Solving the Homeopathic Puzzle One Step at a time: Adaptive Network Nanomedicine
by Iris R. Bell, MD PhD
Introduction to Homeopathy as Adaptive Network Nanomedicine
What is a homeopathic remedy? What is a homeopathic potency? How does a remedy act?
Those questions have fascinated proponents of homeopathy and mobilized the doubts of skeptics for over two centuries. In recent years, various researchers have finally begun to discover important scientific clues to answer these questions. Do we have the final answers? Not yet, but we do have valuable new insights and advances. In our research group, we have summarized our understanding of the available scientific evidence into what we call the “adaptive network nanomedicine” model for homeopathy. [1-5]
The skeptics’ primary objection to homeopathic medicines is that the serial dilution process should progressively remove “all traces” of the original source material. What they obviously assume is that the medicine is either a large dose of a bulk form (ordinary larger form) of a drug for specific drug receptors or nothing at all. In conventional bulk form drug thinking, relatively large material doses of conventional drugs must act on specific drug receptors to produce specific drug effects on local tissues.
What skeptics have not yet realized or acknowledged is that, unlike conventional drugs, homeopathy does not have to depend upon large amounts of bulk forms of remedy source materials to act. [5] Overall, homeopathic remedies are not conventional drugs and overall do not act like conventional drugs. [6] Rather, scientific evidence shows that homeopathic remedies contain detectable amounts of nanostructures [7-24] and act as conveyors of salient information to the organism as a whole. The homeopathic information serves as a meaningful, albeit small, signal that triggers a large magnitude adaptive response by the recipient organism. Multiple other research studies have shown that the homeopathic information can take the form of unique electromagnetic [25,26], optical [27-29], biochemical [30], and/or quantum mechanical [21,31-36] information.
Nanoparticles are extremely small forms of a given material, typically less than 100 nanometers in size. [37] The smallest nanoparticles are sometimes termed quantum dots, which are typically less than 10 nanometers in size. [38-44] Quantum dots acquire quantum mechanical properties such as quantum entanglement and quantum coherence because of their extremely small size that traps atoms and their electrons at the surface of the nanoparticle. [45-49] By comparison, a strand of human DNA is reportedly around 2.5 nanometers in size; viruses range between 17-500 nm in size; and a human hair can range from 80,000 to 100,000 nanometers in width. One nanometer is 10-9 meters, or one-billionth of a meter. [50]
What happens if a specific type of nanoparticle (with a unique material composition, size, shape, and surface properties) arrives by mouth, nasal inhalation, or skin contact? The organism can recognize the nanoparticles as a warning sign or danger signal of more intense danger to come. [51-54] Then the organism responds. [51]
Living systems have various ways of amplifying weak but salient signals that are important for their continued survival in the constantly-changing internal and external environment in which they live. [51,55,56] In the context of survival of the adaptive organism, salient signals from stressors or stimuli or agents that disrupt the internal homeostatic balance require a response to adapt to, reverse, and/or prepare for the same or similar stressors or stimuli or agents at some unknown future higher dose or intensity. [57-59] How can the signal register with the organism enough to trigger a significant response?
