Friday, August 03, 2007

A bad memory

I have just read all the papers on ‘the memory of water’ published in a special issue of the journal Homeopathy, which will be released in print on 10 August. Well, someone had to do it. I rather fear that my response, detailed below, will potentially make some enemies of people with whom I’ve been on friendly terms. I hope not, however. I hope they will respect my right to present my views as much as I do theirs to present theirs. But I felt my patience being eroded as I waded through this stuff. Might we at least put to rest now the tedious martyred rhetoric about ‘scientific heresy’, which, from years of unfortunate experience, I can testify to being the badge of the crank? I once tried to persuade Jacques Benveniste of how inappropriate it was to portray a maverick like John Maddox as a pillar of the scientific establishment – but he wouldn’t have it, I suppose because that would have undermined his own platform. Ah well, here’s the piece, a much shortened version of which will appear in my Crucible column in the September issue of Chemistry World.


I met Jacques Benveniste in 2004, shortly before he died. He had tremendous charm and charisma, and I rather liked him. But I felt then, and still feel now, that in ‘discovering’ the so-called memory of water he lost his way as a scientist and was sucked into a black hole of pseudoscience that was just waiting for someone like him to come along.

This particular hole is, of course, homeopathy. In 1988, Benveniste published a paper in Nature that seemed to offer an explanation for how homeopathic remedies could retain their biological activity even after being diluted so much that not a single molecule of the original ‘active’ ingredients remains [1]. It is common for homeopathic remedies to have undergone up to 200 tenfold dilutions of the original ‘mother tincture’, which is quite sufficient to wash away even the awesome magnitude of Avogadro’s constant.

Benveniste and his coworkers studied the effect of dilution of an antibody that stimulates human immune cells called basophils to release histamine – a response that can provoke an allergic reaction. In effect, the antibody mimics an allergen. The researchers reported that the antibody retains its ability to provoke this response even when diluted by 10**60 – and, even more oddly, that this activity rises and falls more or less periodically with increasing dilution.

The paper’s publication in Nature inevitably sparked a huge controversy, which turned into a media circus when Nature’s then editor John Maddox led an investigation into Benveniste’s laboratory techniques. Several laboratories tried subsequently to repeat the experiment, but never with unambiguous results. The experiment proved irreproducible, and came to be seen as a classic example of what US chemist Irving Langmuir christened ‘pathological science’. (The details are discussed in my book on water [2], or you can read Michel Schiff’s book [3] for a deeply partisan view from the Benveniste camp.)

Benveniste remained convinced of his results, however, and continued working on them in a privately funded lab. He eventually claimed that he could ‘programme’ specific biological activity into pure water using electromagnetic radiation. He predicted a forthcoming age of ‘digital biology’, in which the electromagnetic signatures of proteins and other biological agents would be digitally recorded and programmed into water from information sent down phone lines.

Homeopaths have persistently cited Benveniste’s results as evidence that their treatments do not necessarily lack scientific credibility. Such claims have now culminated in a special issue of the journal Homeopathy [4] that presents a dozen scientific papers on the ‘memory of water.’

In at least one sense, this volume is valuable. The memory of water is an idea that refuses to go away, and so it is good to have collected together all of the major strands of work that purport to explain or demonstrate it. The papers report some intriguing and puzzling experimental results that deserve further attention. Moreover, the issue does not duck criticism, including a paper from renowned water expert José Teixeira of CEA Saclay in France that expresses the sceptic’s viewpoint. Teixeira points out that any explanation based on the behaviour of pure water “is totally incompatible with our present knowledge of liquid water.”

But perhaps the true value of the collection is that it exposes this field as an intellectual shambles. Aware that I might hereby be making enemies of some I have considered friends, I have to say that the cavalier way in which ‘evidence’ is marshalled and hypotheses are proposed with disregard for the conventions of scientific rigour shocked even me – and I have been following this stuff for far too long.

Trying to explain homeopathy through some kind of aqueous ‘memory’ effect has plenty of problems created by the traditions of the field itself, in which ‘remedies’ are prepared by serial dilution and vigorous shaking, called succussion. For example, it is necessary not only that the memory exists but that it is amplified during dilution. In his overview paper, guest editor Martin Chaplin, a chemist at South Bank University in London whose web site on water is a mine of valuable information, points to the surprising recent observation that some molecules form clusters of increasing size as they get more dilute. But this, as he admits, would imply that most homeopathic solutions would be totally inactive, and only a tiny handful would be potent.

