'Samuel Hahnemann was the real father of modern Molecular Medicine': the perspectives of 'Neohahnemannism'

The following article postulates that:






Dr. Sanjib Chattopadhyay,

Principal

Bangabasi Evening College

Kolkata-700009, India

Formerly, Associate Professor, Dept of Zoology

Brahmananda Keshab Chandra College

Kolkata-700108, India

sanjib_chatt@rediffmail.com

Abstract:

Some latest concepts of medicinal science are indebted to Hahnemann's intuition regarding holistic approach of cure. Patient-specific treatment, therapeutic vaccination (both involve proteomics), drug-targeting and drug-delivery technique by applying least amount of medicine within micelle and liposome as 'carrier', all are the recent outcome of his philosophy. Yet, according to many scientists infinitesimally diluted drugs have no molecule of the original remedy left; they therefore are 'non-molecular and non-functional'. Conversely, it has recently been found that during Potentization molecules of the original remedy exists even after 12th centesimal dilution. It can be substantiated that diluting away of molecules is possible so long as the solution remains homogeneous. When homogeneity is lost, few molecules can be obtained up to much higher dilution than 12C. As water has a high Dielectric Constant (DC= 80), it can separate the +ve and -ve charges of the solute molecule wide apart, and form a hydration sheath around the solute molecules, which congregate in the form of nanoparticles. Addition of ethanol (DC = 24) to such an aqueous medium causes reduction of DC. As a result, ethanol mono-layer is formed around the hydrated sheath like 'inverted micelles'. When the solution is further diluted with fresh ethanol and succussed during potentization, ethanol bi-layer capsule is formed around the sheath, like 'drug loaded liposomes'. With the increase of potency the number of ethanol molecules increases around the nanoparticles and the capsule becomes more compact (Here succussion is comparable to sonication). Loss of homogeneity is the main cause of obtaining drug molecule at ultra-high serial dilutions. Due to fall of DC the solute molecules become more concentrated towards the bottom of the vial and non-homogeneity is established. In some cases it may also form top layer. If one tries to transfer a drop of such a dilution to the next vial of fresh ethanol, the 'capsules' gaining much higher speed than the solvent molecule become fluvial, rush to the next container, but most of them cannot properly return to the original vial due to non-homogeneity. Thus, theoretically a dilution may reach (Critical Dilution), where all the solute molecules being fluvial rush with the transferred volume of liquid, so that there is no significant decrease in concentration of solutes between the successive dilutions. When poured upon lactose globules, the ethanol-encapsulated drug molecules (nanoparticles) stick to them and the former acts as 'carrier'. When the medicines are applied to 'Prover' or patients the drug (nanoparticle) loaded 'capsules' move in an enormous speed through the body fluid and strike the lipid bilayer of the affected cell, which undergoes 'flip-flop transition', so that Penetration of drug molecules to the interior, even up to the nucleus becomes possible. In course of journey through the lipid bilayers, the protective ethanol capsules is lost and the medicine molecules directly or indirectly bind with specific transcription factor (deficient repressor or activator) by replacing its original ligand-inducer. Deficiency or down-regulation of a transcription factor (e.g., repressor) can create difference in protein profile between healthy and diseased individual. It may cause accretion of a known deleterious enzyme and/or depletion of a beneficial one from its normal level, much downstream to the said factors, causing a particular combination of symptoms in patients, which appears to have no direct relation with the original pathological symptoms. When such symptoms become similar to drug-induced symptoms of a healthy person, it indicates that the minute metabolic blockage due to deficiency of the same factor is responsible in both the cases. It can be represented by a blockage in the branching pipes of metabolites, which indicates scanty flow of some metabolites and overflow of others. 'Proving' is therefore an indirect way of identifying the factor(s) in terms of symptoms-inducing medicine. Thus, recovery is possible by triggering the said factor, comparable to 'gentle hammering' to that particular point of metabolic blockage. The active principles of medicines mostly are plant products containing alkaloids, exudates of healthy or diseased tissue containing antigens, or come from mineral kingdom. These are actually a ligand-inhibitor of that minute unknown protein factor, as they can directly or indirectly mimic the substrate or product of the respective enzymes, or antigen of the respective antibody, thus can create a 'stress' similar to the disease. They cause expression of symptoms in 'Provers' when applied in high dose. Slight Aggravation of symptoms in patients occur when it is applied in minute dose due to transient increase of the deleterious product and/or further deficiency of the useful one. Transposable elements (or 'jumping gene') and somatic mutation bring variability in diseased tissue cells and the better cell line win over the stress, but the incompetent cells succumb. Thus mutant cells become outnumbered. Lastly, there is an Amelioration due to stimulation of growth of favorable cells or favorable segments of transposable elements. The opposite event occurs in allopathic drugs, because these are primarily 'stress-removers'. Hence, gradually the incompetent cell line outnumber the healthy ones in a tissue. Eventually, the patient gets initial amelioration but final aggravation of disease. As a principle of homeopathy (or Isopathy) it is a stimulatory one, it is similar to 'hormesis' (the achievement of tolerance over a poison by pretreatment of the same), by which the number of competent cells increases in tissue day by day and/or the number of competent DNA segments increases in genome to overcome the induced 'stress'. Exact matching of combination of symptoms between patient and 'Prover' is therefore very crucial. An autoradiographic method based on defective protein-profile of the patient has been suggested to sort out the spesific remedy, i.e., a ligand-inhibitor of the minute deficient protein factor, which can hypothetically induce identical combination of symptoms upon healthy persons. Such a stimulatory method might be effective for any dynamic disease, including cancer and AIDS. Some preliminary success (modulation of protein profile and gene expression profile of cancer patients) has been achieved recently by following the said principle.

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1. What is 'Neohahnemannism'?

Many dignitaries in the field of science were not properly recognized shortly after their inventions or even within their lifespan. Their theories were initially not acknowledged by the scientific community, but they were finally evaluated after a long period or even after their death. This generally occurs to them, who are much progressive in thought than their contemporary workers. The theory of Charles Darwin (1809-1882) was admitted to be the greatest of all biological inventions much later. Eventually, a new prefix 'Neo' was added ( Neodarwinism ) to the name of his theory by the successive workers based on latest scientific knowledge available at that time. Samuel Hahnemann (1755-1843), the father of homeopathy belongs to that category, but a little bit different. At young age, he faced severe obstacles, achieved supreme professional success in maturity, but his theory faced a bitter criticism, polemic, disapproval, and negligence after his death, in spite of gaining wide recognition in several countries. After Hahnemann, Gregor Johan Mendel (1822-1884), also has suffered from extreme heedlessness in the field of science within his lifespan, but when his theory was scientifically explained after his death, he was admitted to be 'the father of Genetics'. This event does not occur in all the persons. Edward Jenner (1749-1823), a contemporary physician of Hahnemann, who discovered vaccination , was also unable to explain his findings scientifically, but he gained fame and celebrity after a brief period of strong resistance, due to high reproducibility of his method, which a homeopathic medicine could not show. Besides that the main point of controversies, so that homeopathy is not getting substantial importance in mainstream medical science so long is not due to lack of experimental evidences, but due to the dearth of a self-explanatory model, absolutely resistant from scientific rejections. The first point of objection assigned by the scientific community is dilution beyond Avogadro's limit , and the second is the science of 'proving, i.e., how such a small quantity of drug can arouse visual response. Some workers of the mid twentieth century and later conceived that since homeopathic medicines are administered orally, their actions, whatever it may, could possibly be mediated through the receptor systems located on tongue and the oral cavity. The drugs must have transmitted specific signals in the receptor cells that could activate specific region of brain hypothalamus in a manner that could possibly help elicit further signals to activate or repress certain transcriptional activities of specific regions of DNA meant for restoration of the damages caused due to disease interaction. In spite of this, we cannot fully admit this idea; firstly, because the effect of homeopathic drug has been observed in unicellular animals, even in cultured cells, free from nerve connections; secondly, all the patients of the same disease do not respond to the same drug; thirdly, stimulation of a nerve requires threshold strength, which in general cannot be imparted by minute drugs. After the invention of homeopathy, as written in Hahnemann's book " Organon of Medicine " more than two hundred years have passed and stimulatory effect of minute dose therapeutic agent to every type of cells in human body was brought to light. Now it became clear that homeopathy is not a placebo therapy, as most skeptics claim, because it is effective on infants, unconscious persons, or even subhuman creatures. The modern modified version of Hahnemann's theory, synthesized in the light of some recent works of cell biology, genetics, immunology, toxicology, molecular medicine, analytical chemistry, and quantum physics requires a new coinage: 'Neohahnemannism'. From the very beginning, homeopathy was undoubtedly a science, but an imperfect one. The author thinks that the theory of 'Neohahnemannism' would make it a perfect science.

2. Really the medicines are Zero-molecular?

The theory that a solution contains finite number of solute molecule was not known during Hahnemann's time, and therefore if the solution is diluted several times a condition may reach where no molecule of the solute remains. Now we know that when the molecular weight of a substance (e.g., sodium chloride, silver nitrate etc) is expressed in gram, it is called mole, contains a fixed number of molecules (=6.023X1023). Suppose, 100 ml original tincture was prepared with one mole medicinal substance, therefore, the number of molecules would be 6.023X1023. One milliliter of such a tincture was dissolved in 99 ml of fresh diluent and succussed well, it would become the first potency solution (1C, or the first centesimal dilution), where the number of molecules would decrease 100 fold (=6.023 X 10 21 ). After the second potentization (2C), the number of molecules would fall into 6.023X1019. By this way when the solution reaches at eleventh potency (11C), it would be 6.023X101. In the next potentization (12C), there would be fractional number of molecule. Hence, practically no molecule of the original remedy would exist in such a solution. How can this solution have any curative power? This was the basic question arisen by the scientific schools to nullify Hahnemann's doctrine. Benveniste was the first man who upraised the polemic by discovering the controversial effect of zero -molecular aqueous dilution of anti- IgE molecules (Davenas et al, 1988) on staining ability of basophil granules. There are so many theories to explain the effect of zero-molecular dilution on living being, or 'Benveniste affair', which is the basic principle of homeopathy also. Among them 'Molecular Imprint Model' (Davenas et al, 1988; Hadji et al, 1991) , 'Tuned Solvent Model' (Sukul et al, 2005) , 'Crystal Water Model' (Pan et al, 2003;Chaplin et al, 2000;Chaplin, 2007) , 'Contonian Model' (Young, 1975;Berliocchi and Conte, 1994;Conte et al, 1994) and 'Fluvial Molecular Model' (Chattopadhyay, 2002 ,2003, 2006;Samal and Geckeler, 2001;Ives et al, 2010; Rao et al, 2007;Chikramane et al, 2010;Chikramane et al, 2012) s are noteworthy. Several workers including Benveniste claimed that non-molecular information travels in the form of electromagnetic wave and application of strong magnetic field might diminish the same (Hadji et al, 1991) . It was advocated that the diluting solute molecules keep an impact on electronic orbit of hydrogen and oxygen atoms of water, which again imparts effect in biological system, so the theory is called 'Molecular Imprint model'. Still, the theory cannot justify why camphor being a crude substance could nullify the effect of 'Belladonna', and how the medicine could retain its curative power for one year or more. After the rejection of Benveniste's work by the editor of 'Nature' different workers all over the world performed several replicas of the experiments, but they got different gradations of results between success and failure. However, nobody can claim cent percent reproducibility of 'Benveniste affair'. In spite of that, it cannot be denied that the previous existence of drug molecule may bring some alteration of spin of electrons in the outer orbital of hydrogen and oxygen atoms of water molecule. According to String theory we can assume that due to contact between the water and solute molecules, the vibration of strings of outer electron orbitals of solute atoms can transfer similar 'vibratory character' to the 'strings' of electron orbitals of hydrogen and oxygen atoms of water. Hence, transitory 'medicine-like electromagnetic signal' may emerge from water molecules. Yet, it cannot remain year after years in a medicine of a pharmacy. 'Tuned solvent hypothesis' is another model, which denotes the special properties of a solvent gained by pre-existing solutes. Here the water molecules being a solvent are 'tuned' in such a manner that even in the absence of solute it shows some special properties of the same, like 'healthy water' on living beings. According to the said hypothesis this 'healthy water' independently moves inside the cell through water channel of the cell and brings salutary effect in conduction of ions, like sodium, potassium, chloride etc. Hydrated ions due to their larger size cannot enter through the pores of plasma membrane by ionic channel . They, therefore, have to shed their hydration layer outside plasma membrane, before entering into the cell. The water molecules that form a hydration sheath outside, become disorganized in diseased cells, as a result, the ions cannot properly shed their own hydration sheath and pass inside. The 'healthy water' with medicinal property that comes from homeopathic drug reorganizes the hydration sheath ensuring the proper passage of ions into the cell. Thus, it explains curative effect. In spite of that, it cannot satisfactorily answer the cause of appearance of 'proving symptoms' in healthy persons by applying such 'healthy water'. In the same way, it cannot explain what superiority such 'healthy water' molecules in higher potencies achieve as well. Crystal Water Model is the chemical form of 'Tuned Solvent hypotheses'. In liquid water, each water molecule forms hydrogen bond between H and O atoms with an average of 3.4 other water molecules at room temperature. Since water molecules are in continuous motion in the liquid state, these hydrogen bonds are constantly being broken rapidly and are reformed (Figure:0, click here to enlarge). Various types of crystals could be formed by the slight rearrangements of hydrogen bonds between water molecules, which can bring variation in spectral properties of water in ice state. It has further been investigated that twenty of the 14-molecule tetrahedral units together containing 280 molecules of water ((H2O) 280), may form a 3 nm diameter icosahedral shape of water cluster . According to several workers, diluting away drug molecules bring some long lasting structural changes in the water crystals, which is said to be responsible for its 'memory' of the non-molecular solutes (Sukul et al, 2005;Pan et al, 2003;Chaplin et al, 2000;Chaplin, 2007) . The model is not convincing, because if we presume that water does store and transmit information of concerning solutes by means of its hydrogen-bonded network, then also it would not work, because, solutes of the body fluid may re-equilibrate them and form newly clustered network with altered information. Moreover, the purest water in earth should be considered grossly contaminated. This contamination may well have a major influence, and itself be influenced by the structuring in the water it encounters. Changes in crystal structure of water can preserve more stable conformations, but it might not represent the entire drug molecule or mixture of more than one drugs. Hence, these complicated theories appear to have nothing to do in explaining homeopathic dilution, because we do not observe a wide difference in action between 'Nux vomica-3' and 'Nux vomica-30' though the former is 'molecular' but the latter is 'non-molecular'. There are some physical models for 'memory of water' as well. Young first reported that high dilutes can be identified using nuclear magnetic resonance spectroscopy ( NMR ) ( Young, 1975) . Yves Lasne later provided the detection technology based on measurement of NMR and beta radiation . Lasne demonstrated that progressively diluting nitric acid even when it crosses Avogadro's limit shows some characteristic radiation, called remanent waves, which was represented mathematically by Rolland Conte and his fellow workers (Berliocchi and Conte, 1994;Conte et al, 1994) . According to them Contonian appearance of remanent wave is the cause of 'Benveniste affair'. It means certain form of 'memory' exists in the form of ' singularity ', a small but highly energized area of space, but this concern with the 'memory of emptiness'. 'Contonian Model' intends to explain potentization above 12th potency. Nevertheless, the emergence of 'singularity' merely by dilution has not been experimentally proved. Moreover, at higher dilution speed of the solute molecules increases enormously, so that absorption of solute molecules to the inner surface of glass vial is elevated exponentially, and the vial may become contaminated with drug molecule. For the same reason, it is difficult to remove the faint smell of an odoriferous liquid from a glass vial even by repeated rinsing with distilled water. In his experiment also, Lasne prepared higher potencies following Korsakovian method, i.e., dilution by emptying and refilling the same vial with fresh diluent. Korsacovian method of dilution might be explained in this way. At higher dilution speed of the diluent-entrapped solute molecules or nanobubble increases enormously, so that absorption of the same to the inner surface of glass vial elevates exponentially. For each newer dilution with fresh alcohol they emerge to the solution and levitates towards the air water surface. However, according to some workers Contonian appearance of remanent wave might merely be due to glass contamination or reaction of soda- glass with nitric acid (Milgrom, 2008) . When the vial is made up of silica glass, such observation was not found. 'Tuned solvent hypothesis', 'Crystal water' and 'Contonian model' raise the frequently asked question: Can a single drop of medicine is able to cure a large number of fishes suffering from ulcer (with identical symptoms), in a pond?

Hahnemann was not solely responsible for the controversies regarding zero-molecular dilution, it was a later development after the discovery of Korsacov's shortcut method, as mentioned earlier, by which 1000, or higher potencies could easily be prepared with a single vial. Hahnemann did not fully approve the method. He has clearly written there, 'I do not approve of your potentizing the medicines higher (as, for instance, up to thirty-six and sixty)'. He did not prefer large-scale industrial production of infinite volume of medicine by the greedy apothecaries to increase profit. In 13th September 1829, Hahnemann wrote a letter to a friend Dr. Schreter expressing disbelief over the effectiveness of these medicines that has reached infinitely high potency. He expressed that there must be some limit. (Britain Journal of Homeopathy v. p. 398). Possibly, he observed the incidents of failure of large-scale preparation procedure of medicines in curing patients. The following measures were probably taken by him to solve the problem: (1) Through out his entire life, Hahnemann primarily used medicines that were centesimally diluted 3, 6, 9, 12 or maximally 30 times. (2) He used to prepare the medicine of his individual patients with his own hand to prevent repeated use from a single vial, and directed the practitioners to do likewise. (3) Hahnemann in most cases did not use liquid potencies, but kept milk of sugar as absorbent medium of the same, which might trap the medicine molecule from the diluent medium.

Fluvial molecular model (Chattopadhyay, 2002, 2003, 2006) is quite different from other theories. It states that diluting away of molecules is possible so long as the solution remains homogeneous. When homogeneity is lost, the Avogadro's limit does not exist. It postulates that if potentization is made strictly following Hahnemann's suggestion, the medicine cannot be non-molecular. We can make a simple observation for understanding fluvial behavior of solute in a diluted solution. When a bottle of lemonade is freshly opened and drunk, there is a sharp taste of soda water. If one deeply occludes the mouth of the bottle with a thumb, shakes it vigorously, and quickly discards some part of the liquid in the same manner for four to five times, the sharpness of taste of the remaining part of the drink would fall significantly. Here the carbon dioxide molecules (solute) of soda water flow away very fast (or become fluvial) with the discarded volume higher than the expected number.

