Homeopathy : Memory of Water

Water Structure and Science

This page forms the entrance to a website concerned with the physical, chemical and biological properties of water.

Liquid water is not a bit player in the theatre of life — it’s the headline act

Water structure = H2O

Many regard water (H2O) as a rather uninteresting substance because it is transparent, odorless, tasteless and ubiquitous. It is the simplest compound of the two most common reactive elements in the universe, consisting of just two hydrogen atoms attached to a single oxygen atom. Indeed, very few molecules are smaller or lighter. Liquid water, however, is the most extraordinary material contradicting its apparently simple molecular constituent. ⇒

Although we drink it, wash, fish and swim in it, and cook with it (although probably not all at the same time), we nearly always overlook the special relationship it has with our lives. Droughts cause famines and floods cause death and disease. It makes up over about half of us and, without it, we die within a few days. Liquid water has importance as a solvent, a solute, a reactant, a catalyst, and a biomolecule, structuring proteins, nucleic acid, and cells and controlling our consciousness. H2O is the second most common molecule in the Universe (behind hydrogen, H2), the most abundant solid material and fundamental to star formation. There is a hundred times as many water molecules in our bodies than the sum of all the other molecules put together, with billions of water molecules per DNA molecule. Life cannot evolve or continue without liquid water, which is why there is so much excitement about finding it on Mars and other planets and moons. It is unsurprising that water plays a central role in many of the World's Religions. This website discusses many aspects of water science. ⇒

Water is the most studied material on Earth, but it is remarkable to find that the science behind its behavior and function are so poorly understood (or even ignored), not only by people in general but also by scientists working with it every day. It can be extremely slippery and extremely sticky at the same time, and this 'stick/slip' behavior is how we recognize the feel of water. The small size of its molecule belies the complexity of its actions and its unique capabilities. Many attempts to model water as a simple substance have failed and still are failing. Liquid water's unique properties and chameleonic nature seem to fit ideally into the requirements for life as can no other molecule. ⇒

Many explanations of the complex behavior of liquid water have been published, with several stirring up considerable controversy. In this website, I have attempted to present and explain these ideas in a self-consistent and balanced manner, which I hope will encourage both its understanding and further work. ⇒

Notes.

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Homeopathy

"The greatest enemy of knowledge is not ignorance, it is the illusion of knowledge" ~Stephen Hawking

 

 

What is homeopathy?

Homeopathy is a branch of alternative medicine, b, i created in 1796 by the disillusioned doctor Samuel Hahnemann, that is based on the surmise that an individual may be treated using minute doses d of natural materials which in larger doses would be expected to cause the same symptoms (the 'like cures like' principle). h Remedies start with such a natural material that is diluted and then subjected to a sequence of further dilutions in purified water or aqueous ethanol with considerable agitation (called succussion, see below) between dilution steps. Each dilution (as shown) results in about a 100-fold dilution and many cycles (e.g., 20, 50, 200) are performed before the remedy is used. a, g

The initial popularity of homeopathy was partially due to the unhygienic crudeness of medical procedures in the 19th century, such as bloodletting. However, 200 years later, homeopathy is still gaining popularity even if its efficacy is often disputed. The cornerstone of homeopathy that the whole clinical picture is considered, on an individual basis with generally lengthy consultations, is not in dispute. In fact, consideration of the 'whole' person is becoming more important as information concerning an individual's genome becomes clearer. However, criticism is leveled at homeopathic 'drugs', particularly as it appears to be 'just water'. Belief in whether or not dilution and shaking can have any effect on the health benefits of water (for an overview of homeopathy see for example, [484a], for a review of homeopathy research see [484b] and for a recent debate concerning Homeopathy see [1363]) depends on the presence of an acceptable working hypothesis for the mode of action (see also magnetic effects) of such shaken and overly diluted material. Certainly, a confounding aspect of any examination of the efficacy of homeopathic treatments seems to be the highly variable nature of supposedly similar homeopathic remedies from different manufacturing sources. [Back to Top to top of page]

Published evidence

In spite of many (most?) people knowing of success stories (and the opposite) concerning the use of homeopathy where it is practiced [120], scientists have difficulty in regarding this form of alternative medicine as any more than a placebo effect. e Analysis of the literature has shown that their is little difference on average between the homeopathic effects and those of a placebo [3743]. This, however does not prove that the two effects are identical in any, or all, cases. The ‘memory of water’ is a popular phrase that is mostly associated with homeopathy [1211] following his and others’ allergy research work [132]. These research teams reported that solutes subjected to sequential physical processing and dilution show biological effects different from those apparent using just the water employed for the dilutions. The subject has drawn much controversy with many 'scientists' simply rejecting it outright without studying the evidence; this 'confirmation bias' is a well-established phenomenon where evidence that supports pre-existing beliefs is readily accepted whereas evidence that undermines pre-existing beliefs is readily discarded. Whether or not this work is correctly interpreted, the value of homeopathy depends on whether it can treat ailments not on whether water has 'memory'. 

Meta-analysis of 89 placebo-controlled trials failed to prove either that homeopathy was efficacious for any single clinical condition or that its positive clinical effects could entirely be due to a placebo effect [121a], thus leaving the scientific door open both ways. Further analysis of this data, however, indicated that some of these studies may have failed to avoid bias and that studies using better methodology yielded the less favorable effects [121b]. A recent analytical review has reinforced the, more negative, view concerning the clinical effectiveness of homeopathic remedies [527]. Further, a recent quality assessment of published experiments on homeopathic preparations has concluded that many were performed with inadequate controls [651]. Although a scientific trial of homeopathy conducted for the BBC and similar work reported on ABC News' 20/20 program both failed to show any homeopathic effect, the experiments they reported have been subject to serious criticism including that of careless scientific methodology and faulty protocols.

