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| ==The Benveniste studies==
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| Human [[basophil]]s are a rare [[granulocyte]] cell type accounting for 0.1–1% of white blood cells; these cells contain large numbers of "granules" which store inflammatory mediators, including in particular [[histamine]]. These cells can be cultured readily and studied ''in vitro''. In these cells, exposure to anti-human-IgE [[antibodies]] triggers a "degranulation" process in which the granules fuse with the plasma membrane to release their contents, including histamine, into the extracellular fluid. At high concentrations (>10<sup>−6</sup> M) histamine binds to H<sub>2</sub> receptors on the surface of the basophils, and regulates the basophil degranulation by feedback inhibition.
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| Basophil activation can be measured in several different ways. First, degranulated cells can be stained and then counted; this is a subjective measurement and is prone to variable outcomes depending on the observer. Second, histamine release into the culture medium can be measured using fluorimetric assays. Third, the fusion of cytoplasmatic granules leads to the expression of the marker [[CD63]] on the surface of the basophils; the percentage of basophils that express CD63 can be determined with [[flow-cytometry]], and correlates well with histamine release.
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| As mentioned above, the discussion about water memory started when in 1988 Jacques Benveniste (1935-2004) a distinguished French immunologist published a controversial paper in ''Nature'' reporting on the action of very high dilutions of anti-immunoglobulin E on the degranulation of human [[basophil]]s.<ref name=Benveniste /> At the high dilutions used, the solutions should have contained only molecules of water, and no molecules of (anti-IgE) at all. Benveniste concluded that the configuration of molecules in water was biologically active.
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| ''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 his laboratory following publication. Benveniste accepted these conditions; the results were replicated in Milan, Italy; in Toronto, Canada; in Tel-Aviv, Israel and in Marseille, France, and the article was accompanied by an editorial titled "When to believe the unbelievable." After publication, the follow-up investigation was conducted by a team including the editor of ''Nature'', Dr 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 the team published in the July 1988 a detailed critique of Benveniste’s study. They claimed 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 published article were paid for under a contract with the French company ''Boiron et Cie''.<ref name=Maddox/>
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| In the same issue of ''Nature'' (and subsequently) Benveniste vigorously attacked the ''Nature'' team’s "mockery of scientific inquiry." <ref>J. Benveniste, ''Dr Jacques Benveniste replies'', News and views, ''Nature'', vol. '''334''' p. 291 (1988) [http://dx.doi.org/doi:10.1038/334291a0 doi] </ref> Subsequent attempts by other labs to reproduce Benveniste's results have failed to reproduce the effects <ref>S. J. Hirst, N. A. Hayes, J. Burridge, F. L. Pearce, J. C. Foreman, ''Human basophil degranulation is not triggered by very dilute antiserum against human IgE'', Nature vol. '''366''', pp. 525–527 (1993) [http://dx.doi.org/doi:10.1038/366525a0 doi]
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| </ref>. However other studies have looked at the effects of very low concentrations of [[histamine]] on degranulation induced by anti-[[Immunoglobulin#immunoglobulin|immunoglobulin E (IgE)]] antibodies, and again reported effects at very low concentrations.<ref name = "Belon" /> As degranulation itself produces relatively high concentrations of histamine in the medium, one would only expect an effect with very high concentrations of added histamine—and indeed the most recent study reported significant effects only at 10<sup>−2</sup> M histamine. These experiments generally involved dilutions of histamine to concentrations of as low as 10<sup>−38</sup> M, and the dilutions were performed conventionally not according to the protocols used in homeopathy.
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| So how is it possible that adding vanishingly low concentrations of histamine to a preparation that is already secreting high concentrations might have any effect? What could possibly explain the extraordinary results reported by Benveniste and others? One difficulty with the basophil preparation is that, in these cells, degranulation can be triggered by many different stimuli, including slight mechanical disturbances and environmental variations in temperature, and is sensitive to small differences in incubation time, making adequate controls very difficult. For example, in the experiments of Guggisberg ''et al.''<ref> Guggisberg AG, Baumgartner SM, Tschopp CM, and Heusser P (2005) Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. ''Complement Ther Med'' 13:91-100.</ref> the authors found no significant effects of low dilutions of histamine, but did find significant effects for row numbers of the microtiter plates—i.e., there was a significant effect simply of the order in which the samples were assayed. They concluded that seemingly, trivial differences in the experimental set up can lead to significant differences of the results.
