A bad memory

[Please forgive the double posting here - it is also on my regular blog www.philipball.blogspot.com - and also forgive its informality, for the same reason. But it seemed relevant to put this up here too.]
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).