Know Thy Immunity

Journal of a Plague is a new column, by Dr. Norman Doidge, that aims to help readers to stand back from, reflect on, and make sense of the pandemic, both in terms of how it is transforming life around us, and how it is affecting our individual psyches—the plague without, and the plague within.

Our column takes its name from A Journal of the Plague Year, the English writer Daniel Defoe’s classic account of the Great Plague of London of 1665. Defoe’s book is full of vivid observations that still resonate: early bouts of denial as the plague first enters London; the rich fleeing the city; the fearful exploited by quacks and con men; the poor dying in the streets; weakly enforced quarantines; moments of hope and human affection amid the creeping desolation.

Doidge is the pioneering author of two ground-breaking books about neuroscience—The Brain that Changes Itself and The Brain’s Way of Healing, which showed that the brain is remarkably more resilient and adaptable than had generally been appreciated. While Defoe’s book was composed years after the epidemic it chronicles, Doidge is writing now, in the midst of a pandemic that has just begun, with no clear end in sight. This new journal will make no attempt, in the midst of fast-moving events, to be a roundup of coronavirus news. Rather, it will be a diary of sorts, where readers can peek in to a scientific and clinical mind at work—as Doidge, also a psychiatrist and psychoanalyst, absorbs and metabolizes what he is seeing, connects what we learn about the virus to what we already know about human development and evolution, and ponders potential lessons for us individually, communally, and as a society.

Some installments will be several thousand words while others may be only a few paragraphs. All of them will be illuminated by Doidge’s deep knowledge of human history and science and how both have been indelibly shaped by disease. They will share one other aspect as well: Many will follow in some way a mysterious and awe-inspiring map that Doidge expands on here, in the second of his journal entries, and that each of us carries around inside of ourselves and which may reveal that we already know far more about the world of contagion than we think we do.

As horrifying as previous pandemics were—some, such as the plague of Justinian, estimated to have wiped out half the population of Europe, or the Spanish invasion of Mexico, estimated to have wiped out an even higher proportion of the Aztecs—we survived as a species. That the catastrophes were so dire also meant that the ongoing selection pressure of contagion became equally immense. This means that we have been “working” on this problem, in evolutionary terms, for a long time—long before modern science came along to help. Indeed, as the biologist J.B.S. Haldane posited 70 years ago, once we left the jungle and switched to agriculture, it is quite likely that adapting to infectious disease became the main driver of natural selection, replacing attacks by large animal predators.

Thus “we,” and “our bodies,” learned a thing or two about contagion, including that no two epidemics are identical. This meant our cellular immune systems had to become “intelligent” in a rudimentary way, and stay “well-informed,” and capable of “recognizing” new invaders and “remembering” them.

But it is not just our immune system that protects us.

Our brain, our ultimate learning organ, also learned to respond to epidemics, and developed circuitry for this task—circuitry rarely talked about, or even seen as related to contagion. Our plastic brain evolved, in a changing world, to change itself in response to both opportunities and threats, and developed adaptive responses to the kind of threat we now face—organisms that are not only invisible, but which like Proteus, change their form to resist us.

It’s Knowledge. We Just Don’t Know We Have It.

So, where is all that purported knowledge now that we need it?

It has been dormant, buried, but it is arising. But if so crucial to survival, why buried, and unknown to us? As we now often say, when dealing with unknowns, paraphrasing the ideas of psychologists Joseph Luft and Harrington Ingham, “there are the things we know, and the things we don’t know, and the things we don’t know that we don’t know.”

But there is a fourth category. There are also things that we know, but that we don’t know that we know. Unconscious knowledge. For such crises as ours now, we have resources, and instinctual endowments, which bring with them a kind of knowledge that we don’t know we have, until it is summoned by a very specific external cue.

