CHAPTER 1

A NEW QUESTION

If I had an hour to solve a problem and my life depended on the solution, I would spend the first fifty-five minutes determining the proper question to ask, for once I know the proper question, I could solve the problem in less than five minutes.

—Albert Einstein

I knew something was up when the psychiatry resident knocked on my office door five minutes before I was scheduled to meet with him and his new patient.

“I just wanted to warn you,” he said. “This one wants answers.”

“What are her questions?” I asked.

“She wants to know why everyone she sees gives her different explanations and different advice. She’s skeptical about the whole shrink thing. She got up at five a.m. to drive here from upstate to get answers from the big shots at the Big U.” He was referring, sardonically but with a smile, to me and our prestigious university hospital.

I asked him to summarize the case. He gave a quick case presentation:

“She’s a thirty-five-year-old married mother of three grade-school-age children whose chief complaint is increasing worry about nearly everything for the past year. Her health, her kids, the economy, driving, everything. She often has a bad feeling in the pit of her stomach, and once or twice a month she has bouts of nausea, but she hasn’t lost any weight. She says she’s irritable and fatigued and has trouble getting to sleep. She is less interested in things, but she’s not suicidal, and she doesn’t have other symptoms of depression. Anxiety runs in her family, but nothing dramatic. Her family doctor couldn’t find any medical causes. I think it’s generalized anxiety disorder, but it could be dysthymia or somatization disorder. I’ll be curious to see what you think. And how you answer her questions.”

When we joined Ms. A in the exam room, she greeted us warmly. When I asked how we could help, however, her voice took on an edge. “I take it that the young doctor already told you about my problems. I drove five hours from up north to get some answers.”

Trying to be empathic, I said, “I understand you have had trouble getting help.” It was as if I had pushed the play button.

“Not only have I gotten no help, but every expert I talk to gives me a different explanation. I started with our minister. He is a nice man, and he was sympathetic, but mainly he just suggested praying and accepting God’s plan for me. I tried, but I guess my faith just isn’t strong enough. Then I talked to my family doctor. He didn’t even do any tests; he just said it was nerves. He said pills for worry are addicting, so he prescribed pills for my stomach, but they didn’t help.

“He sent me to this therapist doctor who wanted me to come twice a week, which I couldn’t afford. He didn’t talk much, and when he did, he kept asking about my childhood and hinting like I had some sexual thing for my father, which I definitely do not! When I told him I was getting worse, he said I was avoiding getting in touch with my memories. I quit going, but he still sends bills for the session I skipped.

“I still felt awful, so I found a psychiatrist in the phone book who was far enough away that people wouldn’t find out. He said my problem was an inherited brain abnormality and that I would have to take medications to correct a chemical imbalance. But he didn’t do any blood tests, either, and when I looked up the pills, it said they might cause suicide. So I decided to get myself down here to the university to get some answers. All I do is worry, and I can hardly sleep or eat, and my husband has had it with my calling him about the kids all the time, so I hope you have some answers.”

“No wonder you are frustrated,” I said. “Four different explanations and recommendations from four different professionals! And we may well have yet other ideas. Could we ask a few more questions to figure out the best plan?”

She was glad to provide more details. She said she had always been a worrier and that her mother had often been nervous. She had never been abused, but her father had often been critical. When she was young her family had moved every few years, so she had always felt out of it at school. Her marriage was stable, but she and her husband fought a lot, especially about his frequent business trips and what to do about their oldest son’s ADHD. She often drank “a few glasses” of wine to help her get to sleep. She said the anxiety had worsened two years previously, about the time her youngest son had started kindergarten and she had started trying to lose weight. Without a pause she went on to say, “But all that has nothing to do with my problem. What I came here to find out is whether it is neurosis or brain disease or stress or what.”

I started to explain that her symptoms resulted from a combination of inherited tendencies, early life experiences, her current life situation, and drinking. She frowned. As I went on to explain that anxiety can be useful but that most people have more than they need because too little can result in disaster, she brightened and said, “That makes sense.” When I told her that several kinds of treatment could be safe and effective and that an excellent cognitive behavior therapist near her home would likely be able to help, she relaxed and said, “Maybe this trip will be worth it.” However, later, as she stepped out of the office, she stared at me and shared a parting comment that still rings in my ears: “Your whole field is confused. You know that, right?”

