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Journal of Cosmology, 2011, Vol. 14. JournalofCosmology.com, 2011 Qualia of the Molecular Biology of Creativity and Thought Ernest Lawrence Rossi1 & Kathryn Lane Rossi2 Professors of Neuroscience1 and Psychotherapy2, La Nuova Scuola Di Neuroscienze Ipnosi Therapeutica (The New School of Therapeutic Hypnosis) and l’Istituto Mente-Corpo (The Mind-Body Institute), San Lorenzo Maggiore, Italy. 1,2 Directors of The Milton H. Erickson Institute of California Central Coast, 125 Howard Ave., Los Osos, CA, 93402, USA.
KEY WORDS: Chalmers, consciousness, DNA microarrays, dreams, evolution, experience-dependent gene expression, psychotherapy, qualia, RNA world.
1. Introduction This paper reviews Chalmers (1996) "Hard Problem of Consciousness" that was originally formulated as follows: "The really hard problem is the problem of experience. When we think and perceive, there is a whir of information processing, but there is also a subjective aspect. . . Why should physical processing give rise to a rich inner life at all? . . . Here, the topic is clearly the hard problem – the problem of experience. . . What makes the hard problem hard and almost unique is that it goes beyond problems about the performance of functions. . . Why is the performance of these functions accompanied by experience? . . . There is an explanatory gap between functions and experience, and we need an explanatory bridge to cross it. . . A full theory of consciousness must build an explanatory bridge . . . To account for conscious experience, we need an extra ingredient in the explanation . . . What is your extra ingredient, and why should that account for conscious experience?" (pp. 6-13).
2. Darwin’s Daily & Hourly Work of Evolution We introduce a new perspective on bridging the explanatory gap between the qualia of consciousness and their biological functions by quoting what Darwin wrote about the daily and hourly operation of evolution in chapter four of The Origin of Species. "It may be said that natural selection is a daily and hourly scrutinizing, throughout the world, every variation, even the slightest; rejecting that which is bad, preserving and adding up all that is good; silently and insensibly working, whenever and wherever opportunity offers, at the improvement of each organic being in relation to its organic and inorganic conditions of life. We see nothing of these slow changes in progress, until the hand of time has marked the long lapses of ages, and then so imperfect is our view into long past geological ages, that we only see that the forms of life are now different from what they formerly were." (Italics added here) We take this apparently casual, intuitive and highly speculative comment by Darwin very seriously because it helped us catch a glimpse of the natural time parameters of the molecular-genomic dynamics underpinning the qualia of consciousness, healing, and problem solving that we witness in our daily and hourly work with our patients in psychotherapy (Lloyd & Rossi, 1992, 2008; Rossi & Nimmons 1992). Figure 1 illustrates how an evolutionary co-creative complex adaptive system that includes culture, qualia, eRNA, genes and the brain can move molecules to facilitate new conscious experiences.
In brief, current epigenetic research explores why and how qualia of experience "dialogues" with the DNA of our experience-dependent gene expression via the signaling functions of RNA molecules (Mattick, 2010; Yarus, 2010). We propose that novel qualia of human experience contribute to the adaptive updating of consciousness on the molecular-genomic RNA/DNA level by modulating brain plasticity via natural variation and selection daily and hourly (Rossi, 1972, 1985, 2000, 2002, 2004, 2007, 2011). We support this proposal in the following sections by reviewing research on this adaptive function of qualia in the daily and hourly cycles of human experience from the quantum to the cognitive-behavioral levels. 3. Evolutionary Complex Adaptive Systems of Consciousness via Quantum Entanglement Consciousness and non-locality in quantum physics and psychology have generated profound quandary seeking resolution (Rossi, 1988 a, b, c). Rapparini (2010), for example, outlined the evolution of complex adaptive systems of the qualia of consciousness via quantum entanglement as follows: "In the course of an evolution process begun with inorganic chemical compounds and proceeding in steps of ever increasing complexity, life, thought and consciousness have emerged as a bonus that cannot be explained on a purely computational basis. Because in quantum physics we no longer have observables representing the ontology of the world, but only observations representing epistemic knowledge, it implies a psychological dimension which so far has been neglected. It is therefore necessary, in order to