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The '''memory of water''' is a phrase mostly associated with homeopathy and the controversial research of Jacques Benveniste and his colleagues. This team reported that particular solutes subjected to sequential physical processing and dilution appeared to have some biological effects that were different from the "control" effects of the water used for the dilutions.
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'''Memory of water''' is a concept postulated to explain how solutions diluted far beyond the point where they should retain any active ingredients might retain some biological activity. The concept arose from experiments by a group led by the French [[immunology|immunologist]] [[Jacques Benveniste]]; the results were published in ''Nature'', and subsequently attacked as unrepeatable - though homeopaths claim they have been reproduced.<ref>Endler PC et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10<sup>-23</sup>. Homeopathy (2010) 99, 25–36</ref><ref>Chirumbolo S et al. Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study. Inflamm Res 
DOI 10.1007/s00011-009-0044-4</ref> The phrase itself was coined by the newspaper ''Le Monde'' in its account of that work in somewhat different form as the "memory of matter" ("''la mémoire de la matière''"). The underlying notion is that [[water]] can somehow "remember" characteristics of molecules with which it had once been in contact. The concept has been widely cited by some [[Homeopathy|homeopaths]] as a possible mechanism for the purported efficacy of their remedies. Chemists and physicists, however, consider the concept to be nonsensical.  In the current scientific view, liquid water is a continuously rearranging hydrogen-bonded network with motions on the picosecond (10<sup>&minus;12</sup> s) time scale; accordingly, there is no room for a water "memory"<ref>Keutsch FN ''et al.'' (2003) The water trimer ''Chem Rev'' 103:2533-77 PMID 12848579</ref><ref>Elsaesser T (2009) Ultrafast memory loss and relaxation processes in hydrogen-bonded systems ''Biol Chem'' 390:1125-32 (Review) PMID 19663683</ref><ref>Keutsch FN, Saykally RJ (2001) Water clusters: untangling the mysteries of the liquid, one molecule at a time ''Proc Natl Acad Sci USA'' 98:10533-40 (Review) PMID 11535820</ref>


Water is not simply a collection of molecules of H<sub>2</sub>O, it contains several molecular species including ''ortho'' and ''para'' water molecules, and water molecules with different isotopic compositions such as HDO and H<sub>2</sub><sup>18</sup>O. These 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. In addition, there are ''always'' adventitious solutes in liquid water. Even double-distilled and deionized water always contains significant and variable trace amounts of contaminating ions, and different samples will differ in the contaminants that they contain.
== Benveniste study (''Nature'')==
In 1988, Benveniste (and colleagues) published a paper in ''Nature'' that indicated that a solution containing a biologically active substance might retain some of that biological activity even when serially diluted beyond the point at which any of the active molecules are present. In particular, they reported effects on a biological process involved in the human [[immune system|immune]] response.<ref name=Benveniste>Davenas E ''et al.'' (1988) Human basophil degranulation triggered by very dilute antiserum against IgE ''Nature'' PMID 2455231</ref>


There is some support for the notion that water can have properties that depend on how it has previously been processed (that is, water has, in some sense, a kind of "memory"). The experimental evidence indicates that the "memory" are due primarily to solute and surface changes occurring during this processing. In particular, water, as a result of repeated vigorous shaking, might include Redox molecules produced from water, dissolved atmospheric gases and airborne contaminants, Silicates - tiny glass "chips",  
Human [[basophil]]s are a [[granulocyte]] cell type accounting for 0.1–1% of white blood cells; these cells contain many "granules" which store inflammatory mediators, including [[histamine]], and they can be cultured readily and studied ''in vitro''. Exposing these cells to anti-human-IgE [[immunology|antibodies]] triggers "degranulation", a process in which the granules fuse with the plasma membrane to release histamine into the extracellular fluid. Basophil activation can be measured in several ways. First, degranulated cells can be stained and then counted; this subjective measurement is prone to variable outcomes. Second, histamine release can be measured using fluorimetric assays. Third, the fusion of granules leads to the expression of [[CD63 antigen]]; the percentage of basophils that express CD63 can be determined with [[flow cytometry]], and correlates well with histamine release.
nanobubbles and their material surfaces, dissolved ions, including from the glassware. It may be contaminated by material that adheres to the surfaces of glassware, for example by bacterial material. There might also be some effects of successive shaking on water structure - "clustering" of water molecules.


These mechanisms are not mechanisms of memory in any cognitiove sense; the term memory here is used as a metaphor, implying only that the past history has a discernible influence on the present properties.
Benveniste reported that very high dilutions of anti-human-IgE (containing no molecules of the antibody) could induce degranulation of basophils. He concluded that it was the 'configuration' of molecules in the water that was biologically active.  The French newspaper ''Le Monde'' covered this, referring to ''"la mémoire de la matière"'' (the memory of matter) and ''le souvenir de molécules biologiquement actives'' (recollection [by water] of biologically active molecules). In English, the phrase that became widespread was "memory of water". ''Le Monde'' made the paper a front page story, pointing out that if this work were correct, it would overthrow many of the foundations of physics.