I had never quite admitted it to myself that clearly. Psychiatrists are supposed to help their patients get in touch with things they are trying to avoid, but Ms. A turned the tables on me. For all case reports, I have modified details so that patients cannot be recognized by friends, relatives, or even themselves, but if Ms. A reads this and recognizes her visit thirty years ago, she will likely be pleased to learn that her pointed observation shattered my denial and set me on a quest to transcend the confusion.

Embedded Shrink

During my early years as an assistant professor of psychiatry, I was embedded, like a journalist in a war zone, in a medical clinic staffed by internal medicine professors, medical residents, and nurse clinicians. Many patients in medical clinics have mental problems, so my help was appreciated. There was also a hope that my presence would encourage resident doctors to have greater sensitivity to patients’ emotional lives. We accomplished that to some degree, but the bigger impact was on me. As I saw and experienced the emotional strains of treating a steady stream of sick patients, I came to appreciate how growing a thick skin can protect the psyche.

The internists often asked me to talk with troubled patients who had tried seeing a psychiatrist and vowed “never again.” Some complained about spending fruitless months with a therapist who said little. Others complained about seeing a doctor for only a few minutes before being sent away with a prescription for a drug that caused side effects. A few told me that their lives had been transformed by a patient, caring therapist, and some described working closely with a doctor for months until finally finding a medication that worked. However, most patients who got good results never told anyone about their treatment, and I was rarely invited to see patients who were doing fine, so I saw many skeptics. I listened to them for hours each week for years, but I was so intent on convincing them to accept help that I never really heard their collective wail of frustration until Ms. A put it in a nutshell: the field of psychiatry is deeply confused.

That does not mean that psychiatric treatment is ineffective. When I told fellow medical students about my career choice, several put on sympathetic faces and said something like “Someone has to care for patients who can’t be helped.” That misconception is as unfounded as it is common. Almost all psychiatric problems can be helped, and treatment remarkably often provides an enduring cure. Patients with panic disorder and phobias get better so reliably that treating them would be boring if it were not for the satisfaction of watching them return to living full lives.

The woman whose agoraphobia had kept her from leaving her trailer for a year was, a few months later, driving to see her sister an hour away. The carpenter who came in with social anxiety so intense he could not eat lunch with coworkers came back a year later to tell us how much he enjoyed his new job giving public presentations all around the state. Even some patients with severe disorders get dramatic benefits. Last week I got an email out of the blue from a patient I saw twenty-five years ago, with a heartfelt spontaneous thank-you, saying that treatment of her severe obsessive-compulsive disorder had transformed and very likely saved her life.

Many books attack the field of psychiatry. This is not one of them. Yes, big money from big pharma results in more corruption in psychiatry than in some other medical specialties. And industry-funded advertising and professional “education” promote the profit-maximizing simplistic view that all emotional disorders are brain diseases needing drug treatment. However, the vast majority of psychiatrists I have known are caring, thoughtful doctors who work hard to help their patients by whatever means works. I recall one psychiatry resident who came in at 6 a.m. every day so his patients, who were mostly struggling with alcoholism, could get to work on time; he was still there at 7 p.m. Another psychiatrist friend took on the toughest borderline patients, despite knowing he would get midnight calls threatening suicide. Then there are the many psychiatrists who treat desperately depressed or psychotic patients, knowing that some will commit suicide and they will be blamed. Most of us lie awake some nights worrying about a patient in a crisis and wondering how to help. However, most patients get better, and the challenge of helping them makes the practice of psychiatry profoundly satisfying.

The challenge of understanding mental disorders is, by contrast, deeply unsatisfying. Several years into my work teaching psychiatry, I was frustrated as well as confused. The field seemed to be narrowing to the slogan “Mental disorders are brain diseases.” The phrase is great for marketing drugs, decreasing stigma, and soliciting donations, but it short-circuits clear thinking. Sometimes it is accurate, but it excludes valuable insights from behaviorism, psychoanalysis, cognitive therapy, family dynamics, public health, and social psychology. Practicing psychiatry based on only one perspective is like living within the walls of a medieval town. Trying to understand different perspectives is like visiting a series of walled towns. To see the whole landscape of mental illness requires a view from a mile high using special glasses that show changes across evolutionary as well as historical time.