complete the picture, to introduce the psychological dimension best represented in the western tradition by Jung and by Buddhist practices in the East. Contrary to Buddhist tradition however, the brain not the mind, is considered here a sensory organ on a par with the other five. In fact, because of quantum entanglement between observer and the observed, it is possible to state that the observer (the brain) is part of the physical world (the observed) whose representations (qualia), as generated by the brain includes the representation of the brain itself. This leads to an innovative definition of qualia and their role in the emergence of consciousness: the mind is the qualia of the brain’s neural mechanisms, this is how the perceiver perceives himself, from within. This is how consciousness emerges (Rapparini, 2010, p. 169). This is what qualia are for: the objectivity of cognition as obtained from the subjectivity of feelings of what happens. . . The closing of the explanatory gap makes it possible for the mind to change the brain by self-directed neuroplasticity in agreement with the Buddhist belief on the mental power of meditation through bare attention. Finally, the concept of entanglement has been instrumental in reaching a definition of consciousness based on the innovative role of qualia." (Rapparini, 2010, p. 173). This leads to the co-evolution of complex adaptive systems of life and the qualia of consciousness from the primordial RNA world over 4 billion years ago (Atkins, Gesteland, & Cech, 2011). 4. Qualia of Complex Adaptive Molecular Systems of Consciousness via RNA World How and why do the complex adaptive systems (Mitchell, 2009) of culture, qualia, eRNAs, genes and brain plasticity co-evolve? Kim et al. (2010) recently described the identification of a new class of 12,000 enhancer Ribonucleic Acid molecules (eRNAs) that are involved in regulating gene expression during neuronal activity in mouse cortical brain tissue (Ren, 2010). The significance of this research as an "extra ingredient" for bridging the explanatory gap between the novel qualia of consciousness and their molecular-genomic infrastructure became apparent in related research on the genome of the zebra finch described as follows by Warren, Clayton et al. (2010. p. 758).
"Cellular decisions, such as differentiation, response to stress, disease progression, and apoptosis, depend upon regulatory networks that control enzymatic activities, protein translocation, and genetic responses. Central to the genetic programming of biological systems is the ability to process information within cellular networks and link this information to new cellular behaviors, in essence rewiring network topologies. . . RNA is a promising substrate for platforms to interface with cellular networks because of the versatile sensing and actuation functions that RNA can exhibit and the ease with which RNA structures can be designed. RNA-based sensing-actuation devices have been engineered that respond predominantly to externally [environmental] applied small-molecule and nucleic acid inputs and control gene expression through diverse mechanisms." (p. 1251, italics added here). It appears that sensitive and fragile "RNA-based sensing-actuation devices" were the primordial molecular qualia signaling epigenetic information from the environment of early earth to the more stable DNA molecule. One possibility is that DNA may have been a mutation in RNA world that began to function as memory molecule which eventually made natural evolution possible from one generation to the next possible. We propose that this adaptive coordination between the sensing (qualia), signaling, and catalytic self-replicating properties of RNA (with A-U, G-C base pairings) interacting with the more stable memory properties of DNA (due to A-T, G-C base pairing) was the original bridge over the explanatory gap between the molecular-genomic qualia and functions of life and consciousness. Wang et al. (2011, pp. 279 & 289) expressed it in this way: "A major surprise arising from genome-wide analyses has been the observation that the majority of the genome is transcribed, generating noncoding RNAs (ncRNAs). It is still an open question whether some or all of these ncRNAs constitute functional networks regulating gene transcription programs. However, in the light of recent discoveries and given the diversity and flexibility of long ncRNAs . . . it becomes likely that many or most ncRNAs act as sensors and integrators of a wide variety of regulated transcriptional responses and probably epigenetic events. . . Together, the ncRNA sensor code appears to be a robust and critical strategy underlying a wide variety of gene regulatory programs." If we are willing to take a philosophical, linguistic and quantum leap from "ncRNA sensor code" to "ncRNA qualia code" such research could be another "extra ingredient" in our evolving theory of the origin of life and the qualia consciousness via the dynamics of RNA/DNA coordination during transcription and translation. Current research implies that the more fragile but versatile molecular RNA signaling software of RNA world became integrated with the more stable DNA memory hardware to initiate the evolution of life as we know it. It is interesting to note that when Gilbert (1986) first introduced the concept of "RNA world" in a bottoms-up approach to the evolution of life and mind, Rossi (1986a, 1986b) began exploring such research from a top-down approach. A comprehensive theory, of course, requires an integration of both approaches to fill in the qualia gaps that remain between them. In the following sections we review the incredibly wide range of qualia-dependent molecular-genomic processes that underpin the deep psychobiological rhythms of human consciousness and experience. 5. Qualia of Consciousness during the Basic Rest-Activity Cycle (BRAC) The top of figure 3 illustrates the 90-120 minute Basic Rest-Activity Cycle (BRAC) of human performance that is the chronobiological foundation of many of the ultradian rhythms (less than the 24 hour circadian cycle) on many levels (Lloyd & Rossi, 1992, 2008). The lower part of Figure 3 illustrates the selection-amplification SELEX (SElection of Ligands by EXponential amplification) cycle in modern experiments of the possible evolution of RNA world (Yarus, 2010). We propose the SELEX experiments as molecular-genomic analogues of the evolution of the BRAC. The qualia of the BRAC are the phenotypes of the RNA/DNA genotypes of transcription and translation.
 It appears as if the art and quality of life is determined by how well we negotiate the qualia-dependent molecular-genomic processes of these alternations between performance, stress and healing in the arts, humanities and sciences as well as the work and play of everyday life. 6. Qualia of Consciousness during the 4-Stage Creative Cycle A cartoon of the qualia of consciousness as experienced during the 4-stage creative cycle in the arts, sciences and everyday life is illustrated in figure 4.
 Recent research reveals many possibilities for exploring the molecular-genomic evolution of the qualia of the 4-stage creative cycle. Ramakrishana (2011), for example, presents an overview of the translation pathway of the eukaryote cell in 4 stages: initiation, elongation, release, and recycling that looks remarkably similar to the dynamics of 4-stage creative cycle. Further, within the process of transcription/translation, Breaker (2011) describes how riboswitches regulate experience-dependent gene expression to form Boolean logical gates, which could function as the molecular infrastructure for the qualia of creativity and thought. "The term riboswitch was established to define RNAs that control gene expression by binding metabolites without the need for protein factors. More recently, the name has begun to be used for riboswitch-like RNAs that respond to temperature. . . Riboswitches need to form molecular architectures with sufficient complexity to carry out two main functions: molecular recognition and conformational switching. Simple riboswitches each carry one aptamer that senses a single ligand and one expression platform that usually controls gene expression via a single mechanism. . . Although simple riboswitches only respond to one ligand type, this restriction in signaling complexity can be overcome by stacking tandem riboswitches from different ligand-binding classes such that gene expression is responsive to more than one chemical signal. Indeed, a natural example of such two-input Boolean logic gate has been observed . . . the tandem arrangement functions as Boolean NOR gate . . . integration of multiple aptamers . . .functions as a Boolean AND gate" (p. 64 -75). Orchestrating RNA/DNA transcription and translation via riboswitches forming "Boolean logic gates" is another extra ingredient" spanning the explanatory gap for decoding the Chalmers hard problem of consciousness. Riboswitch Boolean logic gates could be the molecular-genomic basis of mind-body computation, creativity and thought that takes place in every cell of the brain and body. Further research could now assess how the binding kinetics of simple and complex riboswitches (Breaker, 2011, p. 72) could account for the scalloped fractal dynamics of the basic rest-activity cycle illustrated in figure 5. 7. Qualia of the Molecular Biology of Memory & Learning during Sleep and Dreaming Our psychosocial genomic model of creative psychotherapy that emulates the natural process whereby novel qualia experienced in our waking hours induce mind-brain-gene dialogues during slow wave sleep and REM state dreaming in Ribeiro’s evolutionary theory of sleep and dreaming illustrated in figure 6.
