Dear Colleagues,
My contribution will finalize the discussion on phenomenology in the domains of biology, mathematics, cyber/biosemiotics and physics by the previous speakers (Maxine, Lou, Sœren and Alex) with a “challenging topic” in *3φ integrative medicine*. *You may wish to skip the small font text notes following each underscored phrase like the one below.* *Note 1:* Although this term is often used as synonym for holistic healing (s. ref. list A), its meaning in this context with the prefix 3φ goes much “deeper” into the disciplines’ integration leaving no room for speculations by mainstream scientists. The concept is a linguistic choice of mine for the intended merge of the complexity sciences *ph*ysics and *ph*ysiology with *ph*enomenology for application in modern medicine along the line of integral biomathics (s. ref. list B). It is rooted in the last presentation of Alex Hankey, since it naturally provides the link from physics to physiology and medicine, and thus to an anthropocentric domain implying a leading part of phenomenological studies. To begin, I compiled a précis of Alex’ thesis about self-organized criticality (s. ref. list C) from his paper “A New Approach to Biology and Medicine” -- the download link to it was distributed in a previous email of him -- and extended it with my reflections including some questions I hope you will resonate on. I am curious of your opinion about how to apply the scientific method, and in particular mathematics and information science, to study illness and recovery as complex phenomena. *Alex Hankey: self-organized criticality and regulation in living systems* *There is a continuous growth and change at the end of a phase transition in an organism, i.e. at its critical point, which is the end point of phase equilibrium.* *Both endo and exo, genetics and epigenetics are important for life.* *Self-organized criticality* is a characteristic state of a system at its critical point generated by self-organization during a long transient period at the complexity edge between order/stability/predictability and disorder/chaos/unpredictability. *Regulation of growth, form and function as a balance between health and illness.* The role of regulation and homeostasis in maintaining the structure and function of living systems is critical. Every deviation from a regulated state of being leads to imbalances, failures and subsystem dysfunction that is usually transitory, but could also become life-threatening, if the organism cannot find a way to restore quickly to a balanced, healthy state. Living beings are robust and fault-tolerant with respect to hazards; they possess multiple alternative pathways for supplying and maintaining their existential functions. However, some state transitions in response to severe harms can become practically irreversible, because of the deep evolutionary interlocking between the participating entities and processes. Sometimes the normal functioning of the organism cannot be easily restored by its natural repair processes, especially when adversities reoccur frequently, and the organism fails ill. *Synchronicity of action and information between the building blocks of a living system.* There is a need for every physiological function to be correctly coordinated with all other “peer” functions. Information flows within a living system interconnect all physiological functions and organs at multiple levels into a single mesh of regulatory interconnections. Multiple feedback-control loops enable the cross-functional interlocking of both healthy and ill state changes of the organism. Adjacent/peripheral/secondary homeostasis processes act as fine-tuning catalyzers of substrate ratios and process rates exchanged within the living system. Imbalances of these quantities lead to excess/blockage or scarcity/draining of essential nourishment and information exchange pathways. *Regulation at criticality* not only fine-tunes a process, it *optimizes* it for survival: with respect to a given generation’s available possibilities in the light of the past generations’ possibilities. To survive an organism or a species needs to develop optimal *response-ability* to environmental distress. *New ecological definition of life according to Hankey: self-regulating, self-reproducing systems that maximize efficiency of function to maximize competitiveness in their chosen environment. * *Summary: Elements of self-organized criticality* 1. Criticality 2. Edge of the chaos 3. Self-organized criticality 4. 