The Complexity of the Homeopathic Healing Response Part 1: The Role of the Body as a Complex Adaptive System in Simillimum-Initiated Recovery from Disease.

BACKGROUND: The concepts of complex systems science enhance the understanding of how people develop and recover from disease. Living systems (human beings, animals, and plants) are self-organizing complex adaptive systems (CAS): that is, interconnected networks. CAS maintain life by initiating and carrying out non-linear dynamical changes to optimize survival fitness and function in the context of an ever-changing environment. AIMS: In Part 1 of this two-part paper, we relate concepts from complex systems science to homeopathic healing. The systemic changes of homeopathic healing involve adaptive patterns of responses to salient signals (similia) for reversing disease patterns and generating emergent multi-symptom healing over time. METHODS AND RESULTS: This narrative review relates homeopathic clinical practice theory to complex systems and network research. Homeopathic medicines communicate individually salient environmental information to the organism, with effects that are multi-system and indirect. The body's defense mechanisms recognize the self-similar information that the correctly chosen simillimum medicine at low dose conveys as a weak external/internal environmental stressor or danger signal (hormetin) to mobilize neural and cellular defenses. The body networks then use endogenous cell to cell signaling and amplify the small magnitude signal information. The results are disproportionately large: that is, non-linear, adaptive, modifications across the inter-connected self-organized biological networks/sub-systems of the body. CAS amplification mechanisms for small or weak signals include stochastic resonance, time-dependent sensitization, and hormesis. CONCLUSIONS: The body as a complex system has the capacity for self-organization, emergence and self-similarity over global (overall health and wellbeing) and local (organ) levels of organization. These features are key for future research on the systemic healing that evolves over time during individualized homeopathic treatment.

The Complexity of the Homeopathic Healing Response Part 2: The Role of the Homeopathic Simillimum as a Complex System in Initiating Recovery from Disease.

BACKGROUND: Evidence indicates that homeopathic medicines are complex self-organizing nano-scale systems that generate unique low-intensity electromagnetic signals and/or quantum coherence domains. In Part 1, we reviewed relevant concepts from complex adaptive systems science on living systems for the nature of homeopathic healing. AIM: In Part 2, we discuss the complex-system nature of homeopathic medicines. The aim is to relate the evidence on the nature and properties of homeopathic medicines to the complex systems model for homeopathic healing. METHODS AND RESULTS: The work is a narrative review, with complexity model development for the nature of homeopathic medicines. Studies suggest that homeopathic manufacturing generates nano-structures of source material, silica and silicon quantum dots if succussed in glassware or including botanical source materials; or carbon quantum dots if succussed in plastic or including any organic source materials, as well as solute-induced water nano-structures carrying medicine-specific information. On contact with physiological fluids (e.g., blood plasma), there is evidence that nano-structures additionally adsorb individualized patterns of the recipient's own proteins on to their surfaces to create a unique protein corona coat (shell). Thus, the simillimum may generate a personalized biological identity upon administration. Consequently, a medicine can serve as an individually salient, self-similar information carrier, whose protein corona constituent pattern reflects the individual's current internal state of health/disease. Homeopathic medicine complexity emerges from interactions of the component parts from source, silica from glassware or carbon from plastic containers, solvents (lactose, water, ethanol), adsorbed biomolecule layers from plant or animal sources, and adsorbed biomolecules of the recipient. Low doses of these complex medicines can act as biological signaling agents to initiate hormesis via a network-wide pattern of adaptive responses by the recipient complex adaptive system, rather than as conventional pharmaceutical drugs. Biological mediators of adaptive responses include inter-connected network elements of the cell danger/damage defense system: for example, gene expression, reactive oxygen species, heat shock proteins, cytokines, macrophages, T-cells, and associated brain-immune system mediator pathways. CONCLUSIONS: Every homeopathic medicine is a complex nano-scale system involving multiple inter-connected, interacting components, and emergent properties. Simillimum individualization derives from formation of a unique personalized protein corona shell adsorbed to the reactive surface of the homeopathic nano-structures on contact with the recipient's body fluids. Low doses of such complex nano-structures initiate the adaptive processes of hormesis to mobilize endogenous healing of a disease state. The capacity for self-organization and self-similarity in complex systems is the key to future research on the nature of homeopathic medicines and systemic healing during individualized homeopathic treatment.