==Water in living organisms==
===Follow-up investigations===
Water is essential for functional macromolecular folding, stabilization and activity, transport, membrane formation and protein insertion into membranes; it the intracellular matrix in which biological molecules interact. Understanding exactly how water diffuses when confined in proximity to complex macromolecules inside a cell is therefore an important challenge. The diffusion coefficient of water in biological tissues has been measured using nuclear magnetic resonance, and these have shown that, within a cell, water diffuses much more slowly than pure water in aqueous media. This is at least partly explained by tortuosity effects, macromolecular crowding and confinement effects, but some (but not all<ref>Jasnin M ''et al.'' (2008) Down to atomic-scale intracellular water dynamics EMBO reports [http://www.nature.com/embor/journal/v9/n6/full/embor200850.html 9:543–7.("Our data show that the water between macromolecules in the ''in vivo'' intracellular environment has properties that are essentially the same as those of pure water..." )</ref>) have suggested that the interaction with macromolecules might cause "clustering" of water molecules -that it might change the structure of the intracellular water.
''Nature'' published the article with two unprecedented conditions: first, that the results must first be confirmed by other laboratories; second, that a team selected by ''Nature'' be allowed to investigate the Benveniste laboratory after publication. Benveniste accepted these conditions; the results were replicated by labs in Italy, Canada, Israel and France, and the article was accompanied by an editorial titled "When to believe the unbelievable."


In contrast with this post-hoc analysis of water behavior in cells (proteins may ''cause'' water to arrange in clusters - or not), Patterson proposes, in an invited paper for Chaplin's ''Water structure and science'' resource, "the cluster-domain model (which) depicts the cytoplasmic space as a densely packed world: not as a fluid solution, and not as protein molecules in empty space". Further, it postulates a "protein-water network (...) an energized '''gel''' whose units, protein domains '''and''' water clusters, manipulate pressure and tension to perform mechanical steps." This model is intended "to explain (...) the mechanical and energetic events of the cell (because) the traditional view (statistical mechanical principles) cannot explain (how these events) proceed without failure (...)". According to this model, the interaction of water with macromolecules does not '''cause''' "clustering" of water molecules, it '''is''' a cluster: a “''pressure pixel''”.  
The follow-up investigation was conducted by a team including the editor of ''Nature'', John Maddox, American scientific fraud investigator and chemist Walter Stewart, and "professional [[pseudoscience]] debunker" [[James Randi]]. With the cooperation of Benveniste's  team, under double-blind conditions, they failed to replicate the results. Benveniste refused to withdraw his claims, and in July 1988 the team published a detailed critique of Benveniste’s study. They concluded that the experiments were badly controlled statistically, that measurements that conflicted with the claim had been excluded, that there was insufficient avoidance of contamination, and that there were questions of undisclosed conflict of interest, as the salaries of two coauthors of the article had been paid under a contract with the homeopathic manufacturing company ''Boiron et Cie''.<ref name=Maddox>{{cite journal
  | last =Maddox
  | first =J  | coauthors ''et al.'' | title =‘High-dilution’ experiments a delusion
  | journal =Nature
  | volume =334
  | pages =287–290
  | url =http://br.geocities.com/criticandokardec/benveniste02.pdf
  | doi =10.1038/334287a0 |format=PDF}}</ref>


<blockquote>The cell can be seen, from a somewhat extreme structuralist point of view, as''' organized water'''. There is an incipient order in liquid water, which is given long-range coherence and permanence by the protein framework. In the words of A. Szent-Gyorgyi, '''“Life is water dancing to the tune of solids”.'''</blockquote>
Another group led by Benveniste replicated the findings,<ref>Poitevin B ''et al.'' (1988) In vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica ''Brit J Clin Pharmacol'' [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1387805/ 25: 439-44]</ref> but other groups failed to reproduce the effects.<ref>Hirst SJ ''et al.'' (1993) Human basophil degranulation is not triggered by very dilute antiserum against human IgE ''Nature'' [http://dx.doi.org/doi:10.1038/366525a0 doi 366:525-7]</ref><ref>Guggisberg AG ''et al.'' (2005) Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. ''Complement Ther Med'' 13:91-100</ref> Benveniste  contended that the same conditions were not met in those laboratories, and he never retracted his claims. In the issue of ''Nature'' that carried the critique, Benveniste vigorously attacked the ''Nature'' team’s "mockery of scientific inquiry."<ref>Benveniste J (1988) Dr Jacques Benveniste replies ''Nature''  [http://dx.doi.org/doi:10.1038/334291a0 doi 334:291]</ref>
:: [http://www.lsbu.ac.uk/water/watterson.pdf Enzyme function: random events or coherent action?] (2004) JG Watterson in Pr. Chaplin's [http://www.lsbu.ac.uk/water/index2.html Water structure and science] online resource.


