But modern biology is pointing in a different direction. It is telling us that despite how certainty feels, it is neither a conscious choice nor even a thought process. Certainty and similar states of “knowing what we know” arise out of primary brain mechanisms that, like love or anger, function independently of rationality or reason. Feeling correct or certain isn’t a deliberate conclusion or conscious choice. It is a mental sensation that happens to us.

The importance of being aware that certainty has involuntary neurological roots cannot be overstated. If science can shame us into questioning the nature of conviction, we might develop some degree of tolerance and an increased willingness to consider alternative ideas — from opposing religious or scientific views to contrary opinions at the dinner table.

I call the mental sensation of certainty the “feeling of knowing.” Everyone is familiar with the most commonly recognized feeling of knowing. When asked a question, you feel strongly that you know an answer that you cannot immediately recall. Psychologists refer to this easily recognizable feeling as a tip-of-the-tongue sensation. The frequent accompanying comment as you scan your mental Rolodex for the forgotten name or phone number is: “I know it but I just can’t think of it.” You are aware of knowing something, without knowing exactly what this sensation refers to. The most profound feeling of knowing is the “aha,” a spontaneous notification from a subterranean portion of our mind, an involuntary all-clear signal that we have grasped the heart of a problem. It isn’t just that we can solve the problem; we “know” that we understand it.

To understand what I mean about the feeling of knowing, read the following paragraph at normal speed. Don’t skim, give up halfway through or skip to the explanation. Because this experience can’t be duplicated once you know the explanation, take a moment to ask yourself how you feel about the paragraph. After reading the clarifying word, reread the paragraph. As you do, pay close attention to the shifts in your mental state and your feeling about the paragraph:

A newspaper is better than a magazine. A seashore is a better place than the street. At first it is better to run than to walk. You may have to try several times. It takes some skill but it is easy to learn. Even young children can enjoy it. Once successful, complications are minimal. Birds seldom get too close. Rain, however, soaks in very fast. Too many people doing the same thing can also cause problems. One needs lots of room. If there are no complications it can be very peaceful. A rock will serve as an anchor. If things break loose from it, however, you will not get a second chance.

Is this paragraph comprehensible or meaningless? Feel your mind sort through potential explanations. Now watch what happens with the presentation of a single word: kite.

In an instant, you are flooded with the “aha” feeling that the paragraph makes sense. There’s no time for deep consideration and evaluation. Before you can reread the paragraph, your unconscious mind has already sorted through various possibilities, determined that the sentences collectively fit the description of a kite and sent you notification.

Determining how this involuntary feeling of knowing happens takes us into the enormously complicated details of neurobiology. To simplify them for this discussion, let me borrow a term, “hidden layer,” from the artificial intelligence community.

By mimicking the way the brain processes information, A.I. scientists have been able to build artificial neural networks (ANNs) that can play chess and poker, read faces, recognize speech and recommend books at Amazon.com. While standard computer programs work line by line, yes or no, all eventualities programmed in advance, the ANN takes an entirely different approach. The ANN is based upon mathematical programs that are initially devoid of any specific values. The programmers only provide the equations; incoming information determines how connections are formed and how strong each connection will be in relationship to all other connections. There is no predictable solution to a problem — rather, as one connection changes, so do all the others. These shifting interrelationships are the basis for “learning.”

With an ANN, the hidden layer is conceptually located within the interrelationships between all the incoming information and the mathematical code used to process it. In the human brain, the hidden layer doesn’t exist as a discrete interface or specific anatomic structure; rather, it resides within the connections between all neurons involved in any neural network. A network can be relatively localized or widely distributed throughout the brain. Proust’s taste of a madeleine triggered a memory that involved visual, auditory, olfactory and gustatory cortices — the multisensory cortical representations of a complex memory. With a sufficiently sensitive fMRI scan, we would see all these areas lighting up when Proust contemplated the madeleine.

The hidden layer thus offers a powerful metaphor for the way the brain processes information. It is in the hidden layer that all elements of biology (from genetic predispositions to neurotransmitter variations and fluctuations) and all past experience, whether remembered or long forgotten, affect the processing of incoming information. It is the interface between incoming sensory data and a final perception, the anatomic crossroad where nature and nurture intersect. It is why your red is not my red, your idea of beauty isn’t mine, why eyewitnesses offer differing accounts of an accident or why we don’t all put our money on the same roulette number.

The powerful feeling of knowing arises out of the hidden layer’s unconscious calculation of correctness, be it recognizing a face or believing an idea is right. The greater the likelihood of correctness, as determined by your unconscious, the stronger the sense of certainty.

In his bestselling “Blink,” New Yorker staff writer Malcolm Gladwell describes gut feelings as “perfectly rational,” as “thinking that moves a little faster and operates a little more mysteriously” than conscious thought. But he’s flying in the face of present-day understanding of brain behavior. Gut feelings and intuitions, the Eureka moment and our sense of conviction, represent the conscious experiences of unconsciously derived feelings.

Look at the feeling of knowing in the light of evolution. It explains how we learn. Compare it with the body’s various sensory systems. It is through sight and sound that we are in contact with the world around us. Similarly, we have extensive sensory functions for assessing our interior milieu. When our body needs food, we feel hunger. When we are dehydrated and require water, we feel thirsty. If we have sensory systems to connect us with the outside world, and sensory systems to notify us of our internal bodily needs, it seems reasonable that we would also have a sensory system to tell us what our minds are doing.

To be aware of thinking, we need a sensation that tells us that we are thinking. To reward learning, we need feelings of being on the right track, or of being correct. And there must be similar feelings to reward and encourage the as-yet unproven thoughts — the idle speculations and musings that will become useful new ideas.

To be an effective, powerful reward, the feeling of conviction must feel like a conscious and deliberate conclusion. As a result, the brain has developed a constellation of mental sensations that feel like thoughts but aren’t. These involuntary and uncontrollable feelings are the mind’s sensations; as sensations they are subject to a wide variety of perceptual illusions common to all sensory systems. Understanding this couldn’t be more important to our sense of ourselves and the world around us.

It’s not easy, of course, but somehow we must incorporate what neuroscience is telling us about the limits of knowing into our everyday lives. We must accept that how we think isn’t entirely within our control. Perhaps the easiest solution would be to substitute the word “believe” for “know.” A physician faced with an unsubstantiated gut feeling might say, “I believe there’s an effect despite the lack of evidence,” not, “I’m sure there’s an effect.” And yes, scientists would be better served by saying, “I believe that evolution is correct because of the overwhelming evidence.”

I realize that this last sentence runs against the grain of those who have fought the hardest to establish science as the method for determining the facts of the external world. It is particularly loathsome when you feel that you are playing into the hands of religious fanatics, medical quacks and word-twisting politicians. But in pointing out the biological limits of reason, including scientific thought, I’m not making the case that all ideas are equal or that scientific method is mere illusion. My purpose is not to destroy the foundations of science, but only to point out the inherent limitations of the questions that science asks and the answers it provides.

