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Sunday, September 25, 2011

Neuroplasticity, Psychosocial Genomics, and the Biopsychosocial Paradigm in the 21st Century


Neuroplasticity, Psychosocial Genomics, and the Biopsychosocial Paradigm in the 21st Century

By Garland, Eric L,Howard, Matthew Owen
Published on AllBusiness.com


The biopsychosocial perspective is a foundation of social work theory and practice. Recent research on neuroplasticity and psychosocial genomics lends compelling support to this perspective by elucidating mechanisms through which psychosocial forces shape neurobiology. Investigations of neuroplasticity demonstrate that the adult brain can continue to form novel neural connections and grow new neurons in response to learning or training even into old age. These findings are complemented by the contributions of psychosocial genomics, a field of scientific inquiry that explores the modulating effects of experience on gene expression. Findings from these new sciences provide external validation for the biopsychosocial perspective and offer important insights into the manifold means by which socioenvironmental experiences influence neurobiological structure and function across the life course.

KEY WORDS: biopsychosocial; gene-environment interaction; neuroplasticity; psychotherapy

Like sand on a beach, the brain bears the footprints of the decisions we have made, the skills we have learned, the actions we have taken.

-Sharon Begley, 2007

Social work professionals in the 21st century have adopted the biopsychosocial paradigm. This paradigm, first articulated by the physician George Engel (1977), holds that humans are dynamic systems whose functioning depends on the holistic integration of biological, psychological, and social factors; indeed, according to the biopsychosocial model, these factors are fundamentally interrelated and interdependent. Although Engel rejected the reductionism of the dominant biomedical model of his era, which assumed that molecular biological processes (for example, genes, biochemistry) immutably dictated physiology and behavior, a simpleminded biological determinism nonetheless took root, becoming widely and uncritically accepted. At its inception, there was scant evidence to support Engel's biopsychosocial perspective; however, scientific discoveries of the past decade have provided important new findings validating and elaborating the biopsychosocial paradigm.

Over the past decade, two fields of empirical investigation, neuroplasticity and psychosocial genomics, have offered important findings that may lead to a paradigm shift in our conceptions of psyche and soma and the modes of their interrelationships.These two fields mutually inform one another, depicting interpenetrating biopsychosocial relationships on different scales: Neuroplasticity research describes how neurons within the brain proliferate and grow new connections across the life span, whereas psychosocial genomics describes the processes by which psychological and social experiences activate or deactivate genes, thereby driving the development of new neural pathways. The interplay of these sciences reflects a vision of humans as inherently resilient; psychosocial factors appear to stimulate gene expression within neurons, resulting in alterations to the structure and function of the brain. Discoveries from both fields reveal that experience and learning can contribute to positive change, even at the neurobiological and structural levels.

Social work academicians have embraced the biopsychosocial perspective, yet many are perhaps not fully aware of recent developments in genomic and neurobiological research that have implications for social work and the biopsychosocial perspective.This research provides insights into the very substrates of biopsychosocial change. Thus, we review recent neuroplasticity and psychosocial genomics research and their implications for current understanding and application of the biopsychosocial perspective.


Basic Neurotransmission

The human brain is a complex, self-organizing, biological system, consisting of trillions of interconnected nerve cells called neurons. The operation of neurons results in two distinct forms of information processing: signaling and integration. Each neuron propagates signals via action potentials, electrochemical currents that travel the length of its axon. This current leads to the release of neurotransmitters that traverse synapses, the gaps between neurons. These chemical messages are received via specialized receptor cells at the ends of numerous, tree-like branches of the receiving neuron, called dendrites. The stimulation of dendritic receptors by neurotransmitters leads to integration, whereby large amounts of information from many neurons are summed before reaching a threshold to fire the action potential down the next axon. In this manner, perceptual information from the external environment and the internal milieu of the body is transmitted and processed in the brain, leading to cognition, emotion, and behavior - the essence of human experience.

Origins of Neuroplasticity Research

The brains of infants and children are known to be plastic, undergoing spurts of neuronal development in response to stimulus exposure during critical periods (Mundkur, 2005). This development consists of the genesis of neurons, increased connectivity between extant neurons, and the routing of new synaptic connections between previously unrelated neurons. However, before 1998, it was widely accepted that neuronal connections in the adult brain were immutable; the neurons that populated a given brain area were thought to be fixed in accordance with whatever form and function the genetic code prescribed for that region (Begley,2007). In addition, the conventional wisdom at the time - that no new neurons could be generated after injury or insult to the brain - was held with conviction on the part of leading neuroscientists.

However, on discovery of the growth of new neural tissue, or neurogenesis, in the adult human hippocampus, a brain region responsible for memory (Eriksson et al., 1998), the dogma of the "hardwired brain" was formally repudiated. This finding complemented earlier evidence from primate studies demonstrating that novel sensory experience and learning of new behaviors triggers neuronal growth in the somatosensory and motor cortices, areas of the brain subserving tactile perception and limb movement (Jenkins, Merzenich, Ochs, Allard, & Guic-Robles, 1990; Nudo, Milliken, Jenkins, & Merzenich, 1996). Subsequent to the discovery of neurogenesis in the adult human brain, neuroscience has pursued this une of investigation with vigor, aided by advances in brain imaging techniques such as magnetic resonance imaging (MRI).

Neuroplasticity Research Findings

The growth of neurons has been documented in the brains of adults exposed to a variety of experiences. For instance, violinists evidence neural growth in the portion of their somatosensory cortex devoted to their fingering hand through hours of musical practice (Elbert, Pantev, Wienbruch, Rockstroh, & Taub, 1995); people engaged in the practice of juggling evidence similar growth (Draganski et al., 2004). In addition to such physical training, mental practice may promote neuroplasticity: Neurogenesis can occur in the motor cortex simply through the act of imagining playing the piano (Pascual-Leone, Amedi, Fregni, & Merabet, 2005). Similarly, taxicab drivers develop the areas of their brains involved in spatial relationships by memorizing the labyrinthine streets and avenues of the cities in which they work (Maguire et al., 2000). Although the underlying mechanisms are different, neuroplasticity research suggests that challenging learning experiences can lead to the development of brain tissue in a manner analogous to the ways that physical exercise can lead to the development of muscle tissue.

One area of research that has found significant evidence of mental training leading to neuroplastic modifications in brain activity focuses on the study of meditation. Meditation, although greatly varying in technique and purpose across the diverse spiritual and cultural traditions in which it is used, may be generally defined as the intentional practice whereby one grasps "the handle of cognition" to cultivate a competent use of one's own mental capacities, gaining agency over thought and emotion (Depraz, Varela, &Vermersch, 2003) . Such intentional mental training has been shown to induce functional neurobiological changes.

A study by Lutz, Greischar, Rawlings, Ricard, and Davidson (2004) found marked alterations in the synchronization of neurons as an effect of long-term training in Buddhist loving-kindness meditation, a practice that is thought by some practitioners to promote a state of unconditional compassion and benevolence. Neural synchrony of the type observed in this study may be indicative of coherent and integrated psychological functioning (Williams et al., 2005). The synchronization of brain activity found in some of the practitioners sampled, whose experience ranged between 10,000 and 50,000 hours spent in meditation, was higher than any previously reported in the literature. Such increased neural synchrony was observed not only during the meditative state, but also when the practitioners were not meditating, suggesting that long-term mental practice can induce lasting, trait-level changes, possibly mediated by structural modifications to the brain (Begley, 2007).