A Theoretical Approach to Selection of a Biologically Active Substance in Ultra-Low Doses for Effective Action on a Biological System.

BACKGROUND AND AIM: An approach is offered to selecting a biologically active substance (BAS) in ultra-low dose for effective action on a biological system (BS). The technique is based on the assumption that BAS in ultra-low doses exerts action on BS by means of spin supercurrent emerging between the spin structure created by BAS, on the one hand, and the spin structure created by BS, on the other hand. According to modern quantum-mechanical concepts, these spin structures may be virtual particles pairs having precessing spin (that is, be essentially spin vortices in the physical vacuum) and created by the quantum entities that BAS and BS consist of. The action is effective provided there is equality of precession frequencies of spins in these spin structures. METHOD: In this work, some methods are considered for determining the precession frequencies of spins in virtual particles pairs: (1) determination of energy levels of quantum entities that BS and BAS consist of; (2) the use of spin-flip effect of the virtual particles pair spin, the effect being initiated by action of magnetic vector potential (the spin-flip effect takes place when the varied frequency of the magnetic vector potential equals the precession frequency of the spin); (3) determining the frequencies of photons effectively acting on BS. RESULTS AND CONCLUSION: It is shown that the effect of BAS in ultra-low doses on BS can be replaced by the effect of a beam of low-intensity photons, if the frequency of photons equals the precession frequency of spin in spin structures created by BS. Consequently, the color of bodies placed near a biological system is able to exert an effective action on the biological system: that is "color therapy" is possible. It is also supposed that the spin-flip effect may be used not only for determining the precession frequency of spin in spin structures created by BS but also for therapeutic action on biological systems.

Polycrystalline structures formed in evaporating droplets as a parameter to test the action of Zincum metallicum 30c in a wheat seed model.

BACKGROUND: Polycrystalline structures formed inside evaporating droplets of different biological fluids have been shown sensitive towards various influences, including ultra high dilutions (UHDs), representing so a new approach potentially useful for basic research in homeopathy. In the present study we tested on a wheat seed model Zincum metallicum 30c efficacy versus lactose 30c and water. MATERIALS AND METHODS: Stressed and non-stressed wheat seeds were watered with the three treatments. Seed-leakage droplets were evaporated and the polycrystalline structures formed inside the droplet residues were analyzed for their local connected fractal dimensions (LCFDs) (measure of complexity) using the software ImageJ. RESULTS: We have found significant differences in LCFD values of polycrystalline structures obtained from stressed seeds following the treatments (p<0.0001); Zincum metallicum 30c lowered the structures' complexity compared to lactose 30c and water. In non-stressed seeds no significant differences were found. CONCLUSIONS: The droplet evaporation method (DEM) might represent a potentially useful tool in basic research in homeopathy. Furthermore our results suggest a sensitization of the stressed model towards the treatment action, which is conforming to previous findings.

Hormesis: principles and applications.

Hormesis has emerged as a central concept in biological and biomedical sciences with significant implications for clinical medicine and environmental risk assessment. This paper assesses the historical foundations of the dose-response including the threshold, linear and hormetic models, the occurrence and frequency of the hormetic dose response in the pharmacological and toxicological literature, its quantitative and temporal features, and underlying mechanistic bases. Based upon this integrative foundation the application of hormesis to the process of risk assessment for non-carcinogens and carcinogens is explored.

Benzylisoquinoline alkaloid biosynthesis in opium poppy.