It’s not so unusual. We see this happening in everyday life, in good times. Many a young heterosexual man, focused mostly on young women his age, never much notices or cares for children, until he becomes a father, and then his brain, his emotions, his goals, are reorganized, by a paternal instinct he never knew he had, so that he can become a doting father, and make sacrifices he never imagined possible—sacrifices that are matched to what a child requires. There are examples of these reorganizations relating to infection too. In the first trimester of pregnancy, when a woman is carrying “a foreign body,” (because 50% of the fetus is the father’s contribution) her own immune system is temporarily suppressed so that it doesn’t attack her fetus. During that suppression, when both she and the fetus are more vulnerable to infection, her brain circuitry will compensate, and she will become more prone to feel disgust, in an instinctual way, to protect herself from potentially contaminated food. During that same first trimester, a Harvard-UCLA study shows pregnant women temporarily become more attracted to their own “in-group,” and more wary of “foreigners.” This is thought to be because people outside the woman’s “in-group” could carry infections she and her ethnic group might not have developed resistance to (as say, many Aztecs had not developed a resistance to smallpox). Then, just as intriguingly, in the second and third trimester, when the fetus is less vulnerable, and the mother’s immune suppression stops, these ethnocentric and xenophobic attitudes dissipate. This all goes on unconsciously. This small example shows that there is a circuitry in the brain that is turned on in response to one’s “perceived vulnerability to infection,” and that it changes our emotions, intentions, and behaviors. What the example of pregnant women shows is that this “perceived vulnerability,” might not even be a conscious process.

Instincts are not only mindless and unruly, though they often are. There can be a kind of “knowledge” of the way things are, and even a kind of forethought inherent in them. When a robin that has never laid an egg makes its first nest, and builds it precisely big enough for four eggs—and then lays four eggs—its nest-making seems in some way that we do not understand to have been informed by something akin to an “idea” or “form” of four.

Even if it is not a conscious knowledge, just as the robin’s innate instincts in some way “know” or “anticipate” the coming of the four eggs, our bodies have some know-how in dealing with the microorganisms we co-evolved with. Ever since animals had guts, they had microorganisms in them. Sometimes, they are our tenants, and we their happy landlords, for they help us digest our food. Sometimes they threaten our lives.

We have at least five ways of dealing with threatening microorganisms.

First, we have the immune system, made up of our white blood cells, which, when a person is exposed to foreign organisms, develops antibodies and other means to attack the invaders. This is called our “acquired immunity,” because we acquire it in our individual lifetimes. (We also receive our mother’s antibodies through the placenta in the womb, and through her breast milk, which protects us after birth.)

Second, we receive, at birth, many of our mother’s healthy microorganisms, some of which are helpful, and live in our gut, and even stand guard in our mouths, ready to attack hostile microorganisms as they try to enter us (so go easy on the mouthwash).

Third, there is a kind of protection that is inherited. When our ancestors were exposed to an illness, those of them who had versions of genes that conferred some advantages in dealing with that illness were more likely to survive, and pass those versions of those genes on to their offspring. Over time, those who had these advantages would make up a higher proportion of the population of the descendants. They might have been protected entirely or partially from that illness.

It’s thought that something like this happened when Europeans came to the Americas and met indigenous peoples. The Europeans, who were exposed to diseases like smallpox that seem to have arisen in sedentary agricultural settlements, had a selection pressure to develop some protection against them. The indigenous peoples who as hunter gatherers had not been exposed to such diseases, did not develop the protections against them, and so many—though not all—were decimated. For centuries, Ashkenazi Jews were crowded into tuberculosis-rife ghettos in Europe, and had very low mortality rates from the illness, though they got the disease as often as gentiles. (Right now, there is a controversy in genetics as to whether the same version of a gene thought to have protected Jews from dying from tuberculosis, may also predispose Jews to Tay-Sachs disease, a much rarer condition.) Thus, certain ethnic groups can be resistant to an illness, because their ancestors had, to use the phrase of plague historian William McNeill, “disease experience” with it.

Fourth, there are all the traditional ways people support their own immune systems, through sleep, exercise, diet, vitamins, and sunlight—few of which are being emphasized by public health officials who are, for the moment, more focused on stopping the virus, than on strengthening of the host (you).

But, as I say, there is one other, fifth aspect of how we protect ourselves, not often discussed or thought about, except by a few scientists, and that concerns the role of our brains in protecting us from getting ill in the first place.

In addition to acquired immunity and genetic protection, we also inherit specific brain circuits and mental dispositions to protect ourselves from microorganisms. What is interesting about these circuits is that they initially do not respond to specific individual organisms (as do our immune systems) but to the condition of contagion in general. These circuits contain, implicitly, a map of a world in which there is such a thing as “contagion,” the cause of which we do not perceive or fully comprehend (because microorganisms exist on a different scale than normal perception), and which can be passed on, by some means not always visible to the naked eye, from one person to another. So, what is unique about these brain circuits—their great strength—is they evolved to minimize death from something we cannot see or understand.