As we have seen, the materials science of liquid water, in a similar fashion, is abandoning the random network model of liquid water. The physics and the biophysics of water could be united in a synthesis that may accomodate homeopathy.
After the ''Nature'' debacle, Benveniste became more and more isolated scientifically, and some of his colleagues called for him to resign. He did not lose his job at the French ''National Institute of Health and Medical Research'' (INSERM), but funding was progressively withdrawn, and his lab was eventually closed. According to Lionel Milgrom, a chemist and homoeopath who corresponded with Benveniste, "The knocks that he took made him suspicious of virtually everyone". Yet, despite the widespread scepticism, and despite the failure of several other groups to corroborate his findings, Benveniste continued to study the 'memory of water'. According to [[Brian Josephson]] (who, after winning the Nobel Prize for Physics in 1973 became a champion of iconoclastic ideas) "That's what good scientists do...He probably became more determined because of the opposition."<ref>[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2804%2917339-X/fulltext#article_upsell Benveniste obituary in ''Nature'']</ref>
===Is homeopathy plausible? The structure of liquid water===


<blockquote>"Based on this evidence we would be ready to accept that homoeopathy can be efficacious, if only the mechanism of action were more plausible". Kleijnen J ''et al.''(1991). Clinical trials of homeopathy. ''British Medical Journal'', 302:316–23.</blockquote>
== Other scientists ==
Independently, other studies have claimed to reproduce Benveniste's experiments, including one published in the ''Homeopathy'' journal,<ref>Endler PC et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10<sup>-23</sup>. Homeopathy (2010) 99, 25–36</ref><ref>Chirumbolo S et al. Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study. Inflamm Res 
DOI 10.1007/s00011-009-0044-4</ref> edited by homeopathic doctor [[Peter Fisher]] (see also ''[[Memory of water#Homeopathic coverage|Homeopathic coverage]], below).


In 2003, [[Molecular and Cellular Biochemistry]] published a review of the possible molecular mechanisms underlying the action of homeopathic drugs. In it,<ref name="pmid14619985">{{cite journal |author=Khuda-Bukhsh AR |title=Towards understanding molecular mechanisms of action of homeopathic drugs: an overview |journal=Mol Cell Biochem |volume=253 |pages=339–45 |year=2003 |month=November |pmid=14619985 |doi= |url=http://www.science.smith.edu/departments/Biochem/Chm_357/Articles/homeopathy_molecular%20mechanisms.pdf}}</ref> Khuda-Bukhsh explains that, even in the time of Hahnemann, it was evident that the vehicle or solvent (water or alcohol) was considered the medicine, rather than the molecule. 
In 2003 Louis Rey, a chemist from Lausanne, reported that frozen samples of lithium and sodium chloride solutions prepared according to homeopathic prescriptions showed &mdash; after being exposed to radiation &mdash; different thermoluminescence peaks compared with pure water. Rey claimed that this suggested that the networks of hydrogen bonds in homeopathic dilutions were different. <ref>Rey L (2003)Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride ''Physica A'' 323:67–74</ref>
These results have never been replicated and are not generally accepted - even Benveniste criticised them, pointing out that they were not blinded <ref>[http://www.newscientist.com/article/dn3817 Icy claim that water has memory] ''New Scientist''  11 June 2003</ref>  


The research on the plausibility of homeopathy is an attempt to characterize how the behaviour of the molecules of a solvent could differ depending, first, on the solute that was diluted in it and, second, on the kinetic energy imposed on the solvent ("succusions", "dynamisations", "shakings"); it tries to answer the question: are all water''s'' equal? Should we recognize that "water is water, period", or can some non-random, biochemically significant conformational changes happen in the way water molecules behave with each other, when a molecule is "imprinted" in a solution by dilutions and dynamizations?
In January 2009, [[Luc Montagnier]], the Nobel Laureate virologist who led the team that discovered the human immunodeficiency virus (HIV), claimed (in a paper published in a journal that he set up, which seems to have avoided conventional peer review as it was accepted three days after submission) that the DNA of [[pathogen|pathogenic]] bacteria and viruses massively diluted in water emit radio waves that he can detect.<ref>Montagnier L ''et al.'' (2009) Electromagnetic signals are produced by aqueous nanostructures derived from bacterial DNA sequences ''Interdiscip Sci'' 1:81-90 PMID 20640822</ref> This, he claimed, can also be used to detect the medicine in a homeopathic remedy.<ref name=montagnier>  {{Citation   
|title=Nobel laureate gives homeopathy a boost   
|newspaper=The Australian   
|date=July 5, 2010   
|url=http://www.theaustralian.com.au/news/health-science/nobel-laureate-gives-homeopathy-a-boost/story-e6frg8y6-1225887772305}}</ref><ref>{{citation   
|title= Top 6 unconventional post-Nobel Prize claims   
|author= Alexey Kovalev   
|date= 07 June 2010   
|journal= Wired   
|url= http://www.wired.co.uk/wired-magazine/archive/2010/07/start/top-6-unconventional-post-nobel-prize-claims?page=all }}</ref> The device used to detect these signals was developed by Jacques Benveniste, and was independently tested, with the co-operation of the Benveniste team, at the request of the United States [[Defense Advanced Research Projects Agency]]. That investigation was unable to replicate any effects of digital signals using the device.<ref>Jonas WB ''et al.'' (2006) Can specific biological signals be digitized? ''FASEB J'' 20:23-8 PMID 16394263</ref>