Other research has documented changes in neurobiological function as a result of mindfulness meditation, the practice of cultivating a presentcentered, metacognitive awareness, "a naturalistic state wherein consciousness transcends its content to rest upon the dynamics of its own processes" (Garland, 2007, p. 5). A recent study by Slagter et al. (2007) compared the attentional performance of a group of experienced meditators participating in a three-month mindfulness meditation retreat with that of members of a novice control group who received a one-hour meditation class and were asked to meditate 20 minutes daily for one week. Relative to controls, experienced meditators evidenced significant improvements in attentional performance that correlated with alterations in brain activity.This cognitive enhancement was maintained three months after formal meditation practice, providing suggestive evidence that mental training can stimulate neuroplastic changes in the adult human brain (Slagter et al., 2007).

Although the work of Slagter et al. (2007) and Lutz et al. (2004) provides tentative support for meditation-induced neuroplasticity, neither study examined structural brain changes per se. However, two structural MRI investigations comparing the brains of experienced meditators with those of control subjects matched in sex, age, race, and years of education found that years of meditation experience correlated with increased cortical thickness in brain areas where visceral attention (for example, right anterior insula) and self-awareness (for example, left superior temporal gyrus) have been localized (Holzel et al., 2008; Lazar et al., 2005). These empirical investigations of meditation suggest that mental training may stimulate structural alterations reflective of neuroplasticity.

Clinical Implications of Neuroplasticity Research

The finding that experience and training can lead to the development of new neural connections has key implications. For example, people suffering from what was once thought to be permanent brain injury, as in the case of stroke, can heal through rehabilitation designed to stimulate the damaged area (Taub et al., 2006). However, although largely speculative, it is possible that neuroplasticity may undergird not only rehabilitation of physical illness but that of select psychological disorders as well, mediating natural recovery from mental illness in some cases and improvements related to psychosocial interventions. At present.it has been demonstrated that psychotherapy can induce functional changes in brain activation. For example, a brain imaging study found that people with obsessive-compulsive disorder (OCD) who were treated with a mindfiilness-oriented form of cognitive-behavioral therapy (CBT) exhibited functional changes in the orbital frontal cortex and striatum, two brain structures found to be overactive in OCD (Schwartz & Begley, 2002). Other studies have demonstrated psychotherapy-related alterations in brain circuits involved in depression (for example, Goldapple et al., 2004;Martin, Martin, Rai, Richardson, & Royall, 2001). CBT has also been associated with changes in frontal and temporal brain regions of people suffering from panic disorder (Prasko et al., 2004). Such intervention-related changes in both psychosocial function and neural activity may correlate with neuroplastic alterations to the brain; critically, a combined functional and structural MRI study of practice-induced increases in gray matter found that increased task-specific brain activation led to the remodeling of one of the same neural structures (dorsolateral occipital cortex) that was activated by the practice and learning of the task (Hg et al., 2008).

Neuroplasticity research on psychosocial interventions has just begun. A recent longitudinal study of CBT for women with chronic fatigue syndrome found increases in gray matter of the lateral prefrontal cortex after 16 sessions of CBT (de Lange et al., 2008). Increases in gray matter volume correlated with enhanced cognitive processing speed, suggesting that the neuroplasticity evoked by psychotherapy played a causal role in rehabilitation of cognitive performance after cerebral atrophy resulting from chronic fatigue.

Indeed, neuroplasticity may be the biological mechanism through which psychosocial interventions exert at least some of their therapeutic effects. During psychotherapy, when the client recalls negative or painful life experiences, the clinician may assist in refraining the context so that the experience takes on new meaning (de Shazer, 1988). For instance, in the treatment of people who have experienced traumas such as rape, therapy may help clients to envision themselves as survivors rather than victims. Such reframing or reappraisal may be a critical component of successful biopsychosocial outcomes (Folkman, 1997; Garland, Gaylord, & Park, 2009; PenleyTomaka, & Wiebe, 2002). Some theorists hypothesize that the process of recalling, reconstructing, and reframing memories of past trauma during psychotherapy is mediated by the reorganization and genesis of neurons (Centonze, Siracusano, Calabresi, & Bernardi, 2005; Rossi, 2005a). This hypothesis is founded on evidence that the formation of new long-term memories results from neuroplastic changes in the brain structure known as the hippocampus. Hippocampal changes appear within hours of significant learning experiences (McGaugh, 2000), such as those that can occur during psychotherapy.

Neuroplasticity is mediated at the cellular level through activity-dependent gene expression, the mechanism by which neurons secrete growth factors leading to the "activation of gene transcription in the nucleus that support[s] synaptic connections __ Thus, with every new experience, the brain slightly rewires its physical structure and this rewiring is mediated through the signaling cascade" (Mundkur, 2005, p. 856). Hence, to understand neuroplasticity, we must consider the domain of psychosocial genomics.


Basic Epigenetics

In the 21st century, there is broad agreement that the genome is the basis of human life and a precondition for psychosocial experience. Nevertheless, the question of the respective roles of nature and nurture in human experience and the manner of their interaction in select contexts remains contentious, despite the more than half-century since Watson and Crick (1953) identified DNA as the building block of biological processes.

The DNA code of the human genome does not determine protein synthesis in a one-to-one fashion; instead, genes are subject to epigenetic processes (that is, modifications that do not occur because of changes in the basic genetic sequence of amino acids but, instead, result from biological and environmental influences on the expression of genes as proteins) (Eisenberg, 2004). During gene expression, the genetic code serves as a "blueprint" that guides the construction of proteins from amino acids. However, this construction process is modulated by signals from the internal and external environments, which steer and modify the manner in which basic organic molecules are organized into anatomy and physiology. Although genes prescribe protein synthesis, there is substantial variability in the manner in which they are expressed.

A single genotype, the genetic blueprint of an organism, can be expressed in a multiplicity of distinct physiological and behavioral forms, known as phenotypes.This is evident in Eisenberg's (2004) example of phenylketonuria, a disorder that when untreated may lead to severe mental retardation, psychosis, and seizures. If children with this genetic abnormality are kept on a postnatal diet low in the amino acid phenyalanine, they do not develop these disorders. Hence, although the genotype for phenylketonuria does not change, its phenotypic expression is modified by the environment (that is, nutrition) to which the individual has been exposed. The mechanisms by which such different phenotypes are expressed are just beginning to be understood, but they appear to involve the regulatory effect of internal and external environmental signals on stress hormones, which in turn modify gene transcription processes (Kandel, 1998; Rossi, 2004).

Learning and Other Psychosocial Experiences May Modulate Gene Expression

In addition to physical environmental forces, learning experiences in the social environment can alter gene expression (McCutcheon, 2006). The bidirectional relationship of nature and nurture, genes and environment, was first demonstrated in a series of path-breaking studies of maternal care in rats (Francis, Champagne, Liu, & Meaney, 1999; Liu et al., 1997). In these studies, an inverse relationship was found between the number of stress hormone receptors in a rat's hippocampus and its tendency to exhibit stress reactions. The number of these receptors is dictated by the genotype of the rat. Highly stress-reactive rats give low levels of maternal care to their offspring, who, in turn, exhibit high stress reactivity and later provide low levels of maternal care to their offspring. However, these studies revealed that hormonal and behavioral stress reactions of rat pups, as well as the numbers of their stress hormone receptors, are modulated by the licking, grooming, and nursing behaviors of their mothers. Even if a rat were born with a genotype coding for fewer stress hormone receptors, if it was reared by an adoptive mother providing high levels of maternal care, its genes produced more stress receptors, making it calmer, less reactive to stressors, and more apt to provide maternal care to its offspring. These findings offer some evidence that social behavior may be inherited and transduced via gene expression into neuroplastic alterations in brain structure, leading to psychobiological learning and change.