They have great power to protect, but also important, crucial limitations. Because epidemics can wipe out the entire tribe, these circuits, once triggered, err on the side of being oversensitive to the presence of disease. If they were a medical test, we’d say they have a huge false positive rate.

These contagion circuits and capacities generally lie in wait, because the use-it-or-lose-it brain has much more of a tendency to allow unused capacities to become “dormant” than is generally appreciated. There are sound economic reasons for capacities we are not using to enter a state of dormancy, and for their circuits to be reconfigured and used for other purposes. Though inherited, once they are awakened, it seems they can be influenced by experience as well, as we learn from our exposure to each unique illness that triggers them.

In human beings, the sophisticated “suite” of brain responses we have to infection of the magnitude of the COVID-19 pandemic has been dormant, or relatively so, longer than usual, because of the unique combination of the blessings provided by modern hygiene, medicine, science, and luck, which has given us 100 years since the great 1918 flu pandemic. Of course, it’s not as though there have been no other pandemics—among them AIDS, which killed 32 million people. But for a generation of people, this is their first encounter.

The Pandemic Suite

Right now, as the COVID-19 virus is erupting in the world, “the pandemic suite” is erupting in us, affecting our mental lives. Inside billions of brains, as many switches are all suddenly being thrown.

Because we are all reacting to, and focused on, the same external event simultaneously, there is a tendency to think that everything that we are experiencing is caused by this external event. But we are all, also, simultaneously, undergoing the eruption of an internal experience, the rearing up of the pandemic suite, which includes instinctive emotional, cognitive, sensory, and behavioral reactions. There is an intimate relationship between what is happening externally, and internally, that is easily obscured by the simultaneity.

For instance, most people assume that it is the virus—and the policies and practices we are being advised or compelled to follow now, such as the cleaning protocols, shutting of the borders, shutting ourselves in, and so on—that is driving what is going on in our brains, which are just reacting to these events. But actually, it is, more than one might think, the other way around. The “knowledge” and “action plans” inherent in our biological pandemic suite are the foundation of our public health techniques, and even some of our more advanced medical approaches to dealing with the pandemic. What public health has learned in the last hundred years is in fact a relearning, in large part, tested and retested through evolutionary trial and error over vast time scales.

This is not a romanticized view of our biology. It is one of those rare cases where science and our natural evolutionary history are actually, in significant ways, in accord—which is not surprising in that both attempt to come to grips with the same world. Think of them as two maps. You can lay out the scientific map of how many public health “evidence-based practices” have determined we must deal with this pandemic on top of the map provided by our biology and our archaic heritage, and with a few very important exceptions, the contours align closely. (And where they differ, it is essential to understand why.) And our biological map accords, very closely with many animal behaviors that evolved to respond to contagion.

These inherited maps are based on previous encounters. But the world around us, including the viruses, and our cultural practices (e.g., airplane flights) change, and so the maps need, with each new pandemic, “to be updated,” and, because they are brain maps, they can be. The pandemic suite is plastic, in the same way our brains are plastic, because it is both a part and a product of the brain.

The Immune System You Don’t Know You Have

We eat things, large and small. And they return the favor. We have had macropredators and micropredators since we emerged as a species, feeding upon us, and using our energy for themselves. That is what parasites (which includes viruses) do. This is, as Leon Kass writes in his book, The Hungry Soul, “the great paradox of eating, namely that to preserve their life and form living forms necessarily destroy life and form.” We all know how biology has equipped us to deal with macropredators such as lions, and tigers, large snakes, and alas, other human beings, with the fight-or-flight reaction, and bodies and senses equipped to track and hunt. Less familiar are our adaptations to deal with our micropredators, because they exist on a different and imperceptible scale.

There are two major components to the micropredator protection system.

First, there is the familiar immune system, which is reactive, and starts working once we have been invaded by, or overtaken by a pathogen. In some ways it is a mimetic system, responding to invading self-replicating organisms in kind, with counter attacks, and its own means of replication.

The second system is “the behavioral immune system,” a term coined by research psychologist Mark Schaller from the University of British Columbia, who has devoted his career to thinking deeply about this. It is proactive, and hence protects us from getting sick, by different means. Though not nearly as widely investigated as the cellular immune system—the evidence for the behavioral immune system suddenly is everywhere to be seen. Schaller and his colleagues have presciently and systematically described it at work in animals and human beings alike.