What Causes Mental Disorders?

Like the six blind men each touching a different part of an elephant, each different approach to mental disorders emphasizes one kind of cause and a corresponding kind of treatment. Doctors who look for hereditary factors and brain disorders recommend drugs. Therapists who blame early experience and mental conflicts recommend psychotherapy. Clinicians who focus on learning suggest behavior therapy. Those who focus on distorted thinking recommend cognitive therapy. Therapists with a religious orientation suggest meditation and prayer. And therapists who believe most problems arise from family dynamics usually recommend, predictably, family therapy.

The psychiatrist George Engel recognized the problem in 1977 and proposed an integrated “bio-psycho-social model.”¹ Every year since has brought renewed calls for such integration, for the unfortunate reason that psychiatry’s fragmentation has, if anything, increased. The messy realities of mental disorders are ignored to fit them into the procrustean bed of one or another schema. Learned panels plead for integration, but committees that decide on grant funding and tenure only support projects that fit into narrow disciplines.

Plans for a recent revision of the diagnostic system aroused hope for greater coherence, but the result was increased conflict and confusion. The distinguished psychiatrist Allen Frances chaired the committee that wrote the previous edition of the book that defines each mental disorder, Diagnostic and Statistical Manual of Mental Disorders (DSM).² The title of his recent book captures his dissatisfaction with the revised edition of the DSM: Saving Normal: An Insider’s Revolt Against Out-of-Control Psychiatric Diagnosis, DSM-5, Big Pharma, and the Medicalization of Ordinary Life.³ Debates about diagnosis are so rancorous that they spill onto newspaper editorial pages. The crowning blow was the US National Institute of Mental Health (NIMH) abandoning the official DSM diagnoses for mental disorders.^4,5 So much for a common diagnostic system creating consensus!

The search for brain abnormalities that cause mental disorders has offered another hope for reducing confusion. In a medical school admission interview in 1969, I revealed, perhaps unwisely, that I planned to become a psychiatrist. “Why would you want to do that?” the interviewer asked. “They’re going to find the brain causes for mental disorders soon, and it will all become neurology.” If only that prediction had come true! However, four decades of research by thousands of smart scientists, supported by billions of dollars, has still not found a specific brain cause for any of the major mental disorders, except for those such as Alzheimer’s disease and Huntington’s chorea in which brain abnormalities have long been obvious. For other mental disorders, we still have no lab test or scan that can make a definitive diagnosis.

This is as astounding as it is disappointing. The brains of people with bipolar illness and autism must somehow be different from those of other people. But brain scans and autopsy studies have identified only small differences. They are real, but small and inconsistent. It is hard to say which are causes and which are results of the disorders. None comes close to providing a definitive diagnosis of the sort radiologists provide for pneumonia or pathologists provide for cancer.

Hope for diagnosis based on genetics has also collapsed. Having schizophrenia, bipolar disorder, or autism depends almost entirely on what genes a person has, so most of us engaged in psychiatric research at the turn of the millennium thought the specific genetic culprits would soon be found. However, subsequent studies have shown that there are no common genetic variations with large effects on these disorders.⁶ Almost all specific variations increase the risk by 1 percent or less.⁷ This is the most important—and most discouraging—discovery in the history of psychiatry. What it means, and what we should do next, are big questions.

Leading psychiatric researchers deserve credit for acknowledging the failure and the need for new approaches. In a recent article in the journal Science, several of them wrote, “There have been no major breakthroughs in the treatment of schizophrenia in the last 50 years and no major breakthroughs in the treatment of depression in the last 20 years. . . . This frustrating lack of progress requires us to confront the complexity of the brain. . . . This calls for a new perspective.”⁸ A recent meeting of the Society of Biological Psychiatry solicited presentations on the topic “Paradigm Shifts in the Treatment of Psychiatric Disorders.” And in 2011 the director of the National Institute of Mental Health, Thomas Insel, said, “Whatever we’ve been doing for five decades, it ain’t working. . . . When I look at the numbers—the number of suicides, the number of disabilities, the mortality data—it’s abysmal, and it’s not getting any better. Maybe we just need to rethink this whole approach.”⁹