Substituting believe for know doesn’t negate scientific knowledge; it only shifts a hard-earned fact from being unequivocal to being highly likely. Saying that evolution is extremely likely rather than absolutely certain doesn’t reduce the strength of the argument, and at the same time it serves a more fundamental purpose. Hearing myself saying “I believe” where formerly I would have said “I know” serves as a constant reminder of the limits of knowledge and objectivity. At the same time as I am forced to consider the possibility that contrary opinions might have a grain of truth, I am provided with the perfect rebuttal for those who claim that they “know that they are right.” It is in the leap from 99.99999 percent likely to 100 percent guaranteed that we give up tolerance for conflicting opinions, and provide the basis for the fundamentalist’s claim to pure and certain knowledge.

A related consideration is to distinguish between felt knowledge — such as hunches and gut feelings — and knowledge that arises out of empiric testing. Any idea that either hasn’t been or isn’t capable of being independently tested should be considered a personal vision. Shakespeare does not demand that we accept Hamlet as representing a universal truth. We agree and judge him according to the standards of art, literature and personal experience. Hamlet is neither right nor wrong. If in the future, Hamlet is found to have a gene for bipolar disorder, we are entitled to reassess our initial interpretations of Hamlet’s relationship to his mother. Hamlet is a vision. No matter how seemingly reasonable and persuasive, each begins with a very idiosyncratic perception that seeks its own reflection in the external world. Each writer’s personal sense of purpose drives the arguments, picks out the evidence and draws conclusions. Such ideas should be judged accordingly — as visions, not as obligatory lines of reasoning that must be universally shared.

To retreat from claims of absolute “knowing” and certainty, popular psychology needs to explore how mental sensations play a fundamental role in generating and shaping our thoughts. We can’t afford to continue with the outdated claims of a perfectly rational unconscious or knowing when we can trust gut feelings. We need to rethink the very nature of a thought, including the recognition of how various perceptual limitations are inevitable.

At the same time, if the goal of science is to gradually overcome deeply embedded superstition, it must be seen as a more attractive and comforting alternative, not as inflammatory exhortation and confrontation with a none-too-subtle whiff of condescension. Try to peddle the vision of a cold, pointless world at a Pentecostal revival meeting and you have an inkling of the challenge. In a recent survey, nearly 90 percent of Americans expressed the belief that their souls will survive the death of their bodies and ascend to heaven. Such beliefs, no matter how counter to the evidence, provide the majority of Americans with a personal sense of meaning. If forced to choose between reason and a sense of purpose, most of us would side with purpose. This apparent choice isn’t even an entirely conscious decision. If science hasn’t yet made a dent in such beliefs, it seems unlikely that further efforts will miraculously turn the tide.

Such discussions pose the same ethical problems inherent in placebo treatments. Simply put, a placebo effect is a false belief that has real value. To insist that there is no soul or afterlife is the moral equivalent of taking away the placebo effect arising out of an unscientific belief. Studies have shown that sham arthroscopic surgery can allow some patients to walk comfortably again. No one should recommend sham knee surgery, yet many physicians are comfortable recommending less drastic but unproven treatments for pain.

The answer lies in a personal risk-reward calculation — how to provide comfort without undue side effects or cost. But the intentional use of a placebo comes at a cost. Even without side effects or excessive cost, the precedent of falsely representing benefits of a treatment has its own long-term undesirable effects. The most serious would be the erosion of trust between the physician and patient. On the other hand, eliminating all placebo treatments because they are intellectually dishonest raises its own set of problems, including the cynical zeitgeist of valuing science over compassion. There isn’t an easy solution or right answer; each of us will calculate the risk versus reward according to our own biology and experience.

In medicine, we are increasingly developing ethical standards for complex medical decisions that allow for hope and the placebo effect, yet don’t fly in the face of evidence-based medical knowledge. The guiding principle of the Hippocratic oath is primum no nocerum — above all, do no harm. This same principle should be a cornerstone of how science competes in the world of ideas. Science needs to maintain its integrity while it retains compassionate respect for aspects of human nature that aren’t “reasonable.”

This balance of opposites extends to all aspects of modern thought. For example, it doesn’t make sense to ask someone if he’d like to take a placebo; the very question strips the placebo of much of its intended benefit. Similarly, it isn’t clear how to have a reasonable discussion on the nature of the self that both maintains the integrity of science — the self is an emergent phenomenon and not some separately existing entity — and allows each of us to feel that we are individuals and not mere machinery. I cannot imagine a world in which we fully accepted and felt that we were nothing more than fictional narratives arising out of “mindless” neurons. And I cannot imagine how much empathy we would have with others if we saw disappointment, love and grief solely as chemical reactions. Faced with this chilling interpretation of our lives, it isn’t surprising that most people opt for the belief in material “souls” and/or anticipate that real live virgins are patiently awaiting their arrival in heaven.

F. Scott Fitzgerald described an easy-to-accept but difficult-to-accomplish solution: “The test of a first rate intelligence is the ability to hold two opposed ideas in the mind at the same time and still retain the ability to function.” This juggling act requires us to keep in mind what science is telling us about ourselves while acknowledging the positive benefits of nonscientific or unreasonable beliefs. Each opposing position has its own risks and rewards; both need to be considered and balanced within the overarching mandate — above all, do no harm.

Just as we learn to cope with the anxieties of sickness and death, we must learn to tolerate contradictory aspects of our biology. Our minds have their own agendas. We can intervene through greater understanding of what we can and cannot control, by knowing where potential deceptions lurk, and by a willingness to accept that our knowledge of the world around us is limited by fundamental conflicts in how our minds work.

Which leads us back to the beginning. Certainty is not biologically possible. We must learn (and teach our children) to tolerate the unpleasantness of uncertainty. Science has given us the language and tools of probabilities. That is enough. We do not need and cannot afford the catastrophes born out of a belief in certainty.

From “On Being Certain” by Robert A. Burton, M.D. © 2008 by the author and reprinted by permission of St. Martin’s Press.

What makes Gopnik’s book stand out from the myriad recent books on consciousness is her overarching insight into the sophisticated ways that even infants think and scheme. Citing her work and that of colleagues, Gopnik makes a convincing case that, from a very early age, even before the acquisition of language, we are actively engaged in assessing everything from statistics (probabilities) to right vs. wrong in a moral sphere. Recently I sat down with Gopnick for a conversation about how each of us began our thinking, and how kids might presently be looking at the world.

What inspired you to study the “philosophical baby”?

I’ve know since the first time I read Plato, when I was 11, that I wanted to try to think about some of the great philosophical questions. How do we know about the world? How do we understand other people? What is consciousness? Where does morality come from? But by the time I was 11, I was also the oldest child of six siblings and I had the first of my own three babies when I was 23. So I’ve also always wanted to try to answer some equally deep questions about children themselves. How can they learn so much so quickly? What is it like to be a baby? Why do we love them so much?

Like most parents, I think, my children have been the source of some of my most intense joys and despairs, my deepest moral dilemmas and greatest moral achievements. Childhood is a fundamental part of all human lives, parents or not, since that’s how we all start out. And yet babies and young children are so mysterious and puzzling and even paradoxical. They seem so unlike us, yet they actually are us. Sometimes they seem so brilliant, and then the next minute they do something that seems so dumb.

