Without a doubt, conscious awareness of the healing encounter plays an important role in triggering a placebo response and enhancing therapeutic effectiveness. However, as anthropologists, we must stress that the explanatory mechanisms, that have been discussed from a dominantly psychological and cognitive perspective are neither solely,
, conscious. We find that over-emphasis of conscious awareness in these explanatory mechanisms has left the field experientially starved—that is, this perspective has overlooked direct sensory and embodied experience (or implicit perception). Here we re-orient the discussion to consider how the full range of human experience may catalyze what is commonly characterized as a ‘placebo response’. We re-focus analytical attention on what Ots calls “the intelligent lived-body” (Ots, 1991
) through two alternative frameworks: embodied experience and performative efficacy. As in the previous section, the frameworks we present below are intended as complements to—not replacements for—other approaches to unpacking the black box of the placebo effect.
Scheper-Hughes and Lock argue that there was a “failure to conceptualize a ‘mindful’ causation of somatic states” in clinical biomedicine until the 20th
century when psychiatry and psychosomatic medicine emerged (1987, p.9). In recent years, the recognition that the mind can positively affect the body has been central to many cognitively-oriented studies of the placebo effect (Bandura, 1997
; Bootzin and Caspi, 2002
; Brody and Waters, 1980
; Caspi and Bootzin, 2002
; Moerman, 2002
). However, the comprehensive study of the placebo effect must fundamentally reconceptualize the body—not as the passive site of medical intervention, but as the penultimate multisensory organ and the locus of lived experience (Merleau-Ponty, 1964
The body experiences the intersection of one’s material corpus, one’s sense of self, and the rest of the world through the senses. Sensorial experiences—in the form of sight, smell, taste, touch, hearing, as well as bodily sensations such as dizziness and aesthetic experiences like rhythm—have the extraordinary power to evoke and trigger embodied memories of past experiences, including positive and negative healing experiences (Nichter, 2008
). In addition, sensations—as our mode of perceiving the world—are closely tied to emotions such as pleasure, safety and fear. Examples abound for each of us: the smell of baking apple pie makes us feel warm and secure17
, while the sound of the dentist’s drill makes us feel fear and dread. The feelings associated with the sound of that dentist’s drill may be clearly linked to the memory of specific appointment when the Novocain wore off too early. Alternatively, the sound may just make you cringe and tense your body, without connection to any specific memory. In this case, the sensation (the sound of the drill) and the emotion (fear and dread) leapfrog conscious cognition (memory or meaning) and language (narrative) to trigger a direct reaction at the site of the body.
Direct experiences (sensation, sensory experience, emotion) may be filtered through consciousness and be stored as memory and/or narrative, or they may bypass language and conscious cognition and be etched directly in/onto the body itself “in its sinews and on its surface” (Casey, 1987
). The point is that the body (as the penultimate multisensory organ) is the site of interface with the physical, social, and cultural world, and thus our experience in
the world is perceived, first and foremost, by and in
the body (Merleau-Ponty, 1962
). The experience of being-in-the-world is primarily ‘embodied’ and only secondarily translated into conscious meaning. Csordas cites embodiment as the existential condition—that is, the ‘lived body’ is a “methodological starting point rather than ... an object of study” (Csordas, p.136). However, embodiment, while ‘preobjective’ is not ‘precultural’; “the body is in the world from the beginning” (Csordas. p.9). Thus, approaching the placebo effect from a phenomenological paradigm of embodiment inverts the paradigm of conscious cognition that takes the objectified body for granted. Applying a phenomenological paradigm of embodiment demands analytical attention toward the ways in which placebo effects are manifestations of somatic modes of attention—that is, “the culturally elaborated ways of attending to and with one’s body” (Csordas, 1993
In the last decade, the concept of embodiment as the way we “literally incorporate, biologically, the material and social world in which we live, from in utero to death” (Krieger, 2005
, p. 352, table 1) has gained momentum in some corners of biomedical research (psychoneuroimmunology and psychoneuroendocrinology) and eco-social epidemiology and life course biology. While it is reassuring that biomedicine and public health have begun to pay attention to the interconnections and feedback loops between physiology and direct socio-cultural experience in the world, what are primarily considered are the negative impacts
of embodiment—that is, in the profound effects of stress (Godbout and Glaser, 2006
; Kemeny and Schedlowski, 2007
), trauma (Hinton, et al., 2006
; Hinton, et al., 2001
), and/or social inequalities (Krieger and Smith, 2004
) on the body. Just as negative experiences, like exposure to stress, violence, and trauma, can cut deep grooves into the body such that negative health effects can become that body’s path of least resistance18
, so too, can healthful experiences carve positively embodied pathways to facilitate substantive positive health effects. Nevertheless, with the exception of work on the notions of resilience in social epidemiology and positive psychology (Haglund, et al., 2007
; Southwick, et al., 2005
; Taber, et al., 2007
), little attention has been paid to the positive effects of embodiment. Rather, it appears that many of the positive and resilient aspects of embodiment have been generally dismissed as ‘placebo effects’.