In August 2005 [840], the medical journal 'The Lancet' controversially argued for halting any further research into homeopathy concluding it has no effect other than as a placebo. This judgment was based on its simultaneous publication of a comparative study of 110 matched placebo-controlled trials of homeopathy and conventional medicine [841]. The conclusion was reached, however, in spite of the study apparently showing little evidence of differences between the two groups (homeopathy and conventional) when all the data was considered.cherry picking, from Benjamint444  There were differences when a tiny percentage of unmatched larger trials were cherry-picked for further analysis (that is, 102/110 of the homeopathy studies and 104/110 of the conventional studies were discarded, even though these studies had been carefully chosen in the planning of the study using a priori inclusion and exclusion criteria). c The remaining 6% of the studies, however, still showed positive (if not conclusive, possibly as the number of trials left in this final grouping was so small and unmatched) evidence in favor of a homeopathic effect over placebo. The more negative nature of the eight chosen homeopathy papers was mainly influenced by one single trial. Although Shang's study [841] has come in for considerable and rightful criticism, and there is a strong case for its retraction, as above and [1381, 1382, [1524], it is often put forward in support of the view that homeopathy works no better than as a placebo; a fact that it clearly does not deliver. Other journals play fast and loose with homeopathy research; for example, PLoSONE retracted, for no good reason, an original research article, published in 2016, which described the effects of homeopathic Arnica montana on interleukin-4 treated human macrophages [3712].

There have been several quality studies that support the effectiveness of homeopathy. In one, thirty doctors at six clinical sites in four countries enrolled patients with acute respiratory problems. 281 patients were treated with homeopathy and 175 patients treated by conventional medicine, both with mostly 5-15 minutes consultation times. After 14 days, 83 % of the homeopathy-treated reported a positive response compared with 68% of the conventionally-treated, with 22% of conventionally-treated reporting adverse events compared with 8 % for the homeopathy-treated [2450].

An independent report commissioned by the Swiss health authorities [2457], concluded in 2011, “There is sufficient evidence for the preclinical effectiveness and the clinical efficacy of homeopathy and for its safety and economy compared with conventional treatment.” However, a 2013 review concluded that “There is a paucity of good - quality studies of sufficient size that examine the effectiveness of homeopathy as a treatment for any clinical condition in humans”, there remains questions over the clinical effectiveness of homeopathy with neither proof for nor proof against being conclusively proven. Nevertheless, a 2014 systematic review of randomized placebo-controlled trials of individualized homeopathic treatments concluded that they might have small, specific treatment effects [2276].

Homeopathy is possibly effective in Attention Deficit Hyperactivity Disorder (ADHD). Using a small study involving twenty children age 5-16 followed by ten 'controls' treated similarly but without the 'homeopathic substance', the intervention was associated with improvements in

criminality and anger [2910]. It has been shown that ultra-highly diluted homeopathic remedies have demonstrable anti-viral effects [3487].

Some of the most convincing evidence promoted in favor of homeopathy has been its use with animals. It is challenging to propose how animal studies can show any placebo effect, especially if the study is double-blinded. For example, the homeopathic preparation from the Cocculus indicus plant (cocc 30c) has been demonstrated, in a randomized double-blinded trial, to ameliorate the effects of sleep deprivation in rats [2374]. However, systematic reviews of homeopathy used in veterinary conditions studied by randomized trials have been published with the conclusion that although there is some very limited evidence that such clinical intervention is distinguishable from placebo, evidence concerning the effective use of homeopathy in animals remains indecisive [2447]. A comprehensive literature review of the peer-reviewed literature into the efficacy of homeopathy in replacing the use of antibiotics in cattle, pigs, and poultry has been completed [2826]. From 52 trials performed within 48 publications fulfilling the predefined criteria. 28 trials were in favor of homeopathy, with 26 trials showing a significantly higher efficacy in comparison to a control group, whereas 22 showed no therapeutic effect. Cure rates for the treatments with antibiotics, homeopathy or placebo varied to a high degree, while the remedy used did not seem to make a big difference with homeopathy being sometimes more effective than antimicrobials and sometimes vice versa. However, it was noted that no trial was repeated in a comparable manner and so the efficacy of homeopathy remained unproven [2216]. Although the use of homeopathic immunisation in Cuba against leptospirosis was not a controlled clinical study, the interventions occurred in response to an actual need to save lives. They were not randomised because the interventions were offered to all residents of the targeted communities, A total of 2.2 million residents were given two doses of a highly diluted preparation which gave a level of immunisation comparable to that of vaccine but at much lower cost [3747].

Recent claims to show that homeopathic treatment can ease pain in rats [3442] are somewhat invalidated by the lack of care in the experimental procedures, the paper's poor preparation, and the small sample size [3443]. The publication of such fault-ridden papers does not help the public's perceptions of homeopathy, nor the science behind homeopathy.

The (Australian) National Health and Medical Research Council (NHMRC) has assessed the evidence of the effectiveness of homeopathy [3282a] in a report that has subsequently been very influential in arguing against the effectiveness of homeopathy, particularly in America, France, Great Britain and Australia. This 'information paoer' was not published in a peer-reviewed journal but concluded that there are no health conditions for which there is reliable evidence that homeopathy is effective. However, the report was biased and the authors cherry-picked the evidence used. cherry picking, from Benjamint444 Somewhat surprisingly, it had no homeopathic experts on their 'panel of experts' (in contrast to NHMRC's own guidelines) and was chaired by a member of an anti-homeopathy lobby group. This report has been subject to a commentary [3282b], significant criticism [3282c] and after a worldwide campaign, the Australian National Health & Medical Research Council (NHMRC) has been forced to admit that it did the study twice and to release its original version (2012; The effectiveness of Homeopathy: An overview review of secondary science, prepared by the International Centre for Allied Health Evidence, University of South Australia; available in a subsequently annotated version here). The existence of this report was never disclosed to the public, and the repressed knowledge of it being produced has only just (September 2019) been revealed through Freedom of Information (FOI) requests. This 2012 report says that "there is encouraging evidence for the effectiveness of homeopathy for" several conditions. By subsequent later cherry-picking many original studies were excluded using latterly invented criteria seemingly chosen, and different from those criteria originally planned, to unscientifically discount the many homeopathy-positive studies (>97% of the chosen studies were discounted).