The notion that social experience can lead to changes in gene expression was voiced most prominently by Nobel laureate Eric Kandel (1998), who regarded this observation as the core component of a new paradigm for psychiatry. Kandel (1998) summarized the current state of biological thinking with regard to the relation between social experiences and neurobiology, observing that

the regulation of gene expression by social factors makes all bodily functions, including all functions of the brain, susceptible to social influences. These social influences will be biologically incorporated in the altered expressions of specific genes in specific nerve cells of specific regions of the brain. These socially influenced alterations are transmitted culturally (p. 461).

This powerful claim, although supported by over a decade of rigorous research, has rarely been directly tested. However, advances in psychoendoneuroimmunology, the study of how mental processes affect the immune system, have clearly shown the effects of psychological and social factors on human physiological functions that indirectly involve the genetic replication of cells (Ray, 2004). Such alterations of biological function may be mediated through experience-dependent gene expression, the process whereby social-environmental signals turn genes "on" and "off," leading to alterations in protein synthesis that ultimately result in physiological changes (Pinaud, 2004).

Psychosocial Genomic Hypotheses

Although our genes provide a basic outline for development, environmental influences such as social experiences shape gene expression and ultimately make us unique individuals. This interaction is the essence of what Rossi (2002) has termed "psychosocial genomics," the interdisciplinary study of the processes by which gene expression is modulated by psychological, social, and cultural experiences. Practitioners might profit from knowing more about this new science, for according to Kandel (1998),

insofar as psychotherapy or counseling is effective and produces long-term changes in behavior, it presumably does so though learning, through producing changes in gene expression that alter the strength of synaptic connections and structural changes that alter the anatomical pattern of nerve cells of the brain (p. 460)

Thus, it is conceivable that psychosocial interventions, the tools of social work practice, may produce alterations in gene expression, leading, in some cases, to measurable neurobiological changes. Because stress can affect neurogenesis through alterations in gene expression and transcription (Glaser et al., 1 990;Warner-Schmidt & Duman, 2006) , ultimately leading to dysregulation of affect (Post, 1992), psychosocial interventions designed to reduce distress and improve mood may affect brain structure and function through this pathway. Muenke (2008) has recently suggested that the therapeutic effects of stress-reduction techniques might be mediated by changes in gene expression. In Une with this hypothesis, a recent study of a meditative breathing practice found increased gene expression of the immune factors glutathione S-transferase,Cox-2,and HSP-70 in practitioners relative to controls (Sharmaa et al., 2008). Although this study supports the psychosocial genomic hypothesis, its cross-sectional design does not allow for confident inferences about causality. However, in light of this potential shortcoming, it is noteworthy that another study identified changes in the expression of 1,561 genes involved in the stress response before and after exposure to eight weeks of meditation training (Dusek et al., 2008). Although controlled psychosocial genomic research is uncommon, there are a growing number of psychosocial intervention studies that do measure physiological outcomes such as blood levels of Cortisol or immune factors. For instance, stress reduction interventions have been shown to increase numbers of immune cells and decrease numbers of cells associated with allergic reactivity (Castes et al., 1999) and to improve antibody response to the flu vaccine (Davidson et al., 2003). Intervention-related changes in such biological markers may serve as indirect measures of alterations in gene expression.

The new scientific paradigm outlined earlier provides a perspective on how the biopsychosocial constitutions of practitioners and clients might interact in the act of therapy:

When a therapist speaks to a patient and the patient listens, the therapist is not only making eye contact and voice contact, but the action of neuronal machinery in the therapist's brain is having an indirect, and, one hopes, long-lasting effect on the neuronal machinery in the patient's brain; and quite likely, vice versa. Insofar as our words produce changes in our patient's mind, it is likely that these psychotherapeutic interventions produce changes in the patient's brain. From this perspective, the biological and sociopsychological approaches are joined. (Kandel, 1998, p. 466)

The union of neuroplasticity and psychosocial genomics research represents a synthesis of the social and biological sciences that is nonreductive: It does not dismiss human experience as the product of a neural machine, predetermined by its genetic blueprint. Instead, it is integrative, inclusive, and holistic; this unitary approach reveals the power of thought and emotion, society and culture to affect not only our phenomenological experience but our very neurobiological structure and function. In sharp contrast to genetic determinism, this new paradigm envisions individuals as having the innate potential for agency over the tripartite dimensionality of their biopsychosocial selves.


The social work profession's historical emphasis on the social environment as the context for individual well-being is supported by research over the past decade. Neuroplasticity and psychosocial genomic research indicate that socioenvironrnental forces have the potency to alter human well-being through their effects on neurobiology. Social experience may be transduced through the activation of neurons, leading to modifications in the phenotypic expression of genes and eventuating in structural changes to the brain. Although genes and neurobiology may be the substrates of vulnerability to environmental stressors, they are also, in all likelihood, the substrates of resilience (Cicchetti, 2003; Cicchetti & Blender, 2006).

The sciences of neuroplasticity and psychosocial genomics may provide new empirical bases for social work interventions. Biological measures of change can and should be used to enhance the evaluation of social intervention research. Given the current funding climate and priorities of the National Institutes of Health, research programs designed to evaluate social work practice may be more likely to obtain grant support if interventions studied are evaluated with physiological outcome measures, including those assessing gene expression and neuroplasticity. In time, a given practice may be deemed "evidence based" when, among other criteria, it is shown to result in plastic brain changes or altered gene expression associated with improved biopsychosocial functioning.

Currently, there is a paucity of empirical support for this new paradigm in studies with humans. An abundance of research on higher mammals indicates that experience can trigger gene expression leading to neuroplasticity. As referenced earlier, several studies on humans indicate that learning and training have led to neurogenesis and the reorganization of neural networks. Despite developments in these unes of research, science has only begun to examine the effects of psychosocial interventions on brain structure and function. More research must be conducted in this emerging field, and the social work profession, with its expertise in addressing social problems and enhancing human well-being, can make a vital contribution to this endeavor.

Brain imaging and gene assays may be used to detect the neuroplastic and genomic effects of psychosocial interventions.Technologies such as MRI, functional MRI, and positron emission tomography are capable of assessing the neurophysiological changes associated with psychosocial interventions (Kumari, 2006). Reductions in psychiatric symptoms may be reflected in the alterations in brain metabolism and structure revealed by these imaging technologies. DNA microarray technologies, which can evaluate messenger RNA production in cells and thereby determine which genes are activated (Mimics, Middleton, Lewis, & Levitt, 2001; Raychaudhuri, Sutphin, Chang, & Altman, 2001), have been used to assess alterations in gene expression related to posttraumatic stress disorder (Segman et al. , 2005) , social aggression (Berton et al., 2006) , and depression (Evans et al., 2004). DNA microarrays may become more widely used to measure biological effects of psychosocial interventions in the not too distant future (Rossi, 2005b).

Nevertheless, the funding and specialized training necessary to perform brain imaging and DNA microarrays decreases the likelihood that social work researchers working in isolation could leverage diese technologies for biopsychosocial research. Consequendy, future psychosocial intervention research could involve interdisciplinary teams of social workers, neuroscientists, and molecular biologists, with data from the biological sciences complemented by the insights of social work research. Alternatively, other more accessible biological markers, such as stress hormone levels in saliva, could be measured as a proxy for physiological change induced by psychosocial interventions. For example, salivary Cortisol assays are a relatively inexpensive form of assessment that can be done by many university laboratories. Social work investigators could add this measure to their intervention research protocols.

Whether the impact of psychosocial interventions can be traced at the neuronal, genomic, or grosser levels of physiological response, biological markers will only be meaningful as a complement to selfreport and collateral measures of change. Indeed, Engel's (1977) biopsychosocial paradigm is rooted in the philosophical principle of complementarity (Freedman, 1995); instead of the "either/or" mentality of dualisti c reductionism, biopsychosocial research should embrace a "both/and" logic whereby reports of subjective experience garnered through validated instruments and qualitative interviews are correlated with biological and behavioral data. Such research can add value to social work as a primary mental health and allied health profession and lead to the implementation of interventions with demonstrable physiological, psychological, and behavioral benefits.