As an example of the positively embodied effects of direct sensorial experience, take case of musician and musicologist Clive Wearing, whose amnesia following a brain infection of herpes encephalitis has rendered him unable to maintain his memory for more than a few seconds at a time (RadioLab, 2007
; Sacks, 2007a
; Sacks, 2007b
; Wearing, 2005
). This condition has persisted for over 20 years, with Wearing awakening from what he characterizes as ‘death’ every few minutes. Despite this near complete loss of conscious memory, Wearing’s musical skill and his abiding love for his wife continue to resonate with his very being. In a narrative analysis of Wearing’s case, Oliver Sacks makes it clear that these connections are not the result of conscious, cognitive memories. Rather, they are deeply embodied and sensorial:
Clive and Deborah were newly married at the time of his encephalitis, and deeply in love for a few years before that. His passionate relationship with her, a relationship that began before his encephalitis, and one that centers in part on their shared love for music has engraved in him—in areas of his brain unaffected by the encephalitis—so deeply that his amnesia, the most severe amnesia ever recorded, cannot eradicate it.
Nonetheless, for many years he failed to recognize Deborah if she chanced to walk past, and even now he cannot say what she looks like unless he is actually looking at her. Her appearance, her voice, her scent, the way they behave with each other, and the intensity of their emotions and interactions—all confirms her identity, and his own. (Sacks, 2007a
As this example makes clear, re-experiencing healthful sensations, sensory experiences, or emotions that have been inscribed directly into the body can bypass conscious awareness and ‘meaning’ and prompt what Frenkel (2008)
, following Dreyfus, might refer to as a “skillful and unreflective” response at the site of the body.19
observes that lived experience is also channeled into objects, thus transforming them into powerful symbols which themselves catalyze, stimulate, or trigger powerful, evocative multi-sensorial experience. Spaces and places are also invested with and transformed by lived experience (Basso, 1995
; Cartwright, 2007
; Low, 2003
). Although they are often dismissed as ‘placebo effects’, responses that enhance healing can be directly (unconsciously) triggered by objects (e.g., a band-aid or a pill in conventional medicine) or places (e.g., the sterile doctor’s office, or the warm décor of the Western acupuncturist’s office). Within biomedicine, this effect is illustrated by the emerging literature on optimal healing environments (Dijkstra, et al., 2006
; Malenbaum, et al., 2008
; Schweitzer, et al., 2004
; Ulrich, 1984
The characterization of placebo as meaning, expectation, or even desire is phenomenologically and evocatively dry. Just as illness etched into the body and into symbols and spaces can make us feel or be ill, healing and positive affect can be etched into the body and into symbols and spaces to genuinely make us well. The point is that the body can directly respond to sensory or affective stimuli and it does not require meaning in any consciously cognitive sense to catalyze a placebo response.