We know that water has a high dielectric constant (=80) than other solvents, so it can dissolve almost every solute molecules by separating their positive and negative charges wide apart, but during ritualized succussion and infinitesimal dilution, where the number of solute molecules is depleting drastically, the number of solvent molecule covering the surface of solute molecule becomes progressively increasing (Figure:1, click here to enlarge).Eventually, the entire surface of the solute molecule becomes supersaturated with solvent molecule (Chattopadhyay, 2003) . Besides hydrogen bonding between H2O molecules, a sort of attraction exists between its atoms (H-H, H-O and O-O), called van der Waals force . When these atoms come very close in course of potentization, such kind of attraction between them increases several folds, forming a dense elastic screen around the drug molecule, which brings opposite charges of the same close together and the effective dielectric constant of the solvent falls. The solute molecules thereafter show a tendency to get more concentrated towards the bottom of the solution with the increase of potency.

There is a misconception among some homeopaths that every drop (or milliliter) of a potentized medicine is equally effective in curing diseases, but it is not true. If every drop of intermediate potencies were utilized, the estimated volume of high potency medicine (e.g., 200C) obtained from single drop of original tincture would be much greater than the volume of earth or the sugar required for triturating the same would be greater than the mass of this planet. The pharmacists have to prepare potencies by succussion from a very small fraction of the infinite volume or mass. Actually, the drug molecules lie in progressively smaller portion of the solution with the increase of potency. Suppose, up to third potency there might are 100 out of 100 drops contain drug molecules. From fourth to sixth potency 99 of 100 drops contains the same. From seventh to ninth potency 98/100 and so on, this follows a definite mathematical model. Here, the number of solute molecule does not fall proportional to dilution as ought to be. Lastly, a condition may reach, where 1/100 fraction of the solution may possess the original substance (drug molecules). This is theoretically the 'critical dilution' (Chattopadhyay, 2002, 2003) . If one tries to transfer a drop of such dilution to the next vial after rigorous succussion, all the solute molecules gaining much higher speed than the solvent molecules would rush to the next container along with the drop, like any gaseous substance. These fluvial molecules do not return to the original vial due to progressive attainment of non-homogeneity, preventing the dilution of solute molecules anymore. Starting from 6.023X1023 molecules, i.e., 1 mole (=100) per 100 ml when diluting centesimally with ritualized succussion, fluvial concentration (=Cf) increases gradually due to undue overflowing of solute molecules. Initially, Cf is negligible, so that concentration (=C) of drug in terms of moles per 100 ml falls sharply with the increase of real dilution (=D). However, at high dilutions, nearing to 1024 times, equivalent to 12th centesimal dilution (12C), the value of Cf increases significantly, preventing the diluting away of solute molecules considerably.

(Click here to enlarge) - - - - - - - - (i)

Hence, zero-molecular state (10-24 mole/100 ml) is never reached in single serial dilution, i.e., few molecules remain. It does not mean that if the practitioner administers a medicine of 30th potency from the same vial to different patients it would not work at all, because there would be a 'rich source' of drug molecules left in properly potentized medicine, but if he does so for 1000 or higher potencies the chance of acquainting even single molecule would decrease. For that reason, in several homeopathic pharmacies fresh higher potencies are prepared from 'back potencies' (stock solution of the previous potency) for each patient in order to get better result. It was experimentally observed that when potencies are prepared indefinite times from a highly diluted back potency its efficacy decreases (Chattopadhyay, 2006) , which indicates finiteness of drug molecules in infinitesimal dilution. Obeying Hahnemann's dictum, the pharmacist should prepare each of the intermediate potencies in small (5ml) vials of fresh diluent. After a brief manual strike to a hard elastic support, tiny bubbles would continue emerging from the bottom of the glass vial. Transferring a drop (0.05ml) of the same to the next vial should be made within that period. Succussions should be repeated in an identical way for each intermediate dilution. Lastly, when it would reach to two-steps before the desired potency, the entire volume (5ml) should be diluted with fresh diluent making the total volume 500ml, and kept as 'back-potency', from which the final potency should be made whenever needed and dispensed using lactose sugar globules as the absorbent medium.

We have understood from the above discussion that if succussions are not made between each two successive dilutions, after 12th potency there would be very little chance of acquainting at least single molecule of the original substance. However, if succussions are made the medicine molecules are transferred to the next dilution as Cf, which progressively increases with potency. Chattopadhyay (Chattopadhyay, 2003) has constructed a mathematical model to find out the value of Cf. Initially, at the beginning of centesimal dilution, there would be no significant effect of dilution on van der Waals force, because it is inversely proportional to the seventh power of the distance between the adjacent water molecules that remain wide apart in a low diluted solution, sparsely covering the surface of the solute molecule. Conversely, when the solution reaches to ultra-high dilution, succussions can bring water molecules closer, tightly covering the entire surface of solute molecules, there is a loss of homogeneity and therefore fluvial transfer of drug molecules increases. So, the increase of Cf with dilution becomes sigmoid. Cf is directly proportional to Dn, here n<1 (where n is an indication of potentization efficiency) and it seems to be asymptotic to the critical concentration Cc, when almost all the remnant molecules become fluvial. 'Critical dilution' is an ideal concept, not the real one. One can go very close to it, but never reach. Likewise, Cf value increases with potentization, but nobody can say at which dilution the entire source of solute molecule, expressed as critical concentration (Cc), would be fluvial (Cf= Cc). It is mathematically very difficult and useless also to determine the exact dilution (critical dilution, Dc), at which all the drug molecules that would still remain after endless serial dilution, would become fluvial, So Chattopadhyay defined an easier term, the median critical dilution (Chattopadhyay, 2003) , Dcm to derive the following equation.

(Click here to enlarge) - - - - - - - - (ii)

Hence, median critical dilution Dcm should be defined as a function of dilution, at which half of the maximal possible number of drug molecules, due to succussion and centesimal dilution, would become fluvial. They would be restricted within a critical volume =1ml, when 100 ml is the total volume. Value of Dcm for the same drug might vary widely in different solvents, (e.g., water and ethanol) due to wide difference in dielectric constants.

In the recent years, some supports in favor of the molecular model have become stronger, which postulated that very few molecule of the original substance might exist in an infinitesimal dilution (Samal and Geckeler, 2001;Ives et al, 2010;Rao et al, 2007;Chikramane et al, 2010;Chikramane et al, 2012) . However, before the first decade of 21st century there was no highly sensitive method developed by the workers to detect presence of minutest quantity of molecules in infinitesimal dilution, except some found difference in 'punctured voltage', NMR spectra, and Fourier Transform Infra Red spectra between pure and infinitesimally diluted solutions representing alteration in hydrogen bond structure of water. All these were actually indications of hidden or impregnated drug molecules within the diluent medium.

Fluvial molecular model can explain most of the experimental findings till date. The model states that if the potencies were made strictly following Hahnemann there would be no scope of polemic related to zero-molecular dilution. Some workers obtained preliminary data for the existence of molecule using Raman and Ultra-Violet-Visible (UV-VIS) spectroscopy illustrate the ability to distinguish two different homeopathic medicines (Nux vomica and Natrum muriaticum) from one another and to differentiate, within a given medicine, the 6c, 12c, and 30c potencies (Rao et al, 2007; Demangeat, 2015 ) . According to them succussion might also be responsible for creating very tiny bubbles (nanobubbles) that could contain gaseous inclusions of oxygen, nitrogen, carbon dioxide and possibly the homeopathic source material. We have seen that after each succussion, numerous tiny bubbles emerge from the bottom of the container and the solution becomes frothy for a short period, indicating highly organized state of ethanol molecules than distilled water. We may presume that, ethanol molecules might be oriented around the hydrated drug molecule forming one or more concentric inverted layers. Characteristic changes also appear in NMR spectra. At the beginning of 2nd decade of 21st century some workers brought it to light that 'metallic molecules may exist' by employing some innovative technology, which can be regarded by and large as an experimental support of the 'fluvial molecular hypotheses'. Existence of a metallic element can directly be proved by atomic absorption spetrophotometry better than other means, because each metal can produce flame of specific color when burnt, which is not dependent upon any type of ionic, covalent or hydrogen bonding. Many sensitive methods to identify specific metallic element even at nanogram level were developed. Concentrating the solute several fold it was possible to detect the presence of a metallic element in an ultra-diluted solution. Using atomic spectroscopy, some workers have (Chikramane et al, 2010) found that there are nanogram quantities of the starting material still present in these 'high potency' remedies prepared from metallic salts ('Zincum met', 'Stannum met', 'Cuprum met', 'Argentum met', 'Aurum met', and 'Platinum met'), even after 200C dilution, in the form of nanoparticles. According to them traces of 'nanoparticles of the starting materials' levitate (float) in the 'upper layers' of the solution, which is transferred to new vial for making higher potencies. Later they showed that once the bulk concentration is below a threshold level of a few nanograms per milliliter, at the end of each dilution step, all of the nanoparticles levitate to the surface (Chikramane et al, 2012) and are accommodated as a monolayer at the top. This dominant population at the air-liquid interface is preserved and carried to the subsequent step, thereby forming an asymptotic concentration. It means that that the concentrations of these starting materials, albeit at extremely low (picogram/milliliter) levels, did not decrease as expected with serial dilutions but instead formed an asymptote beyond the 6c potency (dilution factor of 1012), which directly corroborates with the prediction of Chattopadhyay (Chattopadhyay, 2003) . Chikramane et al (Chikramane et al, 2012) thus found that homeopathic medicines prepared using metal powders as the starting raw materials retained them even at extreme potencies of 30c and 200c (dilution factors of 1060 and 10400, respectively), much beyond Avogadro's number. In spite of such enormous dilutions, nanoparticles of the metals ranging in sizes from 5 to 10 nm were detected by transmission electron microscopy (TEM) and electron diffraction (ED). There might be no unanticipated finding of Chikramane et al (Chikramane et al, 2012) , but some workers like Ives et al (Ives et al, 2010) pointed out the following difficulties of the hypothesis included therein. Chikramane et al (Chikramane et al, 2010; Chikramane et al, 2012) hypothesized the formation of nanoparticle or nanobubble complexes that would rapidly rise to the surface of the mixture forming a monolayer, especially at high dilutions. In this way a non-equal distribution of starting material would result during any settling between dilutions. When the top 1% of the solution is used as starting material for the next dilution, as they observed at one plant, and this process is repeated for each 'dilution' step, no dilution in fact occurs. If nanocomplexes rise to the top of a vial, many manufacturers discard this portion of the solution. The question arises 'if the drop is pipetted out from the middle or bottom layer?' For example, the Korsakovian method of remedy manufacture empties the vial and uses the remaining solution from the walls and bottom (not top) of the tube for the next dilution. Finally, even if the persistence of small amounts of any substance were proven, how they could elicit significant clinical responses from the chemicals themselves would have to be explained. One might expect clinical relevance if the concentrations fall within the range of stimulation, which these concentrations appear to be. Actually, Chikramane et al (Chikramane et al, 2010;Chikramane et al, 2012) have not written anything about the significance or superiority of higher dilution over the lower ones. Fluvial molecular model has paved the way towards solution of the problem much earlier by stating that though the original substance in the form of nanoparticles initially remains more concentrated towards the bottom of the solution in most cases, but whenever one tries to transfer, it moves to the fluvial part of the solution like that of a gaseous substance and towards reaching a critical value its concentration becomes asymptotic to dilution (Chattopadhyay, 2003) .

However, we cannot say that it occurs in all medicines, rather it depends upon specific gravity of nanoparticles. If the same is high it will settle down, if it is low it will float. The main thing is the loss of homogeneity, no matter where the layer of nanoparticles initially reside. If we pick even sigle drop of solution the nanoparticles will flow at a higher rate towards the dropper.

The central theme of 'fluvial molecular model' lies in the attainment of non-homogeneity of drug molecule, ultimately the fewer number of drug molecules form nanoparticles, which has been supported by experimental works as follows. Two chemists: Kurt Geckeler of Germany, and his colleague Shashadhar Samal were investigating fullerene (Samal and Geckeler, 2001) , a chemical agent, at their laboratory in the Kwangju Institute of Science and Technology in South Korea. The fullerene molecules were found clumping together, first as clusters of molecules, then as bigger aggregates of those clusters when diluting in aqueous solution. Far from drifting apart from their neighbors, they got closer together. They found that the football (" buckyball ") like molecules kept forming by untidy aggregates in the solution. Conventional notion says that the dissolved molecules simply spread further and further apart as a solution is diluted but their observation was just opposite. To make the otherwise insoluble football-shaped molecules dissolved in water, the chemists had mixed it with a circular sugar-like molecule called cyclodextrin. When they did the same experiments with the same molecules, they found they behaved the same way. So did the organic molecule sodium guanosine monophosphate, DNA and plain old sodium chloride. Dilution typically made the molecules cluster into aggregates five to ten times as big as those in the original solution was. The growth was not linear, and it depended on the concentration of the original. According to Geckeler, the history of the solution is here important. The more dilute it starts, the larger the aggregates. In addition, it only worked in polar solvents, like water, in which one end of the molecule has a pronounced positive charge while the other end is negative. It appears to disobey the second law of thermodynamics , but it cannot be. According to 'fluvial molecular model', when serially diluted the solute molecules get chances to come across with several fresh stocks of water molecule one after other its surface is covered with more water molecule than simple dilution of the same concentration. Hence, the history of serial dilution of the solution is so important. The van der Waals force between similar and dissimilar atoms of water molecule increases aberrantly and hydration layer around the solute molecule gets more compact, opposite charges of solute molecule comes closer, effective dielectric constant falls and the solute gets more concentrated towards the bottom of the solution. Hence, homogeneity of the solution is lost and due to surface tension, the hydrated molecules aggregate as clump. If succussions are made in each steps of serial dilution, such clumping might be avoided.

Entry of silicon materials from the inner coat of glass vial, when the same glass vial is used for preparing potencies following Korsacovian method is another workable hypothesis which explains how the original material remains in higher potencies. The silicon particles of different shape may represent medicinal property or it may carry the original material into solution in the form of nanoparticles. Some workers (Bell et al, 2015) made an exploratory study characterized nanoparticles in homeopathically-prepared Argentum Metallicum, succussed 6C, 30C, and 200C potencies and unsuccussed control solutions. Methods included nanoparticle tracking analysis (NTA), zeta potentials, inductively-coupled plasma mass spectroscopy (ICP-MS) for silver, and ultraviolet visible spectroscopy (UV-vis). It was revealed >2 × 108 nanoparticles/ml in 20 of 21 samples, 200C exhibited the highest nanoparticle concentrations and exemplar transmission electron microscopy of one Verum 30C sample showed scattered silver-like dark nanoparticles embedded in an organic matrix. Glassware-derived silica from succussions may contribute the nanoparticles and coatings for nonlinear source signal amplification to initiate clinical effect. Others workers ( Upadhyay and Nayak, 2011) observed presence of silicon-rich crystalline material as nanoparticles and conglomerates of Colchicum, Pulsatilla and Belladonna and controls, even above dilution level 12C, where the starting-substance is unlikely to be present according to Avogadro's limit by Scanning electron microscopy (SEM) and transmission electron microscope (TEM). According to them during the violent strokes involved in potentization, information arising from the serially diluted starting-substance might be encrypted by epitaxy on nanoparticles present in the resulting homeopathic medicine. In the case of homeopathic medicines, crystalline silica (or silicon) nanoparticles (along with other trace elements leaching from the glass wall of the vial) with interfacial water on their surface may acquire the structural information of the starting-substance during the process of potentization. In the case of homeopathic medicines, crystalline silica (or silicon) nanoparticles (along with other trace elements leaching from the glass wall of the vial) with interfacial water on their surface may acquire the structural information of the starting-substance during the process of potentization. The size distribution of these nanoparticles and their clusters was found to be nearly the same in different potencies. Nevertheless, the opposite was observed in a different study. Other workers (Nandy et al,2011; Ghosh and Chakraborty, 2015) suggested that Drug particle size decreases with increases in potency. Experimenting on on membrane anisotropy, they suggested that the cluster's size decreases with the increasing potency. Thus, after crossing certain limit 'all dilutions are only apparent and not real in terms of the concentrations of the starting raw materials.' It corresponds to Chattopadhyay's hypothesis of 'critical dilution' (Chattopadhyay, 2003) . Therefore, it hardly matters from where one is pipetting the liquid, from the top, middle or bottom of the vial. Initially, the drug molecules show the tendency of being more concentrated towards the bottom of the container. Finally, whenever the tiny air bubbles begin to form from the bottom of the original container during succussion or when the solution is poured into another fresh bottle of alcohol, the solution becomes fluvial, and the drug molecules rush towards the top at air-water surface at much higher speed than the solvent molecule. The said model was supported experimentally by other workers also. Although there might be some medicines where the drug molecules concentrate at the top of solution. Atomic Absorption Spectrophotometry is a very sensitive method, especially for detecting copper and zinc. Very minute amount of those metals were found in five potencies (6C, 30C, 200C, 1000C, and 10000C) of commercially available homeopathic medicine "Cuprum metallicum" and "Zincum metallicum" (Chattopadhyay, 2017). Similarly, presence of various phytochemicals such as flavonoids, alkaloids, saponins, steroids, carbohydrates and amino acids have been confirmed in the Allium cepa 30C and 200C by other workers (Arora et al, 2017).

Most of the homeopathic medicines available in the market contains traces of original drug molecules in the form of nanoparticles, tightly packed with solvent molecules. Alteration of hydrogen bonded network of the solvent is merely the result of tightly packed orientation of the same.

3. What is the role of alcohol or sugar in potentizing a medicine?

Hahnemann noticed that alcohol has more potentizing capacity than water, can 'prevent spoilage and decomposition' of the medicine, and he considered it to be a 'vehicle' that carries medicinal power to the diseased tissue better than water. Screening of solute molecule, as we have seen in the previous section, by excess number of water molecule than the usual in pure aqueous dilutions due to van der Waals force cannot last for a long time and it may be affected by other forces. Excess water molecules can easily be dislodged due to little agitation, or alteration of earth's magnetic field conferring the highly potentized solution into an ordinary one having no special property. Alcohol has got some special protective property so that such type of spoilage can be avoided.