Over the past decade, neuroplasticity research has enriched the biopsychosocial perspective by demonstrating mat psychosocial experiences not only influence neurobiological processes but may actually change die structure of the adult brain. These structural changes consist of increased arborization of neurons, enhanced synaptic connectivity, and even the genesis of new neural tissue. Although neuroplasticity research is in its infancy, recent findings suggest that the effects of psychosocial experiences such as learning and mental training on cognitive, emotional, and behavioral functions may be mediated by alterations to the architecture of the brain.

In turn, experience-dependent modifications to neural tissue may be driven by epigenetic processes (that is, changes in gene expression produced by environmental determinants). The human environment is constandy conditioned by social experiences, which, when transduced by the nervous system into electrochemical signals, may modulate protein synthesis in the nuclei of nerve cells, ultithately leading to changes in the replication and growth of neurons. Social experience can change gene expression, leading to the restructuring of the brain through neuroplasticity. Although tentative at present, empirical investigations of the psychosocial genomic hypothesis will likely proliferate over the next decade.

These new biopsychosocial sciences are consistent with a view of human beings as holistic, recursive systems structurally coupled with their environments in a process of mutual change (thaturana & Varela, 1987). Intentionaliry and volition can generate changes in the structure of the brain, the very organ assumed to produce such mental phenomena (Schwartz & Begley, 2002). With this finding, it is evident that human experience is not driven solely from the bottom up by neurobiology and genetics. Instead, there is growing evidence that psychosocial experience can exert a macrodeterministic, top-down force on our biology. In the philosophy of emergent interactionism, Roger Sperry (1987), Nobel laureate neuroscientist, described macrodeterminism as a higher order, molar level of organization that determines and conditions the activity of lower order, nested subcomponents. Hence, human beings, who are at one level assemblies of organ systems comprising aggregates of cells, which are in turn composed of organic molecules made up of subatomic particles, are not merely the sum of these physical elements. Instead, the consciousness that emerges from the interaction of these components can act back upon its physical substrate. Thought, emotion, and action trigger neural activity, which can lead to a reorganization of the brain, shaping future psychosocial experience. From this perspective, we are not the passive products of neurophysiology and heredity; rather, through our behavior in the social environment, we become active agents in the construction of our own neurobiology and, ultithately, our own lives.

This new paradigm may reveal the empirical foundation of that most central of social work principles - the idea that people have the power to transcend and transform their limitations into opportunities for growth and well-being.



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Eric L. Garland, MSW, LCSW, is a doctoral candidate, and Matthew Owen Howard, PhD, is Frank A. DanieL·, Jr. Distinguished Professor of Human Services Policy, School of Sodai Work, University of North Carolina at Chapel Hill. The development of this article was supported by National Center for Complementary and Alternatila Mediane Grant T32AT003378; a grant from the George H. Hitchings Fund for Health Research and Science Education of the Triangle Community Foundation, Durham, NC; a FrandscoJ. Varela Research Grant from the Mind and Life Institute, Boulder, CO; and an Armfield-Reeves Innovation Grant from the University of North Carolina at Chapel Hill School of Sodai Work. Address correspondence to Eric L. Garland, University of North Carolina at Chapel Hill, 1 9 Copper Hill Court, Durham, NC 27713; e-mail: elgarlan@email.unc.edu.

Original manuscript received September 4, 2007

Final revision received December 9. 2008

Accepted January 29, 2009

Psychosocial Genomics of Mind-Body Healing

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Psychosocial Genomics of Mind-Body Healing

What has psychosocial genomics have to do with mind-body healing? The answer is, "A lot." First, we need a few definitions so we can discuss this...


Psychosocial genomics can be defined as how personal consciousness, activities, and social interactions affect gene expression, and how gene expression affects these.

Another definition would be how psychological and social interactions and activities affect the genome in terms of gene expression and gene expression affects our psychology and social behaviors.

Rossi in his 2002 book, The Psychobiology of Gene Expression, defines psychosocial genomics as "how the subjective experiences of human consciousness, our perception of free will, and social dynamics can modulate gene expression, and visa versa."

A mouthful, no? Well, before we go further into this, we need some definitions for the definition. Sigh!

For the uninitiated, what is a "genome" anyway and what is gene expression?

If your "genetics" is a little rusty, you can get a quick review of some basic genetic concepts here.


In the strict meaning to the word, the genome constitutes the entire set of an individual's genes. In a more dynamic sense, it encompasses not only all the genes, but also the way those genes interact with each other.

Gene Expression

It is not just a matter of what genes an individual has, but what genes are being expressed, when they are being expressed, and to what degree or how much they are being expressed. "Express" here refers to the protein or RNA that is encoded by a gene. For example, for protein coding genes, how much of that protein is actually being produced? That is gene expression is regulated.

A gene is not just simply sitting there pumping out proteins (or RNA) but is dynamically adjusting its output based on feedback from the internal and external environments. You can get a further overview of the regulation of gene expression by clicking here.

Dynamic Dance of Gene Expression

From recent findings in the neurosciences and functional genomics we are beginning to understand how the interplay between behavioral state-related gene expression (a.k.a. nature) and activity-dependent gene expression (a.k.a. nurture) bring about healing through neurogenesis and learning.

Functional genomics has to do with how the genes in the genome function in response to the environment. During embryonic development for example, we see cascades of genes being turned on and off to varying degrees. Even from such simple interactions of touch, we see whole communities of genes responding. So when someone comes up and gives you a hug, rubs your back, etc., your genes respond to that. It is specific genes that respond however.

Mind-body healing is about neurogenesis or brain growth. For neurogenesis to occur, the genes involved have to produce their proteins and have them available for nerve cells (neurons) to use.

As reviewed in the neurogenesis webpage, three things stimulate brain growth: novelty, a variable environment, and exercise. One of the most powerful of these for psychosocial genomics is what Rossi (2002) refers to as the novelty-numinosum-neurogenesis process.


Novelty (that is doing or experiencing something really different) can lead to numinous experiences and numinous experiences are novel.

Numinous refers to supernatural or mystical experience. They are filled with the presence of the sacred or divine. Maslow's Peak Experiences are of this nature. Gerald May (see Will and Spirit: A Contemplative Psychology) refers to these as unitive experiences. They have also been called religious conversion experiences. Buddhism would refer to them as enlightenment experiences (satori or samadi). To a lesser degree they are related to the Aha-experiences that occur during psychotherapy.

These experience are novel and powerful and can generate neurogenesis and healing. They can result in major reorganization of our mind's inner world. This can be life changing.

Darwinian evolution at the level of mind

What novelty and numinous experience do is generate a type of Darwinian variability. Darwinian variability is to mind-body healing and psychosoical genomics as genetic variation is to biological evolution.

Darwinian evolution, that is the biological evolutionary process, turns on the presence of genetic variation. Natural selection then selects for those variants that increase survival and/or reproduction.

Our immune system works similarly. When we are confronted with a disease (virus, bacteria, etc.), a lot of variable immune cells are generated--sort of a hyper mutation process. When one of the mutated immune cells matches up with the invading organism, the matching immune cells undergoes rapid growth and division so that lots and lots of those immune cells are produced and we heal.

Likewise, mind-body healing process requires a type of variation, but at the level of neurons and their interconnecting synapses. Powerful experiences like numinous ones, apparently generate a lot of variation and then the minds natural selection mechanism selects those that are adaptive.

Additional reading:

Rossi, Earnest. 2002. The Psychobiology of Gene Expression. Difficult to read but an incredible journey.