1/f fractal patterns of response *… and beyond* I wish to add a 5th aspect to this definition from the perspective of integral biomathics: 1. *Phenomenology* The latter is a largely studied matter in contemporary medicine (s. ref. list D), at least at the macro, interpersonal *level*. *Note 2*: A level refers to the compositional hierarchy defining levels by scale. *The key question in such a “deep holistic” physically-phenomenological physiology (*3φ*)** is how to define or comprehend (self-organized) criticality operationally within the unifying framework of biomathematics and biocomputation*. Indeed, a single temporary imbalance within a living system regarded as disease involves multiple agents, perspectives and interpretations at all levels altogether, moreover *simultaneously*. *Note 3*: Simultaneously at different levels involves very different sized 'moments' at the different scales. So, how should we approach and take into account the other levels/scales in order to derive a reliable diagnosis and *therapy*? *Note 4*: The notion of “subject” becomes plural (“subjects”) as superposition of quantum states to survive the integration of the multiple first-person subjective descriptions and the standard third-person objective one. Until now criticality has been *non-phenomenological*. *Note 5:* In their 2012 paper “No entailing laws, but enablement in the evolution of the biosphere” Longo, Montévil and Kauffman claim that biological evolution “marks the end of a physics world view of law entailed dynamics” (http://arxiv.org/abs/1201.2069). They argue that the evolutionary phase space or space of possibilities constituted of interactions between organisms, biological niches and ecosystems is “ever changing, intrinsically indeterminate and even (mathematically) unprestatable”.Hence, the authors' claim that it is impossible to know “ahead of time the 'niches' which constitute the boundary conditions on selection” in order to formulate laws of motion for evolution. They call this effect “radical emergence”, from life to life. Yet this applies to abiotic dissipative structures like tornadoes as well. Living beings are not radically different in this respect. In their study of biological evolution, Longo and colleagues carried close comparisons with physics. They investigated the mathematical constructions of phase spaces and the role of symmetries as invariant preserving transformations, and introduced the notion of “enablement” to restrict causal analyses to Batesonian differential cases (1972: “the difference that makes a difference”). The authors have shown that mutations or other “causal differences” at the core of evolution enable the establishment of non-conservation principles, in contrast to physical dynamics, which is largely based on conservation principles as symmetries. Their new notion of “extended criticality” also helps to understand the distinctiveness of the living state of matter when compared to the non-animal one. However, their approach to both physics and biology is also *non-phenomenological*. The possibility for endo states that can trigger the “(genetic/epigenetic) switches of mutation” has not been examined in their model. This is intended to be different in 3φ* integrative medicine*. If we split a human body into macro (patient), mezzo (systems) and micro levels (cells) three distinct questions regarding phenomenology arise: i) *how* these levels pervade into each other with larger scale providing context (boundary conditions) and lowest scale providing raw materials for middle scale to function, monitor and control vital processes, ii) *who/which* are the agents taking care for this to happen spontaneously, and iii) *what kind and role* plays information in the context of i) and ii). After all what we are concerned about is modeling the agency of the systems in the mezzo level. Where should we go from here? In particular, I am interested to know *what kind of scientific-phenomenological methodology can be developed and applied for investigating *the following three major groups of ailments: 1. *oncological diseases* with a particular focus on spatial and temporal heterogeneity both in terms of flawed histological structures and biochemical reactions; 1. *neuro-degenerative disorders* such as vascular dementia, Parkinson and Alzheimer diseases: 1. *altered organ and physiological system failures* such as the Multiple Organ Dysfunction Syndrome (MODS), cardiovascular and autoimmune diseases. In the first group, the *extreme diversity of cancer tissue structures and circulating tumor cells (CTC) concentrations over both spatial and temporal scales* makes the reliable classification, diagnosis, model/hypothesis generation, forecast and treatment of individual patients very difficult. This is a real challenge for modern pathology. Another problem is that pathologists are actually dealing with random tissue and blood samples over irregular periods, which hinder the exact 3D histological reconstruction of the tumor formations and tracing their development over time and space. Using additional means such as diagnostic sonography, CT, MRT and PET images do not improve sufficiently the hypotheses about the individual cancer morphology and development. All this makes tumor classification and diagnosis, even when analyzing high-resolution digital images from biopsy slices by means of virtual microscopy, very difficult and often a guesswork also for experts. The recent advances in high-performance medical scanning and automation systems, computerized visualization