Endobiogeny Systems Theory

2. 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

3. 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

4. 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

6. 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

7. 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

8. 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

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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

18. 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

20. 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

21. 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

22. 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

23. 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

24. 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.

26. 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

27. 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

29. 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

30. 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

31. 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

33. 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

34. 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

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