Good News In Our DNA: Defects You Can Fix With Vitamins And Minerals

Science News

Good News In Our DNA: Defects You Can Fix With Vitamins And Minerals

Electron microscope image of budding yeast, Saccharomyces cerevisiae. UC Berkeley researchers insert variants of human enzymes into yeast to see if these enzymes can be tuned up with vitamins. (Credit: UC Berkeley)

ScienceDaily (June 3, 2008) — As the cost of sequencing a single human genome drops rapidly, with one company predicting a price of $100 per person in five years, soon the only reason not to look at your "personal genome" will be fear of what bad news lies in your genes.

University of California, Berkeley, scientists, however, have found a welcome reason to delve into your genetic heritage: to find the slight genetic flaws that can be fixed with remedies as simple as vitamin or mineral supplements.

"I'm looking for the good news in the human genome," said Jasper Rine, UC Berkeley professor of molecular and cell biology.

"Headlines for the last 20 years have really been about the triumph of biomedical research in finding disease genes, which is biologically interesting, genetically important and frightening to people who get this information," Rine said. "I became obsessed with trying to decide if there is some other class of information that will make people want to look at their genome sequence."

What Rine and colleagues found and report in the online early edition of the journal Proceedings of the National Academy of Sciences (PNAS) is that there are many genetic differences that make people's enzymes less efficient than normal, and that simple supplementation with vitamins can often restore some of these deficient enzymes to full working order.

First author Nicholas Marini, a UC Berkeley research scientist, noted that physicians prescribe vitamins to "cure" many rare and potentially fatal metabolic defects caused by mutations in critical enzymes. But those affected by these metabolic diseases are people with two bad copies, or alleles, of an essential enzyme. Many others may be walking around with only one bad gene, or two copies of slightly defective genes, throwing their enzyme levels off slightly and causing subtle effects that also could be eliminated with vitamin supplements.

"Our studies have convinced us that there is a lot of variation in the population in these enzymes, and a lot of it affects function, and a lot of it is responsive to vitamins," Marini said. "I wouldn't be surprised if everybody is going to require a different optimal dose of vitamins based on their genetic makeup, based upon the kind of variance they are harboring in vitamin-dependent enzymes."

Though this initial study tested the function of human gene variants by transplanting them into yeast cells, where the function of the variants can be accurately assessed, Rine and Marini are confident the results will hold up in humans. Their research, partially supported by the Defense Advanced Research Projects Agency (DARPA) and the U.S. Army, may enable them to employ U.S. soldiers to test the theory that vitamin supplementation can tune up defective enzymes.

"Our soldiers, like top athletes, operate under extreme conditions that may well be limited by their physiology," Rine said. "We're now working with the defense department to identify variants of enzymes that are remediable, and ultimately hope to identify troops that have these variants and test whether performance can be enhanced by appropriate supplementation."

In the PNAS paper, Rine, Marini and their colleagues report on their initial analysis of variants of a human enzyme called methylenetetrahydrofolate reductase, or MTHFR. The enzyme, which requires the B vitamin folate to work properly, plays a key role in synthesizing molecules that go into the nucleotide building blocks of DNA. Some cancer drugs, such as methotrexate, target MTHFR to shut down DNA synthesis and prevent tumor growth.

Using DNA samples from 564 individuals of many races and ethnicities, colleagues at Applied Biosystems of Foster City, Calif., sequenced for each person the two alleles that code for the MTHFR enzyme. Consistent with earlier studies, they found three common variants of the enzyme, but also 11 uncommon variants, each of the latter accounting for less than one percent of the sample.

They then synthesized the gene for each variant of the enzyme, and Marini, Rine and their UC Berkeley colleagues inserted these genes into separate yeast cells in order to judge the activity of each variant. Yeast use many of the same enzymes and cofactor vitamins and minerals as humans and are an excellent model for human metabolism, Rine said.

The researchers found that four different mutations affected the functioning of the human enzyme in yeast. One of these mutations is well known: Nearly 30 percent of the population has one copy, and nine percent has two copies.

The researchers were able to supplement the diet of the cultured yeast with folate, however, and restore full functionality to the most common variant, and to all but one of the less common variants.

Since this experiment, the researchers have found 30 other variants of the MTHFR enzyme and tested about 15 of them, "and more than half interfere with the function of the enzyme, producing a hundred-fold range of enzyme activity. The majority of these can be either partially or completely restored to normal activity by adding more folate. And that is a surprise," Rine said.

Most scientists think that harmful mutations are disfavored by evolution, but Rine pointed out that this applies only to mutations that affect reproductive fitness. Mutations that affect our health in later years are not efficiently removed by evolution and may remain in our genome forever.

The health effects of tuning up this enzyme in humans are unclear, he said, but folate is already known to protect against birth defects and seems to protect against heart disease and cancer. At least one defect in the MTHFR enzyme produces elevated levels in the blood of the metabolite homocysteine, which is linked to an increased risk of heart disease and stroke, conditions that typically affect people in their post-reproductive years.

"In those people, supplementation of folate in the diet can reduce levels of that metabolite and reduce disease risk," Marini said.

Marini and Rine estimate that the average person has five rare mutant enzymes, and perhaps other not-so-rare variants, that could be improved with vitamin or mineral supplements.

"There are over 600 human enzymes that use vitamins or minerals as cofactors, and this study reports just what we found by studying one of them," Rine said. "What this means is that, even if the odds of an individual having a defect in one gene is low, with 600 genes, we are all likely to have some mutations that limit one or more of our enzymes."

The subtle effects of variation in enzyme activity may well account for conflicting results of some clinical trials, including the confusing data on the effect of vitamin supplements, he noted. In the future, the enzyme profile of research subjects will have to be taken into account in analyzing the outcome of clinical trials.

If one considers not just vitamin-dependent enzymes but all the 30,000 human proteins in the genome, "every individual would harbor approximately 250 deleterious substitutions considering only the low-frequency variants. These numbers suggest that the aggregate incidence of low-frequency variants could have a significant physiological impact," the researchers wrote in their paper.

All the more reason to poke around in one's genome, Rine said.

"If you don't give people a reason to become interested in their genome and to become comfortable with their personal genomic information, then the benefits of much of the biomedical research, which is indexed to particular genetic states, won't be embraced in a time frame that most people can benefit from," Rine said. "So, my motivation is partly scientific, partly an education project and, in some ways, a partly political project."

Marini and Rine credit Bruce Ames, a UC Berkeley professor emeritus of molecular and cell biology now on the research staff at Children's Hospital Oakland Research Institute, with the research that motivated them to look at enzyme variation. Ames found in the 1970s that many bacteria that could not produce a specific amino acid could do so if given more vitamin B6, and in recent years he has continued exploring the link between micronutrients and health.

"Looked at in one way, Bruce found that you can cure a genetic disease in bacteria by treating it with vitamins," Rine said. Because the human genome contains about 6 billion DNA base pairs, each one subject to mutation, there could be between 3 and 6 million DNA sequence differences between any two people. Given those numbers, he reasoned that, as in bacteria, "there should be people who are genetically different in terms of the amount of vitamin needed for optimal performance of their enzymes."

This touches on what Rine considers one of the key biomedical questions today. "Now that we have the complete genome sequences of all the common model organisms, including humans, it's obvious that the defining challenge of biology in the 21st century is not what the genes are, but what the variation in the genes does," he said.

Rine, Marini and their colleagues are continuing to study variation in the human MTHFR gene as well as other folate utilizing enzymes, particularly with respect to how defects in these enzymes may lead to birth defects. Rine also is taking advantage of the 1,500 students in his Biology 1A lab course to investigate variants of a second vitamin B6-dependent enzyme, cystathionine beta-synthase.

