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Endobiogeny.systems theory
1. ASEMIP
Endobiogeny: A global approach
to systems biology
Kamyar M. Hedayat, MD
(c) 2013 American Society of Endobiogenic
Medicine and Integrative Physiology
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, biological
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
19. ASEMIP
Biomarkers used in the biology of
functions
(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
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.