We came to know from the previous section that loss of homogeneity is very important in potentizing a medicine, which is effective by the fall of dielectric constant of the solution. The addition of ethanol (Dielectric constant =24) to aqueous medium in order to prepare potency causes a further intensive depletion of dielectric constant. Hence, 'critical dilution' would be achieved much earlier than that of pure water (Chattopadhyay, 2003) . Precipitating ability of alcohol is not a new concept. The method for precipitation of proteins from their aqueous solution by the gradual addition of cold ethanol, as derived by Cohn and Edsall in 1941, is a good example of secondary attainment of non-homogeneity. The positive and negative charges of protein molecules remain separated widely in aqueous medium due to high dielectric constant of water. By the gradual addition of ethanol the attraction between opposite charges within protein molecule increases and they aggregate and precipitate. The concept is true for not only proteins but for all charged molecules, having high molecular weight. Hydrated charged molecules become concentrated at the bottom region of the ethanol solution and if the bound water is removed, the charged molecules become precipitated, nicely implemented in DNA and RNA isolation technique from their solutions. For low molecular substances, or those who are more soluble in ethanol than water, this event does not occur prominently, but there is always a tendency of precipitation. In case of potentization of a homeopathic medicine, the attainment of non-homogeneity is still faster in ethanol because of easier reestablishment of attraction force between opposite charges of drug molecules. Due to special orientation of ethanol molecules during succussion, the hydrated drug molecules would become easily concentrated towards the bottom layer of the solution. That confers it to be a more efficient medium for potentization than that of distilled water, so that the potentization efficiency (=n) of ethanol would be higher than distilled water (vide equation ii), and fluvial concentration in relation to dilution in alcoholic medium would be more hyperbolic (for distilled water, it would be more sigmoid). Ethanol would be able to trap more hydrated drug molecules than water, therefore Cc would increase accordingly. Hence, it is easier to preserve molecularity of drugs in ethanol medium than that of distilled water.

The special orientation of ethanol molecules during potentization can be explained from the concept of micelles and liposome . Ethanol can produce better protective covering around the drug molecule in the following way:

In a crude aqueous extract of the medicinal substance, water molecules form hydration layer around drug molecule (Figure:2, click here to enlarge). Its positive and negative charges remain wide apart. Addition of ethanol to prepare original tincture of the drug produces a monolayer of the same around hydration layer and it brings the charges closer due to lowering of dielectric constant of the solvent (in case of non-electrolyte, it does not occur). Ethanol, being an amphipathic molecule has a polar hydrophilic (-OH) head and a very short hydrophobic (CH2-CH3-) tail. It may be presumed that in the 'mother tincture' (original alcoholic solution) of a medicine it is arranged around hydrated drug molecule like inverted micelles popularly called inverted micelles , as 'water drop in oil' where positive and negative charges of the drug molecule come more closer (Chattopadhyay, 2002, 2003) . This type of inverted micelles are frequently seen in higher alcohols, which due to their large head can accommodate a large number of solute molecules, but due to very small size of ethanol molecules it possibly cannot sequestrate more than one or few solute molecule at a time and for that reason inverted micelles are not observed under ordinary microscope, but when the metalic drugs are observed under electron microscope, nanoparticle, consisting of few number of drug molecules can be seen. This type of micelles might be formed due to hydrophilic interaction between the hydrated layer around the drug molecules and the polar heads of ethanol molecules. The method of sonication is often used in the mainstream medicinal science to prepare liposome, loaded with drug employing double-tailed phospho-lipid molecules in order to deliver minimum quantity anti-bacterial, anti-tumoral and anti-cancerous drugs to the target tissue. The lipid bilayer is formed due to hydrophobic interaction around the aqueous compartment filled with few drug molecules. As the medicine is used in very small amount it can reduce the side effects. 'Potentization' of homeopathic drug may be explained by the same way. Succussion is comparable to sonication (Chattopadhyay, 2002, 2003, 2006) . Sukul has successfully employed sonication technique in preparing potencies. As we have mentioned above, during succussion, ethanol may form bilayer around hydrated drug molecules, where non-polar tails of both the layers come closer due to hydrophobic interaction. With the increase of potency the number of ethanol molecules, forming protective sheath covering each hydrated drug molecule increases and the capsule becomes more compact due to increase of hydrophobic interaction among the tails of ethanol molecules and van der Waals force among the atoms. With the initial increase of potency ranging from 2, 3, 6, 12 etc the number of ethanol molecule contributing to enrich the capsule increases steadily, but when it reaches to a saturation point at higher potencies above 30, further incorporation of ethanol molecule to the existing bilayer becomes harder and after 200th potency it is really tough. One has to repeat hundreds of potentizing steps uniformly to include just one or few ethanol molecules to the capsule making it more small and compact. It also contemplates changes of hydrogen bonded network structure of water-ethanol mixture. Hence the alteration of the network, which was experimentally confirmed, is not the cause but the effect of potentization. Higher potentization increases the number of shielding diluent molecules over the surface of drug molecules, so that its penetrating power increases. Hence, the hypothesis of nanobubble of Chikramane et al in 2010 and 2012 (Chikramane et al, 2010;Chikramane et al, 2012) corresponds to the idea of drug loaded liposome like ethanol capsule of Chattopadhyay in 2002 and 2003 (Chattopadhyay, 2002, 2003) .

Introduction of sugar of milk (lactose) as a 'carrier' of medicinal power by Hahnemann is of great medicinal importance. When the medicine is poured upon lactose sugar the latter can preserve medicinal property for a long time because being a reducing sugar it contains free aldehyde groups that can bind -OH group of ethanol molecules situated at the outer layer of capsule. Hence, the lactose molecules can act as an absorbent medium of ethanol- encapsulated medicine molecules, so that even single small globule of sugar can transfer medicinal property to the patient's body and stimulate vital reactions. Conversely, sucrose, being a non-reducing sugar do not have free aldehyde group, so it cannot be used for the said purpose. When larger number of lactose globules is introduced, it can bring medicinal symptoms to healthy persons, but remains effect-less when small dose is applied. Therefore, a definite dose-response curve can be obtained. This is not possible in liquid medicine, because there is no definite number of high velocity units of medicine ('capsules') per drop, as we have discussed earlier. Hahnemann being a man of insight has revealed the fact within his mind. For that reason, he preferred to use lactose sugar moistened medicine. Hahnemann has utilized this quasi-compound property of lactose mixture in making solution of the insoluble medicines also. Several insoluble compounds may enter into clear solution stage after 3-4 steps of trituration, and then they can easily be potentized with alcohol. As we use chromatography to trap desirable substance from a highly diluted solution by passing the same through a glass column, packed up with absorbent medium, Hahnemann also has mentioned the same technique in his 6th edition of Organon, while preparing 50-millesimal dilution. There he used a thimble shaped cylindrical glass column packed with sugar globule as an absorbent medium of 'medicinal substance' from highly diluted succussed solution. Now imagine, how talented man he was who can prepare 21st century medicine in 18th century.

In case of dry potentization, where lactose alone is used as diluent medium, the basic principle remains the same, i.e., encapsulation of the drug molecule by the diluent medium and loss of homogeneity. When the medicine molecule gets the chance of contacting increasing number of sugar molecule it becomes packed up, cannot be separated from sugar by any means and homogeneity is lost even much earlier than liquid potentization. Sugar-coated medicine molecules form nanoparticles and show tendency of clustered distribution through out the entire mixture as numerous clumps and their number does not decrease proportionally while triturating with fresh sugar. Moreover, like a quasi-compound the medicine cannot be separated easily from lactose. Similar observations of the formation of nanoclusters were made in trituration studies (Chikramane et al, 2012) of lactose with zinc dust (325 mesh, around 44 micron particles). The zinc nanoclusters indicate the formation of 10-20 nm zinc nanoparticles. The formation of nanoparticles from the larger particles highlights the importance of the trituration process in the generation of the nanofraction. The generation of nanoclusters as evident from the TEM analyses. Lactose aids in preventing the aggregation of the nanometer-sized particles formed during the grinding process, thereby effectively segregating the nanofraction from the coarser particles in the subsequent dilution steps.

It might be concluded that fall of dielectric constant of the diluent medium by gradual addition of ethanol and succussion causes loss of homogeneity and formation of nanoparticles. With the increase of potency, the number of solvent or diluent molecules (alcohol) covering the hydrated drug molecules (nanoparticles) increases forming a special type of orientation, which may act as a protective shield around the same. This type of nanomolecular structures are able to stuck up with sugar globule, the latter can thus act as 'carrier' of medicinal property. Moreover, when a drug is repeatedly triturated with sugar, it becomes so inseparably mixed with the same that it can reach the affected tissue by baffling the antagonistic physiological response. Alteration of hydrogen bonded network in homeopathic drug is not the cause of drug action but merely the effect of altered orientation of solvent molecules.

4. How do the ultra-high diluted medicines develop and cure symptoms?

We have seen in the earlier sections that homeopathic medicines, even far above Avogadro's limit of dilution, contain traces of original drug material. A relevant question may arise. How does such a vanishingly minute quantity of medicine can produce symptoms on 'Provers' and cure the patient as well? The cause of developing proving symptoms by highly diluted homeopathic medicines seems to be due to their penetration ability. Hahnemann seems to be overwhelmed by seeing the penetrating ability of homeopathic drugs. He has written a little to explain the mechanism of penetration of drugs on different organs of the body as follows: 'The homeopathic healing art develops from the spirit-like medicine-forces of the crude substances. By means of then untried treatment peculiar to that to a formerly unheard-of degree whereby they all only then become quite penetratingly efficacious and remedial, even those that in the crude state give no evidence of the slightest medicinal power on the human body' ("Organon", 5th ed § 269). He believed that higher potency medicines have more rapid penetration capacity than the lower potencies ("Organon", 5th ed § 287 footnote).

In spite of negligible quantity of original drug, the potentized medicines enjoy greater penetration ability due to achievement of compactness of ethanol capsule in higher potencies to develop proving symptoms over healthy individuals and cure the same in patients. Moreover, with the increase of dilution the compact capsules become speedier. The more compactness the capsule achieves it gets more easy entry to the diseased tissue while moving through liquid connection within minutest capillaries. The ethanol molecules pack the hydrated drug molecule so tightly that no biological process can peel the ethanol bilayer away from the hydrated drug even it can pass unaffected through the road to digestion. Actually, the encapsulated medicines move so fast that no specific channel is required except humor or body fluid, through which it penetrates the target tissue and binds the target enzyme . Medicines prepared with lactose also enjoy greater penetration ability. It is a general tendency of the weak or mutant diseased cells including that of cancerous ones to consume sugar molecules voraciously. When the sugar globules moistened with medicine or the medicine itself is triturated with sugar the molecules remain attached inseparably with the same, like that of a compound of sugar. When the same is administered in empty stomach, it would get an opportunity to enter into the affected tissue. It can bind with minute enzyme (Chattopadhyay, 2002) inside the cell. There are several examples of receptors of that category. Effect of homeopathic drugs in modulating enzyme activity was observed by several workers (Sukul et al, 2002) . Hence, the biomolecules directly or indirectly influenced by homeopathic drugs are nothing but sub-cellular enzymes. The drugs might affect several other molecules involved in metabolism, like DNA, RNA, carbohydrate, fat, hormones, or any other compound. Nevertheless, what is the superiority of these enzymes? This is because the enzymes are the only species of biomolecules that has highly sensitive reversible binding sites for specific substrates and gets affected at once when the same site is competitively preoccupied by a minute inhibitor , which most homeopathic drugs possess. As for example, 'Thea' and 'Coffea' prepared from tea (leafs) and coffee (fruits) contain theophylline and caffeine respectively. Among the known enzymes, phosphodiesterase is one, which binds both the alkaloids , becomes inhibited by the same. Another drug 'Physostigma' prepared from a plant, Calabar bean (Physostigma veneosum), contains eserine (also called physostigmine), which blocks a known enzyme acetylcholinesterase, and it can constrict the pupils. Noticeably, in the mainstream medicine several intermediate metabolites of a biochemical reaction have been discovered by applying enzyme inhibitors. In a tissue extract when an inhibitor of a particular enzyme is applied, the intermediate metabolites become accumulated. By the combination of this technique the steps of glucose breakdown has been identified. In human body, numerous enzymes are interconnected like a network, and artificial inhibition of any, even the minutest one can produce specific combination of symptoms due to accumulation of some metabolites and deficiency of others. Moreover, the same enzyme molecule can function repeatedly in a cell after reversible binding of the inhibitor, so that duration of activity of homeopathic drugs upon 'Provers' may last for weeks. We would have to remember that the enzymes or any other protein factors responsive to homeopathic drugs are ultra-minute. One can isolate just 1 mg thyrotropin releasing hormone (a peptide) from 4 tones of hypothalamic tissue of goat brain from the slaughterhouse, where thousands of goats would require to be sacrifice. Now imagine the minuteness of thet protein factors that are engaged in controlling its synthesis. These minutest species of protein factors reside in the nucleus or very near to the same, but the larger proteins or functional enzymes, regulated by the same generally remain restricted near the periphery of the cells. In several cases, it was observed that substrate of an enzyme even in a very minute concentration can activate the minute protein factors that regulates its synthesis. Hence, the substrate-like competitive inhibitor in a very minute concentration if it is able to reach the target can inhibit the said factor and can bring symptoms to the healthy person or 'Prover'.

According to the suggested hypothesis , (Chattopadhyay, 2002, 2003, 2006) the ultimate cause of any of the chronic disease was deficiency or mutation of one or few minutest enzymes far upstream than the known protein that manifests up or down regulation. As the protein profile of the entire breast cancer patient is not identical, the minutest deficient protein factor also might be different. Stimulation of the same, specific for individual patient is curative. Either any of the drug ingredients influences such an up-regulatory transcription factor of CDK inhibitor protein and stimulates the same, or the ingredient modulates the down-regulatory transcription factor of phosphorylated Retinoblastoma (Rb) and activates the same. It either may stimulate the synthesis of anti-cancer antibodies or activates the natural killer cells to destroy the tumor. Direct deduction could not be drawn so far due to ultra-minuteness of the enzymes involved in regulating cell cycle and non-detectable nature of homeopathic drug ingredients, when ultra-diluted. Had the experiments mentioned above were performed with crude radio-labeled drug extracts, the minute enzyme that binds the same might have been revealed to some extent. In spite of that, there are adequate examples of specific binding of alkaloids, minerals, and heavy metals with functional enzymes or receptors, most of them have already been used as homeopathic drugs. Dimethylamino azo benzene (found in azo dye) and phenobarbital can induce liver carcinogenesis of mice. While studying the protective effect homeopathic drugs over synergistic effect of these carcinogens taking two potencies of 'Chelidonium' Biswas and Khuda-Bukhsh (Biswas and Khuda-Bukhsh, 2002) observed that initially there was an inhibition to lipid peroxidase enzyme activity as the 'primary effect' (within 60 days) and finally there was stimulation of the same as the 'secondary effect' (at 90 and 120 days of exposure), indicating an onset of defense mechanism against carcinogenesis. Acid and alkaline phosphatase activities also showed similar effect. Other parameters of carcinogenesis, like increase of mitotic indices, chromosome aberration, appearance of micronuclei etc also showed ameliorating trend by the said medicine. Hence, Khuda-Bukhsh (Khuda-Bukhsh, 2003) has given emphasis on transcription factor(s), which being the minutest limiting factor of human health might directly or indirectly be modulated by micro-doses of homeopathic drugs. Some evidences were found in favor of the said hypotheses. As for example, homeopathic drug 'Arnica' prepared from a plant Arnica montana possesses an alkaloid helenalin. The main action of helenalin is the inhibition of a transcription factor NFκβ (Klaas et al, 2002), similarly to corticoid steroids. Hence, the said medicine might have some stimulatory effect over the said factor in preventing hemorrhage by the expression of genes. Likewise, Arsenic binding transcription factor Yap8p has also been detected (Ilina et al, 2008 ). Homeopathic drug 'Arsenicum album' might have a stimulatory effect over the said transcription factor. Hence, if we are able to characterize all the transcription factors, based on highest affinity to the medicinal ingredients by autoradiographic method, as mentioned above, cure from any deadly or chronic disease would be possible by homeopathic means. Inability to undergo apoptosis is an important factor in the development and progression of prostate cancer. Homeopathic treatments by 'Conium maculatum', 'Sabal serrulata', 'Thuja occidentalis', and a MAT-LyLu Carcinosin nosode (Thangapazham et al, 2006) on the expression of cytokines and genes that regulate apoptosis was observed. They produced anticancer effects in Copenhagen rats in reducing tumor incidence, tumor growth, and metastasis. There were no significant changes in mRNA levels of the apoptotic genes bax, bcl-2, bcl-x, caspase-1, caspase-2, caspase-3, Fas, FasL, or the cytokines interleukin (IL)-1alpha, IL-1beta, tumor necrosis factor (TNF)-beta, IL-3, IL-4, IL-5, IL-6, IL-10, TNF-alpha, IL-2, and interferon-gamma in prostate tumor and lung metastasis after treatment with homeopathic medicines. The possible mechanisms for these effects include regulation of apoptotic genes and cytokines in the prostate tumors of the said animal. In another study (Bigagli et al, 2014) it was found that homeopathic medicine 'Apis mellifica' modifies gene expression in human cells and has inhibitory effects on regulatory processes of inflammation; in addition, extremely diluted dynamized dilutions (3C, 5C and 7C) still exert significant effects on 5 selected candidate genes (IL1β, CD46, ATF1, UBE2Q2 and MT1X) in RWPE-1 cell line (human immortalized prostate epithelial cells) involved in inflammation and oxidative stress.