and graphical modeling tools, as well the collection of huge amounts of anonymous patient data in specialized medical databases make the impression that the solution of these problems is only a question of more automation, performance, investment and time. However, many pathologists begin to realize a third problem, namely that *tumors appear to be unique in their histological structure and development*, related to the personal history and the overall state of health of the individual patients. This argument reveals the need for developing a more personalized and differentiated medicine that goes over scales without becoming purely symptomatic, causality-driven and reductionistic. Recent research in the other two fields leads to the same conclusion. Therefore, I think that we may be able to develop and test hypotheses about emergence and development of deficiency and illness that will lead to individual therapies in *3φ* integrative medicine. Your ideas regarding this assumption are very welcome. Some interesting questions bridging the previous discussion sessions to this one are: - Why does a human embryo repeat the evolutionary history of its species when going through its development stages? Is it because it is more secure to project and set up the execution of a future life plan by tracing and bodily memorizing a series of evolutionary encoded (successful) “locks” through equilibrium states at the edge of criticality? - Which is the *vital *role of recursion and repetition of life processes including their material and information exchange flows in the criticality driven self-regulation for recovery from imbalances and the reversibility and healing of diseases? How can we effectively model such processes? - Do we make difference between a physicist’s time and a biologist’s time in complex living systems? * I look forward to your feedback and notes on the subject.* *References:* *A. **Integrative Medicine* Integrative Medicine: https://en.wikipedia.org/wiki/Integrative_medicine <http://www.wikiwand.com/en/Integrative_medicine> What Is Integrative Medicine?: http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine Integrative Medicine Research: http://www.journals.elsevier.com/integrative-medicine-research/ Advances in Integrative Medicine http://www.journals.elsevier.com/advances-in-integrative-medicine *B. **Integral Biomathics* Integral Biomathics: https://en.wikipedia.org/wiki/Integral_Biomathics <http://www.wikiwand.com/en/Integral_Biomathics> Integral Biomathics: A Post-Newtonian View into the Logos of Bios https://arxiv.org/ftp/cs/papers/0703/0703002.pdf On Some Recent Insights in Integral Biomathics: https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf. Integral Biomathics Reloaded: 2015 (free access until July 19th 2016): http://www.sciencedirect.com/science/article/pii/S0079610715001509 *C. **Self-organized criticality**:* Self-organized criticality: https://en.wikipedia.org/wiki/Self-organized_criticality <http://www.wikiwand.com/en/Self-organized_criticality> Self-organized criticality (SOC): http://www.johnboccio.com/courses/SOC26/15-SOC.pdf Self-organized criticality: http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf Self-organized criticality – what it is and what it isn’t http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf. *D. **Phenomenology in Medicine* The meaning of illness: a phenomenological approach to the physician/patient relationship: https://baylor-ir.tdl.org/baylor-ir/handle/2104/8286 ; http://hdl.handle.net/2104/8286. Body Matters: A Phenomenology of Sickness, Disease, and Illness: http://philpapers.org/rec/AHOBMA. Suffering Transfigured: Phenomenological Personalism In the Doctor-Patient Relationship: http://elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1658&context=ymtdl . The challenge of neuroscience: Psychiatry and phenomenology today: https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf . Rediscovering Psychopathology: The Epistemology and Phenomenology of the Psychiatric Object: http://cfs.ku.dk/staff/zahavi-publications/Rediscovering_Psychopathology.pdf . PHENOMENOLOGY IN PSYCHIATRY: http://www.wpanet.org/uploads/Sections/Philosopy_and_Humanities/Phenomenology-in-Psychiatry.pdf. *Plamen* ____________________________________________________________ 2015 JPBMB Special Issue on Integral Biomathics: Life Sciences, Mathematics and Phenomenological Philosophy <http://www.sciencedirect.com/science/journal/00796107/119/3> (note: free access to all articles until July 19th, 2016) 2013 JPBMB Special Issue on Integral Biomathics: Can Biology Create a Profoundly New Mathematics and Computation? <http://www.sciencedirect.com/science/journal/00796107/113/1> 2012 Integral Biomathics: Tracing the Road to Reality <http://www.springer.com/engineering/computational+intelligence+and+complexity/book/978-3-642-28110-5> 2011 INtegral BIOmathics Support Action (INBIOSA) <http://www.inbiosa.eu> ____________________________________________________________
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