Another problem, pointed out by David Anick of the Harvard Medical School and John Ives of the Samueli Institute for Information Biology in Virginia, is that if we are to suppose the ‘memory’ to be somehow encoded in water’s structure, then we must accept that there should be many thousands of such stable structures, each accounting for a specific remedy – for several thousand distinct remedies are marketed by homeopathic companies, each allegedly distinct in its action.

Yet another difficulty, seldom admitted by homeopaths, is that the dilutions of the mother tincture must allegedly be made by factors of ten and not any other amount. This is not mentioned in the papers here, presumably because it is too absurd even for these inventive minds to find an explanation. A related issue that is addressed by Anick is the tradition of using only certain dilution factors, such as 10**6, 10**12, 10**30 and 10**200. He offers a mathematical model for why this should be so that masquerades as an explanation but is in fact tantamount to a refutation: “it would be inconceivable”, he says, “that one number sequence would work in an ideal manner for every mother tincture.” Still, he concludes, the convention might be ‘good enough’. So why not perhaps test if it makes any difference at all?

One of the challenges in assessing these claims is that they tend to play fast and loose with original sources, which obliges you to do a certain amount of detective work. For example, Chaplin states that the ability of enzymes to ‘remember’ the pH of their solvent even when the water is replaced by a non-aqueous solvent implies that the hydrogen ions seem to have an effect in their absence, “contrary to common sense at the simplistic level.” But the paper from 1988 in which this claim is made [5] explains without great ceremony that the ionizable groups in the enzyme simply retain their same ionization state when withdrawn from the aqueous solvent and placed in media that lack the capacity to alter it. There’s no mysterious ‘memory’ here.

Similarly, Chaplin’s comment that “nanoparticles may act in combination with nanobubbles to cause considerable ordering within the solution, thus indicating the possibility of solutions forming large-scale coherent domains [in water]” is supported by a (mis-)citation to a paper that proposes, without evidence, the generally discredited idea of ‘ice-like’ ordering of water around hydrophobic surfaces.

One of the hypotheses for water’s ‘memory’, worked out in some detail by Anick and Ives, invokes the dissolution of silicate anions from the glass walls of the vessel used for dilution and succussion, followed by polymerization of these ions into a robust nanostructured particle around the template of the active ingredient initially present. Certainly, silicate does get added, in minute quantities, to water held in glass (this seemed to be one of the possible explanations for another piece of water pathological science, polywater [6]). But how to progress beyond there, particularly when such a dilute solution favours hydrolysis of polysilicates over their condensation?

Well, say Anick and Ives, there are plenty of examples of silicate solutions being templated by solutes. That’s how ordered mesoporous forms of silica are synthesized in the presence of surfactants, which aggregate into micelles around which the silica condenses [7]. This, then, wraps up that particular part of the problem.

But it does nothing of the sort. This templating has been seen only at high silicate concentrations. It happens when the template is positively charged, complementary to the charge on the silicate ions. The templating gives a crude cast, very different from a biologically active replica of an enzyme or an organic molecule. Indeed, why on earth would a ‘negative’ cast act like the ‘positive’ mold anyway? The template is in general encapsulated by the silica, and so doesn’t act as a catalyst for the formation of many replicas. And for this idea to work, the polysilicate structure has to be capable of reproducing itself once the template has been diluted away – and at just the right level of replicating efficiency to keep its concentration roughly constant on each dilution.

The last of these requirements elicits the greatest degree of fantastical invention from the authors: during the momentary high pressures caused by succussion, the silicate particles act as templates that impose a particular clathrate structure on water, which then itself acts as a template for the formation of identical silicate particles, all in the instant before water returns to atmospheric pressure. (Elsewhere the authors announce that “equilibrium of dissolved [silicate] monomers with a condensed silica phase can take months to establish.”) None of this is meanwhile supported by the slightest experimental evidence; the section labelled ‘Experiments to test the silica hypothesis’ instead describes experiments that could be done.

Another prominent hypothesis for water’s memory draws on work published in 1988 by Italian physicists Giuliano Preparata and Emilio Del Guidice [8]. They claimed that water molecules can form long-ranged ‘quantum coherent domains’ by quantum entanglement, a phenomenon that makes the properties of quantum particles co-dependent over long ranges. Entanglement certainly exists, and it does do some weird stuff – it forms the basis of quantum computing, for example. But can it make water organize itself into microscopic or even macroscopic information-bearing domains? Well, these ‘quantum coherent domains’ have never been observed, and the theory is now widely disregarded. All the same, this idea has become the deus ex machina of pathological water science, a sure sign that the researchers who invoke it have absolutely no idea what is going on in their experiments (although one says such things at one’s peril, since these researchers demonstrated a litigious tendency when their theory was criticized in connection with cold fusion).