When the highly diluted medicine is applied to human body it moves within body fluid in an enormous speed and it strikes the lipid bilayer of plasma membrane of the cell so that the bilayer undergoes ' flip-flop ' transition (Figure:3, click here to enlarge), hence entry of drug molecules to the 'interior' of a cell, even up to nucleus is possible. The encapsulated drug molecule has to traverse several lipid bilayers before entering the 'specific compartment', made by the membrane system of the cell, where the target enzyme resides. The lipid layers in each case snatch away some ethanol molecules; consequently the capsule is rendered breakable in course. Ultimately, after reaching 'specific compartment', the capsule disappears and the drug molecule binds target enzyme. For that reason, higher potencies would be required if the medicine has to travel a long distance through smaller capillaries to the target tissue, e.g., skin, than the visceral organs like stomach, liver and lung. On the other hand, if the medicines were required to be directly applied over the eruptions, e.g., for skin diseases, very low potency would be effective. If the medicine is used at right potency it becomes 'penetratingly efficacious'. In case it is used in lower potency than required, it would not be able to reach 'specific compartment'. Administering the same in higher potency than need would be more penetrating but would also fail to give expected result, because it would not be able to shed its tightly packed ethanol bilayer while reaching at the 'specific compartment'. For lower potency drugs the pathological symptoms are much emphasized, while for higher potency drugs concomitant ones in physical as well as mental sphere should be considered, because it works much upstream than the latter. Now we can differentiate 'dilution' and 'potency' in the following way: we know that entrance of sodium chloride into the cell is very much restricted by ionic channels, therefore, highly diluted application of the same in crude form cannot induce any ailment upon a healthy person. However, when it is applied in potentized form as the medicine 'Natrum mur' such channels cannot affect its mobility. It can directly enter into the cell even up to nucleus and can bring symptoms in healthy persons after binding with minute enzymes and cures the patient as well. Likewise, several medicines are prepared from toxic substances. If they are not potentized might be inactivated by detoxification system of the body so that medicinal power would be lost. Likewise, minute concentration of an alkaloid from plant, an allergic peptide or protein from animal, a mineral, a heavy metal, and an antigen, even a small fragment of viral or bacterial DNA after 'potentization' can induce 'proving symptoms' and all of them can be introduced as homeopathic medicine ingredients. As we use vehicles to reach safely to our office, the minute drug molecules, coated by ethanol, reach to their 'working places', i.e., 'specific compartments' of diseased cells. The drug must have similarity with the substrate of minute enzymes, so that after reaching the interior-most part of a cell it competitively binds and inhibits the same. By this way the said agent can indirectly influence the minute enzymes, which can control synthesis rate of specific biochemical products or directly does the same, so that 'proving symptoms' can be induced even in a 200 potency drug when applied in a higher dose to a healthy person. The patient suffering from the same combination of symptoms indicates that the same minute enzyme was originally deficient (Chattopadhyay, 2002, 2003, 2006) or mutant. This is because the said enzyme may act as limiting factor for synthesis of several other enzymes and their deficiency can indirectly be identified by combination of symptoms. Hence, the 'prime cause' of symptoms for patient and 'Prover' is identical. In ideal case, it successfully binds the 'optimal fraction' of the deficient enzyme (Chattopadhyay, 2002 ) , say 1/100th part of the same, the disease becomes slightly aggravated for few days. It means 'simillimum' has been achieved and it would be followed by 'gentle cure' in course. Similarity of symptoms between patient and 'Prover' is thus curative. Hence, theory of 'similia similibus curantur' is thoroughly justified. In case of 'Prover', the medicinal dose is very high, so that it affects enzymes or transcription factors much higher than 'optimal fraction'. There is a difference between dilution and dose as follows: In case the medicine is applied to the patient in the right dilution (represented by potency), but in a much higher dose than required, it would inhibit the target enzyme much greater than 'optimal fraction'; hence, there would be intolerable aggravation of symptoms, as Hahnemann has said. Here the patient himself would act as 'Prover' and he would have to stop the medicine immediately, and apply antidote of the said medicine, if required. As for example, 'Nux vomica' is an antidote of 'Bryonia', and 'Belladonna' is an antidote of 'Aconite'. Thus, the medicinal symptoms may be ameliorated by the application of the antidote.

It may be resolved that in higher potencies the drug molecules remain protected within the capsule of solvent. So they, being unaffected by physiological reactions, get an opportunity to reach the inner chambers of the cell and modulate minute enzyme or even transcription factors to arouse medicinal symptoms in healthy persons. Minute dose of the same cures the patients suffering from similar symptoms. The similarity of symptoms between prover and patients at the minutest level by the application of a particular medicine indicates that the same enzyme or transcription factor (may be minutest and unknown) is the cause of symptoms in both. The said enzyme should be considered as the target of homeopathic medicine.

5. How does homeopathy cure a genetic disease but allopathy cannot?

Hahnemann has said that homeopathy is the new school of medicine that can treat 'familial' (Genetic) diseases. Conversely, allopathy is the opposite method of treatment to that of homeopathy. Both homeopathy and allopathic method can give relief to a particular patient by following definite and discrete principles: Homeopathy cures by 'similia similibus curantur' (like cures like) principle of Hahnemann of nineteenth century, while allopathy by 'contraria contrariis curantur' (opposite cures opposite) logic of Galen of seventeenth century, but they are not both sides of the same coin. From the beginning, there was a confrontation between existing 'old school' of medical system ('allopathy') and homeopathy. Allopathic system were deluded with almost instantaneous amelioration ("Organon", 6th ed § 56), which was just opposite to homeopathic principles. Hahnemann regretted that this 'old school' of medicine does not try to find out 'prima causa morbi', i.e., the hidden root-cause behind morbid symptoms ("Organon", 5th ed. § 6, footnote), hence he termed allopathy as a 'non-healing art', as it renders simple disease into a chronic and incurable one ("Organon", 5th ed. § 75). Modern form of allopathic system suggests that malfunction or malsynthesis of particular enzymes, guided by genes, is the 'root cause' of almost all chronic diseases, but the mode of its treatment by suppressing the disease symptoms has not changed much since Hahnemann's time. It gives a very little emphasis to arouse the internal mechanism of human body or any other organism, unlike that of inanimate ones, to fight against diseases. We should never forget that human body is like complicated auto-recoverable machine. Therefore, the mechanism of cure of almost all the chronic diseases remains hidden within that machine itself. Homeopathic medicines, being similar to the disease causing factors, actually intend to stimulate the curative factors, which definitely subsides the disease causing agents. Thus the homeopathic medicine shows aggravation as 'primary effect' and amelioration as 'secondary effect'. The allopathic medicines counters the disease- causing factors directly. As a result, the 'primary effect' of an allopathic drug always ameliorates, while 'secondary effect' aggravates. Therefore, most allopathic drugs are used lifelong for chronic diseases, notwithstanding the risk of side effects and 'wearing effect' i.e., loss of efficacy in long run. In case any homeopathic medicine causes slight amelioration of a chronic disease at the beginning, we should think that it is 'more allopathic' than homeopathic, and the remedy has not been properly selected. In long run, it would aggravate the disease, as suggested by Hahnemann also. This is because; it is trying to suppress the symptoms by inhibiting the disease causing agents. In most cases, these are related to malfunction of some functional enzymes, gene products, or caused by some parasites, pollutants or other external factors. Even when the said enzymes are extracted from human body (cell-free system) they are affected by allopathic drugs. On the other hand, homeopathic medicine seems to function much upstream to that of functional enzymes. Hence, the effect of such medicine cannot be demonstrated in cell-free system, like that of an allopathic drug, which directly acts upon functional enzymes. Many says that homeopathic drugs have no effect because these are non-molecular. This question does not arise in allopathic drug, because it is applied in a larger dose that can suppress a known deleterious enzyme or any other protein factor, even outside patient's body and terminates the synthesis of offensive products. Homeopathic medicines, according to the modern explanations as described in the earlier sections, contain very minute amount of medicine molecules itself as 'nanoparticles' or 'encapsulated molecules' that can stimulate the minute regulatory protein factors, much upstream in the synthetic pathway of the responsible enzymes. When the said factor is stimulated the medicine is not required to apply through out the life. One interesting observation should be clarified here. Several practitioners of homeopathy have experienced that for acute diseases the suitable remedy can function immediately. Then how it is able to stimulate the process of transcription so quickly? The answer is that: transcription in several places of biological system occurs in lightning speed, but the exact mechanism of the same was not even been properly explained. As for example, the complete embryogenesis in some carps occurs within 18-24 hours. Then why a medicine would not be able to show its action within 1-2 hours?

Before going to the mechanistic pathway of cure we should have a detail knowledge over the root cause of 'familial' or genetic diseases, acceptable by any stream of medicinal science. The ultimate cause of all human genetic diseases remains concealed within the genome. Molecular basis of the same is DNA. Synthesis of mRNA occurs by copying DNA, as a template (with the help of an enzyme RNA Polymerase II ). As the information written within DNA in the language of base sequence is copied in the same language into mRNA, it is called Transcription , which occurs in the nucleus. As because the information stored within mRNA in the language of base sequence is converted to different language in ribosomes, indicated by amino acid sequence of protein or enzymes, it is called translation . The rate of transcription is controlled by different transcription factors , also called regulatory proteins . These are of two types- activator and repressor , which control increase and decrease of enzyme synthesis respectively. The former is synthesized from positive regulator and the latter is from negative regulator element of DNA. Likewise, the operator element , to which the transcription factors bind is of two types- enhancer and silencer . Activator protein, synthesized from positive regulator, binds with enhancer sequence, in most cases it corresponds to promoter of DNA, which binds RNA Polymerase II, responsible for transcription. Likewise, repressor protein, synthesized from negative regulator, binds with silencer sequence. In case of the activator, when substrate of the beneficial enzyme is available in the cell it binds with enhancer element and enhances binding of RNA Polymerase II with promoter element of DNA molecule and facilitates synthesis of functional enzymes in healthy individuals. On the other hand, when the deleterious products are synthesized beyond a threshold level, it can sufficiently bind and activate the repressor that in turn becomes attached with silencer element, preventing the binding of RNA polymerase II anymore with the promoter region. Consequently, the deleterious enzymes cannot be over-synthesized. Enhancer DNA sequence, therefore has the opposite function to that of silencer. According to some workers (Chattopadhyay, 2003) the deficient transcription factors might be the target of homeopathic drugs.

Now, let us see what happens in a diseased individual and how we can cure the same (it is not possible when the mutation of the functional protein itself is involved). In a natural dynamic disease, which has natural aggravation and amelioration cycle, initially, there is no significant abnormality in the functional gene, but due to some mutation at minute level, there is deficiency or down-regulation of some transcription factors, which may cause two types of diseases:

Type-(i): deficiency of an useful metabolite, or

Type-(ii): abundance of a deleterious one.

In both the cases, deficiency (or down regulation due to small mutation in their regulator element) of activator and repressor respectively, are the root causes.

Therefore, the transcription factor, much upstream to the said enzymes, is responsible for both the cases. They may be treated by the following way:

In case of deficiency syndrome (Type-i), the synthesis of a particular beneficial enzyme is decreased (indicated by broken brown arrows), (Figure:4, click here to enlarge) because sensitivity of the activator to the inducer (here substrate of the responsive enzyme) is decreased (down regulated) due to minute mutation; so that the enzyme is synthesized less (indicated by broken brown arrows) and the body becomes deficient of some beneficial products. Hence, disease symptoms may appear. As the homeopathic drugs, due to their minuteness cannot directly show its impact on bulky functional enzymes, but inhibits these activators directly or indirectly, which causes further depletion of functional enzyme and slight aggravation of symptom of patient occurs. Thus, it can create a stress, so that it can be called 'stressor', which later stimulates the synthesis of beneficial enzymes in living cells up to its requirement either by multiplying small competent DNA segments or by division of the competent cell line that can compensate the loss. Stimulation of these minutest deficient regulatory proteins, in any case, causes cure. Protective effect of minute dose drugs in transcriptional level, i.e., during the formation of mRNA from DNA, has been proved by in vitro study also ( Ovelgonne et al, 1995; Van Wijk et al, 1994;Wiegant et al, 1997) . When a stress, either environmental (e.g., heat), or pathogenetic (e.g., bacteria) or toxicological (e.g., arsenic, cadmium etc), is applied upon culture cells, their physiological process become disordered, causing cell damage and cell death. A low dose of the same damaging agents produces some protective proteins (e.g. heat-shock proteins) that increase cellular tolerance. Thus by the application of low dose of the same damaging agents (viz. "stressors") exert a stimulatory action (Ovelgonne et al, 1995) on cell culture; it protects them from harmful exposures of same stress. Hence, the reaction to the stress might be stronger than its action, which may lead to self-recovery. The inhibitor present in homeopathic medicine should, most possibly, be similar or semantic to the substrate of the functional enzyme, so that it may competitively bind and inactivate the same or its activator protein, like a ligand and can manifest deficiency syndrome in healthy individual during 'proving' experiment. Allopathic medicines, on the other hand, would supplement the product or similar substance of the afflicted enzyme. As for example, in Parkinson's disease , a neurodegenerative syndrome caused by a defect in dopamine synthesizing pathway, dopamine (dihydroxy phenylalanine amine) is supplemented as drug to suppress the disease. In some cases, slow but minute application of L-dopa, an immediate precursor (substrate) of dopamine, like that of homeopathic drug, was found very effective. Moreover, very low potencies of dopa are effectively used as homeopathic medicine for the said disease. Similarly, in hypothyroidism patients, a kind of synthetic thyroxin (an iodine containing hormone) is supplemented as allopathic medicine, but when treated by homeopathy, different types of iodine containing medicines like 'Iodum', 'Kali iod' etc are used to stimulate the biosynthetic pathway of thyroxin. In most cases, the lower potency homeopathic medicines are selected based on induced pathological symptoms, which are just opposite to allopathic drugs. However, such kind of interrelationship can rarely be sorted out between allopathic and higher potency homeopathic medicines, because the latter act much more upstream than the former to the enzymes, which are directly responsible for the pathological symptoms. Therefore, larger number of concomitant symptoms indicating mental attributes, in addition to few pathological complaints should be counted before the final selection of remedy.

In case where abundance of deleterious substance is seen (Type-ii), it should be taken that it is due to malfunction, malsynthesis or mutation of the repressor protein synthesized from negative regulator of the same, causing down regulation (Figure:5, click here to enlarge). Here, down regulation, means lesser sensitivity of the repressors towards inducer (here product of the responsive enzyme) to activate the same, indicated by less synthesis of the same (represented by broken brown arrows), resulting increased rate of synthesis of that particular deleterious enzyme (indicated by solid red arrows). As a result, the body is filled up with deleterious products and disease symptoms appear. In case of allopathic treatment of such a patient, a suitable competitive inhibitor (negative modulator) having structural similarity, with the substrate of the deleterious enzyme is often attempted, because it has high affinity for the same due to competitive binding. It instantly inactivates the enzyme. As for example, Cyclooxygenase is an enzyme maximally increases in patients suffering from headache, arthritis, influenza etc. Drugs like Aspirin or Acetyl salicylic acid (ASA) is used to check these diseases by inhibiting the same, but its efficacy decreases in long run producing a 'wearing effect'. We can assume that if a homeopathic medicine prepared from a chemical that can mimic the deleterious product, is applied to a patient, it would competitively bind and inactivate the repressor protein factor, which was already deficient, much upstream to the respective enzyme. It would produce a stress of similar nature and the synthesis of deleterious enzyme and its product would increase slightly. (Such a medicine, therefore, falls under the definition of 'stressor'). Hence, there would be an initial slight aggravation of symptoms. It would create an urge to produce more and more competent cells by cell division that can undergo a compensation cycle more easily to remove the stress completely. Ultimately, the disease becomes cure. As for example, in some patients there is a tendency of producing huge nitrogenous waste product. Their urine turns turbid and offensive in smell, like that of horses. They have a tendency of suffering from uremia, kidney stone, and gout. Eventually, homeopathic medicines, 'Urea', 'Uric acid', 'Nitric acid' etc in lower potencies are used to treat such patients. Another example, homeopathic medicine "Cholesterinum" is prepared from cholesterine. It can act like product of the hyper-active enzyme, so that it can induce a stress and was found effective in reducing blood cholesterol level when it is used in lower potency. However, as the minute protein factor remains much upstream to responsive enzyme, such type of straight-line relation cannot be always established.

According to most of the modern workers (Calabrese, 2008;Van Wijk et al, 2009;Neafsey, 1990;Calabrese and Baldwin, 2002;Stebbing, 2003) , homeopathy is closely related to hormesis. As for example, tolerance (expressed as Tlm or LD 50 ) to a heavy metal increases in fishes that were previously exposed to the same pollutant in minute dose than the others of the same species. Possibly, it stimulates the detoxification mechanism within the body. Hormesis can also be achieved in the opposite way. Effect of heavy metal pollution in affected animals found decreasing by post-treatment of the same or similar heavy metal in minute dose. Probably it alerts the unaffected cells by stimulating their detoxification machinery against pollution. Since the living organism is going to choose from its defense array, the system of tools, best adapted to combat the induced pathological effect, it can immunize the unaffected cells against the incoming malefic agent earlier to its entry. The concept of 'Hormesis' , i.e., attainment of tolerance to a poison by minute pretreatment of the same, is therefore very similar to ' isopathy ', a forerunner branch of homeopathy. It is remarkable that the first remedy introduced in homeopathy was an isopathic one. The curative power of Peruvian bark (Cinchona) in treating marsh-ague (Malaria) was known during Hahnemann's time. In spite of that, some patients after the cure of malaria frequently developed some toxicological symptoms, such as intermittent shivering fever and attacks of various other disorders, like trembling of limbs etc. The symptoms were observed even in healthy persons after treating the same drug. He thus discovered the first homeopathic remedy 'China' from the same plant in minute dose to treat the toxicological symptoms according to the principle of isopathy. Later, he discovered the efficacy of potentizing the medicine to increase its curative power several fold. It is a proven fact that a suppressive drug at high dose is inhibitory, but at low dose after diminishing to certain threshold level, it is stimulatory. This is because, at higher dose, the drug inhibits the respective target enzyme of the downstream metabolites while minute dose of the same directly or indirectly stimulates the upstream transcription factor that has controlling influence over the synthesis of the former. After stooping down to certain critical level the inhibitory effect becomes negligible, only stimulatory effect persists. Hormesis may sometimes cause adverse effect on patient's health. As for example, low doses of anti-tumor drugs stimulate tumor growth (Calabrese, 2008) . Now there must be a possibility that minute dose of a pro-tumor drug, which can grow tumor exactly at the same location, would not fail stimulating the anti-tumor activity in the body. This is the principle of isopathy. The basic difference between hormesis and homeopathy is that the former is reproducible by experimental means, but the latter is not. This is because, in case of hormesis, the cause of symptoms is manmade and well known, but for homeopathy, it is mostly natural and unknown, which varies widely among individual patients. The required amount of crude substance to induce hormesis is much higher than that of homeopathy, because in case of the former, the drug cannot enter into the inner chamber of a cell. According to some authors, like Van Wijk et al (Van Wijk et al, 2009) , who prepared a database of experiments related to hormesis and homeopathy, both the terms are not synonymous or even special cases of each other. Contrary to homeopathy, hormesis also does not need any special technique to prepare the 'active agent'. Alternatively, one cannot ignore some similarities between homeopathy and hormesis, which suggest that there is some connection between them, or perhaps a common basis. The Similia Principle has been discussed in mainstream biomedicine in relation to hormesis. Evidence in support of the phenomenon of hormesis has accumulated year after year and the term has been applied to a variety of stimulatory responses of otherwise toxic substances, which, in low doses, improve health and enhance longevity (Neafsey, 1990; Calabrese and Baldwin, 2002;Stebbing, 2003) .