Opium poppy (Papaver somniferum) is one of the world's oldest medicinal plants and remains the only commercial source for the narcotic analgesics morphine, codeine and semi-synthetic derivatives such as oxycodone and naltrexone. The plant also produces several other benzylisoquinoline alkaloids with potent pharmacological properties including the vasodilator papaverine, the cough suppressant and potential anticancer drug noscapine and the antimicrobial agent sanguinarine. Opium poppy has served as a model system to investigate the biosynthesis of benzylisoquinoline alkaloids in plants. The application of biochemical and functional genomics has resulted in a recent surge in the discovery of biosynthetic genes involved in the formation of major benzylisoquinoline alkaloids in opium poppy. The availability of extensive biochemical genetic tools and information pertaining to benzylisoquinoline alkaloid metabolism is facilitating the study of a wide range of phenomena including the structural biology of novel catalysts, the genomic organization of biosynthetic genes, the cellular and sub-cellular localization of biosynthetic enzymes and a variety of biotechnological applications. In this review, we highlight recent developments and summarize the frontiers of knowledge regarding the biochemistry, cellular biology and biotechnology of benzylisoquinoline alkaloid biosynthesis in opium poppy.

Endogenous morphine: up-to-date review 2011.

Positive evolutionary pressure has apparently preserved the ability to synthesize chemically authentic morphine, albeit in homeopathic concentrations, throughout animal phyla. Despite the establishment of a progressively rigorous and mechanistically focused historical literature extending from the mid 1970s to the mid 1980s that supported the expression of chemically authentic morphine by animal cellular and organ systems, prejudicial scepticism and early dismissal by scientists and clinicians most often obscured widespread acceptance of the biological importance and medical implications of endogenous morphine. The current critical paper presents and evaluates key recent coordinated studies in endogenous morphine research, highlighting those that have advanced our understanding of the functional roles of cognate alkaloid-selective µ(3) and µ(4) opiate receptors. We propose that the expression of endogenous morphine by animal and human cells is designed to mediate homeopathic regulation of metabolic activity via activation of cognate µ(3) and µ(4) receptors that serve as transductive conduits for shortcircuit Ca(++) fluxes. The implications of endogenous morphine coupling to nitric oxide regulation of mitochondrial function, with special reference to the cardiovascular system, are now formulated after many years of neglect.

Ultra high dilution of triiodothyronine modifies cellular apoptosis in Rana catesbeiana tadpole tail in vitro.

BACKGROUND: Ultra High Dilutions (UHD) are diluted beyond the Avogadro limit with dynamization (dilution with succussion). The process of anuran amphibian metamorphosis is controlled by thyroid hormones, including the resorption of the tadpole tail. METHODS: A randomized and blinded study was performed to investigate the influence of triiodothyronine (T3) 5·10(-24)M (10cH) on apoptosis induced by T3 100 nM in Rana catesbeiana tadpoles' tail tips, in vitro. Explants were randomized to three groups: control: no T3 in pharmacological or UHD dose; test: T3 100 nM and challenged with T3 10cH (UHD); positive control: T3 100 nM, treated with unsuccussed ethanol. The apoptotic index and the area of explants of test and control groups at the first and final day of the experiment were compared by t-test. RESULTS: There was no difference in tail tip area between test and control groups, but a significantly higher (p<0.01) index of apoptosis in explants of the test group. CONCLUSION: This data suggest that T3 10cH modifies the effect of T3 at pharmacological dose, opening new perspectives for further studies and investigation of the dose-effect curve.

An analogy between effects of ultra-low doses of biologically active substances on biological objects and properties of spin supercurrents in superfluid 3He-B.

The effects of ultra-low doses (ULDs) of biologically active substances (BASs) (with concentrations of 10(-13)M or lower) on biological objects (BOs), such as cells, organisms, etc., and the properties of spin supercurrents in superfluid (3)He-B are discussed. It is shown that the effects of ULDs of BASs on biologic objects can be specified by the same set of physical characteristics and described by the same mathematical relations as those used for the specification and description of the properties of spin supercurrents between spin structures in superfluid (3)He-B. This is based on the up-to-date physical concepts: 1) the physical vacuum has the properties of superfluid (3)He-B; 2) all quantum entities (hence, the BAS and the BO, which consist of such entities) produce spin structures in the physical vacuum. The photon being a quantum entity, the features of the effects of low-intensity electromagnetic radiation on BOs can be explained using the same approach.