Such quantum effects on water’s memory are purportedly discussed in the special issue by Otto Weingärtner of Dr Reckeweg & Co. in Bensheim, Germany – although the paper leaves us none the wiser, for it contains neither experiments nor theory that demonstrate any connection with water. The role of entanglement is made more explicit by Lionel Milgrom of Imperial College in London, who says that “the homeopathic process is regarded as a set of non-commuting complementary observations made by the practitioner… Patient, practitioner, and remedy comprise a three-way entangled therapeutic entity, so that attempting to isolate any of them ‘collapses’ the entangled state.” In other words, this notion is not really about quantum mechanics at all, but quantum mysticism.

Benveniste’s long-term collaborator Yolène Thomas of the Institut Andre Lwoff in Villejuif argues, reasonably enough, that in the end experiment, not theory, should be the arbiter. And at face value, the ‘digital biology’ experiments that she reports are deeply puzzling. She claims that Benveniste and his collaborators accumulated many examples of biological responses being triggered by the digitized radiofrequency ‘fingerprints’ of molecular substances – for example, tumour growth being inhibited by the ‘Taxol signal’, the lac operon genetic switch of bacteria being flipped by the signal from the correct enantiomeric form of arabinose, and vascular dilation in a guinea pig heart being triggered by the signal from the classic vasodilator acetylcholine. What should one make of this? Well, first, it is not clear why it has anything to do with the ‘memory of water’, nor with homeopathy. But second, I can’t help thinking that these experiments, however sincere, have an element of bad faith about them. If you truly believe that you can communicate molecular-recognition information by electromagnetic means, there is no reason whatsoever to study the effect using biological systems as complex as whole cells, let alone whole hearts. Let’s see it work for a simple enzymatic reaction, or better still, an inorganic catalyst, where there is far less scope for experimental artefacts. It is hard to imagine any reason why such experiments have not been attempted, except for the reason that success or failure would be less ambiguous.

What emerges from these papers is an insight into the strategy adopted more or less across the board by those sympathetic to the memory of water. They begin with the truism that it is ‘unscientific’ to simply dismiss an effect a priori because it seems to violate scientific laws. They cite papers which purportedly show effects suggestive of a ‘memory’, but which often on close inspection do nothing of the kind. They weave a web from superficially puzzling but deeply inconclusive experiments and ‘plausibility arguments’ that dissolve the moment you start to think about them, before concluding with the humble suggestion that of course all this doesn’t provide definitive evidence but proves there is something worth further study.

One has to conclude, after reading this special issue, that you can find an ‘explanation’ at this level for water’s memory from just about any physical phenomenon you care to imagine – dissipative non-equilibrium structures, nanobubbles, epitaxial ordering, gel-like thixotropy, oxygen free radical reactions… In each case the argument leaps from vague experiments (if any at all) to sweeping conclusions that typically take no account whatsoever of what is known with confidence about water’s molecular-scale structure, and which rarely address themselves even to any specific aspect of homeopathic practice. The tiresome consequence is that dissecting the idea of the memory of water is like battling the many-headed Hydra, knowing that as soon as you lop off one head, another will sprout.

In his original paper in Nature, Jacques Benveniste offered a hypothesis for how the memory effect works: “specific information must have been transmitted during the dilution/shaking process. Water could act as a template for the [antibody] molecule, for example by an infinite hydrogen-bonded network or electric and magnetic fields.” Read these sentences carefully and you will perhaps decide that Benveniste missed his calling as a post-modernist disciple of his compatriot Jacques Derrida. It has no objective meaning that I can discern. It sounds like science, but only because it copies the contours of scientific prose. This, I would submit, is a fair metaphor for the state of ‘water memory’ studies today.

I once read a book supposedly about the philosophy of religion which was in fact an attempt to make a logical case for God’s existence. Having stepped through all of the traditional arguments – the ontological, the argument from design and so forth – the author admitted that all of them had significant flaws, but concluded that collectively they made a persuasive case. This group of papers is similar, implying that a large enough number of flimsy arguments add up to a single strong one. It leaves me feeling about homeopathy much as I do about religion: those who find it genuinely helpful are right to use it, but they shouldn’t try to use scientific reason to support their decision.

1. E. Davenas et al., Nature 333, 816 (1988).
2. P. Ball, H2O: A Biography of Water (Weidenfeld & Nicolson, 1999).
3. M. Schiff, The Memory of Water (Thorsons, 1995).
4. Homeopathy 96, 141-226 (2007).
5. A. Zaks & A. Klibanov, J. Biol. Chem. 263, 3194 (1988).
6. F. Franks, Polywater (MIT Press, Cambridge, MA, 1981).
7. C. T. Kresge et al., Nature 359, 710 (1992).
8. E. Del Guidice et al. Phys. Rev. Lett. 61, 1085 (1988).