The structure of liquid water is generally assumed to be a  network of H<sub>2</sub>O molecules forming short-lived (on the order of 10<sup>&minus;12</sup> s) hydrogen bonds. According to this model the existence of long-term structural changes appears unlikely, and if by chance such structures are formed, they will disappear in a few picoseconds.  
In 2010, at the age of 78, Montagnier announced that he would take on the leadership of a new research institute at Jiaotong University in Shanghai, where he plans to continue this work. He claims that the findings "are very reproducible and we are waiting for confirmation by other labs", but said, in an interview with ''Science'', "There is a kind of fear around this topic in Europe. I am told that some people have reproduced Benveniste's results, but they are afraid to publish it because of the intellectual terror from people who don't understand it." Montagnier had called Benveniste "a modern [[Galileo]]", but the problem was that "his results weren't 100% reproducible".<ref>Newsmaker interview: Luc Montagnier. French Nobelist escapes 'intellectual terror' to pursue radical ideas in China. Interview by Martin Enserink ''Science'' 2010 Dec 24;330:1732</ref>


Materials scientists and physicists studying liquid water challenged the assumption that the unquestionably short life of these bonds determine an equally short life to the structures found in water, at the larger scale of 200 or more H<sub>2</sub>O molecules. At an even larger scale, it can be easily observed that a wave keeps existing despite of the constant doing and undoing of hydrogen bonds, and that ice sculptures are also made of H<sub>2</sub>O molecules constantly bonding and separating. In the same way, water clusters of a hundred or more molecules are actually structures that have a longer life than the individual bonds composing it.<ref>See the related sections in Martin Chaplin's [http://www.lsbu.ac.uk/water/ Water Structure and Science] resource for animations.</ref>
== Other healers ==
Claims about supernatural or mystical qualities of water have been made by some "alternative healers". For example, practitioners of the Silva Method<ref>{{citation
| author = Laura Silva Quesada
| title = Healing Qualities of Water and Useful Applications
| url = http://www.silvamethod.com/ne/publications/Healing-Qualities-of-Water.pdf}}</ref> claim to "program" water to heal a person, long after the healer has programmed the water and is personally unavailable. These alternative healers focus on the effects of energies, generated by people, on water. In [[Qigong]] (in Traditional Chinese Medicine):


The 65 reported anomalies<ref>These anomalies are presented and explained (or characterized) in Chaplin's [http://www.lsbu.ac.uk/water/anmlies.html web resource]; also see [[water]] ([http://en.citizendium.org/wiki/Water#The_anomalies_of_water The anomalies of water]) </ref> of water reflect and heterogeneity in its structure: liquid water is a combination of different ''phases'' (a term in materials science to designate 3D arrangements of molecules or patterns) that are ''not'' short-lived, although, at the smaller, molecular, scale, the incessant agitation might evoke the impression that no higher order can exist.
{{quotation|"Subtle, or vibrational, energy is broadly defined as energy that is not generally recognized by mainstream physics and for which there are no means of measurement. ...
It is fundamental to many unexplained phenomena such as the power of spirituality and prayer, the effect of remote intention, the operation of homeopathy, and the functioning of the mind/body information network..."<ref>{{citation
| author = Tom Rogers
| title = Qigong - Energy Medicine for the New Millennium | url = http://www.qigonginstitute.org/html/papers/QigongEMedicine.pdf}}</ref>}}


Rao, Roy, ''et al.'' published preliminary results suggesting that different homeopathic preparations can be distinguished from each other and from controls, using two [[spectroscopy]] techniques that the authors judged better suited to analyze the "co-operative nature of structural differences".<ref name="pmid17678814">{{cite journal |author=Rao ML''et al.'' |title=The defining role of structure (including epitaxy) in the plausibility of homeopathy |journal=Homeopathy |volume=96 |pages=175–82 |year=2007 |month=July |pmid=17678814 |doi=10.1016/j.homp.2007.03.009 |url=http://www.badscience.net//?p=496}} See bottom of the page for a critique of the methodology of this experiment that was published in ''Homeopathy''.</ref>  
Masaru Emoto built a business selling water products. In a series of books &mdash; beginning with ''Messages from Water'' (1999) &mdash; he claimed that ice crystals reflect the words, music, pictures &mdash; even thoughts and intentions &mdash;to which the droplets of water were exposed before being frozen. He also claimed to find effects of 'healing energy' on water ([[Pranic Healing]]):
{{quotation|"After the healers projected their energy toward the water, ... the water that was healed with Pranic energy had impeccable crystal formation while the tap water's internal structure was chaotic."<ref name=PHCG>{{citation
| author = LocalHealers.com | title = Pranic Healing Career Guide | url = http://www.localhealers.com/index.php?option=com_content&view=article&id=133&Itemid=16&type=careercenter}}</ref>}}


Van der Waals bonds determine the interesting properties of fluids. ''(...)''
Emoto makes some remarkable claims:
{{quotation|"So where is the solution to the problem of global warming in this book? Well, because it shows that we can extract energy out of water. For example, the crystal photograph on the cover is shining beautifully. This is a result of when the cameraman and the water resonated."<ref>{{cite web|title=How to Take a Water Crystal Photograph|work=[http://www.masaru-emoto.net/ OFFICE MASARU EMOTO]|url=http://www.masaru-emoto.net/english/ediary200609.html#0915|accessdate=March 24, 2010}}</ref>}}