The "continuum" of a unified theory of diseases.

This essay's theme was inspired by a question asked by a child: 'Why do I get ill?' The question is very interesting, but has no easy answer. This paper discusses a few possible answers to this difficult question. Through the life of a person, from birth to death, there is a "continuum" in the pathological conditions a person may experience. The body, as a whole, suffers deeply any time there is an acute or a chronic condition that is either maltreated or neglected. Chronic and acute diseases in the medical history of a person constitute a rigidly related chain of immune responses in the form of a real "continuum" that at every point in time indicates the end result of this continuum. The idea promoted here is that suppression of diseases, through excess of chemical drugs or other means, many times overwhelms the body's natural defenses and forces the immune system to compromise and start a deeper line of defense, which then constitute the beginning of a new chronic condition. Thus, the original inflammation of an acute condition may continue as a sub-acute inflammatory process on a deeper level. Acute inflammatory conditions must therefore be treated very carefully from their beginnings in childhood in order not to force the immune system to compromise. It is also suggested here that all chronic degenerative conditions have a sub-acute inflammatory character, and that "inflammation" constitutes the main common parameter of all diseases.

A review of three simple plant models and corresponding statistical tools for basic research in homeopathy.

In this paper, we review three simple plant models (wheat seed germination, wheat seedling growth, and infected tobacco plants) that we set up during a series of experiments carried out from 1991 to 2009 in order to study the effects of homeopathic treatments. We will also describe the set of statistical tools applied in the different models. The homeopathic treatment used in our experiments was arsenic trioxide (As2O3) diluted in a decimal scale and dynamized. Since the most significant results were achieved with the 45th decimal potency, both for As2O3 (As 45x) and water (W 45x), we here report a brief summary of these results. The statistical analysis was performed by using parametric and nonparametric tests, and Poisson distribution had an essential role when dealing with germination experiments. Finally, we will describe some results related to the changes in variability, which seems to be one of the targets of homeopathic treatment effect.

The Spin of Electrons and the Proof for the Action of Homeopathic Remedies.

In the last 200 years, the action of the highly diluted homeopathic remedies has been proved by their curative effect on the human organism. In this work, a hypothesis concerning the mystifying question about this action is proposed. The hypothesis suggests that any pathology, either functional or structural, can be detected in the change of the overall energy of the human body. Such energy is constituted by fields of force according to quantum physics. More precisely, every disturbance of the human organism affects the spin on electrons of different elements within the human body, and their reset could take place with an agent similar to the electromagnetic force that created the problem. This statement has been proved by the correct homeopathic treatments, as it can be seen in many published cases. The hypothesis is based on two approaches, the idea of the spin of electrons and the vital force, and their scientific relevance.

Getting the dose-response wrong: why hormesis became marginalized and the threshold model accepted.

The dose-response relationship is central to the biological and biomedical sciences. During the early decades of the twentieth century consensus emerged that the most fundamental dose-response relationship was the threshold model, upon which scientific, health and medical research/clinical practices have been based. This paper documents that the scientific community made a fundamental error on the nature of the dose response in accepting the threshold model and in rejecting the hormetic-biphasic model, principally due to conflicts with homeopathy. Not only does this paper detail the underlying factors leading to this dose response decision, but it reveals that the scientific community never validated the threshold model throughout the twentieth century. Recent findings indicate that the threshold model poorly predicts responses in the low dose zone whereas its dose response "rival", the hormesis model, has performed very well. This analysis challenges a key foundation upon which biological, biomedical and clinical science rest.

Duckweed (Lemna gibba L.) as a test organism for homeopathic potencies.