He also is investigating how enzyme cofactors like vitamins and minerals fix defective enzymes. He suspects that supplements work by acting as chaperones to stabilize the proper folding of the enzyme, which is critical to its catalytic activity. "That is a new principle that may be applicable to drug design," Rine said.

Coauthors with Rine and Marini are UC Berkeley research assistant Jennifer Gin and Janet Ziegle, Kathryn Hunkapiller Keho, David Ginzinger and Dennis A. Gilbert of Applied Biosystems, which also funded part of the study. The work was supported by a University of California Discovery Grant, DARPA and the National Institutes of Health.

Monday, September 19, 2011

Contagion: The Next Pandemic

Scientific American

Features | Health

What Will the Next Influenza Pandemic Look Like?

Predicting pandemics might still be impossible, but with millions of lives at stake, researchers are using the latest science and lessons from history to best prepare for the next big one

flu mask

Planning for the unpredictable: The only thing scientists are certain about the next influenza pandemic is that it will happen--sometime, somewhere. Image: flickr/trendscout

MALTA—Contagion, a film released earlier this month, depicts a gruesome outbreak of an exotic and deadly new virus. In the real world, a not-so foreign infection is circulating among animals every day of every year. If it picks up just a handful of certain mutations, it could start spreading among people, with a mortality rate as high as 60 percent. What is this potent virus? The flu.

Although the 2009 pandemic of influenza A H1N1 ended up being relatively mild—killing about one in 10,000 people who came down with it—it still claimed more than 14,000 lives across the globe. The relatively low mortality rate was a relief to forecasters because the outbreak's origin in Mexico and type had taken many by surprise.

Such surprises have turned out to be one of the few constants in the virus world: "Expect the unexpected," Ab Osterhaus, a professor of virology at the Erasmus Medical Center in Rotterdam, said here Tuesday at the fourth European Scientific Working Group on Influenza (ESWI) conference.

The uncertainty factor makes global preparedness particularly challenging. And given the basic questions that remain to be answered—such as why some healthy people die of the flu and others do not—researchers are using new technologies to look for leads in victims as well as in the virus itself.

Because, as scientists and public health experts seemed to agree: "What is clear is that it is when, not if," Frederick Hayden, of the University of Virginia School of Medicine, said here on Tuesday, referring to the next influenza pandemic—one of many proclamations of coming plague during the meeting that was tinged with just enough urgency to generate attention (and research funding) but not ignite an all-out panic.

Ongoing research is providing some new clues about what type of virus might become pandemic, where it might emerge and who it is most likely to kill.

Mysterious mutations
Topping the worst-case scenario list for most flu experts is a pandemic of H5N1, the "bird flu" which has killed about six in 10 people who have gotten it—a total of at least 550 people since 2003—and has laid to waste hundreds of millions of domestic fowl and wild birds.

Fortunately, so far, it has not been transferred from human to human and has passed to us only via direct contact with animals. But any flu can change rapidly, mutating in each new host. So researchers wonder: Could the dreaded H5N1 ever morph into a disease that could spread among people, via a cough or sneeze, to attach to nasal or tracheal membranes, as the seasonal flu does every year?

To help answer this question, Ron Fouchier, also of Erasmus Medical Center, and his team "mutated the hell out of H5N1" and looked at how readily it would bind with cells in the respiratory tract. What they found is that with as few as five single mutations it gained the ability to latch onto cells in the nasal and tracheal passageways, which, Fouchier added as understated emphasis, "seemed to be very bad news."

The variety that they had created, however, when tested in ferrets (the best animal model for influenza research) still did not transmit very easily just through close contact. It wasn't until "someone finally convinced me to do something really, really stupid," Fouchier said, that they observed the deadly H5N1 become a viable aerosol virus. In the derided experiment, they let the virus itself evolve to gain that killer capacity. To do that, they put the mutated virus in the nose of one ferret; after that ferret got sick, they put infected material from the first ferret into the nose of a second. After repeating this 10 times, H5N1 became as easily transmissible as the seasonal flu.

The lesson from these admittedly high-risk experiments is that "the H5N1 virus can become airborne," Fouchier concluded—and that "re-assortment with mammalian viruses is not needed" for it to evolve to spread through the air. And each of these mutations has already been observed in animals. "The mutations are out there, but they have not gotten together yet," Osterhaus said.

The exact likelihood of an H5N1 pandemic moving into humans is still unknown, pointed out Derek Smith, a professor of infectious disease informatics at the University of Cambridge in the U.K. From a scientific perspective, he noted, "one expects that's a low probability, but it's a really high-impact thing to prepare against—it's like preparing against terrorism."

Despite all of the concern about H5N1, scientists are also keeping an eye out for other emerging varieties. With 16 known forms of influenza hemagglutinin (the "H" in the strain name), nine known varieties of neuraminidase enzyme (the "N" in the name), and different subtypes within each type, the potential for new enzymatic combinations—and recombinations—is great.

Even H1N1 is not yet in the clear. Since the 2009 outbreak in humans, H1N1 has become much more prevalent in pig populations, and, currently, "we are seeing quite large numbers of re-assortments," Malik Peiris, of the University of Hong Kong, said at ESWI. And a swine-origin triple re-assortment of the H3N2 strain had recently infected two children in the U.S., the Centers for Disease Control and Prevention in Atlanta reported earlier this month.

But the basic dynamics of how these diseases spread are still being worked out. "We don’t know enough about how they transmit from human to human—whether re-assortments in pigs makes it more likely or less likely" to spread among humans, Smith said.

In addition to shifts in virulence and method of spread, slight mutations in the virus can also lead to major changes in how easily it can be treated. A single-point mutation, for example, can render it resistant to commonly used antiviral medications, such as Tamiflu.

The body enigmatic
One of the most disconcerting things about influenza pandemics, as opposed to the seasonal flu, is their tendency to sicken—and often kill—the young and seemingly healthy. Underlying risk factors, such as heart disease and neurological conditions, have been linked to higher fatality rates. But as Maria Van Kerkhove, of the Imperial College London's (I.C.L.) School of Public Health, found in a survey of global data following the H1N1 pandemic, no chronic conditions were reported among some 40 percent of people who were hospitalized for the flu and then died.

There is a "massive difference in the way people respond" to the same strain of influenza, noted Peter Openshaw, director of the Center for Respiratory Infection at I.C.L. He and his colleagues are studying samples from hundreds of people, many of whom became severely ill from the H1N1 pandemic strain, to look for clues as to why one apparently healthy 40-year-old might wind up in intensive care whereas another will fight the virus off just fine at home. But because too little is known about these varied reactions, the team is looking everywhere: in human and viral genetics, for traces of bacterial infections, and elsewhere for hints about what might release the "cytokine storm" that kills some people, now seemingly at random, Openshaw said.

Unknown origins
The 2009 outbreak of H1N1 caught most people off guard—not in the least, those charged with tracking new flu strains and outbreaks. Especially after the 2003 emergence of SARS in Asia, most pandemic plans were centered on a Southeast Asian or Asian emergence for the next flu epidemic.

Modeling had predicted that a Southeast Asia–based strain would take some two to four months to spread extensively and arrive in Europe and North America about one to three months after that. That delay would give Western countries three to seven months to develop comprehensive treatment and vaccination plans.

When the flu emerged in Mexico, instead, North America endured the peak of the epidemic without a vaccine.

An outbreak's point of origin can also play a large role in determining how quickly a pandemic is detected. Regions such as Africa and some places in Southeast Asia are still lagging in surveillance capabilities, noted Maria Zambon, of the U.K. Health Protection Agency.