A bioassay for homeopathic solutions has been developed in a plant systen (duckweed) that has shown itself to be reproducible in randomised blinded trials [3746].

The ad hominem dismissal of homeopathy by many in the medical professions is promulgated by the off-hand attitude of the medical teaching staff without the time for a proper examination of the evidence. Certainly the efforts to which studies have been repressed and altered to discount homeopathy seems to me to be indications of a truth. The debate continues, with an excellent overview of this area [2449] concluding 'Plausibility bias has introduced more heat than light into the debate around homeopathy: it has fired the debate without illuminating its information content. We do not deny that homeopathy raises major scientific issues, but we remain convinced that these will eventually be resolved by application of authentic scientific method, especially in the context of further in vitro experiments'

Homeopathic solutions

Homeopathic solutions are not the same as pure water, nor are they the same as conventional dilutions. The homeopathic dilution/dynamization process causes the differences [3710, 3711]. A thorough investigation into the structural differences previously reported between homeopathically potentized (that is, succussed and extremely diluted) and unpotentized nitric acid solutions showed that the effect was lost or changed if different glassware was used [495]. Changes in the thermoluminescence of ice produced from ultra-diluted water have been noted [500 a] but can be explained by remaining trace amounts of material (due to poor mixing, impurities, absorption, nanobubbles (that is, nanocavities) [500d] or other causes) being concentrated between ice crystals [500b]; an explanation supported by later work [500c]. A series of papers from Academician Konovalov has proposed that physical and biological effects of highly diluted aqueous solutions differ from those expected from simple dilution and may be due to the formation of nano-sized (up to 400 nm) molecular assemblies [2207]. There is also the possibility that more diluted samples may be more active due to different hydration status [3707]. k Also, maxima in the biological activity at very diluted concentrations (≈ 10-15 - 10-18 M), below measurable concentrations, have been widely reported [2232]. It has been shown that surface active nanoparticles may be formed during the early succussion/dilution steps. As they concentrate in the solution-air interface, they are not diluted as expected and may still be present in solutions even diluted by factors of 10400 far greater than the Avogadro limit (1023) [2375]. Thus it is probable that nanoparticles remain in homeopathic dilutions and possible that even such low concentrations have biological effects. 

Changes in the NMR relaxation times [1620a, 1620c], thermochemistry [1644] and UV absorption [1620b] of water have been reported in some homeopathic preparations. There is now evidence from (blinded) NMR of a clear memory effect upon dilution/potentization of different substances (water, lactose, copper, gelsemium) as determined by 1 H spin-lattice T1 and spin-spin T2 relaxation time and average H/H distances [3055]. These experiments showed a considerable slowing down of molecular movements around water molecules up to a distance of 0.37 nm. This reinforced the evidence that homeopathic solutions cannot be considered as pure water and that there is a clear memory effect upon potentization.

Solvatochromic dyes allow intramolecular charge transfer, such as (4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl]phenolate shown below. (4-[(E)-2-(1-methylpyridinium-4-yl)ethenyl]phenolate It has been demonstrated that homeopathic solutions influence the supramolecular chemistry of such solvatochromic dyes, enhancing either dye aggregation or dis-aggregation, depending upon the dye structure. Comparable dyes lacking charge transfer are unaffected by homeopathic potencies, suggesting potencies require the oscillating dipole of solvatochromic dyes for effective interaction [2911]. 

A systematic assessment of the in vitro research on high potency effects has shown positive, if only partially reproducible, effects [2238]. This may indicate a stochastic influence similar to that occurring in the (now accepted) Mpemba effect. 

A key feature of any difference between water before and after its use in preparing homeopathic dilutions is likely to be the vigorous shaking (succussion) that must be carried out between successive dilutions. This may produce significantly increased concentrations of silicate, sodium and bicarbonate ions [335, 1207] by dissolution of the glass tubes a. Also, the shaking increases the nanobubbles, and changes their size [1771], and increases the redox molecules [1066, 1751] from the atmosphere. The amount of succussion has been proven to have a significant influence on treatment effectiveness [2983]. Nanobubbles may be insignificant due to their extremely high surface area/volume ratio as it is well known that organic molecules prefer to lie at aqueous interfaces [1889] allowing such solutions to absorb greater amounts of organics from the laboratory atmosphere. Indeed, there is now a body of evidence that diluted salt solutions containing nanobubbles, formed by vigorous stirring, can have clinical effects on immunological diseases [2002] and can promote growth in plants [2014] and animals [2015]. Some molecules (e.g., detergents) preferentially partition at interfaces by many orders of magnitude. Recently, a paper from Nobel prize-winning Luc Montagnier has declared that quite dilute solutions (of DNA) show entirely different properties from the less diluted solutions. The authors propose that these differences are determined by interactions with the ambient electromagnetic field [1602]. f How water may show memory is explored further in the 'memory of water' page.

Does homeopathy work?

Many ridicule homeopathy out of serious consideration as a clinical practice, sometimes resorting to unscientific, unbalanced and unrefereed editorial diatribe. One of the main reasons concerning this disbelief in the efficacy of homeopathy lies in the difficulty in understanding how it might work [2065]. If an acceptable theory were available, then more people would consider it more seriously. However, it is difficult, at present, to sustain an argument as to why a truly infinitely diluted aqueous solution, consisting of just H2O molecules, should retain any difference from any other such solution. It is even more difficult to put forward a working hypothesis as to how small quantities of such 'solutions' can act to elicit a specific response when confronted with large amounts of complex solutions in a patient. A major problem in this area is that, without a testable hypothesis for the generally acknowledged potency of homeopathy (except, perhaps, flawed dilution assumptions [2375]), there is a growing possibility of others making fraudulent claims in related areas. Perhaps this is evidenced by the increasing use of the internet to advertise 'healthy' water concentrates using dubious (sometimes published but irreproducible) scientific and spiritual evidence. [Back to Top to top of page]