Homeopathy has got a special relation with immunology also. Dr. E. von Behring , who got the first Nobel Prize of medicine in 1901 for the discovery of diphtheria-antitoxin and the method of vaccination of anthrax, admitted (in a journal "Beitrage zur Experimentellen Therapie" in 1906) that the method of vaccination, though not properly understood at that time, is an application of Hahnemann's principle (Bellavite et al, 2005) . We know it true because even if the bacteria or any other micro-organisms are inactivated, heat killed or removed from the medium, the diseased exudates itself contain some antigens, which can bring almost similar symptoms, if it is injected to a healthy individual. Minute application of the same immunizes a provisional patient in a disease prone area by increasing the synthesis of antibody in his own blood. Newly discovered technique of 'patient specific vaccination' and 'therapeutic vaccination' (where specific antigens for infectious disease are used as ligand to stimulate synthesis of specific antibody, which are deficient in particular patients), are nothing but modern form of 'Nosodes' of homeopathy. The small peptides of bacterial origin present in the disease exudates, when potentized as such kind of medicine can stimulate the synthesis of transcription factors far upstream to synthesis of proper antibodies. They contain thousands of disease related products that can produce similar stress to normal healthy individuals. In case of patients, it possibly alerts the non-affected cells much earlier before the entry of parasites. Consequently, it is effective to treat the disease of particular patients. Therefore, the hypothesis, as explained here is not an over-speculative or innovative theory, but a synthetic model originated from extrapolating the existing ones.

As a general notion, we can presume that, hormesis is the extensive facet of immunology; whereas homeopathy is the broader aspect of both: hormesis and immunology. Lymphocytic responses to pathogen have more complicated regulatory network than simple example of hormesis. Therefore, we may call it as a specialized type of hormesis. From the above discussion, it appears that hormesis is only possible against toxic or infectious agents, but it seems not always be true. As we witness that there are some minerals used in homeopathy that are not toxic, like that of 'tonics' used as allopathic drugs. Then how can they produce a stress by inhibiting an enzyme? The answer of the question is that the difference between toxic and non-toxic substances is merely out of degree. An apparently nontoxic element if gets the chance of entering into the innermost chambers of the cells in excess amount it may produce a stress. Minute application of the same in potentized form stimulates the mineral utilizing enzymes, so that the mineral cannot be deposited excess within the cell and accumulated in suitable quantity from food and drinks. Most functional enzymes require a small concentration of mineral salts of Na, K, Fe, Mg, and Ca for their activity. If they become congenitally deficient in particular tissues due to unavailability of utilizing enzymes, it can also produce serious disease. There is no difference in opinion in compensating the same between the two disciplines of medicine, but the way of administration differs. If they are compensated in higher dose, as in allopathic drugs, the tissues cannot hold the same and they are eliminated from the body as sweat, urine, and stool. If they are gradually compensated in dry potentized form with lactose, they can be stored within the body. This is the basic principle of biochemic system of medicine, according to many it is a sister branch of homeopathy, discovered by Schussler , where deficiency symptom of twelve mineral salts on healthy person instead of 'proving symptoms' was considered in suggesting remedies.

We know that all the cells of our body arise from a single cell, by cell division. Nevertheless, all of them even in the same tissue are not completely identical, but bear minute genetic variations that are indicated by their DNA sequence, especially in the junk (non-coding) DNA region. There may be several reasons behind, but the predominant one is due to place changes of 'jumping gene' (or transposable elements ), which can rectify mutation in the regulatory elements by the process of natural selection. Thus, the regulatory element, mutation of which causes down-regulation of the transcription factors are rectified and the cells get opportunity to multiply. These are equivalent to Plasmids of bacteria. When such organisms are exposed to stress in environment or exposed to antibiotics these circular elements, which remain transposed into bacterial DNA to bring genetic variability to grow resistance against drugs. The most efficient clones multiply. The same is true for 'jumping genes' of higher organisms. All the cells of a tissue of a chronic diseased individual, therefore, does not remain equally affected; some are badly affected, while others, due to 'jumping gene', become semi-normal or normal. Except ''jumping gene' there are other ways that cause difference between mother and daughter cells. In spite of existence of some preventive genetic mechanisms, some minute errors or mutations occur spontaneously in the genes and with the advent of millions of cell division cycles it creeps into a significant level. With the increase of age the chance of deleterious mutations increases and thus the cell becomes weaker we grow old and die. Allopathic drugs, being the artificial stress-removers supports the undesirable mutations. They make the cellular environment highly favorable for all the cells including the incompetent ones, which get plenty opportunity to grow. The disease symptoms are removed soon and the patient appears to be recovering by the drug, but soon the tissue becomes an abode of worse affected cells, which outnumber the healthy ones and the medicinal dose elevates due to fall of efficacy in course, called 'wearing effect'. As a result, the dose of allopathic drugs increases frequently and they are deposited in healthy tissues, which causes severe side effects. This type of fostering of worse and worst cell line possibly gave rise to cancerous cell type after several generations of dependence over allopathic treatment. Even if the drug is withdrawn after habitual use, several new complaints arise due to ' withdrawal effect ' and ultimately the old disease returns with all pathological symptoms, causing ' rebound effect '.Conversely, if we are able to put an artificial stress by the use of homeopathic drugs to the gene pool the wrong sequenced cells will be to some extent outnumbered by healthy ones. The above-said menaces are totally absent in homeopathic medicines, but cure sometimes takes longer time than allopathic drugs, because it acts much upstream than the latter. Unlike allopathic drugs, the homeopathic ones can decrease the number of incompetent cells in the diseased tissue during the successive generations of cell cycle. The genetically better and best favorable cells that are able to combat with the stress survive and multiply more rapidly than the diseased ones as in clonal selection model (Figure:6, click here to enlarge). The disease would eventually be cure and no more medicine would be required.

We know that homeopathic drugs are effective not only in dividing cells but also in non-dividing ones. Although, the nerve cells cannot divide, it can more effectively produce a variety of protein molecules, called neuropeptides by splicing of mRNA to combat the stressor. There are several minute enzymes associated with their synthesis, might be stimulated by homeopathic drug. Specialized types of cells cannot produce variety of enzymes, most of them remain 'switched off', some are synthesized as 'house keeping enzymes', a very few are expressed as specialized one in bulky amount, as for example, trypsin is secreted only from pancreatic cells, deficiency of which can produce few pathological complaints (e.g., indigestion), but not a generalized symptom. Conversely, different personality, and several mental attributes, which are controlled by the synthesis of hormones, is attributed to the neuropeptides. Larger number of genes is expressed in nerve cells and their deficiency can produce complete generalized symptoms (e.g., burning sensation all over the body), which are more important in selecting homeopathic remedy. There are adequate experimental evidences showing that nervous system gets easily stimulated by homeopathic drugs than other organs. Hence, personality, sensations, inclination, and aversions of the patients are so helpful in screening out the actual remedy. Special emphasis on mental symptoms of the patient in selecting remedy were much essential than wasting time for common pathological ones that are seen in every patients suffering from a particular disease. In that respect, Hahnemann was much more prudent than his contemporary physicians were, because he gave supreme emphasis on mental attribute of the patients in selecting remedies, which differentiates one person from other. All the DNA segments for of the genome of a patient are not equipped enough to synthesize a desirable neuropeptide; some among them are favorable. The most favorable minute DNA segments having maximum capacity to struggle with the stress by means of desirable neuropeptide synthesis possibly make some more copies of the same in junk DNA as transposable elements, when there is a real necessity. It is 'copied and pasted' over the genome, while the undesirable DNA segments for neuropeptides gradually becomes outnumbered. Initially, when first discovered 40 years ago, junk DNA had no known biological function. Later it has been proved that the small mutant sequence upon the junk DNA might alter due to selection pressure. Many types of non-coding DNA sequences do have important biological functions, including the transcriptional and translational regulation of protein-coding sequences. The hypothesis that the disease-causing genetic variants lie in the non-coding DNA (Cobb et al, 2008) was proved much later and it can be inferred that the 'stressors' present in homeopathic medicine can produce an artificial selection pressure to rectify the altered DNA sequence by 'copy and paste' of favorable elements. The idea is therefore synonymous to the concept of selfish gene of Richard Dawkins. 'Selfish', when applied to genes, does not mean 'self-centered' at all. It means, instead, an extremely important quality, for which there is no good word in the English language:'the quality of being copied by a Darwinian selection process' as we have already explained it in case of multiplication of healthier cells in a diseased tissue according to 'clonal selection model'. Stress can therefore induce multiplication of transposable element over the genome and the theory has been supported by experimental evidences (Pecinka and Mittelsten Scheid, 2012) as well. The allopathic drugs, on the other hand, are artificial stress-removers that make the cellular environment highly favorable for replication of all the DNA fragments including the incompetent ones, which get lavish opportunity to increase in number by copy and paste method of the transposable elements. Soon the genome becomes an abode of incompetent DNA segments, which outnumber the desirable ones. As for example, a man being ill with insomnia if begins consuming sleeping pills every day, he soon becomes more and more dependent upon the medicine, its dose steadily increases. Although the same thing may occur naturally in diseased individuals, and we may call it an obstinate and chronic disease. In such case degeneration of organs occur with the advent of age.

Allopathy is actually a generalized treatment and applicable to all the patients suffering from the same ailments and no individualization is required. Yet, in a broader sense, the method of vaccination, which was invented earlier than homeopathy, is an application of homeopathic principle, though there was no individualization required, because it becomes effective upon antibodies and antigenic receptors, located much downstream in the synthetic pathway. The modern science of medicine is therefore sometimes stimulatory, sometimes suppressive and sometimes compensatory or supportive method of treatment. It is neither homeopathic, nor allopathic it might be called 'heteropathic'.

In spite of so many negative points we cannot totally reject allopathic treatment for its life saving potential. In acute cases, where recording of symptoms is impossible allopathic medicine saves life of the patients. Sometimes it is seen that withdrawal symptoms may arise for chronic patients habituated for allopathic drug for a long time after sudden withdrawing of the same. Sometimes administration of both the drugs simultaneously cannot be avoided for that reason. As the homeopathic drug works, according to Figure 4-5, much upstream than allopathic one its efficacy cannot be affected by the latter. After certain span of time, during convalescence, allopathic medicines should slowly be withdrawn leaving no withdrawal symptom. After few months, the already suppressed symptoms may recur and they should be treated with homeopathic drug only. In addition to that, allopathic treatment cannot be nullified in some cases. Patients suffering from surgical removal of vital organ, or having congenital chromosomal or genetic defect involving the whole body cannot be treated pragmatically by homeopathic means. After total necrosis or destruction of the tissue or organ, the latter is ineffective. Here allopathic treatment is the only resort.

From the above discussion, it can be inferred that homeopathic drugs have more penetrating ability than allopathic ones. As a general rule deficiency of beneficial metabolites, as well as abundance of deleterious product, both may be caused by deficit of minutest regulatory proteins. Hence, deficiency of the same is the limiting factor for all natural chronic diseases. Hahnemann's 'law of minimum' is applicable for homeopathic drugs. On the other hand, Allopathic drugs always consider the 'law of maximum'. Therefore, the approach of homeopathic and allopathic drugs is just opposite. Each homeopathic medicine is applicable to minimum number of patients suffering from a particular disease, based on minimal pathological complaints, but many concomitant symptoms and semantic to the stress of deleterious metabolites. It not only administers minimum quantity drugs, but indirectly considers the minutest proteins as limiting factors that are minimally available in the patient's body, but have controlling influence over the bulky functional enzymes. These seem to be nothing but minute enzymes or transcription factors, having influence over the overall metabolism. Allopathy, on the other hand, treats the symptoms, which is maximally available among the diseased individuals, and antagonistic to the stress of deleterious metabolites. Each drug is applicable to maximum number of patients suffering from a particular disease where maximal pathological complaints match, with less emphasis on concomitant ones. For deficiency syndrome of a beneficial enzyme, homeopathic drug is similar to its substrate, but allopathic drug acts like its product. Conversely, for abundance syndrome of a deleterious enzyme, homeopathic drug is similar to its product and allopathic drug mimics its substrate. We have observed in lower organism like bacteria, that minute quantity of substrate or product of an enzyme (or similar other substance) can trigger regulatory pathway, but it is not always seen in higher animals, because the ultimate regulatory gene is located much upstream to the functional enzymes. Hence, the difference between allopathic and homeopathic medicine cannot be established by 'substrate-product relationship', but it lies only in opposite mode of action. When an allopathic medicine is applied to a healthy person, the symptoms opposite to the disease are generated. As for example, an allopathic drug, which is suitable for high blood pressure patient would remarkably decrease the blood pressure of a healthy person. Hence, it is a suppressive method. Homeopathic medicines, conversely, can produce symptoms to the healthy person, similar to the disease, so it is a stimulatory method of treatment. For instance, sulfur is directly used as allopathic medicine to cure skin diseases, but homeopathic drug 'Sulphur' removes the diseases created by allopathic application of sulfur, therefore skin disease, suppressed by the former sometimes recurs for few days before the final recovery. Thus, the allopathic drugs are never 'stressors' like that of homeopathic ones, but 'stress-removers'. Although, initially they remove the stress, but finally, in course of further application, the disease symptoms become worse, because there is no urge left within the cell to get rid of the stress. Hence, the genetic or familial diseases in most cases remains incurable by allopathy, but to some extent curable by homeopathy.

6. What is the meaning of 'vital force', 'disease force', and 'medicinal force'?

The concept of mysterious vital activity was not Hahnemann's own theory; it originated from the idea of C.F.Wolff (1738-1794), who was the teacher of famous biologist von Baer . Hahnemann believed in spiritual power or 'vital force' that makes the difference between animate and inanimate objects ("Organon", 5th ed. § 9-10). He defined the life as a combination of body, mind, and spirit. The spiritual autocratic force that makes the material body dynamic is actually the 'vital force'. According to him 'vital force' is a spirit like, dynamic automatic power present everywhere in the body, which animates our body and preserves life in living being ("Organon", 5th ed § 15). Later he termed it as 'vital energy' ("Organon", 6th ed. § 12). He gave much emphasis on derangement of 'vital force' ("Organon", 5th ed. § 11-12) in diseased individuals, but never explained it. A person, according to him, falls ill if his 'vital force' is morbidly affected by 'disease force'. The idea of affection of 'vital force' by 'disease force' is the sole contribution of Hahnemann. He has described 'disease force' in terms of 'spirit-like power', similar to that of 'vital force'. Diseases are not mechanical or chemical alterations of the material substance of the body and not dependent on material morbific substance, but they are merely spiritual dynamic derangements of life ("Organon", 5th ed § 31 footnote). He did the same for homeopathic medicines also. He termed the curative power of homeopathic drug as 'medicinal force' ("Organon", 5th ed § 20, 30-33). Hahnemann felt that affliction to 'vital force' by polluting agents is the cause of all ailments, but he neither defined vital activity in terms of material science. The body endowed with 'vital force' is constantly fighting with all inimical noxious influences or forces, but either due to long continuous exposure or due to greater strength of 'disease forces' or irregularities in everyday life 'vital force' is deranged, the individual becomes susceptible for disease, which according to him has no separate objective existence.

Much before Hahnemann's era, Zacutus Lusitannus described a patient in mid 1600s, whose urine turns black in air called alkaptonuria , but otherwise he was healthy, he got married and begat a large family. A.E.Garrod , a British physician, minutely observed the same metabolic disorders among his patients, and at the very beginning of twentieth century, he first proposed in his famous book "Inborn Errors of Metabolism" that specific symptoms might be caused by metabolic disorders due to enzyme deficiency or mutation. It was later summarized that some enzymes, responsible for breaking of homogentisic acid (homogentisate oxidase), are either absent or mutant (inactive) in alkaptonuria patients. Therefore, there is an overflow of Homogentisic acid, which is accumulated in blood of patient and excreted through urine, where it is oxidized and polymerized into to a melanin-like substance, which turns black in air. The same metabolic pathway, which begins with the ingestion of phenylalanine, was later shown to be linked with tyrosine. Breaking of the pathway at various steps, due to deficiency of enzymes, can produce three diseases: phenylketonuria (PKU) , tyrosinosis , and albinism with specific combination of symptoms. Phenylketoneuria is caused due to lack of enzyme phenylalanine hydroxylase. The patients are mentally retarded and majority of them generally die before the age of twenty (Figure:7, click here to enlarge). Phenylpyruvate, a product of phenylalanine, is present in urine as an overflowing product, which turns olive green in color by the addition of ferric chloride. Since phenylalanine hydroxylase is metabolically linked with tyrosinase, an enzyme that converts tyrosine to dopa (dihydroxy phenylalanine) towards the pathway of melanin synthesis, PKU patients show less pigmentation in skin and hair. Here dopa is the deficient product.

Whatever be the cause of chronic diseases they may be grouped under two broad categories: curable or incurable. It was later predicted that more than two thousand human metabolic disorders responsible for chronic diseases are caused by malsynthesis of some enzymes, most of them are incurable, because they are congenital, caused by mutation of structural gene, and they do not have natural course of aggravation and amelioration cycle. It means they are non-dynamic diseases, so are incurable by homeopathy. If the ailments are wrongly treated by allopathic drugs for several years or even generations, dynamic nature of the disease is lost. Such non-dynamic disease, having hardly any natural aggravation and amelioration cycle, has no treatment by homeopathy even. Homeopathic treatment is only possible for dynamic diseases; it means the disease involves a large number of dividing cells or multiple duplicating segments of DNA. Others are caused by sudden somatic mutation of DNA due to infectious diseases, pollution, allopathic treatment, life style problem, etc and therefore are curable. Such kinds of diseases are dynamic in nature. It indicates that the genetic constitution is not so static. For a dynamic disease we should consider the metabolic blockage movable, but for congenital and nondynamic diseases (e.g., Phenylketonurea) the blockage is fixed, so that we should admit those are incurable even by homeopathic means. However, all the human metabolic disorders, curable or incurable, are caused by external agents that act upon the individual himself or his ancestors. It causes some kind of obstacles in the metabolic pathway. They can be well represented by 'branching water pipe model', where blockage at any point of the pipe may cause deficient flow of some and overflow at other pipes (Figure:8, click here to enlarge), so that specific combination of symptoms arises (Chattopadhyay, 2002) . When the blockage moves from downstream to upstream, greater alteration of flow rate occurs, more and more complicated symptoms arise. Flow of water in the branching water pipe represents 'vital force'. Although we cannot visualize the 'vital force' or 'energy', but can realize its existence by forceful flow of enzymes that digest away the food materials, gentle secretion of hormones that control activity of enzymes, synthesis of defensive proteins that protect our body from parasites, and rapid synthesis of detoxifying proteins that protect our body from pollutants and poisons. However, the over secretion of hormones that causes some diseases is not an indication of 'vital force', but the inefficacy of regulatory proteins that control secretion of hormones or tumor in the respective endocrine gland. The negative force, which afflicts the 'vital force' and causes overburdening of our body with parasites, pollutants, deleterious metabolites, etc, and reduce the normal flow of useful metabolites, might be called 'disease force', which may represent a blockage in the metabolic pipelines. 'Medicinal force' (homeopathic), on the other hand, is a minute form of force that mimics 'disease force'. It causes stimulation of 'vital force' at the deeper portion (upstream) of the metabolic pathway, so that the obstacle: living, non-living, or just a virtual one, flows away through the pipes. It can be analogized with 'hammering', a type of mechanical procedure, by which the plumbers clear choked water pipe. Noticeably, 'vital force' always spurts from inside to outside of human body. On the contrary, 'disease force' and 'medicinal force' as well, according to Hahnemann's logic, always invade from outside to inside, though the latter is much faster to penetrate the human body than the former due to high dilution of the same. Mainstream medicinal science has described the cause of illness of human being may be external (i.e., environmental, bacterial, viral, or pollution related) or internal (mostly genetic) or both. Conversely, according to homeopathic science of medicine, all the chronic diseases are mostly extrinsic (external) in origin. Then what happens for the genetic and 'familial diseases'? If we think it in a subtler way we would be able to find the answer. Although these diseases appear to be intrinsic (internal) for an individual, but actually caused by extrinsic factors gathered by mutation of the genome of his ancestral generations. So long the 'vital force' remains strong enough it prevents mutation of the genome, but when it gets weaker, the external disease causing factor can induce mutation of the genome. Consequently, when the mutant gene is carried to the next generations the disease seems to be 'internal' in origin, but actually it is external.