So how does this all relate to the placebo effect? From a physical reductionist perspective, the symbolic significance of, or emotional or aesthetic reaction to any given treatment should not have an effect on its outcome. But it clearly does. Our point here is that these symbolic, emotional, and aesthetic elements cannot be boiled down to expectation, desire, or meaning, per se. These elements may be registered directly at the site of the body—bypassing conscious awareness and etching themselves “in its sinews and on its surface” (Casey, 1987
). Yes, there are multiple things held in tension here: conscious awareness vs. direct embodied experience; cultural vs. personal symbols (as well as associated meaning and knowledge); past experience etched on the body vs. emergent experience that is shaped and constrained, but not dictated by the past; rational vs. sensory or emotional responsiveness. However these facets of lived experience are not dichotomies so much as they are nodes in the complex web of what means to be-in-the-world.
The vast majority of research into the physiology of placebo effects has been undertaken by Benedetti and colleagues, who see the placebo effect as a “psychobiological phenomenon” (2005, p. 10390). These researchers argue that “the placebo effect appears to be a very good model to understand how a complex mental activity, such as expectancy, interacts with different neuronal systems” (Benedetti, et al., 2005
, p. 10390). Here, we briefly consider two domains in which neurobiologists are working to unravel the complex neurobiology underlying the placebo effect: placebo analgesia and depression.
Placebo analgesia can be induced by both expectancy and conditioning. Expectancy induced placebo analgesia results in an endogenous opioid response (indicated by reversal by naloxone),23
whereas conditioning results in either
an endogenous opioid response or
a non-opioid response depending on the unconditioned stimulus (Price and Sorensen, 2002
). In an effort to better understand which bodily systems are implicated in expectancy vs. conditioning-induced placebo effects, Benedetti and colleagues (2005)
found that expectancy could antagonize conditioned placebo analgesia and motor performance, and they found no changes in hormone secretion based on expectancy. These findings have important implications for understanding the translation of psychosocial triggers into the neurobiological processes.
Placebo researchers from diverse fields agree that depression and the high rates of placebo response in clinical trials of pharmaceutical and psychosocial antidepressant therapies provides fertile ground for investigating the placebo effect (Benedetti, et al., 2005
; Kirsch, 2002
; Kirsch and Sapirstein, 1998
; Lakoff, 2007
The changes observed in the brain images of placebo responders in depression treatment studies appear to track those changes observed in active treatment responders; however, the patterns of these changes vary according to active treatment, “refuting the hypothesis that placebo response is mediated by changes in a common antidepressant response pathway. These findings additionally suggest that placebo response is also not the result of uncontrolled, unspecific psychological treatment effects” (Benedetti, et al., 2005
, p. 10398).
While researchers of the physiology of the placebo effect are primarily interested in basic science underlying the way “psychosocial context” (very narrowly defined as expectancy and conditioning) is translated into the brain and body, they identify a number of practical implications—which harkens back to Caspi’s (2003)
clinically-oriented message: to optimize care for patients, healthcare providers must learn to catalyze the placebo response in active treatments.
Based on the neurobiological evidence provided by Benedetti et al. (2005)
, it is becoming increasingly clear that the placebo effect cannot be characterized as a singular phenomenon. Rather, placebo effects may be triggered by any number of stimuli, including conditioning, expectancy, therapeutic relationship, and sociocultural meaning. Furthermore, stimuli may act through any number of biological pathways (some identified and others still unknown) including endogenous opioid, immune, and hormonal pathways, among others. By illustrating that placebo responses are yoked to the intervention at the brain level, Benedetti et al. (2005)
demonstrate that placebo responses are not limited to a few neurobiological mechanisms. It may be that every part of the brain
can participate in the placebo response.
