The Harvard surgeon who studied his case, Dr. Henry Jacob Bigelow, noted that “the leading feature of this case is its improbability.… [It is] unparalleled in the annals of surgery.”4 The Boston Post article summarized this improbability with just one more sentence: “The most singular circumstance connected with this melancholy affair is that he was alive at 2:00 this afternoon, and in full possession of his reason, and free from pain.”5
Gage’s survival alone would have made an interesting medical case; it became a famous case because of something else that came to light. Two months after the accident his physician reported that Gage was “feeling better in every respect … walking about the house again; says he feels no pain in the head.” But foreshadowing a larger problem, the doctor also noted that Gage “appears to be in a way of recovering, if he can be controlled.”
What did he mean, “if he can be controlled”? It turned out that the preaccident Gage had been described as “a great favorite” among his team, and his employers had hailed him as “the most efficient and capable foreman in their employ.” But after the brain change, his employers “considered the change in his mind so marked that they could not give him his place again.” As Dr. John Martyn Harlow, the physician in charge of Gage, wrote in 1868:
The equilibrium or balance, so to speak, between his intellectual faculties and animal propensities, seems to have been destroyed. He is fitful, irreverent, indulging at times in the grossest profanity (which was not previously his custom), manifesting but little deference for his fellows, impatient of restraint or advice when it conflicts with his desires, at times pertinaciously obstinate, yet capricious and vacillating, devising many plans of future operations, which are no sooner arranged than they are abandoned in turn for others appearing more feasible. A child in his intellectual capacity and manifestations, he has the animal passions of a strong man. Previous to his injury, although untrained in the schools, he possessed a well-balanced mind, and was looked upon by those who knew him as a shrewd, smart businessman, very energetic and persistent in executing all his plans of operation. In this regard his mind was radically changed, so decidedly that his friends and acquaintances said he was “no longer Gage.”6
In the intervening 143 years we have witnessed many more of nature’s tragic experiments—strokes, tumors, degeneration, and every variety of brain injury—and these have produced many more cases like Phineas Gage’s. The lesson from all these cases is the same: the condition of your brain is central to who you are. The you that all your friends know and love cannot exist unless the transistors and screws of your brain are in place. If you don’t believe this, step into any neurology ward in any hospital. Damage to even small parts of the brain can lead to the loss of shockingly specific abilities: the ability to name animals, or to hear music, or to manage risky behavior, or to distinguish colors, or to arbitrate simple decisions. We’ve already seen examples of this with the patient who lost the ability to see motion (Chapter 2), and the Parkinson’s gamblers and frontotemporal shoplifters who lost the ability to manage risk-taking (Chapter 6). Their essence was changed by the changes in their brain.
All of this leads to a key question: do we possess a soul that is separate from our physical biology—or are we simply an enormously complex biological network that mechanically produces our hopes, aspirations, dreams, desires, humor, and passions?7 The majority of people on the planet vote for the extrabiological soul, while the majority of neuroscientists vote for the latter: an essence that is a natural property that emerges from a vast physical system, and nothing more besides. Do we know which answer is correct? Not with certainty, but cases like Gage’s certainly seem to weigh in on the problem.
The materialist viewpoint states that we are, fundamentally, made only of physical materials. In this view, the brain is a system whose operation is governed by the laws of chemistry and physics—with the end result that all of your thoughts, emotions, and decisions are produced by natural reactions following local laws to lowest potential energy. We are our brain and its chemicals, and any dialing of the knobs of your neural system changes who you are. A common version of materialism is called reductionism; this theory puts forth the hope that we can understand complex phenomena like happiness, avarice, narcissism, compassion, malice, caution, and awe by successively reducing the problems down to their small-scale biological pieces and parts.
At first blush, the reductionist viewpoint sounds absurd to many people. I know this because I ask strangers their opinion about it when I sit next to them on airplanes. And they usually say something like “Look, all that stuff—how I came to love my wife, why I chose my job, and all the rest—that has nothing to do with the chemistry of my brain. It’s just who I am.” And they’re right to think that the connection between your essence as a person and a squishy confederacy of cells seems distant at best. The passengers’ decisions came from them, not a bunch of chemicals cascading through invisibly small cycles. Right?
But what happens when we crash into enough cases like Phineas Gage’s? Or when we turn the spotlight on other influences on the brain—far more subtle than a tamping rod—that change people’s personalities?