In a simpler way, a blockage at particular point of branching metabolic pipelines might be called 'root cause of the disease' and the force which holds the blockage at that particular location is synonymous to 'disease force'. In case of curable diseases, it always maintains a dynamic equilibrium with 'vital force'. Therefore, there is always an aggravation-amelioration cycle: in the presence of some particular external factors the disease symptoms aggravate and in others they ameliorate. It is very important for finding out the correct remedy. In their absence it is almost impossible. However, in case when the 'disease force' is much stronger than 'vital force' (e.g., neural degeneration) there is only aggravation, but no amelioration. These are also regarded as chronic and almost incurable diseases, where the atrophy of organ cannot be prevented by any medicine. Non-dynamic diseases (e.g., Phenylketonuria), as we have mentioned earlier, are totally incurable. Conversely, for chronic dynamic curable diseases, after the application of 'medicinal force', as Hahnemann has said, the symptoms disappear in reverse order of their appearance; and prior to their final recovery, the oldest symptom returns. This can be analogized with the outward motion of the blockage by the pressure of water flow ("vital force") in branching water pipes. Hammering at that particular location of branching water pipe (by means of homeopathic remedy), causes upstream to downstream movement of the blockage, so that the blockage moves back to its original position of entrance. Gradually the diseased cells from inner to outer portions of a tissue regain their initial physiological status. The disease, which was originally suppressed by allopathic treatment, may recur, but soon disappears. It appears that older symptoms are returning. Actually, the bunch of immunity cells (or those who are related to recovery), stimulated by homeopathic remedy, 'runs after' the concealed pathogen, which comes out from their hiding places and manifests some itches and eruptions again before their final departure. This can also occur for metabolic diseases. After the rectification of synthesis, the rate of synthesis of upstream metabolites and then the downstream metabolites are gradually normalized and return to the initial state of disease, and finally cure. However, higher dose of homeopathic medicine can act as an artificial 'disease force'. 'Proving' is therefore nothing but an indirect way of identifying the unknown enzymes/minute protein factor(s) that prevents disease related symptoms in a healthy individual. When a specific drug artificially inhibits such a factor, the symptoms would be visible automatically.

Recording of the symptoms of a patient, as suggested by Hahnemann in "Organon 5th Ed", aphorism 84-92, in terms of particular drug might be called 'anamnesis'. When we cannot directly visualize the probable c ause of a disease but realize it indirectly from the medicinal symptoms by deductive method, it is called anamnesis; but when can visualize the cause by direct experiment, and sort out the probable symptoms by inductive method, it is diagnosis. 'Anamnesis' differs from 'diagnosis' that the latter finds out the actual cause of the disease directly in terms of pathogen or afflicted metabolite, as suggested by modern allopathic sysem. Phenylpyruvate test in urine of PKU patients, as we have mentioned above, is a diagnostic tool, which indicates that deficiency of an enzyme, phenylalanine hydroxylase, is the cause of disease. On the contrary, anamnesis can locate the deficient enzyme indirectly in terms of medicine that can induce similar symptoms related to the disease in healthy persons, which actually may indicate inhibition of the same or similar enzyme. As for example, oudenone and its derivatives are strong inhibitors of phenylalanine hydroxylase. Hence, if oudenone is applied upon a healthy person he would manifest some symptoms like PKU patients. The patients those who are originally manifesting similar symptoms would be termed as oudenone patients. Homeopathy follows such anamnesis principle, but since those enzymes that are inhibited by the same are extremely minute and almost non-detectable by conventional biochemical assays, direct diagnosis of their insufficiency is rather difficult. Take another example, symptoms like intermittent shivering fever and attacks of various other disorders, like trembling of limbs etc is caused by Peruvian bark (Cinchona). These are also curable by minute application of the same as homeopathic medicine ("China"). Hence, the disease is named, according to Hahnemann, in terms of medicine (Anamnesis), which can induce the symptoms in healthy person. Conversely, if we try to investigate the cause, there might be malarial parasite in the patient's RBC, it will then be called Malaria disease (Diagnosis), which can be treated with higher dose of Peruvian bark (Quinine).

As in branching water pipes, the location of single blockage can be identified by observing the flow-rates of each pipe (Chattopadhyay, 2002) ; likewise, identification of rate limiting enzymes in human metabolism is possible by observing quantity of known metabolites. Actually, it is done by means of clinical tests of blood, urine, stool, sputum, sweat etc. As for example, overflow of glucose in urine represents deficiency of insulin hormone, indicating predisposition of several other diseases. These can be treated by homeopathy studying specific combination of symptoms minutely.

In a simpler way, it can be decided that diseases (dynamic disease) curable by homeopathic means following 'similia principle' must have a natural aggravation-amelioration cycle. Disease causing agents naturally possess a power of aggravating the ailments in affected individuals, while cells of the immune system have the 'vital force' that causes prevention and amelioration. 'medicinal force' (homeopathic), on the other hand, stimulates the non-affected cells much earlier than the invasion of disease causing agents; so that 'medicinal force' is called stronger than the 'disease force' and the disease becomes eventually cure.

7. What is the science behind 'anti-miasmatic treatment'?

The term 'miasm' means defilement, stain, polluted material, infective material, and contagious effluvia from human body. Few centuries ago, it was believed that miasm was some form of obnoxious toxic form that arose from bad soil. It was the result of some hideous toxicity. This concept also got into the philosophy of homeopathic medicine. Miasm in homeopathy underwent tremendous changes since then. The concept of internal disability to respond well-selected remedies came forth as the concept of three 'miasms'. The theory of miasm is a matured wisdom of 'similia principle'. It is the sum or total effect of every type of 'disease forces' on human body. It concentrates on the overall symptoms, not only the recent ones, but those were manifested all over the lifetime of the patient, even laid down early in his ancestry. Naturally, they cannot be artificially induced upon the 'Provers' by applying higher dose of any single medicine within a limited span of time. The first miasm was 'psora', disease related to itches and irruptions. When it occurs over the outer surface of the body it is small pox or leprosy. Likewise, when it occurs in the inner surface of the intestine, irrespective to pathogen responsible for the disease, it is dysentery. Similarly, when it occurs at the inner surface of lung it is tuberculosis. The remaining two were 'syphilis', (which indicates the symptoms related to the highly invasive and destructive disease of the same name or any other similar natural diseases having much aggressive power leading to degeneration of an organ, ultimately the nervous system) and 'sycosis' (the symptoms related to Gonorrhea, the fig-wart disease, which can cause small lumps and tumors to any organ due to disproportionate supply of metabolites). The followers of Hahnemann included another miasm 'tubercular' much later than his death, as according to them the disease represent some unique symptoms, not acquainted in other miasms. According to most of the modern homeopaths 'deficiency of useful metabolites due to long term suppression' is the key word of psora, while, 'excess storage of the same due to loss of coordination' is the basic feature of sycosis. Similarly, 'overflow of harmful metabolites to initiate destruction' is the main theme of syphilis, while Tubercular is a mixed miasm, where all the menaces culminate into a gross 'deficiency of both useful and destructive metabolites, in long run causing loss of vital energy'. It should be mentioned here that even the destructive metabolites has got some positive role in maintaining life. These are responsible for routine or programmed cell death or apoptosis , which is essential to restrict the number of cells in our body. It also causes death of weak and malefic cells; otherwise, they might cause tumor or tubercular lesions. In case of cancer, the natural death of malefic cells is absent, hence it is so devastating. According to some modern practitioners it is a form of tubercular miasm, as there is a profound debility and weakness, but according to others it should be ranked as separate miasm, as it represents some fundamental or basic combination of symptoms, unavailable in other natural chronic diseases. The theory of miasm has a close relation with the basic concepts of human genetics and biochemistry, we shall discuss here.

Scientifically, miasm means 'like disease'. As for example 'syphilitic miasm' indicates any disease that has devastating effect on human tissue like that of syphilis proper, including deformity, pus formation, necrosis, and degeneration. Miasm is the exclusive heritage of the humankind. Wild animals in the forest do not suffer from miasm, because they never try to remove the stress, as we do. We always strive to change natural environment in favor of us, endeavor to suppress chronic diseases, so that affected individuals can live long, and reproduce without proper counseling, consequently the afflicted genes become incorporated into the gene pool and later became expressed as different chronic diseases. As psoric, sycotic, syphilitic, tubercular, and cancerous miasm so far have been considered as the five dominant causes of all the natural chronic diseases (except artificial diseases, i.e., caused by injury, surgery, sedative drugs etc), we can consider five branching imaginary pipelines that carries the disease preventing metabolites. If all of them flow normally through the pipelines, the person remains healthy, both physically and mentally, but scanty flow of some metabolites and overflow of others due to deeper and deeper dynamic progression of metabolic blockage indicates susceptibility to different diseases. Miasm, in addition to specific metabolic blockage, makes human body a suitable habitat for different parasites. Even in absence of the causative bacteria, virus, protozoa or any other parasite the affected person manifests several pathological complaints, often seen in the said infections. How could the symptoms appear in absence of the causative organisms? The answer is, due to long lasting suppressive treatment of itches, gonorrhea, syphilis, tubercular, and several other related diseases, generation after generations, the human genome has become modified to such an extent that there is disturbance in the flow of metabolites and the symptoms appear spontaneously. Hence, there is no specific defense mechanism against the pathogens as they do not bring any new symptoms. They live peacefully in the human body causing no deadly illness. It serves the interest of both parasite and host, but some chronic ailments due to specific pathogen associated molecular pattern becomes inheritable.

Psoric, sycotic, syphilitic, tubercular, and cancerous miasm, as mentioned above are not static cause of diseases but dynamic. Psora is the most external cause of disease and cancerouse is the most internal one. We have so many examples, how a suppressive allopathic treatment can make the 'external' disease 'internal'. In other words, causes inward progression of 'disease force'. We know that if a parasite that causes skin eruption is suppressed by an allopathic drug may permeate inside and can affect internal organs. In another example, suppose a patient showed a tendency of suffering from indigestion for few days (acute-miasm, preliminary stage of psora). Due to anomalies related to lifestyle and food habit, it became a perennial problem causing deficiency of secreting digestive enzymes. As the deficiency is the cause of disease, we may call him a patient of psora. An allopathic doctor prescribed pepsin to him in the form of tablets, so that the disease was suppressed, he could digest well, but as the transcription factors responsible for regulating the enzyme-synthesizing gene would have no more work, the gene would fall lazy. Thus, the disease would move downstream to upstream, or 'outward to inward'. Ingestion of excessive food containing high calorie even after consuming ample of digestive tablet and aversion to physical exercise has become the habit of common people nowadays. Eventually, the patient may gain obesity. Simultaneously, due to absence of proper mechanism to combat the excess glucose load, its level in blood would be increasing, and the existing secretion of insulin would not be able to manage the situation because of lacking coordination between transcription factor and hormone. The patient would become diabetic. Here, excess of useful material due to loss of coordination is the cause of the pathological condition. Hence, we would describe him as a sycotic patient. He would be receiving insulin injection every day; soon the entire coordination mechanism between ingestion of food, digestion, storage, and utilization of the same would break down violently. There would be a gross metabolic disorder with excess deposition of fat inside the lumen of arteries of heart tissue, which would be suffering from malnutrition, degeneration, necrosis, destruction, and cell death. Ultimately, there would be severe chest pain due to atrophy of the same. As the destruction is the cause of all the trouble, we may term the patient syphilitic. It may be secondarily caused due to break down of lysosome , the ultimate cause of destruction. Besides, any type of non-individualistic method of treatment, even including vaccination, does the same kind of harm. So long the metabolites flow normally through the psoric pipelines, we remain protected not only from external diseases like itches and eruptions, but also from internal diseases. In Hahnemann's time, many people were subjected to unnecessary vaccination against smallpox in overdose, the flow rate through the anti-psoric pipelines increased enormously. Eventually, they earned more immunity against smallpox, but became susceptible to the diseases related to sycotic miasm, because of consequent deficiency of flow in the neighboring anti-sycotic pipelines. He explained it as the 'bad effect of vaccination'; and he has mentioned some cases where 'psora is converted into sycosis.' Probably for that reason, gonorrhea broke out so violently after the French war, (1809-1814). Now it has been proved that overdose of vaccination against so many germs are harmful to human health. However, in some provinces where a specific disease is prevalent, large-scale vaccination cannot be avoided. In 1929, long after the death of Hahnemann, the anti-bacterial property of penicillin, extracted from a mould, was discovered. Later, after the invention of several other antibiotics, like bacitracin, chloramphenicol, chlorotetracycline, streptomycin, tetracycline etc, loss of lives by parasitic attack including cholera, syphilis, gonorrhea, and tuberculosis were minimized. These were much effective in killing internal germs than sulphur, mercurials, and other similar drugs, but their malicious effect was revealed later. Most of the germs including tuberculosis became resistant to the antibiotics. The side effects of antibiotics were ever increasing, including emaciation, poor growth of bones and teeth, frequent diarrhea, susceptibility to cold, loss of internal immunity, chronic hemorrhage, and loss of vitality. Ability of sulphur and mercurial were limited in killing the germs of the skin (external membrane); but the antibiotics were capable to eradicate bacteria responsible for eruptions and nodules even inside the body, e.g., mucous membrane of intestine or lung (internal membrane), consequently, the 'external' psora, i.e., adverse effect of suppressive treatment, became 'internal'. According to several practitioners, tubercular miasm should therefore be called 'pseudopsora'- the false psora, as mentioned earlier, which grows internally. Discovery of antibiotics are also responsible for budding of cancer miasm. By the use of antibiotics the boils inside human body do not suppurate spontaneously and remain unchanged year after years. In some cases, it undergoes some malignant changes within that period and converted into tumor. Tumor cells, if they grow in human body are generally digested by natural killer cells (WBCs), but due to indiscriminate use of antibiotics generation after generations, these killer cells have rendered inefficient. Hence caner miasm became widespread in human beings than other animals. It can also be stated for AIDS miasm. These predispositions are so widespread among human beings that they can no more simply be called diseases, but elevated into the rank of miasms, as they represent a gross deficiency of the immune system to fight against these diseases.

Now we shall come to the scientific method of anti-miasmatic treatment of the chronic patients. They can be treated well by the respective anti-miasmatic drug. Suppose, a patient came to a doctor, who was suffering from fever of slow and insidious nature, with aggravation of coughing by motion and he had thirst for sufficient cold water. The physician would realize that 'Bryonia' was the remedy. The patient went away and ameliorated very soon, but returned after few weeks, suffering from the same complaints, which recurred. He could not stand erect and sat upon a chair. The doctor came to know from the diseased person that he has a history of suppressing skin rashes by allopathic drug, derived from sulphur. There was a burning sensation prevailing all over his body for last few days. This time the doctor would administer one dose of 'Sulphur' prior to applying 'Bryonia' to the patient. Hahnemann himself has faced similar troubles during his life time. Efficacy of 'Sulphur' in treating such patients was discovered by him after long twelve years of meticulous research. Efficacy of some other drugs for similar constitutive or anti-miasmatic treatment was discovered later. According to the proposed theory, deficiency of more than one minute enzyme is responsible for such ailments unlike 'similia principle', so that long drawn constitutive treatment became essential. Now we can explain the healing art according to 'branching water pipe model' (unpublished work) as follows (Figure:9, click here to enlarge).