Healing in an Evolutionary Context
It is becoming ever more apparent that ‘the placebo effect’ is polymorphic in both its trigger and its expression, and than the mechanisms for placebo responses within the body are diverse. It is also clear that in all societies healing modalities have developed to maximize the placebo response in an attempt to overcome assaults to well-being. This raises the question as to whether the placebo response, like other self-healing mechanisms, may be an evolutionary adaptation.
While it is beyond the scope of this paper to review the evolutionary evidence for self-healing in detail, we would like to describe in brief what we see as a multi-level, cells-to-society approach that supports this evolutionary contention. Let us begin at the most basic level by providing three examples of self-healing—at the cellular, organismal, and psychosocial levels—to illustrate the selective pressures that underpin wellness.
At the most basic, cellular, level, there are multiple mechanisms to repair (“heal”) DNA that has been damaged during cell function or replication. Among these are DNA damage response reactions which can: (1) remove DNA damage and restore the functioning double helix; (2) stop the process of mitosis to allow for repair and prevent the transmission of mutated DNA; (3) alter the portions of DNA that can be transcribed, to protect the cell from damage; (4) initiate programmed cell death (apoptosis), which safely eliminates severely damaged cells (Sancar, et al., 2004
). Cancer appears to be a consequence of these processes being inactivated or overwhelmed (Mahoney, 2007
). In light of the high incidence of DNA errors, the relatively low frequency of cancer occurrence is a testimony to the effectiveness of this system.
A second example of self-healing at the cellular level involves mechanisms to protect cellular structures and processes from damage that would be caused by oxidative stress. In the course of normal cellular function, a variety of reactive oxygen species (ROS) are produced inside cells. In addition, many cells are exposed to oxidation from exogenous sources, such as sunlight or the bloodstream. A large number of mechanisms25
quench reactive oxygen species, repair proteins that have been damaged, and move compounds into safe places inside the cell in preparation for excretion (auf dem Keller, et al., 2006
; Thorpe, et al., 2004
). Considering that much of the basic research on mechanisms for protecting against or healing the damage of oxidative stress has been done on yeast, it is clear that certain ‘self-healing’ properties, such as anti-oxidation mechanisms and DNA repair systems are evolutionarily ancient (Thorpe, et al., 2004
Wound healing and the immune response are the most obvious mechanisms for protection and self-healing at the level of the organism, and they share underlying mechanisms. While we all have biopsychocosocial experiences of wound healing (i.e., a mother’s kiss (Detillion, et al., 2004
)), the full range of overlapping physiological and biochemical mechanisms, that make up and modulate processes of inflammation, proliferation of new cells, and remodeling of tissue to accomplish this wound healing, are extraordinarily complex and not yet fully understood (Schafer and Werner, 2007
; Shilo, et al., 2007
). Wound healing includes the recovery from broken bones as well, and the mechanisms behind the control of each component of the cellular processes involved are similarly not understood (Dimitriou, et al., 2005
Also at the level of the organism, the immune system is made up of components that provide protection from and healing of invasions by undesirable organisms, from single-celled (bacteria, etc.) to complex parasitic organisms. The innate
immune response, which is genetically encoded to recognize and protect against specific structures foreign to cells is evolutionarily ancient, and even bacteria exhibit this response against viruses (Barton, 2008
; Medzhitov, 2007
). The acquired
immune response, which results in what we usually think of as ‘immunity’ due to the creation of new specific antibodies to foreign antigens, is a characteristic of all land vertebrates (Fietta, 2007
; Girardi, 2007
; Medzhitov, 2007
). What we experience as the illness of infection is often the organismal response to invasion. Inflammation, fever, fatigue, even body aches, are the result of cytokines and chemokines released by cells all over the body (local and distant to the site (Murphy, 2007
)) to help defeat invading organisms (Libby, 2007
). Healing from an infection requires that both
the invading organism be essentially eradicated and
the immune response be reduced to a normal level. Chronic infection, chronic inflammation, and autoimmune diseases are all examples a hyperactive immune response (Maggini, et al., 2007
; Netea, et al., 2008
A third, less visible, set of mechanisms at the level of the organism are those that remove toxins from the body, irrespective of whether those toxins are exogenous assaults or endogenous byproducts of normal cellular function or inflammatory immune response. For example, the activities of the cytochrome P450 (cyp450) enzymes are so specific in removing environmental toxins that the human excretion of metabolites can provide information on environmental exposures to chemicals such as PCB and DDT (Lampe and Chang, 2007
; Yi, et al., 2007
While these mechanisms protect the organism from harm, they also heal by removing toxins created in the inflammatory responses, thus enhancing the return of health following infection.