Stephen said...

Exhaustive double blind placebo controlled tests have shown that light blue placebo pills work the best, except for males in Italy - which is thought to have something to do with sports played there. Since i'm not Italian, and don't follow sports generally, i've signed up for the new Robin's egg blue double strength placebo pills to cure what ails me. I use distilled water to wash them down. Distilled water can be considered as the ultimate dilution of every possible kind of tincture, and therefore is good for anything that could possibly ail you. Besides, it's on sale at the drug store across the street, and it can be used as part of a contact lens regimen.

For the placebo effect to work, you need a good story. This is my story, and i'm sticking with it. Of course, this is only used for minor maladies. For anything as serious as a cold, i check with my doctor for advice and aid.

JimmyGiro said...

So what did Maddox do to become a maverick, wiki left me none the wiser?

Philip Ball said...

As Nature's editor, John had a soft spot for the unorthodox and controversial (e.g. Fred Hoyle's "steady state" crew) that made several more staid scientists impatient with him. I doubt that Benveniste's paper would ever have got into print if it wasn't for John. This was one of the things that made working for him so exhilarating and sometimes frustrating.
By the way, jimmygiro, do I know you?

The Factician said...

A year or two ago, my wife reviewed a paper from a lab in eastern Europe that used water with memory for various microbial assays. Even without the magic water, it was one of the poorest quality and poorest controlled set of experiments she had ever seen. Needless to say it was rejected.

Interesting to hear about the background of it. Thanks.

JimmyGiro said...

Maybe Maddox is a product of the 'war' generation. Our times must be so politically dull to them that they could be inclined to stir things up.

As for me, I've witnessed the destructive force of your exhilaration and frustration upon hapless ping pong balls in the sixth form common room at Carisbrooke:

Lisa said...

Interesting post from a 'history of science' viewpoint, about something I never knew about and probably never needed to!

martin chaplin said...

I am glad that Philip Ball has read the papers; I hope others will and form their own opinions. I knew when we were putting these papers together that we would be ridiculed for even making the attempt. Of course I am disappointed that Philip is so negative and he harps on so about historical stuff and some old quotes; perhaps his rhetorical flow just carried him along.
It is important to point out some facts concerning this group of papers and Philip’s review of them. We tried to include all of the relevant theories and areas of experimental data. Some may or may not prove important and others less so; as Philip admits, we tried to show the problems with some of the existing theories and did not duck issues. Teixeira does indeed state “The main purpose of this paper is to recall that this hypothesis is totally incompatible with our present knowledge of liquid water”, (a subtly more telling quote than Philip’s abbreviated version, in italics). Philip ignores Teixeira’s key message that he means ‘pure liquid water’ and states “Even in small quantities, some solutes can modify substantially some properties of pure water”; a major theme in several of our papers. Pure liquid H2O simply does not exist anywhere in the Universe except in computer memory.
I disagree with Philip over playing fast and loose with original sources. I do give the example of dry enzymes remembering their last aqueous pH as an example where there clearly is a memory effect and where this was a puzzle when first observed. I agree that there is an acceptable (if circular and unproven) explanation of this ‘memory’ effect given in the paper I cite. In truth, this example of pH memory was not given as some sort of proof that water has a memory but given in line with the theme of my paper that the ‘puzzle’ of a memory effect disappears with an acceptable explanation. Philip does not mention one of my other examples, that of the memory of melted clathrate solutions, where there is still no acceptable explanation.
I am unsure whether Philip believes I deliberately made the mistake in the citation of Katsir et al’ paper (it should be J. Electrochem. Soc not the non-existent J. Am. Electrochem Soc; am I being paranoid or he?); I apologise for that; it was not a devilish plot but simply my error as I was misinformed when sent the proof. However, Philip ignores all the data in that paper that shows a memory effect in water and concentrates his angst on part (and not even an important part) of the explanation given for the experimental findings. As I state in my paper “too often the explanation is examined more closely than the experimental data”.

Philip Ball said...

I hope Martin does not think it was my intention to ridicule this effort. It does not deserve that (although I imagine it might receive it from other quarters). I was pleased initially by how sanely the discussion was being presented, both in the editorial by Peter Fisher and the beginning of Martin’s overview article. My comments reflect my genuine disappointment at how the quality of the contributions deteriorated. Indeed, I think it was something more than disappointment: as someone who genuinely cares in a geeky way about water science, I felt annoyed by some of the nonsensical claims and their disregard of what has been patiently learnt about the way water behaves.