''(under revision:)''
== Homeopathic coverage ==
To most orthodox scientists, the "memory of water" is not something that deserves serious consideration; the only evidence is the flawed Benveniste work. By contrast, the notion of "memory of water" has been taken seriously among [[homeopathy|homeopaths]]. For them, it seemed to be part of a possible explanation of why some of their remedies might work.
An overview of the issues surrounding the memory of water was the subject of a special issue of ''Homeopathy.'' In an editorial, the editor of ''Homeopathy'',  Peter Fisher, acknowledged that Benveniste’s original method does not yield reproducible results and declared  "...the memory of water is a bad memory: it casts a long shadow over homeopathy and is just about all that many scientists recall about the scientific investigation of homeopathy, equating it with poor or even fraudulent science."  The issue was an attempt to restore some credibility to the notion with articles proposing various, very different theories of water memory, such as: electromagnetic exchange of information between molecules, breaking of temporal symmetry, thermoluminescence, entanglement described by a new quantum theory, formation of hydrogen peroxide, clathrate formation, etc. Some of the proposed mechanisms would require overthrowing much of 20th century physics.<ref name="Homeopathy2007">{{citation
| editor = Martin Chaplin
| date = 2007
| title = The Memory of Water ''Homeopathy'' 96:141-230}}
::Copies of the articles in this special issue are freely available on a private website, along with discussion. [http://www.badscience.net/?p=490 Homeopathy Journal Club] hosted by Bad Science, a blog by Ben Goldacre</ref>


It is known that various phenomena can take place in water. Two physicochemical phenomenas have received special attention in the context of homeopathy research: clathrates and solitons.
In 2010, a team of scientists from India found that some commercially manufactured metal-derived homeopathic remedies in fact contained
nanoparticles of the metals and their aggregates, despite the claimed high-dilution.<ref>Chikramane PS ''et al.'' (2010) {http://www.katonics.com/uploads/2010%20-%20%20Paper%201%20-%20Extreme%20homeopathic%20dilutions%20retain%20starting%20%20materials-A%20nanoparticulate%20perspective.pdf]</ref><ref>[http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WXX-518T4YP-3&_user=10&_coverDate=10%2F31%2F2010&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=3742c7a676d864d32688d36d6edd30a4&searchtype=a Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective]
''Homeopathy'' 99:231-42</ref> In 2015, a study in India found that homeopathic remedies in fact contained
nanoparticles of the resource medicine, despite the claimed high-dilution.<ref>{{cite news  |title=Not ‘sugar pills’, nano particles found in diluted homeo drugs |url=http://m.timesofindia.com/city/bengaluru/Not-sugar-pills-nano-particles-found-in-diluted-homeo-drugs/articleshow/46788906.cms |work=Times News Network |publisher=Bennett, Coleman & Co. Ltd. |date=3 April 2015 |accessdate=4 April 2015 }}</ref> Another team of scientists found that Quartz, Sulfur and Copper Sulfate-derived homeopathic remedies in fact contained
nanoparticles of those substances and their aggregates, despite the claimed high-dilution.<ref>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137246/ Homeopathic Preparations of Quartz, Sulfur and Copper Sulfate Assessed by UV-Spectroscopy]
''Pub Med'' 99:231-42</ref> Traditional homeopathic preparation methods are very different from the controlled microchemical procedures used for serial dilutions in scientific laboratories, and the assumption that homeopathic remedies are in fact diluted to the extent claimed may be wrong. As pointed out in an editorial in ''Homeopathy'', "The skeptics have gotten the homeopathic world so busy trying to defend various theories of water memory that we have overlooked the possibility that some of the material somehow actually persists in highly diluted homeopathic medicines."<ref>Ives JA ''et al.'' (2010) Do serial dilutions really dilute? ''Homeopathy'' 99:229-30 PMID 20970091</ref>


====Clathrate formation and growth====
==References==
Khuda-Bukhsh reviews the research, consistent with some work in general physical chemistry, which suggests that the process of homeopathic preparation might indeed have an effect on water. Assuming, for example, that clathrates form, there is no current understanding, in molecular pharmacology, of mechanisms by which clathrates would have a metabolic effect. The role of clathrates and other crystalline structures in biochemistry is under study. (...)
{{reflist|2}}[[Category:Suggestion Bot Tag]]
 
Clathrates are complexes of water molecules around low-molecular-weight molecules (e.g., methane) or atoms (e.g., xenon) that can cause the growth of other clathrates devoid of central molecules. The presence of clathrates affects the results of mass spectrometry.<ref>{{citation
| journal = Nature
| year = 2007
| volume = 449
| pages = 1033-6
| title =  Clathrate nanostructures for mass spectrometry.
| author =  Northen TR ''et al.''
| url = http://www.ncbi.nlm.nih.gov/pubmed/17960240}}</ref> This would be one technique for validating this hypothesis, by testing for clathrates in homeopathic preparations.
 