Psychiatrists recognize patients’ life crises as opportunities for them to make major changes. Could the same be true for psychiatry?¹⁰

Finding the Future in the Evolutionary Past

The Museum of Natural History was a block south of our medical center. Opening the heavy iron door between two big lion sculptures brings you into the exhibit museum, a place I knew well from taking my kids to see dinosaur fossils. But this time I had an invitation to go through the doors marked STAFF ONLY to join a group of scientists who met weekly to discuss animal behavior. In the first hour, it became clear that their approach was completely different from anything I had learned before.

Instead of asking only about brain mechanisms, they also asked how natural selection shapes the brain and how behavior influences Darwinian fitness. Fitness is the technical term biologists use to refer to how many offspring an individual has that grow up to reproduce themselves. Some individuals have more offspring than others do, so their genetic variations become more common in future generations. Other individuals have fewer than the average number of offspring, so their genetic variations become less common. This process of natural selection shapes bodies and brains that work very well indeed to maximize Darwinian fitness in the natural environment.

Usually traits at some middle value are best. Rabbits vary in boldness. Exceptionally bold rabbits become fox dinners. Timid rabbits flee so fast they don’t get much to eat. Rabbits with intermediate levels of anxiety have more baby bunnies, so their genes become more common. Some people get so-called Darwin Awards for doing stupid things that eliminate them and their genes. The adventurous young man who strapped a rocket booster to his car was going 300 mph when he and his car flattened into a thin layer on a cliff side. Other people fear leaving the house. They don’t die young, but neither do they have many children. People with more moderate degrees of anxiety have more children, so most of us have intermediate levels of caution.

My new colleagues at the museum relied on a simple principle to explain why animals do what they do: selection shapes organisms to behave in ways that maximize their reproductive success. This is not a hypothetical theory; it is a principle that must be true. It provides what I was looking for—a new kind of biological explanation, not just for behavior but also for why organisms are the way they are.

After mostly listening for a few weeks, I finally got up my nerve and shared a theory I had come up with as an undergraduate. Aging is useful, I suggested, to ensure that some individuals die each year so the species can evolve faster when the environment changes. The group got suddenly quiet, but one biologist, Bobbi Low, laughed so hard she was sputtering as she said, “You really don’t know anything about evolution, do you?” It was a friendly laugh, the kind elicited by watching a puppy try to climb stairs. Bobbi and others explained that genes that benefit a species will nonetheless be eliminated if individuals with those genes have fewer than the average number of offspring.

Bobbi suggested that I read a 1957 paper by the evolutionary biologist George Williams. I stopped by the library on the way home and made a copy. As for so many before me, reading it transformed my view of life. Williams pointed out that a gene causing aging could become universal if it gives benefits early in life, when selection is stronger because more individuals are alive then.¹¹ For instance, a genetic variation that causes coronary artery calcification that kills many people by age ninety could nonetheless become universal if it also makes broken bones heal faster in childhood. His paper was so influential that a retrospective was published on its recent sixtieth anniversary.¹² Williams offered a completely different kind of explanation, not just for aging but also for diseases in general. If aging has an evolutionary explanation, what about schizophrenia, depression, and eating disorders?

Over the ensuing weeks, my new evolutionary biology colleagues helped me to recognize that everything in the natural world needs two kinds of explanations. The usual approach describes the body’s mechanisms and how they work; biologists call these proximate explanations. The other kind of explanation describes how those mechanisms came to be the way they are; biologists call these evolutionary or ultimate explanations.^13,14,15,16 My medical education had been entirely about the proximate half of biology, which describes mechanisms, none about the half that explains how bodies got to be the way they are.

Failure to recognize that evolutionary explanations are essential complements to proximate explanations causes enormous confusion. If you ask for an explanation of eyebrows, one person is likely to say they are explained by genes that induce synthesis of certain proteins in certain locations. Another might point out that you also need to describe the process by which eyebrows develop. Another will likely say you need to know about eyebrows in other primates. Someone will likely note that eyebrows keep sweat out of the eyes. And someone will likely raise an eyebrow to demonstrate its utility as a signaling device. The first two explanations describe proximate mechanisms; the others are about evolution.

