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Endobiogeny Systems Theory
 

Endobiogeny Systems Theory

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This is a summary of the big research article of the same name that was published in two parts. This lecture was given at UCSD Center for Integrative Medicine's Journal Club on 6/27/13.

This is a summary of the big research article of the same name that was published in two parts. This lecture was given at UCSD Center for Integrative Medicine's Journal Club on 6/27/13.

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  • The image on the left illustrates the focused view of a reductionist model. It looks at the part at the expense of the wholeThe image on the right illustrates the holistic view, which contextualizes man within the circadian cycle and appreciates the dynamism of his physiology, but lacks a reflective analysis of the particular components of adaptability and adaptation
  • If one accepts the premise that the human organism is a true system, the level of activity of this system must be considered. Most researchers engaging in systems research are going down the level of systems analysis to the most basic rather than going up to higher levels of complexity. In a global systems approach, if one takes the eye, we can demonstrate how a global systems approach contextualizes retinal cells within a larger context while appreciating every level of the system. The images, from top left clockwise:Top Left: Retinal cellsTop Right: Contextualization of retinal cells within the entire occular apparatusBottom Right: Contextualization of the eye within the context of light/dark variations, pineal glandBottom Left: Contextualization of the eye, the pineal gland, and adaptability at the level of the adrenals and the thyroid
  • A global systems approach to medicine will change the way we classify diseases based not on symptoms, but on commonality of physiologic imbalances
  • It is a false dichotomy to chose between reductionism and holism. Endobiogeny encompasses both, which his what is required for a global approach to systems theory.
  • The image in the top right illustrates the network of relationships between various proteins within a single cell within a 24 hour period of time.
  • Figure 2: Chlamydial disease was found within atheromas. Chlamydial disease was then theorized to be the cause of atherosclerosis. Many large scale observational studies were conducted that reinforced this conclusion. However, treating the chlamydia did not change the course of atherosclerosis. Figure 3: Low-grade chronic chlamydial infection, elevated CRP and arterial disease all have in common a dysregulation of the immune system. It is the neuro-endocrine regulators of immune dysfunction that also play a role in he development of atheromas. The same terrain that allows for inflammation and chronic low-grade infections drives the growth of atheromas. The fact that chlamydial organisms are found in the plaque simply means that the chlamdia was playing an accelerating role in the course of the disease but is not the cause of the disease. It is neither necessary nor sufficient for the development of atheromas and atherosclerosis.
  • The relationship between TSH and free T4 is not linear except in a very narrow range of patients. If one takes a TSH of 1 mU/L, across a spectrum patients, the fT4 (pmol/L) can range from 4 to 28. Conversely, for a fT4 of 15, the TSH can range from 0.01 to 25. (the Y-axis is on a log scale)
  • The biomarkers noted are applied in direct and indirect ratios. The use of ratios of biomarkers is not new in medicine, but has had limited use.
  • The thrombotic index is a good example of another indirect index. If one opens up the index and re-arranges the equation with the indices of the indices, one sees that this index captures the factors that are know and validated clinically to participate in thrombo-embolic phenomenon.
  • The human organism, like this Huicholindian work, is a complex series of inter-related and interdependent units of function that interact both with themselves and with the external environment.