====Silicates====
Vigorous shaking of the water in glass bottles can cause small amounts of silica (silicate) fragments or chips to fall into the water.<ref>Demangeat, J.-L ''et al.'' (2004) Low-Field NMR water proton longitudinal relaxation in ultrahighly diluted aqueous solutions of silica-lactose prepared in glass material for pharmaceutical use. ''Applied Magnetic Resonance''  26:465–81.</ref>  Homeopathic drug manufacturers use a double-distilled water in making their medicine, and whatever medicinal substance is placed in the water might interact with the silicate fragments and may change the structure of the water in unpredictable ways. Despite this experimental fact that these silicate fragments occur in homeopathic water, it is still unclear how continual dilution and succussion (vigorous shaking) increases the therapeutic effects of the medicine and reduces the necessity for frequent dosing (which homeopaths claim is generally the result of using the higher homeopathic potencies).
 
====Nano bubbles/Nano particles====
It has been suggested that micro-bubbles and nano-bubbles, caused by vigorous shaking, can "burst" to produce microenvironments of higher temperature and pressure. <ref>Elia V ''et al.'' (2004) Permanent physio-chemical properties of extremely diluted aqueous solutions of homeopathic medicines, ''Homeopathy'', 93:144–50.</ref>  One group of material scientists have estimated that the vigorous shaking involved with making homeopathic medicines changes the pressure in the water, akin to water being at 10,000 feet in altitude.<ref>Roy R''et al.'' (2005) The Structure of liquid water: Novel insights from materials research; potential relevance to homeopathy, ''Materials Research Innovations'' [http://www.rustumroy.com/Roy_Structure%20of%20Water.pdf 9:4].</ref>  These scientists suggest that the homeopathic process of using double-distilled water and then diluting and shaking the medicine in a sequential fashion changes the structure of water.

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Memory of water is a concept postulated to explain how solutions diluted far beyond the point where they should retain any active ingredients might retain some biological activity. The concept arose from experiments by a group led by the French immunologist Jacques Benveniste; the results were published in Nature, and subsequently attacked as unrepeatable - though homeopaths claim they have been reproduced.[1][2] The phrase itself was coined by the newspaper Le Monde in its account of that work in somewhat different form as the "memory of matter" ("la mémoire de la matière"). The underlying notion is that water can somehow "remember" characteristics of molecules with which it had once been in contact. The concept has been widely cited by some homeopaths as a possible mechanism for the purported efficacy of their remedies. Chemists and physicists, however, consider the concept to be nonsensical. In the current scientific view, liquid water is a continuously rearranging hydrogen-bonded network with motions on the picosecond (10−12 s) time scale; accordingly, there is no room for a water "memory"[3][4][5]

Benveniste study (Nature)

In 1988, Benveniste (and colleagues) published a paper in Nature that indicated that a solution containing a biologically active substance might retain some of that biological activity even when serially diluted beyond the point at which any of the active molecules are present. In particular, they reported effects on a biological process involved in the human immune response.[6]

Human basophils are a granulocyte cell type accounting for 0.1–1% of white blood cells; these cells contain many "granules" which store inflammatory mediators, including histamine, and they can be cultured readily and studied in vitro. Exposing these cells to anti-human-IgE antibodies triggers "degranulation", a process in which the granules fuse with the plasma membrane to release histamine into the extracellular fluid. Basophil activation can be measured in several ways. First, degranulated cells can be stained and then counted; this subjective measurement is prone to variable outcomes. Second, histamine release can be measured using fluorimetric assays. Third, the fusion of granules leads to the expression of CD63 antigen; the percentage of basophils that express CD63 can be determined with flow cytometry, and correlates well with histamine release.

Benveniste reported that very high dilutions of anti-human-IgE (containing no molecules of the antibody) could induce degranulation of basophils. He concluded that it was the 'configuration' of molecules in the water that was biologically active. The French newspaper Le Monde covered this, referring to "la mémoire de la matière" (the memory of matter) and le souvenir de molécules biologiquement actives (recollection [by water] of biologically active molecules). In English, the phrase that became widespread was "memory of water". Le Monde made the paper a front page story, pointing out that if this work were correct, it would overthrow many of the foundations of physics.

Follow-up investigations

Nature published the article with two unprecedented conditions: first, that the results must first be confirmed by other laboratories; second, that a team selected by Nature be allowed to investigate the Benveniste laboratory after publication. Benveniste accepted these conditions; the results were replicated by labs in Italy, Canada, Israel and France, and the article was accompanied by an editorial titled "When to believe the unbelievable."