To the advantage of epidemiologists and the public, "the severity of a virus will determine how quickly we detect it," Neil Ferguson, a professor of mathematical biology of infectious diseases at I.C.L., said on Tuesday. The 2009 H1N1 virus had already been circulating in Mexico for some months before the full scope of its potential came to light. "We detected the 2009 virus as late as we did just because it was as mild as it was," he noted. And lingering immunity in the older population further reduced its spread. But if the next virus is more virulent and more rapidly transmitted, "we will detect it earlier," he said.

Subsequent analysis of the spread of the 2009 pandemic showed that it matched up with commercial air traffic from Mexico—spreading more rapidly into the U.S. and Spain, which are strongly socially connected to the Latin American country. If an outbreak were to begin in Asia, however, South America is "a great place to be," because there is very little direct air traffic from Asia to the region, Smith noted on Monday. So by the time the pandemic would arrive in force, a vaccine would likely already be available.

Asia is still at the focus of pandemic watchfulness, especially for hints of H5N1 spread. The virus is relatively common among migratory birds, which it usually does not sicken. As Osterhaus noted, "dead birds don't fly," so the well ones that still carry the disease are free to travel, infecting other flocks—and domestic poultry as well. It can also be spread via human activity, with exports of birds, feathers and other related products.

A recent study of the H5N1 virus in Laos found that some 0.6 percent of ducks sampled showed traces of the infection. And in places like Laos, where local poultry markets facilitate the movement of fowl around the country, the spread of the infection is of great concern to local and foreign health officials. The country has seen a documented outbreak of H5N1 every year since 2006.

Surveillance of the virus has been ramping up throughout Southeast Asia. In Bangladesh, for example, backyard farms predominate, putting fowl in close contact with both humans and migratory birds, so spread to the dense human population is of particular concern. "Bangladesh is in the front line now," explained Syed Ahmed, of the University of Southern Denmark.

Preparing for the unpredictable
With the virus mutating in the dark, hidden cells in billions of birds, pigs and other animals, tracking their changes might seem impossible. "If we're going to [create] the best interventions that we can, we need to understand how they circulate around the world," Smith said of flu viruses. Surveillance of animal populations worldwide has improved vastly in the past decade, boosting the chance that scientists will spot new potentially dangerous mutations early.

But researchers are not simply watching and waiting. Scientists are continually developing new proto, so-called seed vaccines, to test against newly emerging strains of the flu.

And there is plenty to do on the logistics side. The H1N1 pandemic hit Europe later than it did South and North America. And even though the outbreak was milder, thanks to the arrival of the vaccine during the pandemic peak, as I.C.L.'s Openshaw pointed out, many places were still running out of respirators, hospital beds and nursing staff.

"We know that it takes at least four to six months to have a vaccine," noted Sylvie Briand, of the World Health Organization (WHO). And for countries that receive the early waves of a pandemic, a vaccine will likely not come in time to protect people against the virus. "So it's very important to improve clinical response," by having ample medication and facilities to treat those at risk and reduce overall mortality.

Advancing preparedness in one fell swoop, however—even within the comparatively well-equipped European Union—has proved difficult, as Cambridge's Smith pointed out, because countries that are less prepared are so for different reasons—making a one-size-fits-all approach to improving preparedness impractical. And when countries the world-over are thrown into the mix—many of which have far fewer scientific, medical and infrastructural resources—the task is even more of a challenge.

At the end of the day, much of the preparation lays in the hands of policymakers—within "the realpolitik of the department of health," Openshaw noted, adding that he realized that science was only part of the equation that politicians and governmental officials must consider.

In addition to battling the mercurial virus and any political roadblocks, those trying to mitigate a future pandemic face another unpredictable force: public behavior.

In the first days of a pandemic, scientists and policymakers are forced to make consequential decisions—about containment, treatment, prophylaxis—with relatively limited information, "based on a perception," Briand said. And communicating the appropriate message to the public, which might not be well versed in risk and uncertainty, is a difficult task. Cry wolf, and it is likely to cause panic as well as subsequent criticism of overreacting. But fail to instill adequate caution, and the reaction—and mortality rate—will be even worse.

In 2009, for example, the WHO eventually declared the H1N1 pandemic a level 6—the highest designation possible. But that, Briand pointed out, was not indicative of the disease's severity, but rather the extent of its spread. This distinction, which is great in the eyes of epidemiologists, was typically unaddressed in the media and thus in public perception, leading to later claims that officials had oversold the virus's danger.

So, in addition to lab work on the viruses, some scientists are hard at work "thinking about how best to communicate the uncertainty" that is undoubtedly going to arrive with the first wave of the next outbreak, I.C.L.'s Van Kerkhove said. "We learned that from the last pandemic, and we can expect that from the next one."

Unlike other human plagues, such as polio or smallpox, however, "eradication of the flu is impossible," Osterhaus said. The latest scientific and social research has pointed to three important steps to best meet the next pandemic head on, Briand said. Officials must make a variety of plans based on different scenarios; they must remain flexible to respond to rapidly changing situations; and they must keep plans up to date—refreshing stockpiles and reevaluating plans based on the latest science.

Saturday, September 17, 2011

Are Tattoos Toxic? New Research Shows Endocrine Disruptors, Metals and Carcinogens in Tattoo Ink



Research has turned up troubling findings about toxic chemicals in tattoo inks, including phthalates, metals, and hydrocarbons that are carcinogens and endocrine disruptors.

Photo Credit: Dave H/flickr

BROOKLYN, New York The End Is Near tattoo parlor in South Park Slope could pass for one of the neighborhood's upscale boutiques.

Local artwork covers the light blue walls. Ornate body jewelry fills a glass showcase. A stuffed badger greets visitors. There's just one thing that gives the parlor away the unmistakable electric hum of a tattoo needle.

"We're not the seedy underground that used to be," said Trischa, the shop's one-named manager, whose fair skin, revealed by a black tank top, is almost completely painted with ink.

As tattoo shops turn chic, ink's allure has spread into the mainstream. Despite the well-known risks of infection, allergies and scarring, an estimated 45 million people in the United States including 36 percent of adults in their late 20s have at least one tattoo, according to estimates by the U.S. Food and Drug Administration and a Harris Interactive Poll.

Although sleazy "scratcher shops" with unskilled artists and dubious safety records are becoming a thing of the past, scientists are growing concerned about what's going into tattooed skin, not just how it got there.

New research has turned up troubling findings about toxic chemicals in tattoo inks, including some phthalates, metals, and hydrocarbons that are carcinogens and endocrine disruptors.

Tattoo ink trouble is nothing new. The inks, which are injected into skin with small needles, have caused allergic rashes, chronic skin reactions, infection and inflammation from sun exposure, said Elizabeth Tanzi, co-director of the Washington Institute of Dermatologic Laser Surgery in Washington, D.C.

Now a new study published in July suggests that phthalates and other chemical ingredients may be responsible for those problems.

More concerning, these newfound chemicals raise unanswered questions about more serious, long-term risks such as skin cancer.

One of the chemicals found in black tattoo inks benzo(a)pyrene is a potent carcinogen that causes skin cancer in animal tests. Dermatologists have published reports in medical journals on rare, perhaps coincidental cases where melanomas and other malignant tumors are found in tattoos.

Could these chemicals increase the risk of skin cancer in people with tattoos?

"It's possible and definitely warrants additional investigation by the FDA," Tanzi said.

Recently, the FDA launched new studies to investigate the long-term safety of the inks, including what happens when they break down in the body or interact with light. Research already has shown that tattoo inks can migrate into people’s lymph nodes.

For now the long-term health risks if any from tattoo inks remain murky.

"The short answer is we don't know if the chemicals in tattoo inks represent a health hazard," said Joseph Braun, an environmental epidemiologist at Harvard University in Boston, Mass., who was is not involved in the new studies.