Here are examples of the behavioral immune system (BIS) first in animals, then in humans.

The BIS reacts instinctively to avoid foods, and substances, that might infect us. Sheep, horses, and cattle for instance, won’t graze in areas of a field near where they recently defecated, because they might ingest some illness-causing microorganism. What this shows is that even in the animal kingdom, there is some kind of “knowledge” of invisible contagion.

The perceived presence of parasites or pathogens turns on the brain’s disgust circuit, and triggers a disgust-avoidance reaction. But over the course of history different ethnic groups usually lived in different places and had very different disease experiences, and thus developed different resistances, and vulnerabilities to diseases. This explains a lot of our cross-cultural food aversions, and why ethnic groups often find the smell of other groups’ foods disgusting, or are disgusted to learn what animals and insects that other groups eat, showing there is some plasticity to the circuit. The huge range of spices used, whether the animals are eaten while still alive, as are oysters and some insects, or dead, and if cooked, how much, are likely in part a product of the extent to which the local animals and plants threatened to bring infection. My Jewish grandmother was not a bad cook, but she couldn’t conceive of a steak that wasn’t burned until tough as leather, because she was repelled by the concept, “medium rare,”—likely a response, mediated by the BIS, to the risk of pathogens in meat in an age when refrigeration was uncommon.

Avoiding creatures with signs of infection, including members of one’s own species, is one of the key expressions of the BIS, and the most important mechanism underlying our current practices of social distancing, quarantining and lockdown. The prototypes are clear in the many ways animals avoid other species that might be a vector that could bring illness to them, or how they avoid members of their own species that might be ill.

Animals will even use tools to fend off other potential disease-bearing animals, as when elephants will tear off branches, which they hold in their trunks and use to switch away potential flies. And of course the almost ritual cleaning practices of humans are not unique to us. Birds and mammals groom their skins and plumage to get rid of ectoparasites, cats and dogs persecute their fleas for persecuting them, antelopes their ticks, and so on.

But ridding oneself of annoying creatures that bite is one thing. Recognizing something as complex as an illness—one that has many different ways of presenting itself—is another. Yet multiple species including lobsters, chimps, and mice can, by visual and other cues, recognize when members of their own species are infected, and avoid them.

After identifying sick members of their kind, they often isolate them. Jane Goodall wrote of how, when a polio epidemic affected the Gombe chimpanzees, one of the chimps, McGregor, lost the use of his legs and his bladder, and had to drag himself around, surrounded by flies. He was quickly isolated by most of the other chimps. Only four touched him, and in an aggressive way.

Humans may not be able to see micropredators, but we can see skin problems, rashes, runny noses, or that someone is sweating with a fever, or vomiting, and we can smell their malodorous diarrhea. Schaller points out that the signs of active infection, or of physical vulnerability to it, including birth defects, disfigured faces, asymmetries betraying poor development, strong deviations from the norm in movement (poor McGregor), obesity, signs of the ravages of age, all can trigger the BIS. This is the origin of stigmatizing the ill: fear of contagion. Studies by Schaller and colleagues also show that the more vulnerable to infection we feel (say we are ourselves already ill, run down, pregnant, or aged) the more likely we are to feel disgust, and have stigmatizing attitudes toward other infected, or potentially infectious people.

Stigmatization leads to isolation. There were reports by dissidents that during the Wuhan outbreak, the government had people forcibly isolated and taken away in metal boxes and sent men to weld shut the doors of the apartments of infected people, to contain them. This may seem like a modern totalitarian nightmare, but forced confinements until death are not new or unique to China. Daniel Defoe described similarly harsh policies in his Journal of the Plague Year of 1665, in London. We may complain of “sheltering in,” but the alternative, during that plague, was that authorities padlocked people who showed plague symptoms in their houses with any family members, or servants, they had been living with, even if these others seemed healthy, and then set watchmen to guard the windows, and listen to the shrieks, as one after another of the entire family died.