Footnotes

a Note that 'memory of water' effects (if proven) not only require the solution to retain information on dilution but clearly require this information to be amplified to negate the effect of the dilution. [Back]

b Homeopathy is one of a wide range of historical health-care practices like traditional Chinese medicine, acupuncture, yoga, faith healing, chiropractic manipulation, aromatherapy, massage, hypnotherapy and folk medicines such as ginseng. Although there is much testimonial evidence supporting the efficacy of each of these practices, they all remain contentious due to lack of sufficient scientifically-rigorous proof. [Back]

c The 'cherry-picking' is clear although a rationale for some sort of selection is presented post hoc. This analysis suffered from HARKing (Hypothesizing After Results are Known) (N. L. Kerr, HARKing: Hypothesizing After the Results are Known. Personality and Social Psychology Review, 2 (1998) 196-217). The study does not appear to have used a pre-determined rationale, or pre-determined parameters, in discarding trials. It completes no sensitivity analysis and ends up 'dredging' the data in an unbalanced manner, to falsify the conclusions [1524]. Further analysis of the data, provided post-publication, shows that the conclusions would have been different for almost all alternative cut-off points [1524]; that is, they would not support the conclusions that homeopathy is no more than a placebo effect or that homeopathy trials are less competent than conventional trials. [Back] 

d This 'dilution' is usually so extreme that no molecules of the starting material are expected to be found in the final 'solution'. In spite of this, the efficacy (and cost) of the homeopathic remedies are often thought to be greater, the greater the dilution. [Back]

 

e The placebo effect. A placebo is an inert substance or treatment which is designed to have no therapeutic value. However after taking such a placebo in place of a medication, belief that one has taken the medication itself can produce some of the effects of that medication. The placebo effect in drug trials has been reviewed [3744]. It should be noted that placebo (from the Latin 'I will do good') effects constitute real clinical effects [121c] even though they contain just Placebo tabletsfiller, such as lactose, and no active ingredients. They are widely used as control medication in medical trials. Placebos should be judged positively and probably account for a significant proportion of the success of prevailing established medicine [1474]. They may act primarily by relieving anxiety. Curiously, placebos have a greater effect in trials that do not inform patients about the possible placebo intervention, unless the placebo is presented in a positive manner. The cheerfulness and interest of the doctor in the patient also increase the placebo's effectiveness. Additionally, there must be a range of 'placebo effects' of different potencies and having different effects in different situations. As such, they surely overlap with true clinical effects. As an example, it seems clear that antidepressant medications used for many years are not efficacious and any perceived difference from placebo is due to the reduced responsiveness to placebo in the severely depressed [1455]. Placebos work in certain situations. It has been shown in a randomized-controlled trial that open-label placebos reduce test anxiety and improve self-management skills [3748].

Placebos are used in clinical trials where the object is to minimize their effect relative to the therapeutic agent. However when the therapeutic agent is subsequently used, the object is to maximize any additional placebo effect. This introduces some conflict.

It should be noted that many modern medications have no effect in most people; for example, statins, commonly used to lower cholesterol, benefit only 1 in 50 and esomeprazole only benefits 1 in 25 heartburn sufferers. Antidepressants are reported to act through a placebo effect rather than that they contain active ingredients [3744]. It seems strange to this writer that so many of those that dispute homeopathy's efficacy, saying without proof that they believe there is nothing there, are quite happy to accept that there exists a 'placebo' effect where it is known absolutely that there is nothing there. [Back]

f The extraordinary results given in this paper have yet to be independently confirmed. [Back]

g Another dilution method utilizes a clean glass vessel for each dilution step with each step involving a 10-fold dilution. [Back]

h An example is the common onion (Allium cepa), well known to cause stinging of the eyes and as a cause of tears to form. Because of this and the 'like cures like' homeopathic principle, it is thought of as a treatment for the common cold and hay fever when used at a wide range of homeopathic dilutions between 103 - 10400 fold.

 Arnica montana L

Another example is mountain arnica (Arnica montana, Leopard's bane), a daisy-like mountain flower (see right). By itself, it can cause skin irritation and can be fatal if eaten. Because of this and the 'like cures like' homeopathic principle, it is thought of as a treatment for bruising and muscle pain, often by athletes. Typically, medium dilutions of between 1012 - 1060 are used as tablets or in creams 

Arsenic poisoning causes severe vomiting and diarrhea. Because of this and the 'like cures like' homeopathic principle, it is thought of as a treatment for gastroenteritis and food poisoning. The homeopathic derivative (Arsenicum album) is used at a wide range of dilutions between 103 - 10400 fold. [Back]

i Some supposedly scientific sites concerning homeopathy are governed by negligent irrational dogmatists. For example, Wikipedia states explicitly that it encourages mention of studies that show that homeopathy does not work and also states that it does not allow mention of any peer-reviewed published double-blind studies that show homeopathy works. Many authors have been hounded off Wikipedia pages for trying to present a balanced view. On this site, I look carefully at the evidence. [Back]

k This researcher is reminded of a moderately concentrated (~0.1%) solution of human follicle stimulated hormone showing little effect in a biological assay whereas when it was much diluted the specific biological activity was extremely high. [Back]

 

 

 

Memory of Water

Can water have a 'memory' of its previous solutes, environment or processing.?

V Does water have memory?

V Is water special?

V Does the glassware matter?

V Is gas important?

V Does dilution happen as predicted?

V Solutions are more complex than expected

V Peroxide and radical production in water

V Possible scenarios for the memory effect in homeopathic solutions

 

"Maybe I should have thrown the data away"   ~Jacques Benveniste, 1935-2004

but being a serious scientist and believing in his data he could not 

All systems may retain a memory of their previous treatment, whether this is due to the formation of stable contamination, or to the production of energetic heterogeneities. It has been shown that the physical properties not only depends on the initial temperature but also on kurtosis [3112]; the distribution of the particles' kinetic energies from the mean value, a property that may depend on its past history. It should not be surprising that water also may retain a memory of its past history

Does water have memory?