Such amplification response phenomena that whole organisms can initiate include:
(1) stochastic resonance (SR): With SR, a larger amplitude noise enhances a weak signal whose frequency overlaps a subset of frequencies also contained within the noise; [60-66] SR has been demonstrated in animal sensory systems for predator sound, smell, or vibration threats. [67] The unique biology of disease itself can generate the noise within the individual body;
(2) time-dependent sensitization (TDS): TDS results from a repeated intermittent low level stressor or drug or electrical stimulus that initiates progressive enhancement over time of the size of subsequent responses to the same or a cross-sensitized stressor. [68] TDS and/or oscillatory reversal in response direction have been demonstrated in animals and human subjects with psychological or physical stressors, small electrical stimuli, low dose environmental chemicals, drugs, sucrose, endogenous mediators such as cytokines as well as homeopathic remedies; [69-76]
(3) hormesis: Hormesis is a biphasic dose-response relationship involving low dose stimulation versus high dose inhibition or toxicity. [77,78] Researchers have demonstrated hormesis in bacterial cells, plants, animals, and human cells involving stressors, radiation, environmental chemicals, drugs, and homeopathically-prepared remedies. [56,77,79-92]
All of these organism-dependent amplification phenomena depend on the nonlinear dynamics and network organization of the body as a complex adaptive system, [93-95] i.e., the plasticity of function in the living system dealing with changes in its environment. [1-5]
Nanoparticle Nature of Homeopathic Remedies
Starting with a ground-breaking 2010 study by a leading research group at the Indian Institute of Technology, [7] multiple laboratories have found that homeopathic remedies contain nanoparticle forms of the original source materials and/or foster formation of nanostructures in solution. [7-24] These particles have been detected and characterized with electron microscopy and several other advanced modern technologies. Remedies studied include Argentum Metallicum, Aurum metallicum, Cuprum metallicum, Stannum metallicum, Zincum metallicum, Platinum Metallicum, Plumbum metallicum, Silica, Belladonna, Pulsatilla, Cochicum, and Gelsemium as well as other plant source materials.
In nanotechnology, it is well-established that mechanical grinding or milling (e.g., trituration) can generate smaller micro- and nano-particle forms from larger bulk form source materials, including but not limited to synthetic drugs.[96] One study reported a hormetic effect from low doses of milled forms of two conventional drugs. [16]
Succussions are a type of intense mechanical agitation of liquids within containers. Like grinding or milling, modern forms of agitation such as vortexing [97] or sonication (typically ultrasound energy applied to agitate particles) are well-known to break down larger source materials such as eggshells [98], rice husk ash [99-101], plant extracts [15], synthetic drugs [16,96] or larger agglomerated nanostructures [102] into smaller nanoparticle forms. Sonication can also generate nanoparticles from dissolved salts in solution such as sodium chloride or potassium iodide and embed them into glassware surfaces. [103]
Separate studies have also demonstrated that either glass or plastic materials release respectively silica [8,13,104,105] or plastic [106] microparticles into liquid solutions that additional agitation or the simple passage of time degrades into nanoparticle forms. Both micro- and nanoparticle forms of these types of materials commonly released by bottles, vials, tubing, and other packaging [107] have highly reactive surfaces that adsorb onto their surfaces any other materials in solution with them, including organic materials. [108-114]
If the remedy is made in a traditional way by succussions in glassware, then the data demonstrate the release of glass or silica particles into solutions from the agitation process. [104] Silica can play several different roles – i.e., as a biologically-tolerated vehicle to coat, stabilize, and carry the original source material nanoparticles into cells and/or as an electronic and immune system response adjuvant or response amplifier. [115-127]
A recent new study has demonstrated the presence of silica coatings over metal source nanoparticles and nanobubbles in traditional homeopathically-prepared remedies. [12] Glass particles released from the container walls can adsorb also proteins onto their surfaces [105] and subsequently trigger strong immune reactions to proteins in conventional drugs within liquids stored in the glassware, for instance. [108]
Multiple researchers worldwide have contributed to additional data now available. The fundamental findings encompass the following observations:
Intense agitation of plant or animal cell materials can break off small vesicles from cells into smaller particles and even nanoparticle-sized vesicles called exosomes (vesicles 30-100 nanometers in size, containing proteins, DNA, and/or lipids). Exosomes are biologically active signals that cells use to communicate with other cells. [128]
Organic materials such as many different plant extracts and simple sugars [129-141] are capable of biologically generating nanoparticles of silica or metals such as gold, silver, iron, zinc, or copper when put into solution with precursors of these elements. It appears that the resultant green-biosynthesis of nanoparticles leaves biologically active traces of the original plant material on the outside surfaces of the nanoparticles. [134-136,141-151]
During the serial dilution-succussion process into higher potencies, the evidence shows that the nanoparticles can accumulate in certain layers toward the top of a solution, buoyed by bubbles and nanobubbles produced by succussions. [19,152] Successful manufacturing of higher homeopathic remedy potencies requires the effective sampling and transfer of nanoparticles from one container to another (Hahnemannian method) or the repeated re-use of the same piece of glassware for higher potencies (Korsakovian method). Re-used glassware would be likely to contain layers of particles on and in their wall surfaces from step-to-step and over time to release nanoparticles previously-embedded by succussions from glassware walls. [103]
In turn, the nanoparticles would serve as a carrier or delivery vehicle for the homeopathic information available from the original source material. Multiple homeopathic researchers have been reporting observations of electromagnetic [25,26], optical [27-29], biochemical [30] and/or quantum mechanical [21,31-36] information conveyed by homeopathically-prepared materials, all types of phenomena that nanoparticles can initiate. Remedy information can affect solvatochromic dyes in solution that rely on intramolecular charge transfer. [153,154] Solvatochromic dyes are a special type of dye that can change colors due to a change in polarity of the surrounding solvent; solvatochromic effects are sometimes used in molecular sensors and electronic switches, including nanoparticle detection as part of the sensor. [155,156]
The correct remedy or stimulus information for biology may take the form of a salient biochemical, electromagnetic, and/or optical signal of environmental change or even a quantum mechanical effect to which the organism as a whole must adapt with endogenous changes. Such changes support overall survival and resilience in face of change in the internal (e.g., reactive oxygen species activated by nanoparticles) or external (e.g., psychological, physical, chemical, or biological stressors) environment. [51,55]
How could Nanoparticles Cause Biological Effects?
Nanoparticles are recognized in the nanoscience literature as capable of serving as environmental stressors for living cells and organisms.[51] They can activate various biological responses, including endogenous cell signaling mediators, cytokines, and heat shock proteins as part of the damage- or danger-associated molecular patterns (DAMPs) recognized by cells. [51] Signaling mediators are similar to a team relay race in which the arrival of the remedy signal sets the next step into motion, with cell biology taking up the baton. [55]
The process becomes a self-amplifying cascade of biological signaling events into motion across the networks of nervous, immune, endocrine, and metabolic subsystems of the body. [3,4,55,157-160] For instance, exosomes from foods like carrots have been shown to modulate gut function in animals. [128] A number of different homeopathic remedies also modulate cell signaling mediator release and immune function as detected with tests for white blood cell responses and cytokine mediator release patterns. [161-170] One laboratory repeatedly demonstrated hormetic patterns of heat shock protein effects from low dose, homeopathically prepared materials such as cadmium or arsenic. [89-92,171] Both homeopathic remedies and modern nanoparticles can modulate gene expression profiles. [86,172-181]
The nature of the adaptive changes that evolve over time lead to the self-healing of the organism as an emergent complex adaptive system or integrated network of parts. [1,94,95] Homeopathic treatment relies on the salience of the remedy for the individual’s pre-existing, emergent biopsychosocial state of being, not its local drug-like effects. If the homeopathic information is salient, the organism responds to the weak signal from a dose of the correct remedy by adapting with self-amplified changes across the organism as a whole integrated system or network of subsystems/networks. [182-185] The net result is to throw off the pre-existing maladaptive adaptations that originally generated disease symptoms.
Discussion
Skeptics are still likely to argue that nanoparticles are present in such small amounts in homeopathic remedies as to be incapable of producing biological effects in the way a conventional drug or nanodrug can.