The follow-up investigation was conducted by a team including the editor of Nature, John Maddox, American scientific fraud investigator and chemist Walter Stewart, and "professional pseudoscience debunker" James Randi. With the cooperation of Benveniste's team, under double-blind conditions, they failed to replicate the results. Benveniste refused to withdraw his claims, and in July 1988 the team published a detailed critique of Benveniste’s study. They concluded that the experiments were badly controlled statistically, that measurements that conflicted with the claim had been excluded, that there was insufficient avoidance of contamination, and that there were questions of undisclosed conflict of interest, as the salaries of two coauthors of the article had been paid under a contract with the homeopathic manufacturing company Boiron et Cie.[7]

Another group led by Benveniste replicated the findings,[8] but other groups failed to reproduce the effects.[9][10] Benveniste contended that the same conditions were not met in those laboratories, and he never retracted his claims. In the issue of Nature that carried the critique, Benveniste vigorously attacked the Nature team’s "mockery of scientific inquiry."[11]

After the Nature debacle, Benveniste became more and more isolated scientifically, and some of his colleagues called for him to resign. He did not lose his job at the French National Institute of Health and Medical Research (INSERM), but funding was progressively withdrawn, and his lab was eventually closed. According to Lionel Milgrom, a chemist and homoeopath who corresponded with Benveniste, "The knocks that he took made him suspicious of virtually everyone". Yet, despite the widespread scepticism, and despite the failure of several other groups to corroborate his findings, Benveniste continued to study the 'memory of water'. According to Brian Josephson (who, after winning the Nobel Prize for Physics in 1973 became a champion of iconoclastic ideas) "That's what good scientists do...He probably became more determined because of the opposition."[12]

Other scientists

Independently, other studies have claimed to reproduce Benveniste's experiments, including one published in the Homeopathy journal,[13][14] edited by homeopathic doctor Peter Fisher (see also Homeopathic coverage, below).

In 2003 Louis Rey, a chemist from Lausanne, reported that frozen samples of lithium and sodium chloride solutions prepared according to homeopathic prescriptions showed — after being exposed to radiation — different thermoluminescence peaks compared with pure water. Rey claimed that this suggested that the networks of hydrogen bonds in homeopathic dilutions were different. [15] These results have never been replicated and are not generally accepted - even Benveniste criticised them, pointing out that they were not blinded [16]

In January 2009, Luc Montagnier, the Nobel Laureate virologist who led the team that discovered the human immunodeficiency virus (HIV), claimed (in a paper published in a journal that he set up, which seems to have avoided conventional peer review as it was accepted three days after submission) that the DNA of pathogenic bacteria and viruses massively diluted in water emit radio waves that he can detect.[17] This, he claimed, can also be used to detect the medicine in a homeopathic remedy.[18][19] The device used to detect these signals was developed by Jacques Benveniste, and was independently tested, with the co-operation of the Benveniste team, at the request of the United States Defense Advanced Research Projects Agency. That investigation was unable to replicate any effects of digital signals using the device.[20]

In 2010, at the age of 78, Montagnier announced that he would take on the leadership of a new research institute at Jiaotong University in Shanghai, where he plans to continue this work. He claims that the findings "are very reproducible and we are waiting for confirmation by other labs", but said, in an interview with Science, "There is a kind of fear around this topic in Europe. I am told that some people have reproduced Benveniste's results, but they are afraid to publish it because of the intellectual terror from people who don't understand it." Montagnier had called Benveniste "a modern Galileo", but the problem was that "his results weren't 100% reproducible".[21]

Other healers

Claims about supernatural or mystical qualities of water have been made by some "alternative healers". For example, practitioners of the Silva Method[22] claim to "program" water to heal a person, long after the healer has programmed the water and is personally unavailable. These alternative healers focus on the effects of energies, generated by people, on water. In Qigong (in Traditional Chinese Medicine):

"Subtle, or vibrational, energy is broadly defined as energy that is not generally recognized by mainstream physics and for which there are no means of measurement. ...

It is fundamental to many unexplained phenomena such as the power of spirituality and prayer, the effect of remote intention, the operation of homeopathy, and the functioning of the mind/body information network..."[23]

Masaru Emoto built a business selling water products. In a series of books — beginning with Messages from Water (1999) — he claimed that ice crystals reflect the words, music, pictures — even thoughts and intentions —to which the droplets of water were exposed before being frozen. He also claimed to find effects of 'healing energy' on water (Pranic Healing):

"After the healers projected their energy toward the water, ... the water that was healed with Pranic energy had impeccable crystal formation while the tap water's internal structure was chaotic."[24]

Emoto makes some remarkable claims:

"So where is the solution to the problem of global warming in this book? Well, because it shows that we can extract energy out of water. For example, the crystal photograph on the cover is shining beautifully. This is a result of when the cameraman and the water resonated."[25]

Homeopathic coverage

To most orthodox scientists, the "memory of water" is not something that deserves serious consideration; the only evidence is the flawed Benveniste work. By contrast, the notion of "memory of water" has been taken seriously among homeopaths. For them, it seemed to be part of a possible explanation of why some of their remedies might work. An overview of the issues surrounding the memory of water was the subject of a special issue of Homeopathy. In an editorial, the editor of Homeopathy, Peter Fisher, acknowledged that Benveniste’s original method does not yield reproducible results and declared "...the memory of water is a bad memory: it casts a long shadow over homeopathy and is just about all that many scientists recall about the scientific investigation of homeopathy, equating it with poor or even fraudulent science." The issue was an attempt to restore some credibility to the notion with articles proposing various, very different theories of water memory, such as: electromagnetic exchange of information between molecules, breaking of temporal symmetry, thermoluminescence, entanglement described by a new quantum theory, formation of hydrogen peroxide, clathrate formation, etc. Some of the proposed mechanisms would require overthrowing much of 20th century physics.[26]