The BIS can obviously be very harsh. But one can’t begin to temper its more ruthless expressions, if one doesn’t understand what the BIS is up against—not only the pathogen, but other of our instincts that might get us killed. We are very social animals who love to touch, embrace, and huddle together, and the virus, to its devious credit, exploits this physicality, to jump from one person to another. So, the BIS evolved to overcome our more gregarious tendencies, including our passionate altruistic tendencies to hold and soothe people who are not only ill, but also infectious. It is there to shut them down—unless it has good reason not to.

Attempts to persuade people that stigmatizing the sick is a learned behavior, based on nothing but bigoted teaching, so often fail because stigmatizing the sick might not only be learned, but also has instinctual roots, and probably persists, because in the past it conferred a benefit, at least in some situations. To some extent, one goes to medical, nursing, or some related clinical schools, to learn to turn the BIS off in the presence of afflicted people. This “switching off,” works only up to a point, as the daily testimony of terrified health care workers, now undergoing sustained exposure while lacking proper personal protective equipment, attests to. That’s why we call them heroes: We are not so sure we could, or would, do it ourselves.

The behavioral immune system is, as is now obvious, a bit paranoid.

Think of an infection as like a Trojan horse, something that is mistakenly welcomed into you, through an open orifice, which then wreaks havoc.

Think of the cellular immune system as Trojan soldiers, inside their city trying to fight off the invaders, after having foolishly let a wooden horse, secretly filled with stealthy Greek warriors hidden inside, into the city. Now that they are inside the walls, the defenders must make their last stand and work, without rest, from a position of great vulnerability. We can’t always win those fights.

So, the behavioral immune system evolved to prevent those Greeks from getting in in the first place. It says, in so many ways, “beware of Greeks bearing gifts.” The ways it does so is to say: Beware of food that might have pathogens in it, and beware of animals that might be carrying infection, and especially beware of people who might have pathogens on them or in them.

Why beware especially of people? Because if a person, as a member of your species, can be infected by the pathogen, so might you be.

So, the behavioral immune system, being all for disease avoidance, errs on the side of suspicion. It is there to help us recognize potential threats, and potential threats are rarely as clear-cut in appearance as currently active infections. And this can both protect us, and hurt us. Schaller emphasizes that the behavioral immune system often functions unconsciously. This means, it can operate beyond our awareness, and it is hard to use your reason to override a system you don’t know is operating. Given that it is a bit paranoid, switching out of the BIS may prove a challenge for some, when it comes time to return to a more normal life.

I don’t know about you, but my behavioral immune system is going off more than I might like it to. You sneeze, or cough, and I am wary of you, a perfectly decent person.

I’ve even noticed, walking down the street—since the time public health officials began discussing whether aerosols, large droplets, and even speaking to each other might be a means of community transmission, that I had some subtle sensory changes. One day when it was very cold, I passed a young man huddled outside a small red brick apartment. He was smoking a cigarette, minding his own business, looking a bit disconsolate. But then I noticed the plume of his exhalation, which, in the subzero cold, created a cloud of smoke and vaporous condensation much more expansive than I wished it to be since it was coming my way. Can a person’s breath really travel that far?—I marveled with concern. But what really struck me, was how vivid and pungent the burnt smell of his smoke was to me, not at several feet, but at a distance of many yards, and how it triggered an increased wariness to be sharing the airspace with this probably very anxious fellow citizen, who was as stir crazy as I was, and just stepping outside for a smoke, so as not to trouble others. Was I, at that moment, experiencing an up-regulation of sensation, akin to what happened to those hypervigilant pregnant women, who were going through an increased “perceived vulnerability to infection,” as the BIS scientists call it?

Please, fellow citizen, don’t shun me, for being overly sensitive to your expectorations, and throat clearings and fumes, and for shunning you. When I clear my own throat with a small cough, my BIS goes off too, and it persecutes me as well, for a second or two. It’s my comeuppance. Is it COVID, or is it hypochondria? I’ve found it more helpful to understand these passing eruptions as a pseudo-hypochondria, the BIS doing its thing—that is, assuming I’m not at the moment incubating something. Clearly, my BIS hadn’t yet learned that one of the symptoms of COVID-19 is the loss of the sense of smell, not it’s enhancement.

It’s part and parcel of an ancient, imperfect, appendage to the immune system, tilted to fire off false-positive signals. It sometimes makes me momentarily miserable, but it is ultimately there to help. And if I do become infected and ill, I will heed its instructions, and isolate myself further, and not go on my walks, which I hope will be all the better for you and yours.