The ‘memory of water’ is a popular phrase that is mostly associated with homeopathy and the charismatic Jacques Benveniste (see left) [1211] following his and others’ allergy research work [132]. At the time Benveniste was a leading French immunologist who headed a large INSERM laboratory, directed at immunology, allergy and inflammation research. j He reported that when white blood cells with a certain substance on their surfaces are exposed to a certain antibody, they release histamine in a manner that can be visibly monitored using a microscope. This work generated a controversial but 'in good faith' paper reviewed and published by Nature, [132] after referees could find no flaws with the experimental procedure and they had held up publication for two years while awaiting independent confirmation from impartial laboratories in Israel, Italy, and Canada. These research teams reported that even if the amount of that antibody was subjected to sequential physical processing and was apparently diluted many billions of times, until there was essentially none left, it still had an observable biological effect different from those apparent using just the water employed for the dilutions (the 'memory of water' [1112]) a. The subject has drawn much controversy with many 'scientists' simply rejecting it outright without studying the evidence. Also, it has not been more generally accepted after the results were reported by Nature, as not reproducible by Nature's self-acknowledged biased observers (the Editor of Nature, a magician (!) and a malpractice investigator, none of whom had any relevant scientific experience). k and under oppressive, overly-demanding (with over twice the normal weekly load of tests) and unsympathetic, conditions, in a limited and rushed 5-day trial (of 5 years and 5 laboratories work) using poorly responsive basophils, and with negative results from only the one laboratory being cherry-picked from amongst otherwise positive results [133]. The original results [132] were, however, confirmed in a blinded study by the statistician Alfred Spira [346e] and also in a rather bizarre Nature, paper purporting to prove the opposite [346b], i They were subsequently comprehensively confirmed by a blinded multi-center trial [346a], and new results confirm similar phenomena [1585]. In spite of this apparent confirmation by these several laboratories, there are still doubts (expressed by some) over whether the experiments are truly reproducible and whether the noted effects may be due to the origin of the biological samples or human operator effects [1362]. Further support for an effect has been found using NMR [1552]. It is important to note that even if Benveniste's experiments were simply false positives, no conclusions can be drawn over the efficacy of homeopathy. Many negligent critics of homeopathy have ignored this logic.

The 'Memory of water' area was the subject of several peer-reviewed papers in the journal Homeopathy (July 2007), c and the field has been over-viewed [1206]. Although there is much support for water showing properties that depend on its prior processing (that is, water having a memory effect), the experimental evidence indicates that such changes are due primarily to solute and surface changes occurring during this processing. The empirical evidence for specific changes in the physicochemical properties of homeopathic preparations  has been reviewed, concluding that there is evidence for specific physicochemical changes in the homeopathic preparations [3711]. Certainly, simply stirring a solution may have pronounced effects on the vessel's surface charge and chemistry which can last for several minutes after the stirring has ceased [2138]. Another memory scenario concerns individual O:H–O hydrogen bond possessing memory of their physical temperature and pressure history that lasts over periods of minutes [2227]. This hypothesis, although well published in peer-reviewed journals, needs further substantiation. There is evidence from (blinded) NMR of a clear memory effect upon dilution/potentization of different substances (water, lactose, copper, gelsemium) as determined by 1 H spin-lattice T1 and spin-spin T2 relaxation time and average H/H distances [3055]. The experimentally corroborated memory phenomena cannot be taken as supporting the basic tenets of homeopathy although they can explain some effects [1206]. [Back to Top to top of page]

Is water special?

The main evidence against water having a memory is that of the very short (≈ ps) lifetime of hydrogen bonds between the water molecules [1209]. Clearly, in the absence of other materials or surfaces (see later), the specific hydrogen bonding pattern surrounding a solute does not persist when the solute is removed any more than would a cluster around any specified water molecule, or else water would not know which of its myriad past solutes took preference. Indeed the atoms that make up the water molecule only remain together for about a millisecond in liquid water due to proton exchange (see water dissociation). A recent NMR study shows no stable (>1 ms, >5 μM) water clusters are found in homeopathic preparations [712]. It should, however, be noted that the lifetime of hydrogen bonds does not control the lifetime of clusters in the same way that a sea wave may cross an ocean, remaining as a wave and with dependence on its history, but with its molecular content continuously changing. a Also, the equilibrium concentration of any clusters are governed by thermodynamics not kinetics.

Microwave irradiation gives rise to a memory effect on the surface tension of water that lasts for minutes after the effect of temperature rise alone has ended [2208]. An extraordinary paper authored by Nobel prize-winning Luc Montagnier has described memory effects in aqueous DNA solutions that the authors propose depend on interactions with the background electromagnetic field. These effects, if real, require the prior processing and dilution of the solutions and are explained by Montagnier as resonance phenomena with nanostructures derived from the DNA and water [1602]. e

As applied to homeopathy, the 'memory of water' concept should also be extended to the memory of aqueous ethanol preparations, which are also used. Addition of ethanol to water adds an important further area of complexity. Ethanol forms solutions in water that are far from ideal and very slow to equilibrate [1212]. Although usually considered a single phase, such solutions may contain several distinct phases [1297] and more generally consist of a complex mixture dominated by water-water and ethanol-ethanol clusters, where hydrogen-bonding is longer-lived than in water alone [1213]. They also favor nanobubble (that is, nanocavity) formation [1172]. Thus, the peculiar behavior of aqueous solutions (as mostly discussed on this page) is accentuated by the presence of ethanol. [Back to Top to top of page]

Does the glassware matter?

The process of silica dissolution has been much studied [1109, 1207, 2018] (ultrapure water can pick up 0.2 ppb Na+ ion from glassware in just one day), ever since it was proven by Lavoisier about 250 years ago, and fits with this argument. This may explain why glass is preferred over polypropylene tubes in homeopathic preparations. It should be noted that dissolved silica is capable of forming solid particles with complementary structures (that is, imprints) to dissolved solutes and macromolecules and such particles will 'remember' these complementary structures essentially forever. Such chemistry is expected to be preferred at aqueous-air interfaces due to the simultaneous reduction in charge density. It is worth noting that contact with water may change glass surfaces irreversibly [1882]; clearly a 'memory' effect.  [Back to Top to top of page]

Is gas important?