When you read about children, either in ubiquitous parenting books or in memoirs and autobiographies, all you get is the personal. What should I do to make my baby smarter? What did my parents do to make me who I am? The idea of the book was to take a step back from the personal and immediate and think about babies and young children from this wider scientific and philosophical perspective. Thinking about babies could help us understand philosophy and thinking philosophically could help us understand babies.

Why do you think so little has been written about the philosophy of children — that philosophy, for 2,500 years, has essentially excluded thinking about kids?

There are two reasons. Philosophers used to rely on their armchair intuitions about how minds work. If you look at babies casually, your intuition is likely to be that not much is going on. In the ’70s, new video technologies allowed us to develop experimental techniques for investigating babies’ minds. Since then, philosophers are increasingly paying attention to these scientific results, rather than simply relying upon untested intuitions.

The other reason was that for those 2,500 years, there were people who had a great deal of deep experience of babies and who knew all along how important and interesting babies were. But those people were women and the philosophers were men. An Oxford philosopher once told me, “Well, one has seen children about, of course, but one would never actually talk to them.” Now, partly because women like me have become scientists and philosophers, those two areas of human experience don’t seem so separate.

One of the difficulties in knowing how babies think is that they can’t describe their thought processes. Yet psychologists have devised some very ingenious experiments to show that by age 12 to 15 months, infants with very limited vocabulary are already developing a clear cause-and-effect sense of how the world is put together. Without the benefit of much language, how do you think the brain creates this knowledge?

Alan Turing had one of the greatest scientific insights of the 20th century, when he realized that a physical system that was organized in a particular way could do many of the things that a human mind can do. That idea allowed us to build computers, physical systems that can reason and calculate without language or consciousness. The great idea of cognitive science is that the human brain is a computer — though one profoundly different and vastly more powerful than the ones we have now. Once this idea was out there, it made sense to think that babies’ brains were just as capable of computation as adult brains, even though babies might not be able to report what their brains were doing in a self-conscious reflective way. And that’s just what we’ve discovered. In fact, studying babies can give us new ideas about how to design learning computers.

Presumably, if present in very young infants, this ability must be innate, as if our brains are hard-wired to sort out cause-and-effect even before we acquire language.

Well, developmental psychologists won’t say something is innate unless we’ve found it in newborn babies — which is tough, but remarkably, not at all impossible! So babies might actually somehow develop these causal learning methods in the first few months of life. But they certainly are there very early.

How is this different from the ways in which other animals learn about the world?

Animals are certainly more sophisticated than we used to think. And we shouldn’t lump together animals as a group. Crows and chimps and dogs are all highly intelligent in very different ways. Crows are amazingly sophisticated at understanding how physical objects like wires and twigs work. Living with us seems to have led dogs to evolve to be enormously clever at making people think they are loved. You could think of them as Stepford Wolves. But in a way that’s just the point. Animals seem to home in on very particular kinds of causal relationships that are important to their survival. They also rely heavily on trial and error to learn which actions are effective on the world. But human children learn abstract cause-and-effect relationships just for the fun of it, even when they’re not particularly relevant to survival.

Old-line psychologists such as Piaget thought that children didn’t understand cause-and-effect until they were well into their school years. Why didn’t earlier psychologists notice that young children could easily construct complex theories of causation?

Piaget observed babies tremendously closely and he realized just how philosophically important and interesting they were — though much of the observation was actually done by his wife, Valentine. But even closely observing young children doesn’t really tell you what they can do. For example, we’ve discovered that young children have much better cued memory than spontaneous recall. If you ask a 3-year-old an apparently straightforward question like “How does this machine work?” you’re likely to get a sweet look and either silence or stream of consciousness poetry. But if you ask them, “Does the blue block make it go or does the yellow block make it go?” they will give you the right answer. You have to ask babies and children questions in their language, not ours. It’s taken us 30 years to figure out how to do that, and we’re still learning.

Very young children readily imagine a variety of outcomes to any given situation. For example, 2-year-olds can tell you that if their imaginary teddy bear is drinking imaginary tea and spills it, the imaginary tea will have to be mopped up. Is this ability to imagine the what-ifs of life what most separates human from non-human thought?

I think so, though again animals are smarter than we thought. Still, humans have a special ability to think “counterfactually,” to imagine what might have happened rather than remember what did happen, and animals certainly don’t do that as much as we do. For better or worse, we live in possible worlds as much as actual ones. We are cursed by that characteristically human guilt and regret about what might have been in the past. But that may be the cost for our ability to hope and plan for what might be in the future.

If the ability to imagine cause-and-effect begins before children have well-developed language and reasoning skills, does this tell us that the origins of the kinds of questions we ask are also deeply rooted in our biology?

Well, of course, everything about us is rooted in our brains. But brains aren’t fixed by our genes. Instead they are dramatically plastic, capable of changing to fit all those new environments we encountered when we started our Pleistocene wanderings, and the even more remarkable new environments we create for ourselves. Asking questions is what brains were born to do, at least when we were young children. For young children, quite literally, seeking explanations is as deeply rooted a drive as seeking food or water. What we do as scientists and philosophers is an extension of that childhood drive — the questions keep changing but the drive to ask them is what makes us human.

I remember my mother quoting Dr. Spock as “the authority” on child rearing. Now there are theories to satisfy any parenting position. Some psychologists such as Judith Harris have gone so far as to suggest that parenting has little long-term effect on how children think. Where do you weigh in?

This is an interesting case of the way that scientific importance and everyday interests are at odds. Parents tend to focus on very small differences — like whether my kid will be more likely to get into Harvard than yours — among children who are otherwise living in very similar environments. But, scientifically, we wouldn’t expect to be able to say much about differences at that scale. We can’t predict very much about how my parenting, as opposed to that of my friends, will influence my child as opposed to theirs, which is what all those parents want to know.

What do you think makes one a better parent?

Well, I can tell you what won’t make you a better parent or your child any smarter. The science can tell you that the thousands of pseudo-scientific parenting books out there — not to mention the Baby Einstein DVDs and the flash cards and the brain-boosting toys — won’t do a thing to make your baby smarter. That’s largely because babies are already as smart as they can be; smarter than we are in some ways. In the relationship between early experience and later life, there is not a shred of scientific evidence that any of that makes a difference.

That doesn’t mean, as people like Judith Harris say, that parenting itself doesn’t make a difference. It makes an enormous difference. Even the most self-consciously “bad” parent is already putting a lifetime’s worth of effort and energy and care and devotion into the life of their child, effort and care and love that would be saintly if you devoted it to anyone else. It also isn’t that there’s some innate program that requires just a minimal amount of nurturing to unfold. Specific changes and differences in caregiving make a vast difference. Reading and schooling have made an enormous difference to children. Poverty has an enormous impact on children. Children learn all the contours of daily life from their parents. To conclude that parenting has no effect is like saying that because I can’t tell you specifically whether carbon emissions will cause a hurricane in New Orleans this year, global warming has no effect on the weather.