In 2010, a team of scientists from India found that some commercially manufactured metal-derived homeopathic remedies in fact contained nanoparticles of the metals and their aggregates, despite the claimed high-dilution.[27][28] In 2015, a study in India found that homeopathic remedies in fact contained nanoparticles of the resource medicine, despite the claimed high-dilution.[29] Another team of scientists found that Quartz, Sulfur and Copper Sulfate-derived homeopathic remedies in fact contained nanoparticles of those substances and their aggregates, despite the claimed high-dilution.[30] Traditional homeopathic preparation methods are very different from the controlled microchemical procedures used for serial dilutions in scientific laboratories, and the assumption that homeopathic remedies are in fact diluted to the extent claimed may be wrong. As pointed out in an editorial in Homeopathy, "The skeptics have gotten the homeopathic world so busy trying to defend various theories of water memory that we have overlooked the possibility that some of the material somehow actually persists in highly diluted homeopathic medicines."[31]

References

  1. Endler PC et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10-23. Homeopathy (2010) 99, 25–36
  2. Chirumbolo S et al. Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study. Inflamm Res DOI 10.1007/s00011-009-0044-4
  3. Keutsch FN et al. (2003) The water trimer Chem Rev 103:2533-77 PMID 12848579
  4. Elsaesser T (2009) Ultrafast memory loss and relaxation processes in hydrogen-bonded systems Biol Chem 390:1125-32 (Review) PMID 19663683
  5. Keutsch FN, Saykally RJ (2001) Water clusters: untangling the mysteries of the liquid, one molecule at a time Proc Natl Acad Sci USA 98:10533-40 (Review) PMID 11535820
  6. Davenas E et al. (1988) Human basophil degranulation triggered by very dilute antiserum against IgE Nature PMID 2455231
  7. Maddox, J. "‘High-dilution’ experiments a delusion" (PDF). Nature 334: 287–290. DOI:10.1038/334287a0. Research Blogging.
  8. Poitevin B et al. (1988) In vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica Brit J Clin Pharmacol 25: 439-44
  9. Hirst SJ et al. (1993) Human basophil degranulation is not triggered by very dilute antiserum against human IgE Nature doi 366:525-7
  10. Guggisberg AG et al. (2005) Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. Complement Ther Med 13:91-100
  11. Benveniste J (1988) Dr Jacques Benveniste replies Nature doi 334:291
  12. Benveniste obituary in Nature
  13. Endler PC et al. Repetitions of fundamental research models for homeopathically prepared dilutions beyond 10-23. Homeopathy (2010) 99, 25–36
  14. Chirumbolo S et al. Inhibition of CD203c membrane up-regulation in human basophils by high dilutions of histamine: a controlled replication study. Inflamm Res DOI 10.1007/s00011-009-0044-4
  15. Rey L (2003)Thermoluminescence of ultra-high dilutions of lithium chloride and sodium chloride Physica A 323:67–74
  16. Icy claim that water has memory New Scientist 11 June 2003
  17. Montagnier L et al. (2009) Electromagnetic signals are produced by aqueous nanostructures derived from bacterial DNA sequences Interdiscip Sci 1:81-90 PMID 20640822
  18. "Nobel laureate gives homeopathy a boost", The Australian, July 5, 2010
  19. Alexey Kovalev (07 June 2010), "Top 6 unconventional post-Nobel Prize claims", Wired
  20. Jonas WB et al. (2006) Can specific biological signals be digitized? FASEB J 20:23-8 PMID 16394263
  21. Newsmaker interview: Luc Montagnier. French Nobelist escapes 'intellectual terror' to pursue radical ideas in China. Interview by Martin Enserink Science 2010 Dec 24;330:1732
  22. Laura Silva Quesada, Healing Qualities of Water and Useful Applications
  23. Tom Rogers, Qigong - Energy Medicine for the New Millennium
  24. LocalHealers.com, Pranic Healing Career Guide
  25. How to Take a Water Crystal Photograph. OFFICE MASARU EMOTO. Retrieved on March 24, 2010.
  26. Martin Chaplin, ed. (2007), The Memory of Water Homeopathy 96:141-230
    Copies of the articles in this special issue are freely available on a private website, along with discussion. Homeopathy Journal Club hosted by Bad Science, a blog by Ben Goldacre
  27. Chikramane PS et al. (2010) {http://www.katonics.com/uploads/2010%20-%20%20Paper%201%20-%20Extreme%20homeopathic%20dilutions%20retain%20starting%20%20materials-A%20nanoparticulate%20perspective.pdf]
  28. Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective Homeopathy 99:231-42
  29. Not ‘sugar pills’, nano particles found in diluted homeo drugs, Times News Network, Bennett, Coleman & Co. Ltd., 3 April 2015. Retrieved on 4 April 2015.
  30. Homeopathic Preparations of Quartz, Sulfur and Copper Sulfate Assessed by UV-Spectroscopy Pub Med 99:231-42
  31. Ives JA et al. (2010) Do serial dilutions really dilute? Homeopathy 99:229-30 PMID 20970091