Water does store and transmit information, concerning solutes, by means of its hydrogen-bonded network. Changes to this clustering network brought about by solutes may take some time to re-equilibrate. Agitation (succussion) may also have an effect on the hydrogen-bonded network (shear encouraging destructuring), and the gaseous solutes (with critical effect on structuring [294] and possible important production of structuring nanobubbles (nanocavities) [993, 1552]), and such effects may well contribute to the altered heats of dilution with such materials [1143]. The content of

gases in water strongly depends on its prior treatment, and a disturbed equilibrium is restored relatively slowly. Mechanically induced hydrogen bond breakage may also give rise to increased (but low) hydrogen peroxide formation [1066 see equations below] and such effects have been reported to last for weeks [336]. It may be relevant to note that the presence of hydrogen peroxide can take part in and catalyze further reactions with other reactive species such as molecular oxygen and dissolved ozone [1066, 1069, 1751]. Hydrogen peroxide is not often recognized but is present in nanomolar amounts, and may vary with the number of succussion steps and their sequence. This may explain the changes in the efficacy of homeopathic preparations with the number of dilutions [1210]. Light may convert triplet oxygen to the highly reactive singlet oxygen giving rise to other reactive oxygen species and oscillating luminescence lasting many hours [2275]. Also of note are the known effects of low concentrations of reactive oxygen species on physiological processes such as the immune response; with the recent discovery of the importance of low levels of hydrogen peroxide being particularly relevant [1256]. Probably related are recent reports that dilute salt solutions containing oxygen nanobubbles, formed by vigorous stirring, can have clinical effects on immunological diseases [2002]. [Back to Top to top of page]

Does dilution happen as predicted?

Dilution is never perfect, particularly at low concentrations where surface absorption may well be a major factor, so that dilution beyond the levels that can be analytically determined remains unproven. Remaining material may be responsible for perceived differences between preparations and activity. Of course, the water used for dilution is not pure relative to the putative concentration of the 'active' ingredient; even the purest water should be considered grossly contaminated compared with the theoretical homeopathic dilution levels. This contamination may well have a major influence, and itself be influenced by the structuring in the water it encounters. Although it does, at first sight, seem unlikely that solutes in diluted 'homeopathic' water should be significantly different from a proper aqueous control, it has recently been cogently argued that the concentrations of impurities can change during the dilution process by reactions initiated by the original 'active' material [531], and this process has been mathematically modeled [1210].

A further consideration about 'the memory of water' is that the popular understanding concerning how homeopathic preparations may work not only requires this memory but also requires that this memory becomes amplified during the dilution; this amplification, necessitated by the increase in efficacy with extensive dilution, being even harder to explain. Samal and Geckeler have published an interesting, if controversial, paper [272a but see 272b] concerning the effect of dilution on some molecules. They found that some molecules gather in larger clusters on dilution rather than the smaller clusters thermodynamically expected. Just the presence of one such large μm-sized particle in the 'diluted' solution could give rise to the noticed biological action (of course, some such preparations may be without any action, being without such clustered particles). a

However, it remains to explain this particular phenomenon, which appears to disobey the second law of thermodynamics. A possible explanation is that such biologically-active molecules can cooperatively form icosahedral expanded water networks (ES) to surround and screen them by the formation of face-linked icosahedra, similar to as expected in the minimal energy-related poly-tetrahedral Dzugutov clusters [295]. So long as such an icosahedral network structure requires the help of more than one neighboring such cluster to stabilize its formation then, in more concentrated solution, the molecules dissolve normally. However, as they are diluted (typically beyond about one clathrate-forming group per twelve icosahedral water clusters; 3,360 water molecules) no neighboring such clusters are available and the clusters coalesce to form larger clusters of biologically-active molecules within their own ES-related water network (so releasing some of the water).

This tendency for particle formation is ultimately due to the hydrophobic effect and the tendency to form a small surface with the water. Overall the balance is expected to be rather fine between water cluster stabilization and particle cluster stabilization. Such, or similar, particles have been shown to have a preference for the surface of  the solution with this interfacial concentration preserved (see also [3609] ). The particles are carried over during dilution steps even well below super-Avogadro dilutions (>1023 x) [1942]. With the concentration unable to reduce below a few ng mL-1 whatever the dilution [2375] (see right, showing the expected dilution in green, the actual dilution in blue and the concentration of gold nanoparticles trapped at the liquid/air interface that are retained for the next 'dilution', shown in red).

Other workers have also shown non-monotonic dilution behavior [2508, 2520]. It may be that the number of succussion steps is more important than the 'expected' dilution [3710]. [Back to Top to top of page]

Dilution of gold nanoparticles, from [2375]

 

Solutions are more complex than expected

Water is not just H2O molecules. It contains a multitude of molecular species including ortho-water and para-water molecules, water molecules with different isotopic compositions such as HDO and H218O, such water molecules as part of weakly-bound but partially-covalently linked molecular clusters containing one, two, three or four hydrogen bonds, and hydrogen ion and hydroxide ion species. Apart from such molecules, there are always adventitious and self-created solutes in liquid water. Perhaps surprisingly, distilled and deionized water actually contain significant and varying quantities of contaminating ions. Often the criteria for ‘purity’ is the conductivity, but this will not show ionic contaminants at nanomolar, or even somewhat higher, concentrations due to the relatively high conductivity of the H+ and OH- ions naturally present. Other materials present will include previously dissolved solutes, dissolved gases dependent on the laboratory atmosphere, gaseous nanobubbles [500d], material dissolved or detached from the containing vessels [1207], solid particles and aerosols (also dependent on the laboratory history) entering from the gas phase, redox materials produced from water molecules [1066], and other solutes produced on standing [509c, 1898] d and homeopathic processing [1210]. Liquid water is clearly a very complex system even before the further complexity of molecular clusters, gas-liquid and solid-liquid surfaces, reactions between these materials, the consequences of physical and electromagnetic processing and the addition of ethanol are considered. Any or a combination of these factors may cause 'memory' of past solutes and processing in water. Some of these solutions are capable of causing non-specific clinical effects whereas others may cause effects specifically linked to the solution's (and laboratory) history, as outlined below [1206]. Both temperature and magnetic fields affect the infrared spectrum of water (showing their effect on water clustering) and these effects remain for a considerable time (≈ 1 hour) after the magnetic field is removed or temperature changed [1697]. After a magnetic field is applied perpendicular to the air/water interface for an hour, a difference in evaporation rate is still observable between treated and non-treated water for 40 minutes after removal of the magnetic field [2939]. It has been shown that (still) mineral water can be magnetized and retain this magnetization for more than a day, supposedly due to the production of magnetic nanobubbles. [1780].