There’s a more profound philosophical, and even moral point, here. We can’t predict much about how our parenting will influence our children in the long term. Many people may achieve great things as adults, in spite of or even just because of, the fact they were miserable as kids. But we have enormous power over our child’s lives when they are children. We can determine whether our children thrive as children, and whether they remember that thriving childhood as adults. Isn’t that actually more important? Instead of anxiously asking will my caregiving make my son go to Harvard 20 years from now, why not proudly think my caregiving will make my son have just the life that I shape for him, right now, with my particular jokes and quirks and devotion?

Do you think your work has made you a better parent?

Being a developmental psychologist didn’t make me any better at dealing with my own children, no. I muddled through, and, believe me, fretted and worried with the best of them. But I think it did make me even more appreciative of the richness and complexity of children’s minds, and watching them certainly made me a better scientist.

In the ’80s, as I began to wonder how we come to understand others people’s minds, my 2-year-old, Andres, had to cope one night with pineapple with kirsch as dessert. For months afterward, he would thoughtfully remark, apropos of nothing, “Mommy, you know, pineapples — they’re yummy for you but yucky for me.” And that became the germ for a whole line of studies that showed that toddlers are far from being the egocentric solipsists we once thought, and how they, and therefore we, start to understand that other people can want something different than we do.

Children, by being less focused, have a greater general awareness and ability to imagine than us older fossils. Is there a take-away message for how to maximize a child’s free spirit and imagination while, at the same time, forcing her to spend the hours necessary to learn algebra, geometry and the capital of Peru?

The message is that there is a necessary trade-off between two different kinds of intelligence — a trade-off built right into our evolutionary nature. On the one hand, there is our childhood ability to imagine and explore a very wide range of possibilities and to learn new causal maps without caring about their immediate usefulness. On the other, there is our adult ability to put that learning to work to plan and act effectively, swiftly and automatically. Babies and young children are useless on purpose. They are unable to focus, plan and act, so they can wander and dream and play. We grown-up caregivers do the planning and acting for them.

For most of history, education, in the form of apprenticeship, was about turning the discoveries of early childhood into the narrow, focused, automatic competencies of adulthood. But sometime in the 17th century, we discovered that we could reproduce this evolutionary division of labor among adults. We could have professional scientists, for example, who just got to explore and learn about the world without exploiting it for any useful purpose. And we could have institutions like universities, where adults got to do the same thing. Or at least were supposed to; the real function of universities is mostly assortative mating. So we began to try to develop both types of intelligence at once, to have a school system that rewards flexibility and imagination and competence at the same time.

I think we should encourage a kind of cognitive bilingualism in both adults and children. We should have times in our lives or institutions when we can learn and explore and play, and other times in which we can plan and execute and work. An unsung joy of caregiving and child rearing is that it gives you a wonderful opportunity to recapture the imagination and play of childhood at the same time that you’re doing the most important kind of adult work there is.

“The Philosophical Baby” is not exactly a how-to book for parents. But if it were, what can reading it do for parents?

It will do the same thing that reading about the stars does. You gaze up at the stars and they’re awesome. And then you read about astronomy and the next time you gaze at the stars you realize, “My God, they really are awesome.” Parents gaze at their children, when they’re not driving themselves crazy with parenting books, and think, “They’re amazing!” And what I can tell them is, “You don’t know the half of it, they’re even more amazing than you think!”

Since its original description in the late ’70s, experts have held widely divergent views about the cause of fibromyalgia; some even doubt that it is a real condition. Recently, though, with the advent of fMRI scans, researchers have shown that patients with fibromyalgia have different responses to pain than the “normal” population. This discovery holds out “proof” that fibromyalgia is a definitive organic condition requiring specific treatment. That may be good news for people who suffer from the mysterious condition, but it’s great news for the pharmaceutical industry, which can march to the U.S. Food and Drug Administration and seek authorization for a drug to cure the now official disease. Which is exactly what Pfizer did in 2007, earning approval to treat fibromyalgia with Lyrica, already a blockbuster drug.

But hold on. Is that possible? Can an fMRI scan determine the presence or absence of disease? To date, no evidence convincingly shows that fMRI, designed to measure cerebral metabolism, is sufficient to diagnose a specific underlying disease. So what’s going on here?

Let’s begin with a closer look at fibromyalgia itself. Despite strong convictions on all sides, nobody knows whether fibromyalgia is a primary medical condition, part of a larger constellation of other ill-defined conditions, such as chronic fatigue or irritable bowel syndrome, or a label given to a variety of physical complaints that arise out of various mental states, such as anxiety and depression. There haven’t been any reproducible and clear-cut objective findings, such as blood and lab tests, X-rays or anatomical abnormalities on biopsy, to provide a satisfactory understanding of the disease. Even the 1990 American College of Rheumatology diagnostic criteria — widespread muscle pain of more than three months, unassociated with other known illnesses, and the presence of at least 11 tender points over 18 muscle groups — are nothing more than subjective patient descriptions.

By the way, I don’t mean to denigrate patients who experience pain associated with fibromyalgia. My concern is the notion that an fMRI can distinguish between psychological states and so-called “organic” processes that affect how we experience pain. And how patients and physicians respond to the uncertainty of fibromyalgia is often dependent on how they think about “real” vs. “imagined.” Popular mythology has it that if you have physical complaints that arise out of worry and anxiety, the symptoms aren’t as “real” as if they are caused by disease. But this distinction between “real” and “imagined” is both philosophically naive and unfair to patients with psychological conditions.

If you think an inert sugar pill (placebo) is a powerful analgesic, taking it can reduce your level of pain from, say, a dental procedure or wear-and-tear arthritis. Conversely, if you are given the same sugar pill and told it is a new untested drug and might make your pain worse, you might experience more pain (nocebo effect). Your imagined expectation of what the pill might do will affect both your pain perception and what changes will be seen on functional brain imaging. Nowhere in this schema is there any suggestion that changes in pain perception arising out of imagination aren’t real. Placebo-induced relief of pain is clinically identical to pain relief from standard analgesics such as morphine.

Now consider one of the central features of fibromyalgia — an increased number of areas sensitive to ordinary pressure. If you believe you have a condition that makes you more sensitive to painful stimuli, you may well experience more pain than those who believe they aren’t sensitive to painful stimuli. This difference in pain appreciation or description, and the attendant brain changes on fMRI, will not reflect any underlying disease; both will be the reflections of your own self-perception. Even such personality traits such as optimism or pessimism (half-empty vs. half-full), or one’s attitudes toward the medical establishment, can make critical differences.

With this basic principle in mind, let’s look at what fMRI studies are telling us about fibromyalgia. In 2002, Georgetown University researchers compared how 16 women with fibromyalgia and 16 pain-free control subjects responded to both painful and nonpainful stimuli (a small piston generating various amounts of pressure to a thumbnail bed). They found that control subjects required more than twice the amount of pressure to elicit the same degree of pain and fMRI activation as fibromyalgia patients.

The authors concluded: “These results, combined with other work done by our group and others, have convinced us that some pathologic process is making these patients more sensitive. For some reason, still unknown, there’s a neurobiological amplification of their pain signals.”

Perhaps that is true, but amplification of pain signals can also occur simply from imagining an increased pain, as seen with the nocebo effect. So can simple anxiety.