The Nobel Prize–winning ethologist Niko Tinbergen expanded the distinction in a 1963 article that described what have come to be known as “Tinbergen’s Four Questions”: What is the mechanism? How does the mechanism develop in an individual? What is its adaptive significance? And what is its evolutionary history?¹⁷ After relying on them for years, I finally saw that two are proximate and two are evolutionary and that two are about a slice in time, while two are about change across time. They fit nicely into a neat two-by-two table. When I added a slide showing the table in my lectures, the audience was more interested in the table than in my talk. When I put a PDF of the table on my website, it spread fast.

TINBERGEN’S FOUR QUESTIONS, ORGANIZED¹⁸

	PROXIMATE	EVOLUTIONARY
SLICE IN TIME	What is the mechanism?	What is its adaptive significance?
SEQUENCE ACROSS TIME	How does it develop in an individual?	What is its evolutionary history?

Tinbergen’s questions made me recognize that some late-night debates with medical school classmates arose from mistakenly thinking the questions are alternatives. They aren’t. Answers to all four are necessary for a full explanation. The questions also made me realize that many things I had thought of as abnormal were actually useful. My medical education taught the details of the mechanisms in stomach cells that secrete acid and their role in causing ulcers but nothing about how stomach acid kills bacteria and digests food and why too little acid is as big a problem as too much. We learned all about the causes of diarrhea but little about its role in clearing toxins and infections from the GI tract. Coughing clears foreign matter from the respiratory tract. Fever is a carefully controlled response that fights infection. Even pain needs to be understood in terms of its function as well as its mechanisms; people born without the ability to experience pain usually die in early adulthood.¹⁹ I started to think about the utility of anxiety and low mood.

While many things that seem useless turn out to have a function, others are abysmal designs. The eye would be better without a blind spot. The birth canal is too narrow. Cancer protection mechanisms are insufficient, as are those that protect against infection. Ability to regulate eating is weak. Anxiety and pain are often excessive. I started wondering full-time about why selection left the body riddled with such imperfections.

When George Williams visited for a conference, he was easy to recognize; he looked remarkably like Abraham Lincoln. I knew his 1957 paper was admired, but no one had told me that he was one of the leading biologists of the twentieth century, certainly not Williams himself. He didn’t talk much, but when he did, everyone paid attention. Over beer, he explained how he had come up with his idea that selection can preserve the genes that cause aging. I saw a way to test his theory. It predicts that mortality rates should increase with age for some animals in the wild. The alternative theory, that genes for aging are outside the reach of selection, predicts that mortality rates should stay the same across the adult life span.

A few months of library work would be needed to find data on mortality rates for animals in the wild. I told my psychiatry department chair, John Greden, about my idea. He was new in the job and eager to encourage creativity, so he said I could devote half time to the project for the summer. By fall, I had found the data and a way to calculate how strongly selection was acting on aging in wild animals: very strongly indeed.²⁰ George’s theory was right: genes that speed aging are not all unfortunate mutations whose effects come too late in life to be eliminated by natural selection; some give advantages that increase reproduction earlier in life. The idea has been confirmed in many studies that bred beetles and fruit flies for longer or shorter life spans.^21,22 Selecting for earlier reproduction results in a shorter life span. Selecting for longer life span results in fewer offspring, especially in the wild. Aging has an evolutionary explanation.²³

By the next time George visited, I knew enough about evolutionary biology to have a coherent conversation, and my research on aging had been published. I told George I thought that evolution could offer a new kind of explanation not just for aging but for diseases. He had been thinking the same thing. We decided to write a paper about how evolution could be useful for medicine.

During the first several months of our work, we made a fundamental mistake: we tried to find evolutionary explanations for diseases. Why, we asked, did natural selection shape coronary artery disease? Why did it shape breast cancer? Why did it shape schizophrenia? Finally we recognized our mistake. We were Viewing Diseases As Adaptations (VDAA). VDAA is a serious error that remains common in evolutionary medicine. But diseases are not adaptations. They do not have evolutionary explanations. They were not shaped by natural selection. However, aspects of the body that make us vulnerable to diseases do have evolutionary explanations. Shifting the focus from diseases to traits that make bodies vulnerable to diseases was the crucial insight that became a cornerstone for evolutionary medicine.