There are numerous examples of the slow equilibration in aqueous solution. Thus, it can take several days for the effects of the addition of salts to water to finally stop oscillating [4] and such solutions are still changing after several months showing a large-scale (≈ 100 nm) domain structure [1148]. Also, water restructuring after infrared radiation persists for more than a day [730], and water photoluminescence changes over a period of days [801]. Changes to the structure of water are reported to last for weeks following exposure to resonant RLC (resistance inductance capacitance) circuits [927]. Conductivity oscillations (≈ 0.5 Hz) at low concentrations of salts also show the poor tendency to equilibrium in such solutions [661]. Succussion, by itself, has been shown to be 'remembered' for at least 10 minutes as solitons (that is, standing waves) [893]. Treatments by strong magnetic fields (0.8 T) have been shown to leave a memory effect lasting several days [2676, 3590]. Extremely low-frequency electromagnetic fields (ELF-EMF) have significant and effects on liquid water that last for minutes after the field is removed [1896 ]. h Electromagnetic-treated water has been proven to have diverse biological effects on both animal and plant cells [2219 ]. 

It has been found that clathrate hydrate nucleation is faster in solutions that once formed the clathrates but where it had been subsequently dissociated for periods up to several hours [1391]. f Thus the solution shows a 'memory effect' of its previous history, although it is likely that this is due to retained super-saturated gas concentrations [1429] or nanobubble formation [2350]. Other interesting examples of the memory of water are the Mpemba effect and the observation that hot water pipes are more likely to burst than adjacent cold water pipes [959]. In both effects, water seems to remember whether it has been recently hot or cold even when subsequently cooled. The Mpemba effect is a well-proven phenomenon that also seems to be caused by unexpected solute and time effects and is described and explained elsewhere.

Explanation of homeopathy on the basis of water crystals (IE, [124, 125]) is unconvincing as such crystals appear to be artifacts and, even as proposed, the effect of body fluid ions would be to immediately 'dissolve' them. 

There is a strange occurrence (the ‘pH memory‘ effect), similar to the ‘memory of water’ but unconnected to it, in enzyme chemistry. Here, an effectively non-existent material still has a significant effect. Enzymes, prepared in buffers of known pH, retain (remember) their own specific pH-dependent kinetic properties even when the water is removed such that no hydrogen ions are present [1208]. These ions seem to have a pH effect even in their absence, somewhat against common sense at the simplistic level. b [Back to Top to top of page]

Peroxide and radical production in water

H2O --> e-(aq) + H· + ·OH + H3O+ + OH- + H2O2 + HO2· + H2 + O2·- + 1O2

 

Free radicals (for example, hydroxyl radicals) and free (hydrated) electrons can be introduced into water by techniques such as electrochemistry, ultrasonics, by direct water photolysis by ultraviolet radiation (≈ 150 nm, [497], 253.7 nm, [3102] disinfection or simply by agitation. Such processes are catalyzed by the trace amounts of Fe2+/Fe3+ present even in purified water. Clearly, any such reactions create a memory-effect for that processing as molecules are created, and reaction processes initiated that would not otherwise be extant. Radicals, for example, can initiate chain reactions involving cascades of reactions; for example, a single ·OH radical may result in the formation of 34 peroxide molecules [3102]. Such hydroxyl radicals may also be created by 190-300 nm radiation exciting an electron from the hydroxide ion [3022]. Water may also be split by electrolysis, or mechanical methods such as ultrasonics, or stirring with a catalyst [739], to give H2 and O2 and some associated free radicals such as the highly reactive hydroxyl radical. In particular, low concentrations of hydrogen peroxide (H2O2) may be produced from water (H2O) by any process that moves clusters of water relative to each other such as mechanical vibration and stirring [1066]. Such shaking partially destroys the inherent natural coherence of the water. H2O2 is stable for years when shielded from light and free from transition metals.

(H2O)n(H2O pull leftH-OHpull right OH2)(H2O)m --> (H2O)n(H2O + H· + ·OH + OH2)(H2O)m

2 ·OH --> H2O2

without the need for molecular oxygen but increased by it [1066], for example, 

       (normal triplet oxygen)       3O2 + ·H --> HO2·                                               

                                               HO2·+ ·H --> H2O2

                                               HO2·+HO2· --> H2O2 + 1O2     (highly reactive singlet oxygen)

 Peroxide may break down under UV irradiation to form strongly oxidizing hydroxyl radicals and then more superoxide,

λ = 250≈ 420 nm 

hν + H2O2 --> 2 ·OH

·OH + H2O2 --> HO2· + H2O 

Also, triplet oxygen may convert to singlet oxygen under near-infrared irradiation in solution [2275]., in spite of this transition being 'forbidden' in isolated molecules

3∑g     λ = 1264 nm     1Δg

3O2 --> 1O2

  1O2 + H2O --> HO2· + ·OH

slow  

Reactions can occur with other materials such as bicarbonate,

 ·OH + HCO3- --> ·CO3- + H2O

·CO3- + ·OH --> CO2 + HO2-

  ·CO3- + H2O2 --> HCO3- + HO2· 

The micrometer-sized water droplets (microdroplets) formed during succussion may cause the spontaneous reduction of

organic molecules, so producing permanent changes to the solution (a clear memory effect) [3653]. The presence of such active oxygen species and gases or their mixtures in water may have significant and long-term 'memory' effects by reacting with extraneous solutes and initiating chain reactions. Some products are quite stable, and they can certainly be determined after stirring. [Back to Top to top of page]

Possible scenarios for the memory effect in homeopathic solutions

Various possible scenarios for the retained efficacy of homeopathic solutions are presented In the Table below [1206].