In a subsequent 2007 study, the researchers used the same pain-eliciting techniques but different functional brain scans to look for differences between fibromyalgia patients and controls. This time they found a single region of altered activity between fibromyalgia patients and control subjects — in the right thalamus. The severity of this difference correlated with the degree of fibromyalgia symptoms; the greater the difference, the worse the patient’s symptoms were likely to be. The authors speculate that the findings “are likely the result of neuronal dysfunction.”

But a closer look at this study suggests an alternative interpretation, one more consistent with the notion of how anticipation and expectation can alter brain function.

The researchers found fibromyalgia patients who believe their pain is the result of some external factor, such as a prior injury or exposure to toxic chemicals, experience a higher degree of altered activity on imaging studies. That belief also leads to a higher depression rating on the study questionnaire. The authors comment that attributing clinical symptoms to an external source, even in the absence of clear-cut evidence, is a characteristic feature of chronic pain patients who don’t respond well to treatment.

In short, the described functional imaging findings correlate with patient expectation and belief. What we can’t know is whether the beliefs cause the functional change or are the result of the alleged change. And, more important, there is nothing on the scan to point to whether this activity is or isn’t “normal.” Nevertheless, the authors conclude, “there is really something wrong going on in the brains of the patients with fibromyalgia.”

Of course there is a physiological explanation for the pain of fibromyalgia. Ultimately there is a physiological explanation for all experience, whether it be pain, love or the hallucinations of acute psychosis. The issue isn’t whether a condition is associated with “brain changes” on functional imaging, but whether such changes reflect a specific organic disease as opposed to a psychological state of mind.

And let’s not kid ourselves. Researchers at big pharmaceutical companies are fully aware of the subtleties of how fMRI is performed and what interpretations can be drawn from even questionable studies. They realize that studies on chronic pain are notoriously difficult to interpret and prone to faulty interpretations. They understand overall results can be skewed by underestimating or misassigning the placebo effect. But the stakes are enormous; finding medical literature to support a claim that will dramatically boost sales is like striking gold.

Once a condition has been “authenticated,” it’s only a matter of time before Big Pharma steps in with a treatment. Armed with such “objective” fMRI evidence that fibromyalgia is a bona fide condition, Pfizer undertook a series of clinical studies that showed that some patients with fibromyalgia did experience at least partial relief of symptoms with Lyrica. (On a scale of 1 to 10, the fibromyalgia patients achieved an average reduction in symptoms of 2, whereas the controls given placebo had a 1 point reduction.)

As the result of these studies, in 2007, the FDA approved the use of Lyrica for the treatment of fibromyalgia. (Since the approval in 2007, it has been estimated that worldwide sales of Lyrica have increased 30 percent, to well over $2 billion annually.) Without making specific claims about what fibromyalgia is or how Lyrica works, Pfizer, on its Web site, states that “recent research suggests that changes in the central nervous system may be responsible for the chronic pain that comes with fibromyalgia.” It adds that nerve damage may occur because of an infection or injury.

Suggesting that patients with fibromyalgia might have altered or damaged brain cells is based in part on fMRI studies. From there it’s a short commercial step to suggesting that there could be an underlying infection or injury to fibromyalgia, for which there is no convincing evidence to date.

What isn’t mentioned on the Pfizer’s fibromyalgia Web site is that Lyrica has been approved in Europe for the treatment of generalized anxiety. Lyrica was shown to be effective in providing relief of both emotional symptoms, such as depressive symptoms and panic, as well as physical symptoms, including headaches and muscle aches. Yes, another way of thinking about the benefit of Lyrica is that it helps relieve the muscle aches and pains associated with generalized anxiety and that these may be the same aches and pains as described by patients diagnosed with fibromyalgia. (Without objective lab studies, this distinction is impossible to make.)

Now, perhaps a counterargument could be made that the fMRI changes in fibromyalgia are different than those with generalized anxiety. But to make this argument, we would need to have clear-cut and reproducible findings specific to fibromyalgia, and we should know precisely what such specific regional differences mean, from what the brain is doing to how accurately these changes predict both behavior and what the person is experiencing. So far, we have none of the above.

The fMRI is a wonderful, rapidly evolving technology; much of the research is in its infancy and will undoubtedly change as both the machinery and our understanding of the techniques improve. Meanwhile, the follies of bad and excessive interpretations continue to be both well documented and generally overlooked in the popular press. Of these excesses, I can imagine none with more potential for harm than “objectifying” a clinical syndrome without good peer-reviewed additional data.

The primary tenet of medicine is to do no harm. Everyone involved in the study of controversial conditions such as fibromyalgia — physicians, researchers, pharmaceutical companies and the FDA — has a huge moral obligation to be sure that questionable conclusions aren’t foisted on the public as the final word, particularly without a clear understanding of whether such claims have their own adverse side effects. If beliefs change brain function, false beliefs in the mechanism of a condition can have real and lasting adverse effects.

If a patient believes that there is something “wrong with my brain,” the effects can be disastrous. Anyone who has been told of a possible abnormality on a lab test knows how hard it is to shake off that disturbing knowledge even when repeat studies turn out to be normal. If a single lab test result can generate persistent anxiety despite contrary evidence, imagine the degree of negative expectation generated in those with fibromyalgia when they watch the woman in the Pfizer TV ad claim “my fibromyalgia is real.” If negative expectation (the belief that you are more sensitive to pain than others because of a condition that has altered your pain perception) plays a significant role in the production of fibromyalgia symptoms, Pfizer runs the risk of creating or augmenting the very symptoms it is trying to treat. Talk about a vicious feedback loop!

Before jumping to conclusions about diseases and their causes, we need a more comprehensive and philosophical approach to how we integrate new technologies with basic understanding of human nature. We need to look at how thoughts, beliefs and expectations can generate or affect physical symptoms, and vice versa. And we need to abandon concepts like “real” and “all in your head” once and for all.

It’s astounding that a trait normally considered admirable — one usually sought out in choosing personal relationships, colleagues and associates — is now seen as synonymous with being emotional and partisan, as though being empathetic makes one less rational and reasonable. It’s understandable, given the deplorable nature of partisan politics, that conservative critics would come up with a unified denouncement of whomever Obama chooses. But why settle on an argument that flies in the very face of modern cognitive science and the understanding of how our brains function?

At the heart of the misunderstanding are erroneous assumptions that stripping empathy from decision-making will necessarily improve the quality of the decision, and that one has the ability to consciously control his or her feelings of empathy.

Anyone familiar with modern psychology is aware of the concept of emotional intelligence — that good decisions combine reason and awareness of one’s feelings. As many recent popular cognitive science books have pointed out, the vast majority of our thoughts originate outside of awareness. They stem from neural networks that silently combine our basic biological predispositions with past experience, both remembered and long-forgotten. Present at the very origin of our thoughts, and integral to the final shape of each of our decisions, are the various inherent biological traits that make each human unique.

For example, someone who’s prone to taking risks will have a different perspective on any risk-reward decision than someone who is inherently timid. These differences don’t begin as conscious choices; our biology guides our thoughts in these varying directions. Part of this difference is as basic as our DNA, such as a gene for dopamine-receptor activity being strongly correlated with risky behavior.