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| Benveniste never retracted his claims. On the contrary, later he founded the field of "Digital Biology",<ref>[http://www.digibio.com/cgi-bin/node.pl?nd=n1 Overview of DigiBio] Website retrieved May 7, 2009 </ref> which is based on the assumption that molecules emit [[electromagnetic radiation]] in the frequency range 20 Hz to 20 kHz,<ref>[http://www.digibio.com/cgi-bin/node.pl?nd=n3 What is Digital Biology?] Website retrieved May 7, 2009 </ref> the same range as sound waves audible by humans.<ref>To avoid misunderstanding: [[electromagnetic wave|electromagnetic (EM) waves]] have no relationship to sound waves. Sound waves are propagated by material particles and hence cannot propagate in vacuum, while EM waves can. Furthermore, neither theoretical nor experimental [[molecular spectroscopy]] can explain the existence of molecular EM waves in this region of extremely low frequencies. Moreover, unless it is shown what feeds them, Benveniste's EM waves seem to contradict the principle of conservation of energy</ref> By means of an amplifier, electromagnetic coils and a PC sound card Benveniste claimed that he was able to digitize and store the molecular signals. The digital information (possibly after sending it over the internet) could be replayed to a biological system making it believe that it is in the presence of its "favorite molecule". Since Benveniste's description of his experiments is too vague to even begin thinking about trying to reproduce them, and since his theory is not only primitive and underdeveloped, but also in complete contradiction to the well-established principles of molecular spectroscopy, it is fair to call Digital Biology a [[pseudoscience]].
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| On the contrary, in 1997, he declared that the memory could be transmitted across a digital telephone link, suggesting that the memory involved electromagnetic signals.<ref name = digibio/>
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| ==Water in living organisms==
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| Water is essential for living organisms at every level; at the molecular level in living cells, it 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 [[NMR spectroscopy|nuclear magnetic resonance]], and these have shown that, within a cell, water diffuses much more slowly than pure water in aqueous media. This is 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.
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| <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>
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| ==Water structure as a basis for homeopathy==
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| <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>
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| [[Homeopathy]] involves the use of 'remedies' that typically involve "ultradilution" of [[drug]]s; dilution well beyond the point at which ''any'' of the original molecules are still present, combined with vigorous shaking at each stage of dilution. [[Samuel Hahnemann]], the 18th century founder of homeopathy, recognised that the vehicle or solvent (water or alcohol) must be considered as the medicine, rather than the molecule<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 |pmid=14619985 |doi= |url=http://www.science.smith.edu/departments/Biochem/Chm_357/Articles/homeopathy_molecular%20mechanisms.pdf}}</ref> Research on the plausibility of homeopathy is thus an attempt to characterize how the behaviour of the molecules of a solvent might differ depending, on the solute that was diluted in it and on the kinetic energy imposed on it (by "shaking"). 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>−12</sup> s) [[hydrogen bonds]]. Some scientists have questioned whether the very short life of these bonds determines 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 might 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>
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| Many 'anomalies' <ref>See Chaplin's [http://www.lsbu.ac.uk/water/anmlies.html web resource</ref> of water reflect a heterogeneity in its structure: liquid water is a combination of different ''[[phase]]s'' (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.
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| Two physicochemical phenomena have been given particular attention by proponents of homeopathy: [[clathrates]] and [[solitons]]. ''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. Thus this is a mechanism whereby low concentration contaminants can influence the apparent properties of water.<ref>{{citation
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| | journal = Nature
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| | year = 2007
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| | volume = 449
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| | pages = 1033-6
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| | title = Clathrate nanostructures for mass spectrometry.
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| | author = Northen TR ''et al.''
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| | url = http://www.ncbi.nlm.nih.gov/pubmed/17960240}}</ref>.
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| Vigorous shaking of water in glass bottles can cause small amounts of silica (silicate) fragments to fall into it <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> and saturation of water with components of air. 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.
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| It has been suggested that micro-bubbles and nano-bubbles, caused by vigorous shaking, might "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> Some scientists have estimated that the vigorous shaking involved with making homeopathic remedies 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>
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| ==References== | | ==References== |
| {{reflist|2}} | | {{reflist|2}} |
Memory of water is a phrase used by homeopaths to explain how the aqueous (water) solutions they use as remedies might produce the results that they claim to see in their patients. Homeopathic remedies deliberately use extremely high dilutions, so it is unlikely that a therapeutic dose contains even a single molecule of substance other than pure water. This has led homeopaths to speculate that a possible explanation for the observed responses is "memory of water"; the water somehow "remembers" the biologically active molecules that it has once been in contact with, and that "memory" produces therapeutic effects.
Chemists and physicists generally see this notion as nonsense. The consensus of scientists working in the field is that liquid water exists as a continuously rearranging hydrogen-bonded network with motions on the picosecond (10−12 s) time scale.[1]. A picture of a quickly rearranging network is very difficult to reconcile with liquid water structures that are sustained for more than a few picoseconds. Accordingly there is no room for a water "memory" in the current scientific view on the liquid.