We spent days discussing the appendix, wisdom teeth, inflammation in the coronary arteries, cancer, and, of course, the human back. George saw the implications more clearly than I did and insisted on giving our article the grand title “The Dawn of Darwinian Medicine.” Our book, Why We Get Sick: The New Science of Darwinian Medicine, reached a wider audience and encouraged the growth of what is now called evolutionary medicine. There are now a dozen books on the topic, a scientific society, a journal, international conferences, and classes in most major universities.

Evolutionary medicine is not a method of practice or in any way an alternative to standard medicine. It just uses the principles of evolutionary biology to solve health problems the same way we use genetics and physiology. Evolutionary psychiatry is the part of evolutionary medicine that asks why natural selection left us vulnerable to mental disorders.

The New Question

The usual questions in medicine are those of a mechanic: How does the body work? What is broken? Why did it break? How can we fix it? These are proximate questions about how bodily mechanisms work and how they differ in people with a disease: What immune system mechanisms cause multiple sclerosis? What brain abnormalities explain why some people have schizophrenia? Answers to these questions advance the most important goal: finding causes and ways to fix problems. Asking such questions and finding their answers has vastly improved human health. If medicine is to use only one-half of biology, this is the half with the big practical payoffs.

The other, evolutionary half of biology poses questions that take an engineer’s point of view: How did the body get to be the way it is? What selection forces shaped this trait? How do variations influence reproductive success? What trade-offs limit its reliability? In its general form, the new question asks, Why did natural selection leave our bodies with traits that make us vulnerable to disease?

The question is new, but it is close to one of the oldest questions. Why is life so full of suffering? Debated in religious and philosophical contexts for millennia as “the problem of evil,” answers have proved elusive.^24,25,26 The Greek philosopher Epicurus recognized the conundrum 2,400 years ago; a slight adaptation of David Hume’s terse summary is widely quoted: “Is God willing to prevent evil, but not able? Then He is not omnipotent. Is He able, but not willing? Then He is malevolent. Is He both able and willing? Then whence cometh evil? Is He neither able nor willing? Then why call Him God?”²⁷

Ever since, philosophers and theologians, especially those in the Abrahamic tradition, have struggled to explain evil and suffering. Possible explanations have a special name, “theodicies.” There are many of them, because none is fully satisfying.²⁸ The problem is also central to Buddhism, whose first noble truth is “Life is suffering.”^29,30 Its second noble truth is that suffering is caused by desire, more specifically the inability of ever fully satisfying desire. The third is that relief from suffering requires recognizing that desire is an illusion. An evolutionary view explains why we have desires, why we can’t satisfy them, and why it is so hard to set them aside: our brains were shaped to benefit our genes, not us.^31,32,33

Reconciling the ways of God to man is far beyond the scope of this book. Explaining the prevalence of evil and suffering in general is also out of reach. However, most suffering is emotional suffering. Anxiety and low mood exist for the same reason as pain and nausea: because they are useful in certain situations. They are often excessive for good evolutionary reasons. There are also good reasons why we are vulnerable to addiction, schizophrenia, and all the other mental maladies. Reasons plural, because several are relevant in different combinations depending on the disorder.

Trying to explain why mental life is so often painful, and why thinking and behavior so often go awry, reveals another equally profound question. How can mindless selection that maximizes only reproductive success have shaped brains that make committed loving relationships and meaningful happy lives possible? Most people’s lives are nothing like the selfish competition for money and sex imagined by naive Darwinians. People meditate, pray, cooperate, love, and care for others, even strangers. Our species is remarkably endowed, not only intellectually but also socially, morally, and emotionally. Understanding the origins of love and morality is a crucial foundation for understanding social anxiety and grief and the deep relationships they make possible.

Jonas Salk, the inventor of the polio vaccine, said, “What people think of as the moment of discovery is really the discovery of the question.” We have a new question.