Studies on empathy reveal a similarly strong biological component. Even at a personal experiential level, we suspect that some people are naturally more empathetic than others. How much empathy can be achieved through parenting and proper education remains an open question. But such efforts are the hallmarks of how civilized people can overcome the barbarism of pure self-interest. The converse, trying to avoid feelings of empathy, hardly seems like a noble goal.

Until the recent criticism of Obama’s mention of what he seeks in a Supreme Court justice, I had never heard of or considered how empathy might impair judgment. After all, sound judgment is based upon considering all possible information that is available, rather than discarding observations or feelings that aren’t strictly “reason-based.” Furthermore, having a feeling doesn’t mean that you must act on it — unless you believe we have no element of free will, not even the veto power over biased thoughts.

The idea that we can cleanse our thoughts of allegedly negative influences arising out of empathy is profoundly misguided. Listen to the argument of Richard Epstein, a legal scholar and professor of law at the University of Chicago. “Empathy matters in running business, charities and churches,” he argues. “But judges perform different functions. They interpret laws and resolve disputes. Rather than targeting his favorite groups, Obama should follow the most time-honored image of justice: the blind goddess, Iustitia, carrying the scales of justice.” Only one who subscribes to the scientifically outdated notion that we can step back from our thoughts in order to judge them, and strip them of unconscious and emotion-laden influences, could come up with such a half-baked idea.

But to play devil’s advocate, what if one could eliminate empathy from decision-making? Exactly how would this improve our thinking on complex moral issues? Consider for a moment Harvard neuroscientist Joshua Greene‘s view of a famous moral philosophy dilemma:

“A runaway trolley is hurtling down the tracks toward five people who will be killed if it proceeds on its present course. You can save these five people by diverting the trolley onto a different set of tracks, one that has only one person on it, but if you do this that person will be killed. Is it morally permissible to turn the trolley and thus prevent five deaths at the cost of one? Most people say “Yes.’”

Now consider a second scenario. “Once again, the trolley is headed for five people. You are standing next to a large man on a footbridge spanning the tracks. The only way to save the five people is to push this man off the footbridge and into the path of the trolley. Is that morally permissible? Most people say “No.’”

Why the difference? Aren’t pulling the switch and pushing the man into the path of the trolley morally equal in terms of saving the maximal number of lives?

According to Greene, “our differing responses to these two dilemmas reflect the operations of at least two distinct psychological/neural systems.” One system “tends to think about both of these problems in utilitarian terms: better to save as many lives as possible.” This system depends on the dorsolateral prefrontal cortex, a part of the brain associated with “cognitive control” and reasoning — a region felt to be “more controlled, perhaps more reasoned, and relatively unemotional.”

But on fMRI, a second anatomically different neural system — the superior temporal sulcus, posterior cingulate and medial frontal gyrus — responds quite differently, generating a relatively strong, negative emotional response to pushing the man off the footbridge dilemma but not to pulling the switch.

Though not exactly a scientific term, this difficulty or revulsion in pushing the man off the footbridge is often referred to as the “ick factor,” a reflection that certain behavior is intrinsically disgusting or revolting, irrespective of whether it is reasonable. For most people, shoving a man to his death “feels like murder,” while pulling an impersonal lever constitutes a “rational decision.” Whether or not this cognitive dissonance is strictly reasonable is irrelevant; this is how humans think.

What Greene’s studies (duplicated by others) suggest is that brain systems involved with moral judgments must balance utilitarian concerns with deeply rooted emotional tendencies. Both modes of thinking arise out of unconscious brain mechanisms that jostle for priority outside of conscious control. It isn’t hard to imagine that one’s degree of personal empathy toward any situation will be a major factor in how these two systems eventually arrive at a decision. Indeed, fMRI studies show that feelings of empathy are activated in the same general regions as the emotional system that prevents you from pushing the man off the bridge.

From a strictly utilitarian perspective, pushing the man off the bridge is the correct decision. By empathizing with the man and deciding that pushing him is the wrong choice, you are condemning five people to death to save one. In those rare real-life circumstances where the moral decision gets down to a black-and-white calculation, it might seem relatively easy to determine what’s best for society. But even here, the decision has wide-reaching implications not apparent in this simple calculation. If we consistently push one man off a bridge to save five innocent people, we will have an entirely different culture from one that balks at the notion of pure utilitarianism at the cost of any innocent lives. Imagine a society in which you knew that you could, at any moment, be sacrificed for a “greater good.”

But few complex decisions have an obvious, easily calculated solution. We cannot know with certainty that a war is just, embryos have “souls,” or whether an unconscious patient wishes to be kept alive. In such situations, we must look to our feelings. All good legal opinions arise out of a balance between deeply rooted moral feelings and conscious deliberations.

Not surprisingly, one group has consistently been shown to have a much higher percentage of willingness to push the man off the footbridge — those with injuries to the emotional decision-making brain centers. Italian researchers have shown that patients with “focal ventral medial prefrontal cortex lesions” were more willing than controls (volunteers with no evidence of any brain injury) to judge personal moral violations as acceptable behaviors, yet on impersonal judgments, they were comparable to controls. In short, they lacked the “ick” feeling that prevented the controls from making morally revolting choices.

Such prefrontal cortical injuries, if acquired early in life and before normal social skills develop, have been correlated with a variety of personality traits that are commonly bundled together under the labels of sociopath or psychopath — lying, stealing, violence, and lack of remorse after committing such violations.

Some cognitive scientists suspect this at least partially explains adult sociopathic behavior. The suggestion is that there is a subtle functional deficit in the circuitry for processing emotions key to making moral decisions. Kent Kiehl, a Yale psychologist investigating the biological roots of psychopathy, has demonstrated that criminals without a sense of remorse differed from criminals with a sense of guilt: The remorseless psychopaths had far less activity in those regions that automatically and quickly process moral emotions. Paul Eslinger, Penn State College of Medicine neurology professor, after uncovering similar results in a group of patients clinically diagnosed as sociopaths, suggests, “‘Snakes in suits’ may have specific neural deficits that preclude social emotional responses.”

Years ago, I had dinner with a highly respected California State Supreme Court Chief justice, an old friend of mine nearing the end of his career. After musing on some of his many difficult decisions, he turned to me and said, “Robert, I have always identified with the underdog and felt that society had an obligation to protect those without a voice. Do you think I was wrong?”

His question still haunts me with its humility and self-reflection. After all his years on the bench, he continued to re-evaluate how his feelings for others impacted his opinions. Indeed, it’s this wise approach to recognizing the limits of pure reason that we want in our justices, not folks with the blind and scientifically unjustifiable belief that they can keep emotions out of their decisions, or that empathy is somehow a dirty word. But then you need a heart to appreciate how empathy is the basis of good law.

Unfortunately, nearly a year has passed and nothing has changed. Last week, I turned to my local PBS station, KQED, and ran headlong into yet another program of medical self-promotion. Mark Hyman, M.D., a family physician, was talking about “brain fog” and “broken minds” and how such “conditions” could be cured or prevented by using “The UltraMind Solution” — a combination of books, DVDs and home questionnaires.