In July, scientists reported their discovery that the chemical dibutyl phthalate, a common plasticizer, along with other substances, are found in black tattoo inks. In the study of 14 commercially available inks, they found low levels of dibutyl phthalate in all of them.

"The substances found in the inks might be partially responsible for adverse skin reactions to tattoos," wrote the dermatologists from Germany’s University of Regensburg.

For phthalates, which can mimic estrogen or disrupt testosterone, exposure of fetuses and infants is the major concern. In infant boys, prenatal exposure to dibutyl phthalate has been linked to feminization of the reproductive tract. In men, phthalate exposure has been linked to sperm defects and altered thyroid hormones.

But phthalates in tattoo inks may not carry the same risk.

"Phthalates are cleared from the body within hours, and unlike many phthalate exposures, those from tattooing will not be continuous," said Shanna Swan, a reproductive epidemiologist at the Mount Sinai School of Medicine in New York who studied the effects of phthalates on infant boys.

Phthalates applied to the skin in a lotion were absorbed and metabolized in a 2007 study, and the same thing is likely to happen with phthalates in tattoo inks, Swan said.

"While this is a potential source of high exposure, it might not last very long and may not present a risk to health," Braun added.

Nevertheless, Swan said pregnant and nursing women should minimize any exposure to phthalates.

In addition to phthalates, heavy metals such as lead, which can harm the reproductive and nervous systems, also were found in a study of 17 different black inks from five manufacturers.

Colored inks often contain lead, cadmium, chromium, nickel, titanium and other heavy metals that could trigger allergies or diseases, scientists say. Some pigments are industrial grade colors that are "suitable for printers' ink or automobile paint,” according to an FDA fact sheet.

Black tattoo inks, often made of soot, also contain products of combustion called polycyclic aromatic hydrocarbons (PAHs), according to a 2010 study by the German scientists.

The PAHs in the inks include benzo(a)pyrene, which was identified in an Environmental Protection Agency toxicity report as "among the most potent and well-documented skin carcinogens." It is so potent that it is routinely used in animal tests to grow tumors. Also, it has been linked to skin cancer in shale oil workers, and the EPA has classified it as a probable human carcinogen.

"Tattooing with black inks entails an injection of substantial amounts of phenol and PAHs into skin. Most of these PAHs are carcinogenic and may additionally generate deleterious singlet oxygen inside the dermis when skin is exposed to UVA (e.g. solar radiation)," wrote the study authors. They said the PAHs could "stay lifelong in skin" and "may affect skin integrity," which could lead to skin aging and cancer.

Scientists are debating the possible tattoo-cancer link, based so far on a handful of malignant skin tumors found in tattoos and reported in medical literature.

"Even though cases of malignancies such as melanoma, basal cell carcinomas, squamous cell carcinomas and keratoacanthomas have been reported for the past 40 years, it remains unclear what role tattoos play in their pathogenesis," wrote scientists from France’s University of Montpellier in a 2008 study, "Skin Cancers Arising in Tattoos: Coincidental or Not?"

Dr. Wolfgang Bäumler, a dermatology professor at the University of Regensburg who was involved in the phthalate and PAH studies, said that "substances such as phthalates and also the PAHs should increase the health risk" for chronic health problems such as cancer. But the extent is unknown, Bäumler said, because "epidemiological studies are missing."

Epidemiological studies won't be easy. In theory, scientists could track a large number of tattooed people and see whether they developed problems such as skin cancer near their tattoos. But that's impractical, said Geoffrey Kabat, an epidemiologist at the Albert Einstein College of Medicine in the Bronx, N.Y.

That's because getting a tattoo still is considered a risky behavior, and following a group of people who may have risk-taking behaviors smoking or riding motorcycles would compromise a study, Kabat said.

"This would also make an epidemiologic study a fool's errand,” Kabat said.

The FDA has the power to regulate tattoo inks and any added colorings under the Federal Food, Drug, and Cosmetic Act. But the agency has never flexed its regulatory power, citing lack of evidence of safety concerns and other public health priorities.

"Because the dyes and inks used in tattoos have not been approved by FDA, we do not know the specific composition of what these inks and dyes may contain," an FDA spokesperson told Environmental Health News. "Therefore, we are unable to evaluate for chronic health concerns, such as cancer."

Now, the FDA is getting curious about the ingredients. In 2003 and 2004, the FDA received its largest cluster of complaints, more than 150, from people on the giving and receiving end of tattoos. Since that time the FDA has begun more research on tattoo inks to answer fundamental questions, according to the FDA spokesperson.

One major question investigated by the FDA is where does the ink go when the tattoo fades over time or from sun exposure?

Preliminary results show that a common pigment in yellow tattoo inks, Pigment Yellow 74, may be broken down by the body's enzymes, according to the FDA. Sunlight also breaks it down into colorless components of unknown toxicity. Also, when skin cells containing ink are killed by sunlight or laser light, the ink breakdown products could spread throughout the body.

Previous studies have shown that tattoo inks move into people's lymph nodes, but “whether the migration of tattoo ink has health consequences or not is still unknown,” according to a 2009 FDA consumer update. Lymph nodes are part of the body’s system for filtering out disease-causing organisms.

The FDA said "as new information is assessed, the agency considers whether additional actions are necessary to protect public health."

Because of the chemicals involved, California requires all tattoo shops to warn customers. A state law, known as Prop 65, requires warnings whenever people are exposed to chemicals linked to cancer, birth defects or other reproductive harm. The warning is included in the release forms that people sign before getting tattooed in California.

The lack of FDA regulation and the California warnings haven't slowed the tattoo business, where respected artists command between $125 and $200 per hour. Artists today build relationships with dedicated clients, who rarely ask about the long-term risks of tattoo inks.

"I don't have any clients that ask me that," said tattoo artist Jorell Elie of The Honorable Society in West Hollywood, Calif. "I don't really tattoo as many one-time clients anymore so most of my clients are fully aware of any if any risks that go into getting tattoos."

One of Elie's clients, Eric Blevens, of Brooklyn, has nearly a dozen tattoos. His latest, done by Elie, is a tribute to his pit bull, named Kweli, and covers most of the left side of his torso. During a recent vacation, Blevens said Elie constantly bugged him about keeping his tattoos shielded from the sun, which could cause the art to fade.

Aside from a small reaction to pink pigments, Blevens hasn't had any problems with tattoo inks and said he considers them safe. Through his relationship with Elie, any safety concerns he may have had in the past have faded.

"I genuinely trust him," Blevens said. "He shows a lot of concern and care for his work."

Even people with more simple tastes don't seem concerned about the safety of tattoo inks. Melissa Taylor, a 30-year-old mother and banker in Warner Robins, Ga., said she hasn't worried much about her ink. She got a small butterfly tattoo, about the size of a 50-cent piece, on her left hip when she was 19 and hasn't had any problems.

"I did a little bit of research because I wanted to go to a good, reputable place, not some hole-in-the-wall," Taylor said.

That kind of research is exactly what Jordan Bayley, manager of Fly Rite Studios in Brooklyn, recommends. Every artist is different, and cities and states have different regulations since the act of tattooing is regulated at the state and local level.

The dangers of putting tattoo needle to skin have been widely publicized and are taken seriously by tattoo artists. Disposable needles are the norm. Surfaces are sterilized with hospital-grade cleaners.

Most customers, however, are more concerned with how the tattoo will look years down the road.

"People usually don't come in worried about health concerns," said Mario Delgado, the owner of Moth and Dagger Tattoo Studio in San Francisco, Calif. "People are more concerned about getting a good tattoo."

Brett Israel is a researcher, writer and former intern at Environmental Health News.