Observing the affinity of symptoms of medicines upon the 'Provers', as mentioned in homeopathic literature, a hypothetical metabolic pathway of healthy individual can be constructed. In addition to relationship between the drugs (kindred remedies), their overlapping symptoms, duration of their activity, and anti-miasmatic properties are important in drawing 'branching water pipe' diagram for homeopathic medicines, where the locations of hypothetical unknown enzymes, sensitive to particular drugs were placed accordingly. Among more than two thousand existing homeopathic remedies, very few were incorporated. Closer location of medicines in the linear array represents close affinities, indicated by overlapping of symptoms between the drugs. Towards the origin of the pipelines each nearest neighbors like (from below to above) 'Sepia', -'Nitric acid', -'Hepar' -'Mercury', -'Carbo veg', - 'Causticum', - 'Lachesis', - 'Lycopodium', - 'Phosphorus',- 'Calcarea Phos', - 'Graphites', and - 'Arsenic' locations share some common or overlapping features, and they can be administered one after another, if the metabolic blockage is shifted to the next location, indicated by alteration of symptoms. There are seven imaginary terminals of the pipelines in the diagram. The first three terminals represent acute miasmatic disorders. Thousands of metabolites bearing anti-inflammatory, anti- external hemorrhagic, anti-bacterial, anti-febrile, anti-indigestive, and anti-depressant properties that are always synthesized in our body, flow through acute miasmatic pipelines. Secretion of useful metabolites including digestive juices and other exocrine glands, anti-itch and eruptive materials, which are responsible for external (surface) immunity, even secretion of sweat and sebaceous glands flow through psoric pipeline. When there is a blockage just below the origin of psoric pipeline itches and eruptions would appear as a consequence of overflowing, but the secretion of anti-inflammatory, anti- external hemorrhagic, anti-bacterial, anti-febrile materials would decrease. The patient would often suffer from fever, allergy, headache, loss of appetite etc. Secretion of storable useful materials, influenced by endocrine glands, especially, the hormones responsible for specific coordination within the body system, like testis, ovary and pancreas and some immunological materials responsible for immunity against venereal diseases flow through sycotic pipelines. When there is a blockage just below the origin of sycotic pipeline, an overflow of useful materials may occur. As a result, diabetes and other metabolic disorders may emerge. Moreover, warts, nodules and gonorheal lesions may emerge over skin due to greater synthesis and overflow of related antibodies. Endogenous destructive materials that are responsible for killing foreign bodies, also self, detoxifying metabolites, anti-necrotic substances and those are responsible for pus formation and wound healing, substances for proper growth of teeth and bones, anti- internal hemorrhagic substances that prevent internal hemorrhage, materials responsible for internal immunity, secretion of thyroid, thymus, and adrenal glands, having generalized metabolic coordinating function, can flow through syphilitic pipelines. When there is a blockage just below the origin of syphilitic pipeline, an overflow of destructive materials may occur as a result, causing necrosis. Moreover, deadly dryness, chancre and syphilitic lesions may emerge over the skin. Due to deficiency of useful materials that flow through sycotic pipeline, gum, teeth and bone decay quickly. It should be mentioned here that thyroid has got some degenerating capacity. Injection of thyroxin in tadpoles causes degeneration of tail. Adrenal is responsible for 'fight and flight' mechanism. However, its increase causes suicidal tendency in some mammals. Hence, it appears that both the glands may become affected by syphilitic miasm, indicated by excess secretion of both. At cellular level, the miasm may cause overflow of some metabolites that trigger bursting of lysosomes- the 'suicidal bag'. Anti-tubercular products are responsible for gross deficiency of both useful and destructive materials. Secretion of pituitary, conferring supreme generalized type of coordination, and the growth materials like calcium, responsible for enlargement of bones, flow and the materials responsible for apoptosis run through tubercular pipeline. If there is a blockage below the origin of tubercular pipeline the patient becomes tall, lean and thin in appearance, bearing delicate health, easily affected by cold, showing deformity and decay of muscle and bones, suffering from osteoporosis due to outflow of calcium from the body and look like 'pigeon chested'. They became over-sensitive, gloomy, and sluggish in nature. As the miasm can bring more generalized symptoms including growth of muscle and bones, it appears that it has got the capacity of afflicting pituitary gland. It is seen that in human body, the glands that located upper have an influence over their subordinates. As for example, thyroid has influence over gonad as it is located at the upper position. Likewise, Pituitary has a control over both of them. Therefore, affliction of the upper one can bring more generalized symptoms, indicating deeper progression of 'disease force'. Cancer miasm indicates the deepest advancement of 'disease force' and the worst deterioration of 'vital force'. It has an adverse influence over every type of metabolic functions of the body. Even programmed cell death or apoptosis cannot occur in cancer affected individuals due to blockage above the origin of tubercular pipeline. Due to highest grade of debility, cancerous miasm is comparable to affliction of the brain, hypothalamus, or nerve tissue that can secrete neuropeptides. We may imagine that the secretion of the materials responsible for controlling cell cycle, cell growth, proofreading enzymes, along with cancer suppressing metabolites, which are detectable by clinical tests, flow away through cancerous pipelines.

Scanty flow of metabolites through acute-miasmatic pipes due to blockage at any place symbolizes acute ailments, including loss of appetite, indigestion, weakness, debility, anxiety, malaise, sudden external hemorrhage, inflammation, and acute febrile condition. These blockages are very shallow in nature, so that sometimes they may be eliminated spontaneously without applying any medicine. Progress of blockage (due to suppressive allopathic treatment) towards the deeper position, near 'Sulphur' point, indicates psora, where in addition to the above symptoms, there is a tendency of itches and eruptions appearing all over the skin, like smallpox, scabies, and leprosy. During the time of Hahnemann and even earlier, sulphur was widely used as a crude drug to suppress itches and eruptions by allopathic doctors; as a result, the effect of sulphur pollution upon human health became deep-rooted. Treatment of homeopathic 'Sulphur' cures such type of chronic ailments. This was similar to the idea of isopathy, closely related to hormesis.

Homeopathic medicines like 'Aconite', 'Ferrum', 'Arnica', 'Belladonna', 'Bryonia' etc being short active remedies with comparatively smaller number of chronic symptoms involving the whole body and mind, but mainly acute ones, were placed towards the terminals. 'Sulphur' being the 'king of anti-psoric remedies' was placed just below the origin of anti-psoric pipeline. If there is a blockage at 'Sulphur point', excess eruptive materials would flow through psoric pipelines, consequently itches and eruptions would appear over the skin, as if to protect the body systm from external enemies. 'Thuja' could show salutary effect over sycosis, so that it is called the 'king of anti-sycotic remedies'. 'Thuja' was placed just below the origin of anti-sycotic pipelines. Hence, if there is a blockage at 'Thuja' point, excess of useful materials, e.g., glucose, triglycerides, cholesterol etc would flow through the sycotic pipeline. They would be accumulated within the body. Side by side anti-psoric materials would not flow properly, so that natural immunity against the acute diseases decreases, they would suffer from affection of external parasites, well represented in diabetic patients. During the life span of Hahnemann and even earlier the allopaths used crude mercury to treat venereal diseases. While practicing as an allopathic doctor, Hahnemann was unable to cure frequent cases of venereal chancres, especially, complicated with itches, or with the dyscrasia of condylomatous gonorrhea by long continued or frequently repeated erroneous treatment with large doses of mercurial preparations. Yet, he claimed to have noticed gradual development of 'masked venereal diseases' by the use of the said drug and many concomitant symptoms, including pus formation, bubo, chancre etc like those of syphilis. Chronic mercury poisoning is characterized by neurological and psychological symptoms, such as tremor, changes in personality, restlessness, anxiety, sleep disturbance and depression, which are the characteristic features of syphilis miasm. Occurrence of coronary heart disease by mercury exposure with no previous history of cardiovascular disease also indicates syphilis miasm. Metallic mercury may cause kidney damage and proteinuria. It is an allergen, which may cause contact eczema. In the mercury-polluted areas of the earth, it was reported that people become weak and susceptible to several diseases; they suffer from abdominal pain, headache, diarrhea, hemolysis, and chest pain. Decay of teeth and bones in mercury exposed individuals also indicates syphilis miasm. Some of the said symptoms might have similarity with syphilitic symptoms proper in terms of devastating effect. Potentized mercury salt cannot bring the all the excrescences upon a 'Prover' after short-term exposure in tolerable concentration, but for long-term exposure many symptoms related to the said miasm may be expressed. For that reason, 'Mercury' is called the 'king of anti-syphilitic remedies', which is placed below the origin of syphilitic pipeline. If there is a blockage at 'Mercury' point, excess of destructive materials that can cause necrosis and pus formation in tissues would flow through the pipeline. Simultaneously, deficiency of anti-psoric and anti-sycotic materials would occur. There is practically no single or ideal remedy, which can cover all the symptoms associated to tubercular miasm. However, 'Phosphorus' and 'Calcarea Phos' were found very effective in solving most of the problems of these patients. So they were placed below the origin of anti-tubercular pipeline. In the diagram, 'Arsenic', a cancer causing element, being deepest among the remedies, indicates longest duration of action, therefore having larger number of deep-seated chronic symptoms, indicates the ideal remedy of cancer miasm. A recent WHO evaluation (Geneva: World Health Organization, 2001) concludes that arsenic exposure via drinking water is causally related to cancer in the lungs, kidney, bladder and skin, the risk increases with increasing exposure. Moreover, during Hahnemann's time sulphur, mercury, lead etc were widely used as allopathic medicines of inorganic origin. Nowadays almost all allopathic medicines are carbon compound. Hence, homeopathic medicine 'Graphites' has a special significance. Therefore, 'Arsenic' and 'Graphites' were placed much upstream than the other drugs, very near to the origin of all the flows. Any blockage at the place causes alteration of almost the entire flow, as a consequence in addition to cancer miasm the four others - tubercular, syphilitic, sycotic, and psora would appear together, which would prevail all over the body. It does not mean that symptoms related to all the medicines would appear simultaneously. This is because medicinal symptoms appear together due to both deficiency of some and overflow of other metabolites, indicated by particular medicine. For 'Arsenic' deficiency is mostly the causative agent, overflow is negligible. Deficiency of nutrients, vitamins and minerals, deficiency of natural reactions, deficiency of immunity, vital heat, and deficiency of destructive materials even apoptosis causing factors would become the salient feature of such patients, resulting a gross deficiency of 'vital energy'. There would be scanty flow in 1st-7th pipelines, but overflow in the 8th pipeline that carries cancer related metabolites. The said remedy is applicable to patients having familial history of suffering from all the five miasms. The same is true for deep acting 'Graphites' also. Besides, other deep-rooted medicines like 'Calcarea Phos', 'Phosphorus' 'Lycopodium', 'Lachesis', 'Causticum', and 'Carbo veg' cover four miasms: tubercular, syphilitic, sycotic, and psora, so they were placed below the origin of tubercular pipeline. 'Mercury', 'Hepar', 'Nitric acid', 'Sepia', and 'Lilium tigrinum', have influence over three miasms: syphilitic, sycotic, and psora, so they were placed below the origin of syphilitic pipeline. Likewise, 'Thuja' and 'Antim crud' can cover two miasms: sycotic, and psora, so they were placed below the origin of sycotic pipeline. 'Sulphur' can cover only one miasm: psora, so it was placed below the origin of psoric pipeline. 'Pulsatilla', 'Alumina' etc show several features of anti-psoric remedies, so they were placed just below 'Sulphur' location. The Acute miasmatic remedies that we frequently use, like 'Bryonia', 'Belladonna', 'Nux vomica', 'Rhus tox', 'Arnica', 'Aconite' etc. have few anti-psoric features, so they were placed near the terminals of the psoric pipelines. Still, some medicines are there, like nosodes, which are very specialized and can cover single miasm, because they are prepared from disease exudates, which can bring most of the pathological complaints of the representing disease only, when applied upon healthy individuals. For that reason, 'Carcinocin' covers only cancer miasm, so that they were placed towards the terminal of anti-cancerous pipeline. 'Tuberculinum' exclusively indicates tubercular miasm. 'Syphilinum', mostly covers syphilitic miasm; 'Medorrhinum', for sycotic and 'Psorinum' mostly represents psora (Hence, several symptoms of 'Psorinum' are similar to 'Sulphur', others are dissimilar). All of them possibly can stimulate killer T-lymphocyte that can digest away tumors of psoric, sycotic, syphilitic, tubercular or cancerous origin and/or can stimulate respective B-lymphocytes that can secrete specific antibodies (immunoglobulins) antagonistic to those diseases.

Apart from miasm, in homeopathic literature predisposition of a disease is often called diathesis , which came from ancient medical literature, much earlier to Hahnemann. Miasms were actually broader aspects of diatheses. Each miasm has been subdivided into several diatheses to explain the root cause of hundreds of existing diseases. Like that of miasm the tendency of overflowing of some metabolite and deficiency of others is the actual cause of diatheses. The difference is that in case of the latter the number of metabolites becomes less due to further channeling of the same (not shown in the figure for simplification). All the diatheses have a definite linkage with the known metabolic pathways. Blockage of one or more minute metabolic pathways produces lactic acid, oxalic acid, lithic acid, and uric acid diatheses. The deficiency of any minute sub-cellular enzyme, which is somehow linked with urea cycle in liver, may cause the tendency of excess deposition of urea or uric acid in the body resulting uric acid diathesis. The patients become susceptible to gout, rheumatism, kidney stone, nephritis, and gallstones. Such stones can also be formed by oxalic acid diathesis. The diatheses, as mentioned above, can be detected from blood sample or urine by single test and effectively treated with 'Lycopodium', 'Urea', 'Nitric acid', 'Senna', 'Natrum sulph' etc, if other concomitant symptoms match. Scrofulous, tubercular, hemorrhagic, rachitic, rheumatic, and neurosycotic are the other examples of diatheses, which can easily be detected by clinical test, but as the alteration of metabolites are numerous, and might be endocrinological, hematological, immunological or neurological in origin, therefore, cannot be identified by single trial. The same is true for miasm also. Therefore, more meticulous attempts of chronological recording specific combination of symptoms, even of previous generations are required. According to many the psoric miasm has eruptive-scrofulous (example of remedy: 'Psorinum', 'Alumina' etc.), hemorrhagic (e.g., 'Arnica', 'China' etc.), nervous (e.g., 'Hyoscymus'), and gouty type (e.g., 'Rhus tox', 'Bryonia' etc.) diatheses; sycotic miasm has lithic-uric acid (e.g., 'Natrum sulph'), rheumatic-gouty (e.g., 'Sabina', 'Medorrhinum' etc.) and neurosycotic (e.g., 'Argentum nitricum') type diatheses; syphilitic miasm shows suppurative-ulcerative (e.g., 'Syphilinum'), neurosyphilitic (e.g., 'Aurum met'), and strumous or scrofulous goiter (e.g., 'Plumbum') diatheses. According to Hahnemann's literature tubercular was initially a diathesis. Later it was elevated into the rank of miasm. It can be subdivided into three diatheses: tubercular-scrofulous (e.g., 'Baryta carb'), tubercular-hemorrhagic (e.g., 'tuberculinum'), and rachitic (e.g., 'Calcarea carb'). Therefore, a blockage at 'Sulphur' point would have an impact over all the diatheses, as mentioned above, included under psora miasm, though predominantly it represents irruptive-scrofulous diathesis. Similarly, a blockage at 'Thuja' point would have an effect over all the diatheses, not only belongs to sycosis miasm, but also under psora. Likewise, a blockage at 'Mercury' point would have an impression over all the diatheses under syphilis, sycosis, and psora miasm. A blockage at 'Calcarea Phos' or 'Phosphorus' point can bring an affection not only on tubercular diathesis, but also a faint impression will remain over all the diatheses under syphilis, sycosis, and psora miasm as well. Consequently, the patient affected by the said miasm will have a very low vital activity.

The method of anti-miasmatic treatment, as we have exemplified earlier, the application of 'Sulphur' to the patient caused elimination of 'psora', and the patient got permanent relief by applying 'Bryonia'. After few days, the previously suppressed rashes reappeared over his skin, but disappeared very soon, and gradually he became completely cure. When initially the patient came there were two metabolic blockages, one at 'Bryonia' and another at 'Sulphur' point, causing scanty flow of 1st-3rd terminals and overflow at the 4-th terminal. The symptoms of 'Sulphur' became expressed in a complete form after removing 'Bryonia' blockage (return of the older symptom). The patient could not get permanently well due to constitutional insufficiency of metabolites that flow through the 1st-3rd terminals, therefore the blockage at 'Bryonia' point may reappear like silting of a drying up river. The deficiency symptoms continued to recur so long the 'Sulphur' blockage was not eliminated by the gentle 'hammering' with the said remedy. Nowadays, permanent cure of a patient applying single constitutional remedy is very rare due to the following reasons: (i) Greater number of metabolic blockages so that symptoms do not match with single remedy; (ii) Blockage at the deeper portions of the branching pipelines causing complete drying up of the 'rivers' of essential metabolites, so that symptoms cannot express properly making the selection of the remedy difficult. During Hahnemann's time, it was possible, because the environment was not so much polluted, people were not so much dependent upon allopathic drugs, and their lifestyle including food habits were comparatively simple. Marriage between two patients suffering from different miasm or diatheses generation after generations caused blockage at multiple places of branching water pipe. Whenever more than one diathesis is inherited from paternal and maternal sides, it can produce more complicated disease including cancer. Availability of a patient based on complete symptoms of a particular medicine is very rare nowadays (It was possible in Hahnemann's time). Moreover, the symptoms would not appear in a complete form, like 'Sulphur patient', 'Thuja patient' etc unless we remove the blockages from the terminals of the pipelines by applying acute or short-active remedies like 'Bryonia', 'Belladonna' etc., generally in lower potencies. Removal of all the blockages would require much intuition and take longer time span. Therefore, they should be treated in a systematic manner. The basic protocol for treatment for all the patients should be the same irrespective of nature of the disease. The healing art should always start from outward to inward, i.e., from the terminals, as far as possible, to the origin of the pipelines. Thereafter, if almost all physical and mental symptoms match, the most suitable medicine should be applied in higher potency. The blockage, in the form of suppressed metabolite ('disease force') would flow towards the terminals and hence the old original symptoms would return. This is because, the blockage picture of the pipelines would indicate all the features of initial affection represented by symptoms. After removal of all the blockages the water would begin to flow again through all the pipelines equally. Therefore, the direction of cure is always inward to outward, opposite to the direction of affection. The patient would be certainly cured after few days. Let us take the case of a patient, who is suffering from a small tumor, located at the upper lobe of the left lung. He is chilly, but has a burning sensation prevailing all over his body. The patient is quite intelligent, oversensitive, apathetic or indifferent to his friends. He is quite apprehensive. He has some religious insanity. He is sad and avoids conversation. Music makes him sad. There is no history of cancer in his family. However, his grand father died in whooping cough and asthma, indicating presence of tubercular miasm in his family history. He himself is a patient of high blood pressure (syphilitic miasm). The patient has warts and nodules in his body, also he has some fixed ideas (sycotic miasm). He has once suffered from measles in his childhood (psora miasm). As all the four miasms are present, the physician should choice the constitutional remedy from the deep anti-miasmatic stem comprised of 'Carbo veg', 'Causticum', 'Lachesis', 'Lycopodium', 'Phosphorus', and 'Calcarea Phos', as shown in the diagram. Presently he is suffering from fever with heat and redness of head, with coolness of rest of the body. We would have to find out the correct remedy. Initially, he was treated with 'Arnica'. (Several other remedies would be required, if there are other symptoms due to multiple blockages). After the removal of the blockage he expressed the symptoms of pneumonia with rusty, blood colored sputa. Therefore, the final remedy should surely be 'Phosphorus' in its higher potency, to which most of the physical and mental symptoms would be recovered. Here the symptoms of 'Phosphorus' could not appear in a discrete form before the removal of blockages from the terminals of the pipelines.