OBJECTIVES: A bioassay with duckweed (Lemna gibba L.) was used to study the effects of homeopathic potencies on the plant's growth rate. Screening included 12 substances: argentum nitricum, copper sulfate, gibberellic acid, 3-indole acetic acid, kinetin, lactose, lemna minor, methyl jasmonate, metoxuron, phosphorus, potassium nitrate, and sulfur. Each substance was tested in the potency range 14x-30x. Controls were unsuccussed and succussed water. DESIGN: In randomized and blinded experiments, duckweed was grown in either potentized substances or water controls over 7 days. Frond (leaf) growth was measured regularly with a computerized image analysis system and growth rates were calculated for different time intervals (day 0-7, 0-3, 3-7). Additionally, a water control run with unsuccussed water as the only test substance was performed to determine the variability of the bioassay. RESULTS: For the water control run, the between-group coefficient of variance for groups of five replicates was 0.87% for the frond area-related average specific growth rate r(area) compared to 1.60% for the frond number-related average specific growth rate r(num). Thus, the former is the preferred parameter to be used. Of twelve tested substances, potentized argentum nitricum, phosphorus, and kinetin significantly (p<0.05, analysis of variance F-test) affected the main parameter: frond area-related average specific growth rate (day 0-7). Segmented area growth rates (day 0-3 or 3-7) were affected by potentized argentum nitricum, gibberellic acid, lactose, and phosphorus. CONCLUSIONS: The described experimental set-up with L. gibba as test organism appears to be a promising new model system to investigate effects of potentized substances. Yet larger sets of replication experiments with selected test substances and systematic negative controls are necessary to verify the effects found.

Kangfuxin promotes apoptosis of gastric cancer cells through activating ER­stress and autophagy.

Gastric cancer is a leading cause of cancer­associated mortality worldwide. In studies on the mechanisms of antigastric cancer drugs, autophagy and endoplasmic reticulum (ER) stress have been demonstrated to serve an active role in gastric cancer. The organic extract of Periplaneta americana (also termed American Cockroach), which is named Kangfuxin (KFX) in China, has been used clinically as a traditional Chinese medicine against disorders, including stomach bleeding, gastric ulcers, tuberculosis, burns and trauma. However, the role of KFX and its mechanism in gastric cancer remains to be elucidated. The present study aimed to determine the effects of KFX in vitro against cultured the human carcinoma SGC­7901 cell line, and to explore the potential mechanism of the anticancer effects of KFX in gastric cancer. SGC­7901 cells were treated with different concentrations of KFX for varying amounts of time. As a result, KFX treatment decreased the ratio of apoptosis regulators Bcl­2/Bax, activated ER stress and induced significant apoptosis in SGC­7901 cells. Furthermore, KFX was able to restore the ER stress activation blocked by 4­phenylbutyrate. In addition, KFX activated autophagy in SGC­7901 cells. These results demonstrated that ER stress, autophagy and the apoptosis­inducing effects of KFX in SGC­7901 cells may achieve promising anticancer effects in numerous other types of cancer. In particular, ER stress may serve an essential role in KFX­induced anticancer effects on gastric carcinoma and a secondary role in autophagy.

Models for the study of whole systems.

This article summarizes a network and complex systems science model for research on whole systems of complementary and alternative medicine (CAM) such as homeopathy and traditional Chinese medicine. The holistic concepts of networks and nonlinear dynamical complex systems are well matched to the global and interactive perspectives of whole systems of CAM, whereas the reductionistic science model is well matched to the isolated local organ, cell, and molecular mechanistic perspectives of pharmaceutically based biomedicine. Whole systems of CAM are not drugs with specific actions. The diagnostic and therapeutic approaches of whole systems of CAM produce effects that involve global and patterned shifts across multiple subsystems of the person as a whole. For homeopathy, several characteristics of complex systems, including the probabilistic nature of attractor patterns, variable sensitivity of complex systems to initial conditions, and emergent behaviors in the evolution of a system in its full environmental context over time, could help account for the mixed basic science and controlled clinical trial research findings, in contrast with the consistently positive outcomes of observational studies in the literature. Application of theories and methods from complex systems and network science can open a new era of advances in understanding factors that lead to good versus poor individual global outcome patterns and to rational triage of patients to one type of care over another. The growing reliance on complex systems thinking and systems biology for cancer research affords a unique opportunity to bridge between the CAM and conventional medical worlds with some common language and conceptual models.

