their breath for long periods of time can show near-miraculous reversion of Crohn’s disease, accelerated healing, remission of rheumatoid arthritis and management of Parkinson’s symptoms. It also explains my own experience with the sudden disappearance of canker sores. These environmental triggers can pacify and redirect the responses of the sympathetic nervous system. And so by altering the environment, practitioners learned a back door to directly communicating with the immune system. In other words, if the immune system is a pack of wolves attacking the body’s invaders, and maybe even motivated by the sympathetic nervous system, then managing physical stress and doing breathwork gives those wolves chew toys.
That’s the placebo effect in action. There’s no medical intervention that a doctor might recognize, but the therapies work by utilizing the body’s own in-built healing mechanisms. Another way to look at it is that the placebo effect is what happens when the different levels of our Russian-doll consciousness synchronize together, so that the distinctions between individual and environment all react appropriately to their environmental position. In this way, the placebo effect isn’t so much about an individual body finding its innate healing power as it is about experiencing flow between different layers.
To be clear, this interpretation of the immune system is not going to endear me to the medical mainstream. The standard view of the immune system is that it is a sophisticated machine that operates on well-established—purely mechanical—principles. My professor would say that macrophages aren’t hunting, but that the chemoreceptors on their skin are mechanically detecting cytokines on bacterial cell walls and responding according to an unvarying program. Suggesting that the immune system has some level of subjectivity, or its own independent consciousness, goes against everything in medical textbooks. Following me any further is at least a tacit acknowledgement that the medical world might need a paradigm shift. Then again, it’s a paradigm shift that has been a long time coming.
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A little over a century ago, an Estonian-born philosopher named Jakob von Uexküll coined the term umwelt to make sense of consciousness in the animal kingdom. Translated as “self-world” or “environment,” umwelt is the way that an organism’s senses frame its experience. Using umwelt means putting yourself in that organism’s shoes (or paws, flagella or tentacles, if you prefer). Every living creature has an umwelt of its own based on how it senses the environment. Perceiving that umwelt requires a level of empathy usually absent in hard sciences.
For instance, I have a small gray tiger-striped cat named Lambert who spends an inordinate amount of time meowing at my feet, chasing bugs and napping on my sofa. While we both inhabit the same space, we have radically different assessments of what’s happening around us. He sees the world from about a foot off the ground but can alight on the roof of my house in three small leaps, showing that he can think about vertical space more dynamically than I ever would. He’s aware of a million different scents and markings from other animals that I can’t detect. He knows his name; that’s the sum of his English abilities. Even so, he seems to know if I’m happy or sad. His purrs rumble through his body when he’s happy and comfort him when he’s sick. These are just a few parts of Lambert’s umwelt.
Von Uexküll applied the concept to try to understand how insects saw the world. He writes, “Take for instance the eyeless tick who is directed to [her] watchtower by a general photosensitivity to her skin, the approaching prey is revealed to the deaf highway-woman by her sense of smell. The odor of butyric acid that emanates from the skin glands of all mammals acts on the tick as a signal to leave her watchtower and hurl herself downwards.” And thus the tick had motivation. But why stop there? Why not go further down the microscopic ladder into the tiny cells that make up our immune system? This is the sort of thinking you need to use to start contemplating the Wedge for the Russian dolls inside of you. Instead of thinking about how you feel the environment around you, instead consider how your actions change the ecosystem inside your skin.
If you want to talk with a macrophage, you first need to think like one. Of course, this offers more than a few challenges. While I think a macrophage has some semblance of consciousness and subjectivity, it has such a minute form of it that human words could never do it justice. We do know that it (and every other semi-autonomous cell) senses and responds to its environment. There are baths of neurotransmitters and hormones, changes in blood pressure, and maybe even sounds that vibrate through the body from the outside world.
The environment that we as humans inhabit, the world that influences our actions, thoughts and stress levels, translates into chemical signals that make up the umwelt of the immune system. These chemical and physical signals are the immune systems’ lens to what’s happening outside the skin. I like to think of our bodies as jumbles of concentric and constantly interacting bubbles, where each bubble is an umwelt of another subjective experience: The skin senses the environment, the muscles sense the skin and brain, the gut senses food, and bacteria in the gut break that food down and release energy and nutrients that are resources for the body to use. Somehow all these different parts form the great mass of interactions for a single animal. Humans are superorganisms.
The trillions of cells that make up our bodies are an ecosystem regulated by complex relationships and innumerable interactions. While it may never be possible to reductively compute every single connection, we can understand the overall tone based on whether or not the system is in equilibrium. When an ecosystem functions well, it’s homeostasis; if it’s in decline or in the midst of unsustainable growth (as with cancer), then it’s heading into trouble. The system could end up in a state of constant vigilance and, to use Feinstein’s term, become allostatic and never return to normal.
In the modern world, real life-threatening events are few and far between. Instead, we use our sympathetic nervous system to tackle mundane challenges.
There’s almost no chance that I’ll confront a dangerous animal any time in the next few months. Instead, it is far more likely that I fret over my rising health insurance premiums, worry about taxes or burn through an all-nighter to meet some deadline or another. I’m stressing against obstacles in a remote future. These sorts of existential threats have no biological precedent. I deal with stress by mashing away at a keyboard or quietly strategizing in my mind. There’s no physical output to match.
Now, look at this from the perspective of the macrophage and B-cells in my bloodstream. When my credit card company calls and tells me that someone in Nigeria has just charged a couple thousand dollars to my account, the cells receive that message as a bath of adrenaline. They’re being primed to fight, but there is no fight to be had—no person to punch or lion to run from. They’re confused. It’s no wonder that stress leads to illness: This type of stress is an evolutionary mismatch.