Endobiogeny Systems Theory Endobiogeny Systems Theory Presentation Transcript

  • ASEMIP Endobiogeny: A global approach to systems biology Kamyar M. Hedayat, MD (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Goals • Discuss general concepts presented in Endobiogeny: A Global Approach to systems biology, part 1 (Glob Adv Health Med. 2013:2(1):64-78)and part 2 (Glob Adv Health Med. 2013:2(2):32-56) • Discuss research opportunities • Discuss training opportunities (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP INTRODUCTION ““Living systems are organized in such a way that they form multi-leveled structures, each level consisting of subsytems which are wholes in regard to their parts, and parts with respect to the larger wholes ”--Fritjof Capra, The turning point: science, society and the rising culture, p. 43 (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Reductionism and Holism • Reductionism: explaining complex phenomena by the properties individual components • Naïve reductionism: belief that reductionism leads to a complete understanding of living organisms • Holism: evaluating complex phenomenon that arise from individual components • Naïve Holism: qualitative, subjective evaluation can sufficiently explain complex phenomenon • Systems Theory: Complex systems are composed of individual sub-systems that are both independent and inter-dependent on other sub-systems as well as the whole (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Differing views REDUCTIONISM HOLISM (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Systems Theory (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology “Systems theory looks at the world in terms of the interrelatedness and interdependence of all phenomenon, and in this framework an integrated whole whose properties cannot be reduced to those of its parts is called a system.” Fritjof Capra, The turning point: science, society and the rising culture, p. 43
  • ASEMIP Determining level of study (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology Biological information is encoded in a multi-scale information hierarchy: DNA, RNA, proteins, interactions, biolog ical networks, cells, tissues and organs, individuals and, finally, ecologies. The important point is that the environment impinges upon each of these levels of the hierarchy and modulates the digital informational output from the genome. Thus, systems-level investigations demand the collection of data at each relevant level of the hierarchy between the phenotypic measurement (features of the cell) and the core digital genome—Leroy Hood et al., Institute for Systems Biology39
  • ASEMIP Implications in Nosology (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology Human disease network and Disease Gene Networks reveal the complex polygenetic basis of disease and proposes a classification of disease based on complex physiologic activity, rather than on phenotypic expression of symptoms. From Goh KI, Cusick ME, Valle D, Childs B, Vidal M, Barabasi AL. The human disease network. Proc Natl Acad Sci U S A. May 22 2007;104(21):8685-8690. Figure 1: Human Disease Network
  • ASEMIP OVERVIEW OF ENDOBIOGENY (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Endobiogeny: A theory of terrain • Presented by French physician Christian Duraffourd, MD in the early 1980’s • Terrain: functional expression of structural constitution in its internal equilibrium – Dynamic and Ceaseless – Consists of Inductive and Reactive elements
  • ASEMIP Endobiogeny: A theory of terrain • Terrain – Constitution: Genetic heritage, potential capacity of the structure – Structure: materialized constitutive elements that assure life. The achievement of constitution – Function: all the biologic and metabolic mechanics that assure functioning of structure and dynamics of the organism
  • ASEMIP Manager of the System • In order to ensure the integrity of the system, the manager must possess 3 qualities: 1) Ubiquity of interaction with each structural element 2) Constancy of relationship with those elements 3) Auto-regulation. (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Elements of the Endobiogenic Method • Theory of Terrain • History • Physical Exam • Systems-based biomarker interpretation • Rational clinical phytotherapy • Allimentation • Lifestyle (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP A false dichotomy Reductionism • Quantitative • Smallest functioning part at expense of big picture • Hierarchy • Categorical • Separate • Unrelated • Static • Control Holism • Qualitative • Big picture at expense of the part • Relationships • Individualized • Interconnected • Inter-related • Dynamic • Creative chaos (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology ENDOBIOGENY
  • ASEMIP THE BIOLOGY OF FUNCTIONS "The new mathematics...is one of relationships and patterns. It is qualitative rather than quantitative and thus embodies the shift of emphasis that is characteristic of systems thinking—from objects to relationships, from quantity to quality, from substance to pattern." Fritjof Capra (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Need to use biomarkers Advantages • Objective • Quantitative • Accurate • Reproducible • Minimally invasive Short-comings • Binary • Reductionist • Confusion of – Cause vs. Effect – Cause vs. Effect vs. Mechanism (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Cause, Mechanism, Effect (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Rational for use biomarkers • Endocrine management: – Endocrine system is true manager of the terrain – Endocrine activity cannot be accurately evaluated by direct serum measurement. • Biomarkers and the endocrine system – Known for nearly 100 years that changes in biomarkers associated with specific endocrinopathies – Changes in biomarkers result of endocrine management of metabolism • Systems analysis