I don’t agree with Martin’s interpretation of José Teixeira’s paper. I don’t think he is saying that ‘water memory’ is incompatible with what we know about the purely hypothetical ‘pure water’ studied in computer simulations. Rather, he seems to be suggesting that any explanation for alleged ‘memory effects’ cannot appeal to the structure of liquid water. He recognizes that solutes can have important effects even at apparently low concentration – but to my reading, he says so as a criticism of the poorly constrained procedures typical of the preparation of homeopathic remedies, which make it hard to know how to interpret the experimental results.

It did not occur to me for a moment to imply that Martin’s mis-citation of Katsir et al. was intentional, and I’m rather saddened to see that he feels I might harbour such suspicions. Partly, I simply wanted to alert readers to that mistake – but I confess that I was also mindful of the fact that, when in a case like this the devil is in the details, one needs to take care to get those details right.

That paper by Katsir et al. reports some very curious results – and one of the authors of the study is a friend whose work I respect very much. But I can’t help feeling that Martin is being a little disingenuous when he complains that I ignore the experiments themselves and focus on a relatively unimportant part of the explanation given for the experimental findings. In his overview, Martin says of this work that it shows how “Nanoparticles may act by themselves or in combination with the nanobubbles to cause considerable ordering within the solution, thus indicating the possibility of solutions forming large-scale coherent domains.” Now, I may be misinterpreting what he means, but I understood this to refer to ‘considerable ordering’ of water structure – that, after all, is what is usually implied by talk of ‘ordering’ within aqueous solutions, and the reference to ‘large-scale coherent domains’ seems to echo the terminology of Del Guidice’s hypothesis of quantum-mechanically induced ‘coherent domains’ of water. So I looked through Katsir et al. in search of some evidence of ordering of water structure. And the only reference to this is the one I mention, where the authors talk speculatively about ‘ice-like’ ordering of water round nanobubbles – an idea that draws on the hypothesis of Franks and Evans regarding hydrophobic solutes, which is now over 50 years old and generally discredited. So it is not clear to me that the criticism expressed in my discussion was misplaced.

I hope Martin will take my comments in the friendly way that they are intended. I think we will disagree on some of these issues. But I think we agree on the notion that the collection of papers at least has the value of laying out the arguments so that others can make up their own minds.

Dana Ullman, MPH said...

First, to clarify things, "Dana" is also a man's name (as it is in my case). Fret not, you're not the first to assume that I am a woman.

I think it is quite admirable that scientists are exploring the tough and complicated issues that surround the mechanism of action of their medicines. However, proof or disproof of a theory of this mechanism does not disprove the system of homeopathy.

In reference to mechanism of action...I personally do not know a single doctor (or patient) who refused to take aspirin just because s/he didn't know how it worked (until relatively recently).

When you consider the history of attacks against homeopaths or simply researchers who have investigated it, one must attribute high courage to all of the authors who contributed to the special issue of HOMEOPATHY (July 2007). Instead, you attribute "quantum mysticism" to some of them, even though life itself is FULL of mysteries.

Ultimately, the best scientists (and science journalists) are the most humble. Humility is a worthy goal.

Your column chose to critique Elia for an explanation he chose to give for the effects he and others had observed, but you didn't choose to describe his data which he has gotten published in various respected journals.

Likewise, you ignored the data of Rao, Roy, Bell, and Hoover. Roy has had 15 articles published in NATURE, and his material sciences lab at Penn State is internationally renown. His and his team's work should not be ignored.

In your response to Martin Chaplin, you wrote: "But I think we agree on the notion that the collection of papers at least has the value of laying out the arguments so that others can make up their own minds."

In light of this statement, your NATURE column could have presented both sides of the argument rather than providing more critique than description of the issues. This way you would have encouraged people to read this body of work and to make up their own minds.

Peter Fisher said...

This critique focuses entirely on theoretical issues, completely ignoring the considerable numbers of experiments, some new, some previously published, reported in this special issue of Homeopathy. The largest section is experimental, but from reading the blog, one would assume that no experimental data is included. Ball even criticises one of the papers in the theoretical section for not reporting any. If you are so keen on experiment, Dr Ball, why ignore it?

The fact that there is no satisfactory theoretical explanation for experimental findings does not invalidate those findings. One of the purposes of bringing this material together was to identify common themes, and in this it was very successful. Among the salient themes which emerge are:
• Water, prepared by the homeopathic of successive dilution and succussion, exhibits anomalous properties which can be detected by a range of chemical and physical methods.
• Trace amounts of contaminants including silica and dissolved gases are important in determining those properties. Ball obscures this point by quoting our sceptical author, Jose Teixeira as saying that pure water cannot have a ‘memory’, but omitting to mention that he immediately qualifies this by pointing out that the homeopathic preparation process does not result in pure water. This point is taken up by several of the authors.
• The findings suggest organisation at a mesoscopic scale. No author disputes that, on the microscopic scale, water structure is extremely short-lived.
• Several experiments yield completely unexpected yet convergent results on the temporal aspects of these phemonena.