 

Mechanisms for 'the memory of water' as applied to homeopathy

Specific clinical effects   

 

Remaining undiluted material on surfaces 
Aerosol material reintroduced              
Bacterial material introduced 
Imprinted silicates
Remaining particle clusters

Processing products remaining within interfaces

Non-specific clinical effects 

Dissolved silicates and silicate particles 
Nanobubbles and their material surfaces
Redox molecules produced from water
Natural water clustering
Stabilized water clustering
Ions, including from glassware
Ethanol solution complexity

 

Footnotes

a A related phenomenon may be the occurrence of conductivity oscillations (≈ 0.5 Hz) at similar concentrations of salts at the low concentration limit of obedience to Kohlrauch's law (Onsager's formula) Λm = Λmo - αc½, where Λmo is the limiting molar conductivity, α is a constant and c is the molar concentration [661]. [Back]

b This example of ‘pH memory‘ was later explained briefly as the enzymes' acidic and basic groups retaining their charge when in an anhydrous environment [1208]. This explanation is accepted but remains unproven independently, and is derived from a circular argument that does not inform on how the charge is retained. There remains some puzzle to the extent that a single group in a molecule can either be charged or not charged; it cannot be fractionally charged. Thus the enzyme might be expected to behave as containing a mixture of charged and uncharged groups rather than, as found, fractionally charged groups as in the hydrated enzyme (two easily distinguished scenarios). Perhaps there is sufficient hydration water retained to ensure this, but this author does not believe that this has been shown. Whatever, the ‘puzzle’ of the enzyme’s memory will disappear with an acceptable explanation. Later work has shown that freeze-drying may cause a significant change in the extent of protonation of pH indicators [2986] with the final pH depending on the water remaining. Also, the acidity may change considerably during the freezing process even if the final pH of the freeze-dried material is close to its initial state [2987]. [Back]

c These papers are freely available online, where they are followed by a mixed bag of comments. [Back]

d This paper on autothixotropy has been criticized on two grounds [1610]. (1) The structures arising in the water can be destroyed by shaking while the solution preparation involved much shaking. However, the described destruction is at the macroscopic level (» µm) whereas the structuring could still arise on the microscopic level; (2) The autothixotropic effect requires the presence of some ions in the water. However, the distilled water used (in contrast to deionized water that does not show autothixotropy) contains ions. Further work appears to confirm the autothixotropy phenomenon [1898]. [Back] 

e The extraordinary results given in this paper have yet to be independently confirmed. [Back] 

f A recent paper casts doubt on this finding [1650] whereas another supports it [2351]. It appears that this memory effect depends on the clathrate-forming solutes used [2867]. [Back]

g The Nobel-prize-winning physicist Brian Josephson has reinforced the argument that the speed at which things happen at the microscopic level (e.g., the level of molecules) cannot be equated with the lifetime of the macroscopic system involved with the illustration of the superconducting state. This state can have a very long lifetime (with 'persistent currents' in superconducting rings, which have been found to persist for years), but the 'turnover rate' in terms of how long the constituent electrons stay in any given state before being scattered is extremely short. [Back]

h Such experimentally-evidenced effects may not be shown using (theoretical and model-specific) molecular dynamics simulations [2346]. [Back]

i This paper was bizarre because the data it produced showed a positive effect (therefore actually supporting the 'memory of water' conclusions). The Authors dismissed these positive conclusions out of hand as 'a source of error for which we cannot account', so leaving the remaining data (that is, only the data which agreed with their headline disproof). It should be noted that the statistical report upon which this paper was based states that ' One interpretation is that there are, after all, differences between the treatments...' [346c] but this statement does not survive into the final version published by the journal 'Nature'. The Authors have refused to release their raw data [346d] for unbiased statistical analysis. Nature, also recently published a paper on 'ultrafast memory loss' in water that, perhaps ingenuously, appears to misinterpret this 'memory of water' concept, as it only concerns the 'memory' of single water molecules, not clusters or larger amounts of water molecules [750]. Overall the episode reflects badly on the, otherwise respected, journal 'Nature'. [Back]

j Two years later Benveniste unfairly lost his job with INSERM due to narrow-mindedness and the bad publicity generated by the rebuttal in the journal 'Nature'. For the last 14 years of his life, he championed not only 'the memory of water' but also an even more controversial theory that 'information can be transmitted over telephone lines'. [Back]

k Although the Editor of Nature, (Maddox) initially stated that the investigation into the data would be by 'independent investigators' it was heavily biased including and led by Maddox himself, who had already stated that he did not believe the data, 'There is no physical basis for such an activity' and "A journal really has to have an opinion". The magician that Maddox chose to help his 'investigation' was James Randi (“The Amazing Randi”), well-known for his skeptical views concerning complementary medicine in which he later made his living having retired from 'magic'. The third investigator was Walter Stewart, a zealot dedicated to uncovering scientific fraud. It was Stewart who found MIT biologist Thereza Imanishi-Kari guilty on 19 charges of research misconduct, only for all these charges to be overturned eight years later by an appeals panel of the U.S. Department of Health and Human Services (D. Kevles, The Baltimore Case: A Trial of Science, Politics, and Character (W. W. Norton & Co., New York, 1998)). Stewart was later described as evil by Kevles as determined to find and prove scientific fraud at any cost as a vindication of his own belief that fraud is rampant in the scientific community. Maddox had an exaggerated zealotry for disproving the data, and so was certainly not independent. Maddox stated 'None of us has first-hand experience in the field of work at INSERM 200'. Maybe, he did not wish to risk whether a truly independent review by knowledgeable experts would come up with the result he required. [Back]

 

https://www.youtube.com/watch?v= 

 

https://www.youtube.com/watch?v=BWYlMSHOGBw

https://www.youtube.com/watch?v=R8VyUsVOic0