Besides science, the theory of miasm has its own philosophy also. The physical ailments related to all the five miasms, as described above, according to many authors, have been transmitted from the mental sphere of the patients as well. As we start our life from single cell, all the successors of the same bear the same 'mind'. As for example, psoric patients are seen to be highly irritable and oversensitive to natural things. Therefore, hypersensitivity of skin reactions, over-secretion of allergic materials is a common feature of their physiology. There is a suppression of emotion, desire, and anger. Hence, most diseases are caused due to suppression of skin reaction, general debility and weakness in digestion. Sycotics have a tendency of concealing facts and excess accumulation of wealth greater than their need, therefore they have a loss of coordination between other members of the society. Analogically, the cells of their body consume nutrients higher than their requirement, do not response to endocrine secretion, and perform poor metabolic function. Syphilitics have an inborn inclination to destruction of self and others. The cells produce more destructive and toxic materials than the normal ones. Their cells have a tendency of secreting hydrolyzing enzymes through lysosome. Eventually, they die at an early age and may cause necrosis in tissue. In appearance, tubercular and cancerous patients show a loss of vitality in their body and mind. Therefore, all the cells of their body suffer from extreme deficiency of vital metabolites, useful or destructive.

During Hahnemann's era, genetics was not developed as a subject, so that the science of miasm was the only alternative of explaining 'familial diseases'. The theory of miasm was a substitute of genetics at that time. From the idea of mixing of more than one affliction together to produce a complicated miasm, it appears that he believed in 'blending mode of inheritance', the commonest theory at that time. Modern genetics believe in 'particulate mode of inheritance' by means of genes or DNA fragments, but it cannot nullify his observation because; most chronic diseases are inherited with a particular combination of symptoms, attributed to a large number of linked genes, often called syndromes that can be compared with his concept of miasm. Secondly, complication of inherited diseases in the subsequent generations is possible by contamination due to pollutants, bacteria, virus, or faulty allopathic treatment. Thirdly, it is often seen that predisposition of disease or diatheses are more or less heritable. Whenever more than one diathesis, are inherited from paternal and maternal sides, can produce more complicated disease including cancer. Hence, the theory of miasm, like that of similia principle, is highly acceptable. o:p>

The difference between 'similia principle' and 'miasm' is out of degree. The latter is the extended version of the former, where more number of minute enzymes or transcription factors are affected. Therefore, it can be rarely treated with single remedy. Hence, the treatment requires systematic application of anti-miasmatic medicines one after another and generally needs a longer time forpermanent curation.

8. Whether the latest trend of medicinal science is purely homeopathic?

Amazed by the sixth sense of Hahnemann about 'contagious principle' regarding homeopathic management for contagious bacterial diseases, some believe that he can justly be called the 'father of Bacteriology', though the role of bacteria on human disease was not revealed then. From the above discussion, we could understand that homeopathic remedies, being very minute in amount, cannot bind, and trigger synthesis of antibody directly, but can stimulate the minute enzymes or receptors directly or indirectly, which in the form of cascade reaction can influence the same by means of transcription factors. Overwhelmed by his modern thought of medicine we cannot desist ourselves in calling him as the 'real father of modern Molecular Medicine'. A true homeopathic doctor like him, though does not necessarily possesses a sound expertise on the said discipline of modern medicine, becomes motivated by the same insight. His idea of treatment was much superior to his contemporary workers; even the entire wisdom of 'Molecular Medicine' along with all its recent progresses is running far behind homeopathy. The latest ideal of the modern medicinal science are: (1) to 'ensure cure by applying least amount of medicine' to avoid side effects, (2) 'drug targeting to the affected tissue' for the safety of unaffected organs, and (3)'individualization of treatment' due to genetic variability among the patients. Hence, there is no doubt that homeopathy is the forerunner of the modern science of medicine, because they are used in minutest quantity, having highly penetrating ability and homeopathy itself is a very much individualized method of treatment from the very beginning. 'Bryonia' can cure fever of one patient according to specific combination of symptoms and 'Rhus tox' of another. Lack of proper penetration ability of the crude drugs to the diseased tissue cells and attenuation of detoxification mechanism of the diseased tissue causes failure of ordinary allopathic drugs, therefore the use of a 'vehicle' that can form a shield against detoxifying agents to guarantee drug delivery to the target tissue was essential. Application of 'vehicle', therefore, became no more a unique heritage of Hahnemann's method, but has gradually became corollary to the drug delivery system of mainstream medicine as well. A number of technological advances have been made in that area leading to the development of sophisticated systems that allow drug penetration, targeting, and ensures sustained release of medicines in a controlled way. These are micelles, liposomes, niosomes, cyclodextrins, prodrugs, vaccine adjuvants, nanoparticles, emulsions etc. Here drug molecules remain attached to different kinds of 'vehicles' (e.g., oils, higher alcohols, phospholipids etc) that ensure its delivery to the target tissues. Micelles, as we have mentioned earlier, are small (4-10 nm), stable spherical droplet like aggregation of about 50-100 amphipathic molecules of fatty acid or higher alcohol, hydrophobic units of which are all hidden in its interior, away from surrounding water, while their hydrophilic polar groups are oriented on the outer surface of the droplet, closely associated with surrounding water molecules. For drug delivery purposes, hydrophobic drugs may be solubilized within the core of the micelle or, alternatively, conjugated to the micelle-forming polymer. Likewise, liposomes were discovered in the mid 1960s and have since gained recognition in the field of drug delivery. The mixture of drug and suspending phospholipid molecules in an aqueous medium is sonicated by high frequency sound to give a dispersion of closed vesicles that are quite uniform in size of about 50 nm in diameter. Antitumor, anticancer and antibacterial agents can be trapped in the aqueous compartment and by this way delivery of drugs to target tissue becomes possible. Such liposomes can be adsorbed onto the cell surface, fused with the cell membrane, and release their contents into the cell cytoplasm, or the drug can enter cell via micro-pinocytosis. Yet due to large size, it is not always effective to penetrate smaller target cells. Most of them are excreted through liver and kidney. To solve the difficulty, tissue specific antibody-coated micelles and liposomes have been introduced to ensure the entry of the minimum quantity poisonous inhibitory substance to the target tissue. As they carry suppressive drug, it may induce resistance in the affected tissue, the efficacy of the same may fall in course. On the other hand, homeopathic medicines though discovered much earlier, has managed to solve all the problems quite unexpectedly, or by the intuition of a genius like Hahnemann in the gentlest way. It uses alcohol as 'vehicle' and due to special orientation of the same, as we have discussed earlier, can act like 'drug-loaded liposome', but being much smaller and speedier than liposome, it can get an easier entry to the target cells, even up to the nucleus. As it does not carry a suppressive drug, but the stimulatory one, minutest quantity of medicine is sufficient enough to arouse vital response. Since the drug itself is the ligand of the target enzyme, therefore coating of the same with a separate ligand (antibody) is not essential to reach the target.

The disease symptoms of human being has become so much diversified and complicated nowadays than Hahnemann's epoch that exactly 'Prover' like symptoms in patients are acquainted very rare, as a result, desirable results are not obtained by applying conventional medicines prepared from natural plant products or other sources. It is possible that introduction of biotechnological tools in homeopathy would do the same more easily with certainty. It would assure cent percent similarity of symptoms between 'Prover' and the patient and assure the treatment of most difficult diseases.

In most of the natural chronic diseases of the modern times, the causative enzyme is minute, unknown and multiple, so that generalized treatment becomes more difficult. Considering the fact that no single enzyme species could be responsible for the disease in all the patients, individualistic method of treatment is gaining importance in modern mainstream medicine. All the chronic patients of a particular disease might not be showing the same kind of deviation in their protein profile and they should be treated individually and not generally. Protein profile test by gel electrophoresis , proteomics , and drug screening are now becoming an indispensable part of modern 'allopathic' treatment for chronic patients. For any kind of chronic disease, as we have mentioned earlier, there is a disproportionate flow of metabolites through different channels: some are excess and overflowing, some are scanty, while the others are normal. Relevant to that the same feature is reflected in their protein profile: some are excess and bears high density (HD), some are scanty and represented by low density (LD) bands (Figure:10, click here to enlarge) , while others are normal. In extreme cases, there is a mutant protein that shows different mobility pattern, and thus alters in band position. Bottom of the slab contains smallest protein factor(s), having highest mobility, either disappears or very scanty. Such a band was marked by arrow. These deficient proteins should be the target of stimulatory method of treatment. However, they are so minute and remain so congested in the gel slab that their identity and density cannot be easily compared with control. The latest biotechnological device, called Molecular Medicine detects the deficiency of beneficial enzyme, as well as over synthesis of deleterious one that is responsible for disease of individual patient by densitometry, after gel electrophoresis, screens out a stimulator (positive modulator) of the former or an inhibitor (negative modulator) of the latter enzyme by autoradiographic method (also called 'photo affinity labeling method') and applies the same compound as a medicine. Being a patient specific approach of treatment like that of homeopathy, it can show salutary effect on several chronic diseases, but at the same time being a suppressive method, it cannot cure a patient permanently. Like any other suppressive technique, the number of drug addicted weak cells gradually increases in tissues, and the patient becomes more and more vulnerable to disease and dependent on medicines. We can remove such difficulty by applying a specialized method. Most possibly, the minutest protein factor(s), deficiency of which is responsible for the disease, having controlling influence over the synthesis of other bulky functional enzymes should be the target of the the drug (actually, ligand-inhibitor of the minute deficient protein). Higher dose application of the same could induce patient-like symptoms in healthy persons ('provers'). If the same is stimulated by slow but minute application of the inhibitor, there might be chance of cure. Screening out of the ligand of the minutest deficient protein and stimulating the same is not an easy task as mentioned above. Firstly, there is a chance of cross-reaction between the minute drug ingredient and other bulky protein molecules present in the patient's body. Secondly, such an experiment cannot be supported on ethical ground, because each patient would require an individual 'Prover'. Fresh trial with several radioactive probes, which are very costly and should be restricted in use, would be essential for each patient. Thirdly, to sort out the deficient enzyme from thousands of minute overlapping bands is next to impossible. Lastly, those minute protein factors generally remain protected within the innermost compartment of the cell, covered by selectively permeable endomembrane system; the crude drug might not be penetrating enough to reach there.

Theoretically, if a layman applies homeopathic medicine one after another to a patient by trial and error method there is a little chance of recovery, but an experienced doctor can find out the suitable remedy with single effort by comparing patient's symptoms with medicinal symptoms. Likewise, if we hypothetically use radio-labeled probe one after another for each patient to ensure its binding with the target enzyme it would be much laborious. In order to solve the above problems and for large-scale application of treatment for a huge number of patients, suffering from different chronic diseases, a standard experimental protocol similar to Western Blotting has been suggested by Chattopadhyay (Chattopadhyay, 2002) applying two dimensional gel electrophoresis (for the better resolution of protein bands as spots) on the tissues of normal healthy persons and measuring their normal protein content in terms of density. Binding of different drug ingredients to the spots and competitive replacement of one successful probe with a better one would be detected by autoradiographic method (Figure:11, click here to enlarge). Suppose, two spots could glow by the application of radio labeled drug ingredient I-1 (e.g., radio labeled form of Strychnine, the alkaloid of 'Nux vomica') then the same should be eluted away by non-labeled I-1. The plate would appear dark. Suppose, application of I-2 could not resume glowing of the former spots, but the blaze appeared in two new points and again it was vanished by the application of non-labeled I-2. After the application of labeled I-3, the blush at the initial point (arrow) would restore (due to replacement of non-labeled I-1 by labeled I-3). The spot was seen along with two new specks, which would be replaced later by other more efficient ligands. Ultimately, all the spots would be identified based on binding of the best ligands (I-1 to I-8) as an integrated autoradiograph. Hence, there would be no cross reaction possible with other proteins while using the ingredients as medicines. Suppose, a chronic patient came with deficient spots, indicated by low density (LD) in I-1 and I-2 locations, as shown in the figure. Mixture of those drugs, in non-labeled form, potentized several times with plentiful ethanol might be applied to him as 'individualized medicine' (Chattopadhyay, 2002) . It does not go against homeopathic philosophy, because majority of medicines introduced by Hahnemann himself were mixture of two or more drug ingredients, as for example, 'Nux vomica' contains mainly two alkaloids, strychnine, and brucine. 'Chelidonium' contains five alkaloids sanguinarine, chelidonine, chelerythrine, berberine, and coptisisine as well. Applying the same to healthy individuals, the 'proving symptoms' were recorded by Hahnemann and his followers. However, the induced symptoms of single ingredient were hardly noticed. Hence, the application of single ingredient medicine in homeopathy is very limited. In the proposed method, based on biotechnology, such a condition would never arise because no 'Prover' would be essential. As we have dearth of knowledge regarding the rate of synthesis of minute enzymes or transcription factors depending upon variable environmental factors in healthy individuals, both control and diseased tissues should be cultured for few generations in standard nutrient medium before electrophoresis. In choosing medicine ingredients, emphasis should be given to them that can bind lower molecular weight proteins that are present within the nucleus. This is because they are most possibly the upstream protein factors having influence over few other dependent ones, having higher molecular weight. Excess or less secreting functional proteins thus can be rectified. Ligands of larger molecular weight proteins that are generally present in the periphery of the cells in bulky amount should not be taken into account in selecting medicines. This is because, stimulation of the minute proteins that have controlling influence over those will certainly rectify the dependent ones (Chattopadhyay, 2002) . It would check overflow of some metabolites as well as would compensate the scanty flow of others (Chattopadhyay, 2002) .

There are some indirect evidences both in protein profile and gene expression profile in support of the proposed hypothetical method, especially in the viewpoint of cancer cell treatment by homeopathic drugs. Endless survival and proliferation potential of tumor or cancer cells is actually caused by deficiency or inactivation of its cell cycle regulatory protein cyclin -dependent kinase (CDK) inhibitors p27 . Consequently, it seems logical that up-regulation of CDK inhibitors would activate the regulation mechanisms and control survival and proliferation in cancer cells (Roy et al, 2009) . Chemo-preventive agents have also been described as having similar effects on the regulation of CDK inhibitors to induce pro-apoptotic response (Singh and Agarwal, 2006) . The ultra-diluted natural homeopathic remedies were found preventive and or therapeutic agents for breast cancer and worthy of further study. Frenkel et al (Frenkel et al, 2010) conducted an in vitro study to determine whether products prescribed by a famous family of homeopathic doctors in Kolkata, India have any effect on breast cancer cell lines. They studied four ultra-diluted remedies ('Carcinosin', 'Phytolacca', 'Conium' and 'Thuja') against two human breast cancer cell lines and a cell line derived from immortalized normal human mammary epithelial cells. The remedies exerted preferential cytotoxic effects against the two breast cancer cell lines (Frenkel et al, 2010) , causing cell cycle delay or arrest and apoptosis of the cancer cells. These effects were accompanied by altered expression of the cell cycle regulatory proteins, including down-regulation of phosphorylated Retinoblastoma ( Rb ) protein and up-regulation of the CDK inhibitor p27 protein, which were likely responsible for the cell cycle delay (or arrest) as well as induction of the apoptotic cascade. Both were manifested in the activation of caspase 7, an apoptosis-associated protein, and cleavage of poly (ADP-ribose) polymerase (PARP), another apoptosis-associated protein, in the homeopathic medicine-treated cells employing Western Blotting technique (Frenkel et al, 2010) . Methylation-specific epigenetic process and gene expression profiles of HeLa cells treated with ultra-high dilutions of two plant extracts, 'Hydrastis canadensis' 30C and 'Marsdenia condurango' 30C, were analyzed against placebo 30C (Saha et al, 2015) as control for alterations in gene profiles linked to epigenetic modifications. Methylation-specific restriction enzyme assay elucidated differential epigenetic modifications in drug-treated and control cells, as evident by microarray gene expression profiles of many genes associated with carcinogenesis in HeLa cells in vitro. In all cases the probable explanation is the same: minute amount of medicinal molecules enveloped with tightly packed solvent get an easy entry inside cell and modulate the binding of activator or repressor with operator of DNA molecules, so that the synthesis rate of mRNA alters and expression of genes increased for a stipulated period, which brings the symptoms in Provers and when applied in minute dose slightly aggravates and ultimately cures the patients, suffering from similar ailments.

9. What is the future of 'Neohahnemannism'?

The theory of 'Neohahnemannism' that we have discussed in the text puts forward with experimental evidences the view that if serial dilutions are made strictly following Hahnemann's dictum, faint traces of drug molecule remains even in infinitesimally diluted solution. He realized that it is possible in freshly prepared medicines with limited application, but is very difficult in industrially prepared large scale ones. We came to know from the text that the drug molecules are tightly packed with water and ethanol molecules, so that they can reach up to the nucleus and thereby influence minute protein factors, which are deficient or inactive (down-regulated) to arouse physiological stress. Therefore, overdose of the medicine becomes inhibitory (in case of 'Provers') and minute dose becomes stimulatory (as in patients). If the medicine is wrongly selected and repeatedly administered to the patient, medicinal symptoms (like that of 'Provers') may appear without any sign of cure. As directed by Hahnemann, 'Proving' experiments with new and new drugs are essential. Nowadays, there are some legal and ethical restrictions to introduce human beings as 'Provers'. Hence, the discovery of new medicines, which would perfectly match to the patient's individualistic symptoms as well as pathological complaints became difficult. Even we do not have the complete knowledge about all the minute protein factors regarding their physiological functions, abundance period, environmental effect, potential binding affinity with medicinal substances, and minute toxicological responses of the same upon human beings, so that, we cannot artificially induce patient-like symptoms in healthy individuals. Therefore, the development of modern scientific philosophy like 'Neohahnemannism' is essential. The proposed model would neither require endless proving experiments upon the healthy subjects, nor any subjective knowledge about the protein profile of the patient. Only the binding and optimal inhibition of the minutest protein factors, which are deficient, would automatically correspond to Hahnemann's concept of 'Similimum', ultimately resulting constitutional change of the patient towards the direction of cure. We expect that a suitable and highly sensitive biotechnological tool based on the philosophy of the proposed model would soon be devised, which would be helpful enough to eradicate diabetes, hypertension, cancer and AIDS forever in an individualistic way (irrespective of names of the diseases). Although, the estimated cost of the series of experiments with radio-labeled probes, as mentioned here, might be almost equal or even higher than Human Genome Project . However, being a heuristic approach of medicine, the research works of 'Neohahnemannism', similar to immunotherapy, will continue year after years with the discovery of newer medicines, tailor-made to each particular individuals, whose efficacy would never fade away like the generations of allopathic drugs in saving human lives.

10. References

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Dedicated to my beloved mother who died recently in cancer