To ignore these experimental findings just because early attempts at a theoretical understanding do not quite stack up is to put the cart before the horse. But it is no doubt a good method for stifling progress in just about any emerging scientific area…

Le Canard Noir said...

Dana said:

However, proof or disproof of a theory of this mechanism does not disprove the system of homeopathy.

So, just what is it that would disprove homeopathy? To me it looks like all of physics, chemisty and biology disprove homeopathy. All the large and well controlled studies disprove homeopathy. What more do you want?

You cling to your belief on the basis of anecdotes, some shabby test tube experiments and some half-cocked pseudo-trials.

Come on Dana, isn't it about time you said what would give you pause for thought? Or are you too closed minded to consider the possibility that homeopathy is nothing more than an elaborate placebo inducing ritual?

James Silverthorne said...

Supporting the contention that an ultra-dilute potentized agent (dilution past the Avogadro Constant) can be active: For 8+ years, Washington Homeopathic Products, a US manufacturing homeopathic pharmacy, has made and sold an ultra-dilute odor abatement solution. It is formulated to quickly decrease concentration levels of some odors and/or to decrease the rate of odor production from biological sources. The solution is misted into air and/or onto materials. "Odor Off" demonstrates its chemical activity on indoor air-borne odors and on odor-producing materials (for example, cat urine in litter box).

The observed decreased odor concentration levels are not expected to be caused by placebo responses of the targets nor by spontaneous remissions of the "ailment" being treated.

WHP has told me that customers using the product in varying situations report that this ultra-dilute, odor abatement agent is reliably efficacious. See search term: odor off.

Rolfe said...

Mr. Ullman has complained that some papers have not been commented on here, including the "data" of Rao and Roy. I and some friends spent some time scrutinising the UV spectroscopy data in that paper, and we were shocked by the elementary mistakes and missing information.

We wrote a letter to the editor of the journal, Peter Fisher, but he has not as yet replied. I copy that letter here, in the hope of informing the debate about that paper, at least.

27th August 2007.

Dr. Peter Fisher,
Editor, Homeopathy,
The Royal London Homoeopathic Hospital,
60 Great Ormond Street,
London, WC1N 3HR.

Dear Sir,

We wish to draw to your attention serious anomalies and incongruities in the UV absorption data presented in the paper by Rao et al., published in your July 2007 issue [1].

In a study of this nature, which in effect is examining multiple samples of ethanol, the over-riding concern must be absolute uniformity in the source of the solvent. For the data to be valid, it is essential that every drop of ethanol used must be sourced from the same stock bottle. However, the authors fail to make any mention of this point, and it is clear from the results presented that the source of ethanol in this investigation was most certainly not uniform.

The most striking anomaly is the UV spectrum presented for "plain ethanol", a single trace repeated three times in figure 3. The provenance of this sample is not recorded. This trace reveals extremely high absorbance (greater than 0.8 absorbance units) at 250nm, falling off steeply towards 400nm but still above 0.4 units by 350nm, and demonstrating an absorbance peak of 0.65 units with a lambda-max of about 330nm. It is simply impossible to represent this trace as being ethanol of any recognised degree of purity. Spectroscopic grade ethanol has an absorbance of less than 0.05 units between 250 and 400nm [2], and even USP/NF pharmaceutical grade ethanol has an absorbance of less than 0.3 units at 250nm, falling off to less than 0.1 units by 270nm [3]. If the substance measured by the authors as "plain ethanol" was indeed ethanol at all, it is clear that it contained extremely high levels of impurities, possibly including acetone.

In contrast, the spectra of the samples which were diluted and succussed (Nat mur, Nux vomica and the "succussed ethanol" with no mother tincture), and which were presumably all supplied by Hahnemann Laboratories as detailed on page 178, demonstrate substantially lower levels of impurities. While still not being spectroscopic grade ethanol, these samples could well represent ordinary pharmaceutical grade ethanol. The authors claim these samples are "different", however the evidence presented for this is weak to nonexistent.

Figure 1 presents one trace each for Nat mur and Nux vomica, each at 6C, 12C and 30C potencies. The traces are said to be "representative", however with no information on repeatability or how the "representative" traces were selected, it is impossible to say whether there is any real difference between any of the six spectra.