However, if I match those same stress sensations to actual physical stresses, then my immune system would have something to do. The wolves would have their chew toy.
The Wedge has shown me that it’s possible to reconcile the way that our external environment affects our internal one. We can use our sensations of the stresses of the world to consciously send signals to the unconscious parts of our bodies.
But I’m also a realist. Even though many medical conditions we suffer from today come from evolutionary mismatches, few humans alive today will actually return to an ancestral lifestyle that gives us exactly the right external inputs to harmonize our internal ecosystems. Indeed, if we traveled back in time a few thousand years, we’d probably agree that our ancestors didn’t have it half as good as we have it now. And for all the failings of Western medicine, it offers evolutionarily unthinkable powers to treat acute illnesses. That doesn’t mean that we can’t at least try to be mindful of the sort of signals that we are sending our bodies and try to develop a more robust concept of human health.
Broadly speaking, working with the immune system and our inner worlds means paying more attention to the bounty of sensations that are available to us. This includes the five main senses—sight, smell, touch, taste and sound—but also the interoceptive sense that we develop when we quiet the outside world and look inward.
In the face of an illness, the first thing we should ask is what practices make us feel better. What things make us feel worse? These are basic tenets of what Harvard psychologist Ellen Langer calls “mindful health.”
Practicing mindful medicine doesn’t require a totally new worldview. It’s safe to say that every patient suffering from a chronic disease that’s resistant to medical intervention is already practicing mindful medicine. Let’s say you suffer from irritable bowel syndrome, or chronic back pain. Both conditions are notoriously difficult to treat, and you can expect numerous unhelpful doctor visits on your path to recovery.
When a treatment doesn’t solve the problem, you head to another doctor and try a new therapy. That search mandates a certain level of attention to your body. This is a version of the interoception that Feinstein tries to train with float tanks. Eventually, by modulating different inputs, you figure out what makes you feel better. This is the human process. It’s just as much a part of the scientific method as it is the wellness revolution. In many cases, the recovery has as much to do with the healing power of the body itself as it does with the treatment. Recovery might well be little more than regression to the mean: the mighty placebo effect.
In previous chapters, I used the concept of “flow” to describe how the sum total of individual actions can form a system far greater and more complex than the sum of its parts. I also note that flow states use the sensory information available to a person to choose the most optimal physical response to a given action. To my mind, equilibrium in a healthy body means that all of the pieces that make us up are in a state of flow. The inside world and outside world communicate harmoniously and tune the entire physical system. This is what homeostasis should be: communication through flow.
It’s the same skill of cooperation that allows me to throw kettlebells with a partner and feel a connection to something greater than myself. Working with the placebo effect means finding flow with your interior self—using careful application of stress and recovery so that all the parts work together. The Wedge works on all those levels.
In many indigenous traditions around the world, the concept of “medicine” doesn’t depend on a chemical agent or physical intervention. For those traditions, medicine is often a much broader concept that incorporates anything that changes our bodies or perception of the world for the better. Sensory stimuli, environmental variability, meditation and even prayer all have a role to play in generating and maintaining human health. These all correspond to the key frames of the Wedge: stress, sensation and orientation.
Whatever the placebo effect actually is, the medical community agrees that its results are subjective. And while that subjectivity is often cast as its most critical weakness, there’s a case to be made that subjectivity is also its greatest strength.
Of course, none of this is to say that medical interventions and drugs prescribed by Western doctors are bad, or even that they are wrong. Nothing in this book should make you eschew your doctor’s prescription for a sauna. What I am saying, though, is that Western medicine often loses the forest for the trees and often lacks the vision to see the larger picture. We should try to understand any chemical we take from the perspective of the superorganism and from the umwelt of our insides.
As we will see, sometimes a drug that causes a chemical change in our sensory system can be exactly the type of psychological stress we need to wedge a deeper look into our own biology.
8 One interesting exception to this is promising new cancer treatments that train the immune system to directly target cancer cells and destroy them. These groundbreaking therapies bolster and improve immune function. Another exception are vaccines that train the immune system to recognize and destroy specific viral pathogens. Yet calling vaccines “Western medicine” fails to recognize that Chinese doctors used smallpox inoculations as early as 1000 A.D., and that the first true vaccine arrived in 1796 in France, when the medical paradigm was based on the four humors. Even though it was in Europe, the medicine of that era wouldn’t be accepted in modern hospitals.
9 Autoimmune illnesses and cancer share other similarities. They both seem to arise out of environmental mismatches. Citing the work of Yale immunobiologist Ruslan Medzhitov, Siddhartha Mukherjee wrote in the New Yorker that cancer is best understood by dissecting cellular environments and inter-cell relationships. He writes: “What Medzhitov calls ‘new rules of tissue engagement’ may help us understand why so many people who are exposed to a disease don’t end up getting it. Medzhitov believes that all our tissues have ‘established rules by which cells form engagements and alliances with other cells.’” Physiology is the product of these relationships. So consider our internal-denominator problem. There are tens of trillions of cells in a human body; a large fraction of them are dividing, almost always imperfectly. There’s no reason to think there’s a supply-side shortage of potential cancer cells, even in perfectly healthy people. Medzhitov’s point is that cancer cells produce cancer—they get established and grow—only when they manage to form alliances with normal cells. And there are two sides (at least) to any such relationship.
10 “Morphology” is just a fancy word for the form and structure that a living thing takes. Morphologically identical animals look identical even if they come from different evolutionary lines.