Before I could change the channel, I heard Dr. Hyman make the following comments: “The way we think about disease, mental illness, and our brain aging, actually has nothing, nothing to do with how our body actually works … The way we think about disease is all wrong … the name of the disease tells us nothing about the real reason or the causes of them. Diseases don’t exist.”

Surely this rather unconventional opinion should have caught the attention of those responsible for airing this program on public television. I find it hard to believe that this type of rhetoric can be seen as consistent with mainstream medical wisdom, even by those who are not well versed in science.

If Dr. Hyman is correct, then we should disregard present medical knowledge and research. And yet, to justify his pet theories, Dr. Hyman cherry-picks from the very medical literature that he thinks approaches disease from the wrong perspective. Take, for example, his opinion that “the most remarkable scientific finding of the last decade is that you can have an inflamed, sore and swollen brain.” And from his blog site: “New research proves that almost all brain problems are connected to or caused by inflammation.” Indeed, Dr. Hyman opines that “if you treat the inflammation, the symptoms go away.”

To support this fringe opinion, Dr. Hyman has used what I refer to as a cut-and-paste technique; he takes isolated observations out of context to generate a theory not proven or justified by the findings.

He begins by saying that Martha Herbert, M.D., neurologist at Harvard, “has found that kids with autism have swollen large brains on MRI.” But what Dr. Herbert has written on the National Autism Association Web site is that “children with autism tend to have heads that are larger than normal,” but when “you look at the brains of these children with large heads using an MRI scan, they usually look normal.” Her conclusion: “At the current time, we do not understand the relationship of the large brains to the autism in these children.”

Note to Dr. Hyman: Larger is a measurement of size and isn’t synonymous with swollen.

Equally puzzling is his line of reasoning in assigning inflammation a primary role in diseases as diverse as autism and Alzheimer’s. Dr. Hyman cites the observation of Johns Hopkins neuroscientist Dr. Diana Vargas that there is evidence for “inflammation in the spinal fluid and brains of autistic children.” But in her paper, Dr. Vargas points out that “there has been no direct evidence linking findings in the peripheral blood to immune activity in the brain of autistic patients; the most comprehensive postmortem study reported no inflammatory changes or glial reactions.” (Glial cells are the non-neuronal brain cells that, among other things, protect against pathogens and remove the debris of neurons that have died.) However, with new techniques, Dr. Vargas believes that she has demonstrated glial reactions in the brains of autism sufferers.

Finding such glial cell changes, if confirmed in other laboratories, wouldn’t be particularly surprising. Glial cells respond to all sorts of insults. Dr. Vargas has found similar findings in widely disparate disorders, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis — all diseases for which the underlying causes remain poorly understood, but are associated with destruction of neurons specific to that illness. Perhaps the glial reactions seen by Dr. Vargas are nothing more than a normal response to damaged or dead neurons.

An appropriate analogy would be a bacterial sore throat. The streptococcus organism causes the sore throat; what we see on examination of the throat is inflammation of the underlying tissues. But it wouldn’t make sense to say that the inflammation caused strep throat; rather it would be a response to the strep. In order to blame inflammation as the primary cause, one has to abandon the traditional disease model — the position that Dr. Hyman takes at the start of his program.

Note to Dr. Hyman: Association is not causation.

There is no need for a further line-by-line dissection of Dr. Hyman’s claims. His opinions are clearly controversial both in terms of content and logic, and it doesn’t take a medical degree to spot them. Nor does it take more than a few minutes on the Internet to uncover the discrepancies between Dr. Hyman’s comments and the actual research cited.

My first exposure to public television was in 1955, watching “Science in Action,” a program locally produced by the California Academy of Sciences. Through the years, I have felt that PBS has provided many of the best science programs on television. Science is a method of thought. It’s through good science programs that we learn how to think, including how to properly assess conflicting information. I would hate to see their airtime curtailed because of lack of funding.

But showing dubious science like Dr. Hyman’s “The UltraMind Solution” on pledge nights, as KQED has been doing in past weeks, is to demean viewers’ reasons for watching public television. Apparently PBS’s mission is to raise money by exploiting viewers’ gullibility at the expense of trustworthy programming. If so, it has achieved its goal — and undermined the central reason for having educational TV in the first place.

I suspect we all wonder what, if anything, Madoff feels when directly confronted by those he has utterly destroyed. He cooked the books and perpetually lied to his investors. He pulled off the ongoing deception with an utter insensitivity to others. If shown videos of interviews of his victims, would he wince, laugh or simply shrug dismissively and say, “There’s a sucker born every minute.” For me, a glimpse into Madoff’s brain can shed light on the origins of how we treat each other, and perhaps most important, why we treat each other so poorly.

If there’s any single attribute that separates Madoff from the average Wall Street thief, I’d suggest that it’s his extraordinary ability to read what others think and desire, and especially to know what will give them the greatest satisfaction. (In technical jargon, this ability to read another’s thoughts is referred to as Theory of Mind). 

From a neurological perspective, a prime candidate for how we learn how others think is the mirror neuron system. In turn, it’s been proposed that this ability to read the mind of another makes it possible for us to experience empathy toward others. We know what they’re thinking and feeling and this triggers a similar response in us.

Behavioral neurologist V.S Ramachandran has referred to mirror neurons as “empathy neurons” or “Dalai Lama neurons.” He believes this system, by allowing us to understand the intentions and desires of others, is the principal driving force behind “the great leap forward” in human evolution. As a result of such claims, the mirror neuron system has risen to the level of accepted folk psychology. According to U.C. Berkeley psychologist Alison Gopnik, “Mirror neurons have become the ‘left brain/right brain’ of the 21st century.”

But Madoff’s behavior raises serious questions about the relationship between mirror neurons and empathy — and represents a golden opportunity to study the as yet puzzling connection between them.

Over a decade ago, Italian neurophysiologist Giacomo Rizzolatti and his colleagues studied motor control in macaque monkeys by placing electrodes in the region of a monkey’s pre-motor cortex responsible for hand movements. To their surprise, they noticed that these neurons fired both when a monkey reached for an object and when the monkey observed someone else (other monkeys and researchers) reach for an object such as a peanut or bit of banana.

The resulting interpretation has been that you recognize the intentions of others by equating their action with what you would do under the same circumstances. These neurons mirror the activity of others and allow you to see the world “from the other person’s point of view.” Marco Iacoboni, collaborator with Rizzolatti and author of “Mirroring Others,” has written that this system is capable of automatically assigning intention to another.

(Although it’s not possible to directly isolate and detect mirror neurons in humans, functional studies — both fMRI and transcranial magnetic stimulation — strongly suggest that we possess a similar brain system, primarily in the inferior frontal and inferior parietal regions).

To have played his investors as flawlessly as he did for several decades, I’m tempted to say that Madoff knew his investors’ minds better than they did — presumably good evidence for a well-functioning mirror neuron system. But contrary to Ramachandran’s view that mirror neurons are synonymous with “empathy neurons,” Madoff gets a zero in the empathy department. Just watch Madoff on the news, disdainfully and without any outward appearance of contrition, remorse, guilt or embarrassment, push his way through a crowd of angry onlookers and reporters. Contrast this contempt and disregard for his accusers with his savvy, sophisticated understanding of what his neighbors might expect from him, and we get a sense of the disconnect between understanding the thoughts of others and genuinely sharing their feelings.