Figure 2 purports to address this point, but then fails to present the necessary data. The legend declares that 10 samples of each of the six remedy preparations were analysed. The accepted way to present such data would be as mean absorbance ± standard deviation for each wavelength point, or at least for a representative selection of wavelength points. Statistical analysis could then be used to demonstrate whether or not there was a real difference between any of the remedies or potencies. However, the authors have instead chosen to present only two traces for each preparation, as "envelopes of differences". The derivation of these traces is not explained, although we surmise that "extreme" high and low traces for each preparation were chosen to provide an impression of the range of results obtained. This is not an appropriate method of handling data of this nature, as most of the information is lost and statistical analysis is rendered impossible.

A further difficulty with figure 2 is that the upper (open circles) trace in the top graph of fig 2a (30C Nat mur) appears to be a duplicate of the upper (filled circles) trace in the top graph of fig 2b (30C Nux vom). Comparison with other traces of the two remedies indicates that this trace is really one of Nux vom, which has been duplicated into the Nat mur graph in error.

Paucity of data, ambiguity of presentation and lack of statistical analysis prevent any conclusions being drawn from the information in figure 2.

Comparison of figure 2 with figure 1 reveals that all six traces presented in figure 1 are taken from figure 2, in each case the filled-circles traces. If indeed the traces in figure 2 represent the extreme range of results obtained, this is startling, as the traces in figure 1 are stated to be "representative". In addition, while it does appear that the Nux vom samples tended to demonstrate higher absorbances than the Nat mur samples (excluding the obvious mistake noted above), in two out of the three potencies the higher Nux vom trace from fig 2 has been chosen for inclusion in fig 1, thus exaggerating the apparent difference.

Figure 3 (b and c) again repeats the same six traces as figure 1, this time grouped by remedy. Presented in this way, it is clear that there is absolutely no difference between the three potencies of Nat mur, and that while variation between the Nux vom potencies is a little more pronounced, again all three appear to come from the same population. The same is true of the three potencies of "succussed ethanol" presented in fig 3a.

On simple visual inspection it does appear that there may be genuine differences between the three remedies (although no statistics are presented to allow this to be tested), with the Nat mur showing the lowest absorbtion and the Nux vom the highest, with the succussed ethanol lying somewhere between. Nevertheless, these differences are entirely consistent with small differences in purity of the ethanol stock used for preparation of the three remedies - small, that is, relative to the very high level of impurity evident in the "plain ethanol" sample presented alongside. This degree of variation in UV absorbance is entirely to be expected between different batches of pharmaceutical grade ethanol, which is not prepared with spectroscopic analysis in mind. The authors make no mention of having stipulated to Hahnemann Laboratories that all material sent to them should be prepared from the same stock bottle, and the data presented indicate that the different remedies, possibly prepared at different times, simply came from different bottles of ethanol.

We hope you will agree that these are very serious points, and it is regrettable they were not identified by your own scrutineering process. It is clear that the data presented are wholly inadequate to support the authors’ assertion that UV spectroscopy can differentiate between the two remedies, and between different potencies of the remedies. If the authors wish to test their assertion so that it can be substantiated it will be necessary to repeat the work from the beginning, ensuring that all samples used in the study are sourced from the same bottle of stock solvent, that all duplicate preparations for precision assessment are separately prepared de novo from the mother tinctures, and that sufficient data are generated to allow robust and valid statistical analysis of the results.

Yours faithfully,

1. Rao, M. L., Roy, R., Bell, I. R. & Hoover, R. (2007) The defining role of structure (including epitaxy) in the plausibility of homeopathy. Homeopathy 96, 175-182.
2. Sigma Aldrich catalogue, ACS spectrophotometric grade ethanol 95.0%, at
3. Sigma Aldrich catalogue, USP/NF grade ethanol 190 proof, at

shpalman said...

It's Del Giudice not Del Guidice. This is not the only author's name which Lionel Milgrom can't spell, though.

smurfix said...

A homeopathic odor reducer. Nice.

Kindly tell me where I might be able to find a double-blind study which shows that the stuff is any more effective than plain ordinary water.

Thank you.

Jnan R. Saha said...

You cite work of Jacques Benveniste where he showed some IgE has some effect at 10**120 dilution and published in 1988. I was sorry to see that Dr. Benveniste was ridiculed all over in Scientific Journals. It was a Trio including Magician Randy under Dr. J. Walter Stewart of NIH. I have not seen anybody mention that one mole of any substance would have 6.02 X 10**23(Avogadro number) molecules. One mole of IgE probably has 200,000 gms. Dr. Benveniste probably used 1 mg or less of the substance to start with. That amount IgE would have maximum number of IgE particles calculated as follows.
6.02 X 10**23/(200,000X1000) which is less than 10**16.
That means if Dr. Benveniste diluted 10 fold serially, the 17th tube virtually would have no IgE. If he replicated many times up to 20 tubes, he was right in his assumption. In the last 21 years I have not seen any one calculated the number of molecules at each dilution in his experiment. You may be interested to know that Earth has only 10**48 Particles(upper bound). That means that if you take the whole Earth crush it and serially dilute, 49th tube may not have any particle.