"The central hypothesis of Ribeiro’s (2004) evolutionary theory of sleep and dreaming is that dreams are probabilistic simulations of past events and future expectations. The adaptive function of such simulations is to construct and explore novel behaviors for future survival. A salient function of dreams is to utilize memories processed during the circadian cycle of waking, sleeping, and dreaming for the creation, selection and generalization of adaptive scenarios about the world. Ribeiro et al. (1999, 2002, 2004, 2008) provide extensive details about what they call the "cognitive role" of focusing activity-dependent gene expression and brain plasticity for adaptive behavior during the two major phases of sleep. This theory proposes that the first phase of slow-wave (SW) sleep evolved from rest in early reptiles as a quiescent, "offline state" suitable for the consolidation of new memory and learning. Consistent with much current neuroscience research, these researchers believe that this cognitive role takes place through the reverberation of novel waking patterns of neuronal activity during SW-sleep. The second major phase of sleep, rapid-eye-movement (REM) dreaming, which is characterized by heightened cerebral activity, first evolved in early birds and mammals as a post SW-sleep state that was capable of facilitating memory consolidation by activating gene expression to make the proteins needed for generating the activity-dependent synaptic plasticity of neurons, that became the neural correlates of adaptive behavior. Mammals then evolved extended REM states of dreaming to prolong neuronal reverberation in novel ways that could promote memory reconstruction in a behaviorally adaptive manner rather than mere rote record of past events. In brief, sleep and dreaming became an inner stage for integrating past events with current novel experiences to simulate and creatively replay the present as a rehearsal for future adaptive behavior." The intensity of important life turning points (adolescence, marriage, divorce, trauma, war etc.) are associated with vivid dreaming that activates qualia-dependent gene expression and brain plasticity illustrated in figure 7.
8. Qualia of the Creative Psychosocial Genomics Healing Experience (CPGHE) An overview of our new protocol for facilitating the "Creative Psychosocial Genomics Healing Experience" in psychotherapy is illustrated in figure 8.
A DNA microarray analysis of the white blood cells of human subjects was performed immediately before, within one hour after, and 24 hours after being administered the Creative Psychosocial Genomic Healing Experience (CPGHE). The rationale, administration, and scoring of this new protocol now is freely available at "http://www.ernestrossi.com/ernestrossi/Neuroscienceresearchgroup.html. We found that the qualia of the CPGHE are associated with (1) a molecular-genomic signature for the up-regulation (heightened activity) of genes characteristic of stem cell growth, (2) a reduction in cellular oxidative stress, and (3) a reduction in chronic inflammation as illustrated in figures 9 and 10.
 These three empirical associations are an initial beta version of the molecular-genomic signature of the qualia of the CPGHE that requires further replication. These results have been partially confirmed in related research using DNA microarrays to compare qualia-dependent gene expression in beginning and advanced students of meditation. It was found that the "relaxation response" associated with meditation also reduces chronic inflammation and oxidative cellular stress (Dusek et al., 2010). 9. Summary This update and decoding of the Chalmers Hard Problem of Consciousness has skirted the precipices of metaphysics in seeking what is currently known about qualia of the molecular biology of life and mind that are ready for further experimental evaluation. We reviewed research on the evolutionary continuum of RNA world from quantum entanglement to the qualia of consciousness during the 90-120 minute basic rest-activity cycle of the 4-stage creative process in the chronobiology of performance and stress. The epigenetic and informational dynamics of riboswitches that form "Boolean logic gates" for mediating adaptive changes in behavior and consciousness via RNA/DNA transcription/translation suggests how decoding the Chalmers Hard Problem of Consciousness could generate the foundations for a new science of the qualia of the molecular biology of creativity and thought. There is experimental evidence for the role of novel qualia-dependent gene expression and brain plasticity encoding adaptive memory and learning while awake and during REM dreaming. This motivated our pilot study of the Creative Psychosocial Genomic Healing Experience as a new model for evidence-based molecular-genomic research on psychotherapy. Replicating research on how the Creative Psychosocial Genomic Healing Experience facilitates qualia-dependent gene expression associated with the up-regulation of (1) stem cell activation, (2) the down-regulation of chronic inflammation and (3) oxidative stress is now a priority for translational research on human health and well being.
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