Consider this letter that Madoff posted in his apartment building:

Dear neighbors,

Please accept my profound apologies for the terrible inconvenience that I have caused over the past weeks. Ruth and I appreciate the support we have received.

Best regards,

Bernard Madoff

If Madoff’s mirror neuron system appears clinically intact, and mirror neurons are key to the development of empathy, what allowed him to muster the callous indifference to ruin so many friends and associates? The obvious candidate would be something awry in the emotional centers and empathy circuitry that allow each of us to feel another’s pain and suffering.

In general, there appear to be two distinctly different, albeit overlapping, types of empathy: intellectual empathy, or knowing what someone is feeling; and affective empathy, or experiencing the same feeling as the other person. For example, a life insurance salesman and his wife can attend a funeral of her co-worker. The salesman might understand the mourners are grieving, and yet the sight of their weeping doesn’t affect him emotionally; instead he might feel a bit giddy that the mourners would be easy marks for some term insurance policies. His wife, on the other hand, might become overwhelmed with real grief.

One of the best-studied examples of this disconnect between understanding the feelings of others and sharing their feelings is the patient “Elliott,” described by neurologist Antonio Damasio in his book “Descartes’ Error.” Following the removal of a benign brain tumor, Elliot underwent a dramatic personality change. Although his imaging studies showed bilateral damage to his prefrontal cortex, he scored above average on standard intelligence tests, including some designed to detect frontal lobe damage. He responded normally to standard tests of personality, and retained his ability to speak and reason about topics such as politics and economics.

What was strikingly different was his affect. Although he was able to intellectually recognize emotional content, he now was unable to feel these emotions. When shown pictures of gory accidents such as a decapitated car accident victim, or a child drowning, Elliot reported having no emotional response at the same time as he remembered previously having had strong emotional responses to similar photos. His ability to intellectually experience empathy was disconnected from any affective response.

Even the neural substrates of affective empathy aren’t neatly organized; they vary according to what emotion is being experienced. If you see a woman in danger and feel fearful for her, your amygdala — a limbic system structure critical to experiencing fear and trembling — will light up on fMRI. If you witness quarterback Joe Thiesmann’s leg being broken on Monday Night Football, the anterior mid-cingulate cortex and the anterior insula — two regions that process pain perception — will go into overdrive.

But do we really need to have prior similar experiences to empathize with others? This is the fundamental argument underlying the theory that the mirror neuron system, by providing the ability to read the thoughts and feelings of others, is essential for empathy.

In a January 2009 study, French neuroscientist Nicolas Danziger wanted to see whether a person could empathize with an unfamiliar emotional state. He studied a group of patients with congenital insensitivity to pain — a rare condition present at birth and related to genetic changes in sensory nerves. Such patients have never felt physical pain sensations and have no idea what pain feels like. Interested in seeing how these patients would respond to seeing others in pain, Danziger showed them photos of a person getting her finger caught in gardening shears and a video clip of Theismann’s leg being broken.

Surprisingly, some of the pain-insensitive patients responded on fMRI similarly to normal controls — their pain perception regions lit up. Others had the anticipated lack of response. The difference between the two groups correlated with the degree of empathy that was elicited on a standard empathy assessment questionnaire. The authors concluded that those patients who responded had the “empathy trait.”

If this study pans out and can be duplicated under a variety of similar circumstances, the inference is profound: Each of us is wired differently for feeling the pain and suffering of others, irrespective of our past personal experience.

So is empathy an inborn trait?

One piece of evidence comes from observations on the Autism Spectrum Disorder. Thought to have a strong genetic predisposition, patients with autism and Asperger’s syndrome commonly are unable to grasp what others are thinking and feeling. Listen to this mother of a toddler with Asperger’s syndrome describe his reactions to his 8-month old brother crying whenever he fell down, bumped his head or pinched a finger. “My son asked me the most puzzling questions such as ‘Why is that baby crying?’ ‘Why is he doing that?’ and, my favorite, ‘Can’t we take that noisy baby back to the store and get a new one?’” If genes play a significant role in the Autistic Spectrum patient’s lack of empathy, it stands to reason that there might be a similar genetic contribution to the experience of empathy in all of us.

Further support comes from studies on antisocial behavior, both in young children and in adult “psychopaths.” (I’m using the unfortunately biased term “psychopath” to denote folks with chronic antisocial behavior who lack remorse for their actions, as opposed to antisocial behavior in which remorse and guilt are present.)

Looking at 3,600 pairs of 7-year-old twins, the British Twins Early Development Study found antisocial behavior in 7-year-olds generally fell into two categories: those with normal degrees of empathy and those described as callous and lacking in empathy. The former group was felt to be primarily environmentally mediated (learned behavior), whereas those lacking in empathy demonstrated that their antisocial behavior (primarily bullying and conduct disorders) strongly ran in families. In a subsequent fMRI study, this non-empathic group was shown to have decreased activation of the amygdala in response to looking at fearful faces. In other words, those who lack proper emotional responses to negative stimuli are more likely to have genetic underpinnings to their disorder.

Perhaps the most compelling predictive data supporting the “bad seed” hypothesis is a 25-year study showing that, as early as the age of 3, there are temperamental and physiological difference between those who show psychopathic tendencies as adults and those who don’t. In the early ’70s, 1,800 3-year-olds were observed and rated on several psychological scales, including their degree of fearfulness and inhibition. Twenty-five years later they were reexamined. Those with the higher psychopathy rating scores were found to be significantly less fearful and inhibited and more glib, charming and manipulative.

The authors concluded that children with a low level of fearfulness may be more likely to develop antisocial personality as adults. I’m always leery about accepting purely questionnaire-based studies at face value, but being able to predict the bad seeds at age 3 is hard to entirely ignore.

Although it’s painfully obvious that we don’t know what makes Madoff tick, it is hard not to speculate. If there is such a thing as empathy deficiency, Madoff would be its poster child. Perhaps this was a trait that he shares with his mother, Sylvia Madoff, who was registered as a broker, but in the 1960s was forced to close shop as part of an agreement with the Securities and Exchange Commission not to further investigate her brokerage. (I know it’s impossible with our present state of knowledge to sort out nature from nurture, but the above studies on empathy certainly suggest the possibility of there being a primary biological contribution.)

Even if true, a genetic predisposition for lack of empathy cannot possibly excuse Madoff’s behavior. We all have genetic predispositions for various personality traits — it is our struggle against baser biologic urges that distinguishes us from the rest of the animal kingdom. Deferring to biology as explanation or excuse for a behavior is to abandon all notions of what it means to be human.

Madoff can’t repay his victims, but we can learn from him. That’s why he should be forced to participate in medical studies as part of his sentence. The best cognitive scientists, philosophers, geneticists and sociologists should be allowed to administer to him whatever non-invasive and ethically appropriate clinical studies they can dream up. See if any pattern emerges that is sufficiently reliable to qualify as predictive. Even if our present knowledge is insufficient to draw conclusions, Madoff would make a great set of data points. Perhaps one day he can give something back to society by teaching us about human empathy, and its limitations.