I received my Masters in Biochemistry in 1960, long before you were born as I see you in the picture. I worked with IgE in the early Sixties. If you do not challenge my calculations, I will be interested in hearing from you. You can send me an e-mail or write to me. Regards,
Jnan R. Saha
9 Village Green
Wesley Hills, NY 10952

Jnan R. Saha said...

My Grandfather was Homeopath, he taught all the local Homeopaths. He died 64 years ago. I saw people lined up in the morning for Homeopathic Medicine. Anyone receiving the medicine did not come back for the same symptoms. When I was in High School and learned about Avogadro's number, it kept me thinking that at higher dilutions not a single molecule of the substance that was diluted left in any dose of Homeopathic Medicine. I thought it was Placebo or Psychological effect. I visited Bangladesh and India and found people were still getting Homeopathic treatments. This is probably real Alternative medicine and Dr. Benveniste was right for his assumptions.

Jnan R. Saha said...

What language were the last posts. I can ask some one to translate it.

Wallace Sampson said...

I came across this post today after browsing through a few commentaries of homeopathy's resurgent efforts at respectablility.

I analyzed the Benveniste Nature paper when called by Newsweek magazine for comments on reports of his claimed success.

Although trained as a hematologist, I was not familiar with the basophil degranulation technique, which was predominantly an immunological test for effects of stimulators of histamine. It took me several weeks to understand what the Benveniste lab had done and the problems the data presented. I wrote a reply explaining that even if the work was perfomed authentically, the resulting conclusions were not valid.

In short, when I re-plotted the findings as described, the graph showed 2 major findings and conclusions.

1) Each preparation run varied so much from the previous or following ones that the concentration of maximum activity of of each run could be the same as the minimum activity of one or more other ones. Therefore, one could not predict the result of one run to that of the next. Each preparation had unpredictable effects. Conclusion: A homeopath has no idea whether a specific homeopathic preparation would have an effect or no effect.

2) The selected measure of effect (amount of histamine release by basophils on stimulation by specific antigen-antibody complex)is a measure of the effect of an allergic stimulus, not an inhibitor of a stimulus, thus a measure of severity of asthmatic or rhinitis reaction. Thus, the homeopathic dilution was not measured not as a treatment result, but of a stimulus result.

Also, the homeopathic treatment was the same at ultrahigh dilutions as it was at the original undiluted preparation. Therefore, the effect of homeopathic ultra-high dilutions in this experiment proved that homeopathic dilutions cause or stimulate allergic reactions such as asthma, instead of reducing them.

One must conclude from these conclusions that the Benveniste experiments disproved homeopathy, and were not evidence as proof as claimed.

Parenthetically, the free trip to Paris for the three skeptical observers was unnecessary.

I published a short report of this in Skeptical Inquirer in the Summer, 1989 issue. The Nature editor, Dr. Maddox refused to publish the letter, stating he had closed the issue.

Jnan R. Saha said...

Dear Dr. Sampson:
I have read your piece and I understand. But the Mathematics does not make everything clear. I was trained as a Chemist in the Fifties. I read Benveniste’s Papers quite thoroughly. You will see one paper in the Bibliography, where one Allergist treated with 10**60 dilution of grass and published in Science. When we lived in New York City my son was very allergic to a host of substances and needed frequent trips to Presbyterian Hospital in early Seventies. The Doctor found him allergic to grass among other substances. I asked the Doctor how he determined my son’s allergy. He replied by injecting ultra diluted grass and other substances. My wife and daughter also suffered from allergy.
However, we moved to Suburbia sometime later. None of my family members suffered ever since for 34 years. I concluded it was the City atmosphere that was causing the problem.
Now I want to talk about my Grandfather who died about 60 years ago. He was a very respected Homoeopath and taught all the local Homoeopaths. When I was young I saw every morning patients lined up and got Homoeopathy medicine. At that time Homoeopathy was the only choice in some areas in the country where I came from. When I went to College, I asked myself did those medicines really accomplish anything?
I want to make only want point, the whole Earth has only 10**48 particles. Please think about it. I am not writing in favor of Homoeopathy, but the whole discussions make one wonder. Regards,
Jnan R. Saha

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