On chemical medicine, thermodynamics, and homeopathy.

The author indicates why homeopathic medicine is an example of future information medicine, a member of the more general psychophysiologic medicine group. Using standard chemical thermodynamics, it is readily shown that the driving force for all chemical reactions involves the logarithm of chemical activities for the different species involved. Because chemical activity is given by the product of concentration and thermodynamic activity coefficient, such reaction driving forces involve the sum of ln gamma ( j ) and ln c(j) for the j-species. Homeopathy involves the dilution of cj and succussion, which can increase gamma (j) ; thus, when c(j) goes to the ultradilution state, the thermodynamic driving force for change does not disappear as is assumed by many and, in fact, can even increase through the ln gamma ( j ) terms. Going to a more complex reference frame for viewing nature, one can, at least, qualitatively show how oscillating and decaying properties in time can occur for homeopathic remedies.

Kinetic analysis of pancuronium interaction with sodium channels in squid axon membranes.

The interaction of pancuronium with sodium channels was investigated in squid axons. Sodium current turns on normally but turns off more quickly than the control with pancuronium 0.1-1mM present internally; The sodium tail current associated with repolarization exhibits an initial hook and then decays more slowly than the control. Pancuronium induces inactivation after the sodium inactivation has been removed by internal perfusion of pronase. Such pancuronium-induced sodium inactivation follows a single exponential time course, suggesting first order kinetics which represents the interaction of the pancuronium molecule with the open sodium channel. The rate constant of association k with the binding site is independent of the membrane potential ranging from 0 to 80 mV, but increases with increasing internal concentration of pancuronium. However, the rate constant of dissociation l is independent of internal concentration of pancuronium but decreases with increasing the membrane potential. The voltage dependence of l is not affected by changine external sodium concentration, suggesting a current-independent conductance block, The steady-state block depends on the membrane potential, being more pronounced with increasing depolarization, and is accounted for in terms of the voltage dependence of l. A kinetic model, based on the experimental observations and the assumption on binding kinetics of pancuronium with the open sodium channel, successfully simulates many features of sodium current in the presence of pancuronium.

Historical blunders: how toxicology got the dose-response relationship half right.

Substantial evidence indicates that reliable examples of hormetic dose responses in the toxicological literature are common and generalizable across biological model, endpoint measured and chemical class. Further evaluation revealed that the hormetic dose response model is more common than the threshold dose response model in objective, head-to-head comparisons. Nonetheless, the field of toxicology made a profound error by rejecting the use of the hormetic dose response model in its teaching, research, risk assessment and regulatory activities over nearly the past century. This paper argues that the hormetic dose response model (formerly called the Arndt-Schulz Law) was rejected principally because of its close historical association with the medical practice of homeopathy as a result of the prolonged and bitter feud between traditional medicine and homeopathy. Opponents of the concept of hormesis, making use of strong appeals to authority, were successful in their misrepresentation of the scientific foundations of hormesis and in their unfair association of it with segments of the homeopathic movement with extreme and discreditable views. These misrepresentations became established and integrated within the pharmacology and toxicology communities as a result of their origins in and continuities with traditional medicine and subsequently profoundly impacted a broad range of governmental risk assessment activities further consolidating the rejection of hormesis. This error of judgment was reinforced by toxicological hazard assessment methods using only high and few doses that were unable to assess hormetic responses, statistical modeling processes that were constrained to deny the possibility of hormetic dose response relationships and by the modest nature of the hormetic stimulatory response itself, which required more rigorous study designs to evaluate possible hormetic responses.