First, that assumption is not likely true for very low potency remedies. For example, it is well-established that microparticles and nanoparticle forms made by milling or grinding larger forms of source materials, including even conventional drugs, are generally more bioavailable and can enter cells more readily than can ordinary larger bulk forms of the “same” material. [186] Because of the enhanced bioavailability of nano-forms, producing direct, drug-like effects of a nanoparticle form of a given agent often requires an orders of magnitude lower dose to avoid toxicity. [187,188] In that situation, a remedy would still be producing some direct drug-like action or effect with the nanoparticle form in a low potency remedy, but amount needed might be 10% or 1% (cf., 1X,, 2X) of what the ordinary bulk dose of drug requires. [187,188]
Second, low doses of nanoparticles shown to be present in low and higher potencies of homeopathic remedies can still initiate biological effects. As noted above, in homeopathy, unlike conventional medicine, the goal is not to produce a clinically direct effect of inhibition of function. Rather, as Hahnemann stated in the Organon of Medicine, the goal of homeopathic treatment is to produce an indirect effect, i.e., to activate the counter-action of the body. [189] The counter-action only requires recognition of the stimulus as a warning of future danger from the direct action of a larger dose of the drug or a different cross-sensitizing agent. If the counter-action reverses a pre-existing disease state of the organism (understood as a maladaptive disease state induced by prior large magnitude stressors), the treatment brings about a reversal in direction of the (mal)adaptive patterns, i.e., a healing response or recovery without risk of treatment-related toxicity.
How do we understand Hahnemann’s concept of “counter-action” for a given remedy? In modern terminology, “counter-action” translates into the adaptive response of the recipient living organism [158] or cell interacting with the remedy. Remedy effects thus depend on the biological plasticity of the organism to occur. [77,88,190-194]
Summary
The scientific evidence shows that homeopathic remedies contain low but measurable amounts of nanoparticles. The composition of these tiny structures include remedy source materials as well as silica or perhaps plastic nanoparticles, depending on the type of succussion container used. In traditionally-made higher potencies prepared in glassware, the nanoparticles are hybrids in composition, with remedy source material cores and silica coatings. Trituration alone, a form of mechanical grinding or milling, is sufficient to generate source nanoparticles at the lowest potencies; no glassware or succussions are necessary. Plant extracts and sugars like lactose or sucrose or honey can also biologically generate (reduce) and stabilize (cap) nanoparticles from silica or metal precursors in solution with them.
Nanoparticles in higher potency homeopathic medicines may not necessarily produce a direct drug-like effect. They merely need to elicit an indirect adaptive response amplified by the subsystem networks of the cell or organism as a whole. Hormesis and other types of adaptive responses to nanoparticles involve the biology of the organism as a whole complex, self-organizing living system. The salience of the correct remedy to the individual as a whole system is what matters in initiating the response.
In modern scientific terminology, an organism is a complex adaptive system or network of interrelated subsystems (e.g., immune, endocrine, metabolic, nervous). The parts and pathways are interconnected; the whole (global) is greater than the sum of the parts. In fact, in a living complex adaptive system, the emergent global properties of the whole modulate the functioning of the parts. At the same time, each part sends information across the organism to other subsystems and modulates the functioning of the whole complex adaptive system, just as the global whole modulates functioning of the parts. [195,196]
Research shows that nanoparticles from a wide range of source materials can initiate the adaptive phenomenon of hormesis, which is known to depend upon biological changes in the recipient organism. Hormesis is a non-linear dose-response relationship in which low doses can produce effects, often beneficial effects, in a direction opposite to those that higher, larger or toxic doses of the same material can produce. The hormetic stimulus or stressor can be given before or after the toxic dose that could induce or has induced damage to the organism (preconditioned or postconditioned hormesis respectively). Researchers in many different laboratories have found hormetic effects from nanoparticles of environmental agents, drugs, and elemental materials such as silica and silver, in addition to radiation alone.
Change in one subsystem leads to change in multiple other subsystems and the overall or global larger system as a whole. In homeopathic philosophy, the complex adaptive system or network model maps conceptually onto Hering’s Law of Cure – self-organized change occurring from the inside out, hierarchically from above downwards, and in reverse order of time of appearance of symptoms. [93-95] The correct remedy serves as the trigger or stimulus to set healing in motion. The organism as a complex adaptive system, not the remedy per se, carries out the self-healing process. [197]
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