Thus, from an evolutionary perspective, biological mechanisms that provide protection from harm and enhance healing are central components of organismal survival. Certainly, the capacity to recover from insults would enhance individual fitness, and any genetically encoded biological traits that enhanced fitness in this way would be under positive selective pressure.
On a psychosocial level, the complex interrelationships between brain function and self-healing mechanisms are being studied within the fields of psychoneuroimmunology and psychoneuroendocrinology (DeVries, et al., 2003
). For example, psychosocial stress, especially within social interactions, and negative emotional states such as depression, can alter hormonal factors and hinder fertility (Novack, et al., 2007
). These psychosocial conditions can also hinder wound healing and the function of the immune system. As an example, caregivers (often adult children) of Alzheimer’s patients show greater susceptibility to infection, slower immune responses, and slower wound healing (Christian, et al., 2006
; Damjanovic, et al., 2007
; Detillion, et al., 2004
; Mills, et al., 2004
). Further, it appears that physical states such as chronic infection can precipitate or worsen psychological conditions, including depression, demonstrating that these are truly interrelationships
rather than unidirectional causal pathways (Irwin and Miller, 2007
). What is clear is that the body-mind is highly integrated, and insults in any location can affect the organism as a whole. The concept that the body and mind are somehow distinct—encoded in language such that there is no scientific word to effectively connote full integration between the two—is clearly an inadequate picture of the human organism.
On the basis of this evolutionary evidence, we argue that the neurobiological mechanisms of healing discussed above, can link direct embodied experience—including performative and sensory experience—to changes in immunologic, endocrinologic, and pain responses. These responses would be under positive selective pressure throughout mammalian and human evolution. Given the varieties of human experience (with variation in physical environments, population size, family and social structure, and sociocultural experiences across the lifecourse), local biocultural feedback loops are likely to exert selective pressure on a range of self-healing responses. Further, as the substrate for selection is random variation, the variants available for selection will differ among populations. For both of these reasons, it seems highly plausible that there would be a wide variety of mechanisms that link the body-mind to local biocultural conditions, and hence provide populations with a broad range of sites for interventions with the potential to enhance health. Given the genetic and psychosocial variability among individuals and between populations, the likelihood that a single mechanism will enhance healing in all individuals in all situations is highly unlikely. Assuming that the ‘placebo response’ is a highly polymorphic trait in human populations that has been under local selective pressure for thousands of years, it is reasonable to expect that pluralistic healing modalities would emerge that trigger a ‘placebo response’ in multifarious ways.27
Thus we suggest here that what has been disparagingly called the placebo effect, and has been relegated to the category of a nuisance28
in randomized clinical trials, is in fact an evolutionarily adaptive trait. It is adaptive (for the individual and the social group) to be well, and the mindful body will use every tool at its disposal (material, social, psychological, and symbolic) to maintain or restore well-being. The ability of an organism to respond to resonant (rather than precise) therapeutic triggers would be under positive selective pressure. For the individual organism, responding to a ‘placebo’ may enhance the probability of wellness and the survival of offspring, and thus, may be a precursor to biological adaptation that produces an enduring and reproducible therapeutic effect. In addition, any social mechanism that would support or trigger a placebo response (such as ritual, empathy, altruism, positive social relations, etc,), and would enhance the resilience of the organism to return to wellness, would be under positive selective pressure on a social level.