The Benveniste study
In 1988, a French immunologist, Jacques Benveniste, and a group of colleagues published a paper [2] in the prestigious English journal Nature. Their data indicated that diluted water, ethanol or propanol might retain some qualities of various materials that had once been dissolved in it. In particular, they claimed to have measured effects on human immune response.
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, however, the phrase that became widespread was "memory of water". Le Monde considered the paper important, making it a front page story, and correctly pointing out that if this work were correct, it would overthrow many of the foundations of physics.
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 his laboratory following publication. Benveniste accepted these conditions; the results were replicated in Milan, Italy; in Toronto, Canada; in Tel-Aviv, Israel and in Marseille, France, and the article was accompanied by an editorial titled "When to believe the unbelievable." After publication, the follow-up investigation was conducted by a team including the editor of Nature, Dr 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 the team published in the July 1988 a detailed critique of Benveniste’s study. [3] They claimed 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 published article were paid for under a contract with the French company Boiron et Cie.[3].
Subsequent attempts by other labs to reproduce Benveniste's results have failed to reproduce the effects. [4] [5]
Benveniste has never retracted his claims. In the same issue of Nature that carried the critique, Benveniste vigorously attacked the Nature team’s "mockery of scientific inquiry." [6]. He has maintained his position in later publications as well.
Homeopathic coverage
Despite the general skepticism of scientists, and the failure of others to replicate Benveniste's results, the notion of "memory of water" is still taken seriously among homeopaths. An overview of the issues surrounding the memory of water and its relationship to homeopathic medicine was the subject of a special issue of the leading journal on homeopathy.[7] The articles in this issue propose widely varying mechanisms for 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. without any mechanism singularly standing out as the definitive explanation. Some of the proposed mechanisms require revolutionary new physical principles overthrowing much of 20th century physics. Remarkably, all explanations concentrate on water and its alleged special properties, the fact that—according to Benveniste et al.—ethanol and propanol also have memory is completely ignored.
Digtal biology
Benveniste never retracted his claims. On the contrary, later he founded the field of "Digital Biology",[8] which is based on the assumption that molecules emit electromagnetic radiation in the frequency range 20 Hz to 20 kHz,[9] the same range as sound waves audible by humans.[10] By means of an amplifier, electromagnetic coils and a PC sound card Benveniste claimed that he was able to digitize and store the molecular signals. The digital information (possibly after sending it over the internet) could be replayed to a biological system making it believe that it is in the presence of its "favorite molecule". Since Benveniste's description of his experiments is too vague to even begin thinking about trying to reproduce them, and since his theory is not only primitive and underdeveloped, but also in complete contradiction to the well-established principles of molecular spectroscopy, it is fair to call Digital Biology a pseudoscience.
References
- ↑ F. N. Keutsch, J. D. Cruzan, and R. J. Saykally, Chemical Reviews, Vol.103, pp. 2533-2577 (2003)
- ↑ E. Davenas, F. Beauvais, J. Arnara, M. Oberbaum, B. Robinzon, A. Miadonna, A. Tedeschi, B. Pomeranz, P. Fortner, P. Belon, J. Sainte-Laudy, B. Poitevin and J. Benveniste, Human basophil degranulation triggered by very dilute antiserum against IgE, Nature, Vol. 333, pp. 816-818, 30th June, 1988.Free text on DigiBio site. Non-free text on Nature site
- ↑ 3.0 3.1 Maddox, John; James Randi and Walter W. Stewart (28 July 1988). "‘High-dilution’ experiments a delusion" (PDF). Nature 334: 287–290. DOI:10.1038/334287a0. Research Blogging.
- ↑ S. J. Hirst, N. A. Hayes, J. Burridge, F. L. Pearce, J. C. Foreman, Human basophil degranulation is not triggered by very dilute antiserum against human IgE, Nature vol. 366, pp. 525–527 (1993) doi
- ↑ Guggisberg AG, Baumgartner SM, Tschopp CM, and Heusser P (2005) Replication study concerning the effects of homeopathic dilutions of histamine on human basophil degranulation in vitro. Complement Ther Med 13:91-100.
- ↑ J. Benveniste, Dr Jacques Benveniste replies, News and views, Nature, vol. 334 p. 291 (1988) doi
- ↑ 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
- ↑ Overview of DigiBio Website retrieved May 7, 2009
- ↑ What is Digital Biology? Website retrieved May 7, 2009
- ↑ To avoid misunderstanding: electromagnetic (EM) waves have no relationship to sound waves. Sound waves are propagated by material particles and hence cannot propagate in vacuum, while EM waves can. Furthermore, neither theoretical nor experimental molecular spectroscopy can explain the existence of molecular EM waves in this region of extremely low frequencies. Moreover, unless it is shown what feeds them, Benveniste's EM waves seem to contradict the principle of conservation of energy