Consider the powerful effects of the small molecules we call narcotics. These molecules alter consciousness, affect cognition, and navigate behavior. We are slave to these molecules. Tobacco, alcohol, and cocaine are self-administered universally for the purpose of mood changing. If we knew nothing else about neurobiology, the mere existence of narcotics would give us all the evidence we require that our behavior and psychology can be commandeered at the molecular level. Take cocaine as an example. This drug interacts with a specific network in the brain, one that registers rewarding events—anything from slaking your thirst with a cool iced tea, to winning a smile from the right person, to cracking a tough problem, to hearing “Good job!” By tying positive outcomes to the behaviors that led to them, this widespread neural circuit (known as the mesolimbic dopamine system) learns how to optimize behavior in the world. It aids us in getting food, drink, and mates, and it helps us navigate life’s daily decisions.*
Out of context, cocaine is a totally uninteresting molecule: seventeen carbon atoms, twenty-one hydrogens, one nitrogen, and four oxygens. What makes cocaine cocaine is the fact that its accidental shape happens to fit lock-and-key into the microscopic machinery of the reward circuits. The same goes for all four major classes of drugs of abuse: alcohol, nicotine, psychostimulants (such as amphetamines), and opiates (such as morphine): by one inroad or another, they all plug into this reward circuitry.8 Substances that can give a shot in the arm to the mesolimbic dopamine system have self-reinforcing effects, and users will rob stores and mug elderly people to continue obtaining these specific molecular shapes. These chemicals, working their magic at scales one thousand times smaller than the width of a human hair, make the users feel invincible and euphoric. By plugging into the dopamine system, cocaine and its cousins commandeer the reward system, telling the brain that this is the best possible thing that could be happening. The ancient circuits are hijacked.
The cocaine molecules are hundreds of millions of times smaller than the tamping rod that shot through Phineas Gage’s brain, and yet the lesson is the same: who you are depends on the sum total of your neurobiology.
And the dopamine system is only one of hundreds of examples. The exact levels of dozens of other neurotransmitters—for example, serotonin—are critical for who you believe yourself to be. If you suffer from clinical depression, you will probably be prescribed a medication known as a selective serotonin reuptake inhibitor (abbreviated as an SSRI)—something such as fluoxetine or sertraline or paroxetine or citalopram. Everything you need to know about how these drugs work is contained in the words “uptake inhibitor”: normally, channels called transporters take up serotonin from the space between neurons; the inhibition of these channels leads to a higher concentration of serotonin in the brain. And the increased concentration has direct consequences on cognition and
emotion. People on these medications can go from crying on the edge of their bed to standing up, showering, getting their job back, and rescuing healthy relationships with the people in their life. All because of a subtle fine-tuning of a neurotransmitter system.9 If this story weren’t so common, its bizarreness could be more easily appreciated.
It’s not just neurotransmitters that influence your cognition. The same goes for hormones, the invisibly small molecules that surf the bloodstream and cause commotion at every port they visit. If you inject a female rat with estrogen, she will begin sexual seeking; testosterone in a male rat causes aggression. In the previous chapter we learned about the wrestler Chris Benoit, who took massive doses of testosterone and murdered his wife and his own child in a hormone rage. And in Chapter 4 we saw that the hormone vasopressin is linked to fidelity. As another example, just consider the hormone fluctuations that accompany normal menstrual cycles. Recently, a female friend of mine was at the bottom of her menstrual mood changes. She put on a wan smile and said, “You know, I’m just not myself for a few days each month.” Being a neuroscientist, she then reflected for a moment and added, “Or maybe this is the real me, and I’m actually someone else the other twenty-seven days of the month.” We laughed. She was not afraid to view herself as the sum total of her chemicals at any moment. She understood that what we think of as her is something like a time-averaged version.
All this adds up to something of a strange notion of a self. Because of inaccessible fluctuations in our biological soup, some days we find ourselves more irritable, humorous, well spoken, calm, energized, or clear-thinking. Our internal life and external actions are steered by biological cocktails to which we have neither immediate access nor direct acquaintance.
And don’t forget that the long list of influences on your mental life stretches far beyond chemicals—it includes the details of circuitry, as well. Consider epilepsy. If an epileptic seizure is focused in a particular sweet spot in the temporal lobe, a person won’t have motor seizures, but instead something more subtle. The effect is something like a cognitive seizure, marked by changes of personality, hyperreligiosity (an obsession with religion and a feeling of religious certainty), hypergraphia (extensive writing on a subject, usually about religion), the false sense of an external presence, and, often, the hearing of voices that are attributed to a god.10 Some fraction of history’s prophets, martyrs, and leaders appear to have had temporal lobe epilepsy.11 Consider Joan of Arc, the sixteen-year-old-girl who managed to turn the tide of the Hundred Years War because she believed (and convinced the French soldiers) that she was hearing voices from Saint Michael the archangel, Saint Catherine of Alexandria, Saint Margaret, and Saint Gabriel. As she described her experience, “When I was thirteen, I had a voice from God to help me to govern myself. The first time, I was terrified. The voice came to me about noon: it was summer, and I was in my father’s garden.” Later she reported, “Since God had commanded me to go, I must do it. And since God had commanded it, had I had a hundred fathers and a hundred mothers, and had I been a king’s daughter, I would have gone.” Although it’s impossible to retrospectively diagnose with certainty, her typical reports, increasing religiosity, and ongoing voices are certainly consistent with temporal lobe epilepsy. When brain activity is kindled in the right spot, people hear voices. If a physician prescribes an anti-epileptic medication, the seizures go away and the voices disappear. Our reality depends on what our biology is up to.