and relative relationships – Body is a true system – Blood-based biomarkers will be most informative of system activity when applied in a qualitative manner using ratios (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Biomarkers used in the biology of functions (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP CBC: Biomarker-NeuroEndocrine relationships Biomarker Neuro-Endocrine RBC Androgens at tissue level WBC Estrogens at tissue level PMN Estrogens with respect to immunity, inflammation, anabolism Monocytes FSH activity within gonadotropic axis (direct), relative efficiency of estrogens during adaptation (inverse), peripheral androgen activity relative to that of estrogens (direct), immune dysregulation. Eosinophils Intensity of ACTH solicitation adrenals (direct), relative efficiency of cortisol activity (inverse). Risk of Inflammation, thrombosis, immune and other activities due to insufficient cortisol activity Basophils Intensity of ACTH solicitation adrenals (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP CBC (cont.) Biomarker Neuro-Endocrine relationship Lymphocytes Related to three factors: cortisol, estrogen, and TSH. Cortisol (inverse): reduces circulating lymphocytes, augments destruction; Estrogen (inverse): augment infiltration of lymphocytes into tissues; TSH (direct): metabolic needs of body, degree to which TSH used to modulate thyroid activity. Platelets Mobilized by adrenaline; adsorber, transporter of calcium, serotonin; participates in thrombosis, wound healing, inflammation (via histamine) Hemoglobin Marker of the degree of alpha-sympathetic activity in adaptation. (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Bone Stroma biomarkers Biomarker Relationship Osteocalcin Glucose regulation (insulin sensitivity), Fat regulation (adipocyte growth), ATP production (number and efficiency of mitochondria), Endocrino-metabolic efficacy of estrogens Alkaline phosphatase Related to effects of intracellular growth factors, cell turnover and energy demand (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Systemic Enzyme Biomarkers Biomarker Neuro-Endocrine relationship CreatineKinase Thyroid metabolic efficiency (inverse): Ultra-acute energy demand, Mitochondrial efficiency (inverse), Lactate dehydrogenase Thyroid metabolic efficiency (direct): oxidation of glucose relative to demands of the organism, as seen in: cardiac ischemia,405, 406 muscle turnover,389 rapid cell and tissue growth,407 hemolysis,408, 409 and cancer.410-412 (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Endocrine biomarker Bio- marker Relationship TSH responsiveness of the thyroid to stimulation (inverse), immune demand of body, anabolic solicitation by estrogens (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology Figure 8: TSH relationship to T4 From Hoermann R, Eckl W, Hoermann C, Larisch R. Complex relationship between free thyroxine and TSH in the regulation of thyroid function. Eur J Endocrinol. Jun 2010;162(6):1123-1129.
  • ASEMIP Ratios in medicine (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Direct and Indirect ratios Direct Indices • Direct relationship of biomarkers • Genital Ratio (GR) – RBC/WBC • Adaptation Index – Eosinophils/Monocytes Indirect Indices • Indirect relationship of direct indexes and other indirect indexes • Genital ratio corrected =GR × Starter Index GR=RBC/WBC =(RBC × Starter)/WBC
  • ASEMIP Thrombotic index =Thrombogenicx Evoked Histamine x Genital Ratio – Thrombogenic: 10 x (Bone remodeling x Apoptosis x Necrosis)/Metabolic yield = (Bone remodeling x Apoptosis xNecrosis)(Evoked Histamine x Genital Ratio)/Metabolic yield • Relationships in index: risk of thromboembolism is result of triad of factors, necessary but not sufficient: – 1) Risk of thrombus formation (due to necrosis206-208 or apoptosis205) – 2) Histamine activity,209-211 – 3) Elevated androgens212-220 • Consistent with known pathophysiologic mechanisms of thromboembolic phenomenon. (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP RESEARCH, LEARNING AND PRACTICE (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Endobiogeny around the world • Europe – France: Home of Endobiogeny – UK: taught in conjunction with Middlesex University – Lithuania: Taught through affiliation with medical school (starting 2014) • Americas – US: Fellowship underway – Mexico: Official form of medicine, used by public health system • North Africa – Tunisia: Masters degree in endobiogeny (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Areas of research • Cancer • Autoimmune disorders • Neuro-psychiatric disorders • Cardiovascular disorders • Septic Shock • PTSD (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Opportunities for learning • US, France, Lithuania, Tunisia • 2 year fellowship, 260 learning hours – History – Physical examination – Biology of Functions – Integrative, clinical use of medicinal plants (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP CONCLUSIONS (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Conclusions • There is nothing new in the tendency to take obvious things for granted and to postpone logical thought…For many centuries we were satisfied to accept life itself without questioning and without inquiring as to its beginnings, variations and potentialities. Now we have some desire of understanding how life began, of its continuation and limitations Manfred Sakel, MD, 1938 (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP Conclusions • Endobiogeny is a theory of terrain • Offers a Global systems approach to biology – Quantitative – Qualitative – Humanistic – Clinical solutions open to all forms of treatment, prefers medicinal plants, diet, lifestyle (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology
  • ASEMIP DISCUSSION (c) 2013 American Society of Endobiogenic Medicine and Integrative Physiology Huichol Indian thread work