Influences on your cognitive life also include tiny nonhuman creatures: microorganisms such as viruses and bacteria hold sway over behavior in extremely specific ways, waging invisible battles inside us. Here’s my favorite example of a microscopically small organism taking over the behavior of a giant machine: the rabies virus. After a bite from one mammal to another, this tiny bullet-shaped virus climbs its way up the nerves and into the temporal lobe of the brain. There it ingratiates itself into the local neurons, and by changing the local patterns of activity it induces the infected host to aggression, rage, and a propensity to bite. The virus also moves into the salivary glands, and in this way it is passed on through the bite to the next host. By steering the behavior of the animal, the virus ensures its spread to other hosts. Just think about that: the virus, a measly seventy-five billionths of a meter in diameter, survives by commandeering the massive body of an animal twenty-five million times larger than it. It would be like you finding a creature 28,000 miles tall and doing something very clever to bend its will to yours.12 The critical take-home lesson is that invisibly small changes inside the brain can cause massive changes to behavior. Our choices are inseparably married to the tiniest details of our machinery.13
As a final example of our dependence on our biology, note that tiny mutations in single genes also determine and change behavior. Consider Huntington’s disease, in which creeping damage in the frontal cortex leads to changes in personality, such as aggressiveness, hypersexuality, impulsive behavior, and disregard for social norms—all happening years before the more recognizable symptom of spastic limb movement appears.14 The point to appreciate is that Huntington’s is caused by a mutation in a single gene. As Robert Sapolsky summarizes it, “Alter one gene among tens of thousands and, approximately halfway through one’s life, there occurs a dramatic transformation of personality.”15 In the face of such examples, can we conclude anything other than a dependence of our essence on the details of our biology? Could you tell a person with Huntington’s to use his “free will” to quit acting so strangely?
So we see that the invisibly small molecules we call narcotics, neurotransmitters, hormones, viruses, and genes can place their little hands on the steering wheel of our behavior. As soon as your drink is spiked, your sandwich is sneezed upon, or your genome picks up a mutation, your ship moves in a different direction. Try as you might to make it otherwise, the changes in your machinery lead to changes in you. Given these facts on the ground, it is far from clear that we hold the option of “choosing” who we would like to be. As the neuroethicist Martha Farah puts it, if an antidepressant pill “can help us take everyday problems in stride, and if a stimulant can help us meet our deadlines and keep our commitments at work, then must not unflabbable temperaments and conscientious characters also be features of people’s bodies? And if so, is there anything about people that is not a feature of their bodies?”16
Who you turn out to be depends on such a vast network of factors that it will presumably remain impossible to make a one-to-one mapping between molecules and behavior (more on that in the moment). Nonetheless, despite the complexity, your world is directly tied to your biology. If there’s something like a soul, it is at minimum tangled irreversibly with the microscopic details. Whatever else may be going on with our mysterious existence, our connection to our biology is beyond doubt. From this point of view, you can see why biological reductionism has a strong foothold in modern brain science. But reductionism isn’t the whole story.
FROM THE COLOR OF YOUR PASSPORT TO EMERGENT PROPERTIES
Most people have heard of the Human Genome Project, in which our species successfully decoded the billions-of-letters-long sequence in our own genetic codebook. The project was a landmark achievement, hailed with the proper fanfare.
Not everyone has heard that the project has been, in some sense, a failure. Once we sequenced the whole code, we didn’t find the hoped-for breakthrough answers about the genes that are unique to humankind; instead we discovered a massive recipe book for building the nuts and bolts of biological organisms. We found that other animals have essentially the same genome we do; this is because they are made of the same nuts and bolts, only in different configurations. The human genome is not terribly different from the frog genome, even though humans are terribly different from frogs. At least, humans and frogs seem quite different at first. But keep in mind that both require the recipes to build eyes, spleens, skin, bones, hearts, and so on. As a result, the two genomes are not so dissimilar. Imagine going to different factor
ies and examining the pitches and lengths of the screws used. This would tell you little about the function of the final product—say, a toaster versus a blow dryer. Both have similar elements configured into different functions.
The fact that we didn’t learn what we thought we might is not a criticism of the Human Genome Project; it had to be done as a first step. But it is to acknowledge that successive levels of reduction are doomed to tell us very little about the questions important to humans.
Let’s return to the Huntington’s example, in which a single gene determines whether or not you’ll develop the disease. That sounds like a success story for reductionism. But note that Huntington’s is one of the very few examples that can be dredged up for this sort of effect. The reduction of a disease to a single mutation is extraordinarily rare: most diseases are polygenetic, meaning that they result from subtle contributions from tens or even hundreds of different genes. And as science develops better techniques, we are discovering that not just the coding regions of genes matter, but also the areas in between—what used to be thought of as “junk” DNA. Most diseases seem to result from a perfect storm of numerous minor changes that combine in dreadfully complex ways.
But the situation is far worse than just a multiple-genes problem: the contributions from the genome can really be understood only in the context of interaction with the environment. Consider schizophrenia, a disease for which teams of researchers have been gene hunting for decades now. Have they found any genes that correlate with the disease? Sure they have. Hundreds, in fact. Does the possession of any one of these genes offer much in the way of prediction about who will develop schizophrenia as a young adult? Very little. No single gene mutation is as predictive of schizophrenia as the color of your passport.