Homeopathy and the Structure of Memory

I wanted to write something in time for World Homeopathy Awareness Week since homeopathy is such an amazing phenomenon. But though the promotional week is now over, I’m sure you can remember it. You will have memories of some of the things that were written and said.

Souvenir Shop in Venice

Memories are so important for human beings. They enrich the present and allow us to navigate from the past into the future. We like to wallow in the pleasant ones, ever returning from holidays — as my family did from Venice last weekend — laden with photographs and souvenirs to enhance our store of recollection. Even bad memories are, like Venetian souvenir shops, almost impossible to avoid, such is their ubiquity in our experience.

Memory is also central to the modern interpretation of homeopathy, the complementary medical practice of treating like with like in which substances that induce certain disease symptoms are serially diluted in water and succussed (i.e. shaken) to be ‘potentised’ as remedies. The technique was first proposed at the end of the 18th Century, prior to the development of our present-day theories of the atomic and molecular nature of matter. These revealed homeopathic dilutions to be so extreme that not a single molecule of the original symptom-inducing substance remains in the preparations used for treatment. To explain the efficacy of the remedies, it has now been advanced that water retains a memory of the molecules that have been diluted away and thereby transmits their therapeutic benefit.

As I said, it’s an amazing phenomenon.

Curiously, homeopathy appears to echo the body’s natural healing process, which also relies on memory to combat disease and illness. The adaptive immune system is a thing of wondrous complexity but I just want to tell you about one small part of it to reveal something of how memory works that can also shed light on homeopathic mechanisms.

The immune system battles day by day, hour by hour, minute by minute against an onslaught of mostly microscopic invaders. A key element of this complex defence mechanism is the population of B-cells, which are producers of molecules known as antibodies.

The human body has the capacity to generate enormous numbers of different antibody molecules: the DNA that codes for antibodies within each B-cell is split into pieces and only assembles into its final form — from a large choice of similar but not identical parts — as the cell matures in the bone marrow. In a sense every B-cell contains a deck of DNA cards for antibody parts but can only use the hand that it is dealt during maturation to make one type of antibody molecule. When it is released into the circulation, each new B-cell therefore carries and codes for a unique antibody. But there are billions and billions of B-cells and the quasi-random assemblage of parts means that a huge diversity of different antibody molecules is made.

Antibody Molecule

The antibody — initially displayed on the surface of the B-cell — is Y-shaped, with two identical arms. The end of each arm, (the most variable region between different antibodies — indicated by arrows in the picture here) can stick to the surface of an invading pathogen, but will only do so if it happens to make a good fit with the molecule displayed on the surface of a microbial pathogen. The body relies entirely on its capacity to generate many different antibodies to make sure there is at least one that will stick to the invader.
The picture below shows in spectacular detail the intimate interaction between a haemagglutinin molecule from the surface of a ‘flu virus that has just been found by an antibody that can latch on to it.

Can you see how closely the shape of the antibody fits the contours of the haemagglutinin molecule? The embrace is intimate but rigid. Solid. Though there may be some flexing as the two molecules come together, the association is tense one, more like wrestlers locked in a stalemate than lovers sleepily caressing in the early morning.

Antibody-Haemagglutinin Complex

I have deliberately revealed the underlying structure of bonded atoms (red oxygens, blue nitrogens and cyan or yellow carbons) in the antibody molecule on the right of the picture. If you think the molecular structure is horrendously complex, then good: that’s because it is. The antibody is elaborate and convoluted because it has to be complementary in shape and surface chemistry to the structure of the protein on the microbial invader that it targets. Its conformation is fixed by the sequence of amino acids making up the protein chains of the antibody, which dictate precisely how it folds into a unique structure that happens to bind — in this case — to the surface of haemagglutinin.

We call this binding ‘recognition’ though it is recognition by touch rather than sight and — at least at first — occurs only by chance. It is not based on memory, but crucially allows a memory to form.

The initial contact between the antibody on the B-cell surface with the ‘flu protein causes the B-cell to divide, producing many daughter cells that release free antibody molecules of exactly the same structure into the bloodstream. These rove around and tag for destruction any other ‘flu viruses in the neighbourhood. In this way — though I am simplifying greatly — the infection is eventually mopped up.

But just as importantly, some of the B-cells turn into long-lived memory cells that retain the ability to make the antibody that ‘recognised’ the ‘flu haemagglutinin. Their function is to be on the look-out in the weeks, months and years to come for re-infection by the ‘flu virus. If this happens, an encounter between the antibody on the memory cell surface and the ‘flu protein is sufficient to trigger a very rapid response, which again floods the circulation with antibody molecules of the same structure, thereby preventing the infection from getting established.

Working together, B-cells and antibodies can lay down powerful immunological memories. The secret of the success of this system is in the preserved structure of the molecules, encoded by the DNA sequence of the shuffled antibody gene and expressed in the ornate three-dimensional architecture of the protein chains that form the antibody.

With World Homeopathy Awareness Week fresh in our minds, it is appropriate to ask: why did evolution, which has always taken such a make-do attitude to developing the faculties of living things, not choose to work with water to construct an immune system capable of remembering its enemies? Surely, given the prodigious feats of memory attributed by homeopaths to this glistening, life-giving fluid, Nature could have fashioned a watery armour to protect us from disease?

This has not happened of course because memories require fixed structures and water is a liquid. In this form, it is no more capable of remembering molecules than of being sculpted.

Instead the immune system revealed by scientific analysis shows us that the sophisticated mechanism needed to fight off infection has been built from shaped materials. The potency of an antibody is derived from its ability to form a structure that is uniquely specified by the sequence of amino acids in the protein chain. The potency of the B-cells that give rise to them lies in the eloquent DNA structure through which the amino acid sequence is coded. And remembered.

The antibody molecule in the picture above may be off-putting to some because of its near impenetrable irregularity. But to my mind — and I confess to the predilections of a structural biologist here — it represents a winsome confluence of form and function. Paradoxically perhaps, the elegance of that understanding was won by brutish methods. Time and again we have found that only by asking the harshest questions and sifting our data with the severest eye can we lay a hand on those bright nuggets of insight that are worth keeping.

If you take a softer, gentler approach that is satisfied by more superficial observations, then understanding just leaks through your hands, like water.

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32 Responses to Homeopathy and the Structure of Memory

  1. Austin Elliott says:

    That one felt like a labour of love, Stephen.
    Long ago I used to have to give 1st yr undergrad cell biology lectures (sic) one of which was on “The immune system” (yep, all of it in a single 50 min lecture). I seem to remember that the multiple ways antibody diversity was generated was one of the main themes I used to talk about.
    As to the homeopaths… well, what more can one say? They, of course, believe – any and all evidence to the contrary – that water can retain _”ghost structures”._ David Colquhoun always used to quote the original paper that showed that the rearrangement time of any H-bonding network in water was of the order of femtoseconds… so that, even if one postulated the kind of _”remedy shaped hole”_ the homeos sometimes refer to, it would be, to coin a phrase:
    bq. _”Gone in 10-to-the-minus-13 seconds”._
    Come to think of it, perhaps we should copyright that line as the title of a future post/talk/documentary.

  2. Stephen Curry says:

    Ha – nice of you to notice Austin.
    Yes, it was deep breath time before launching on this topic. You have so much more experience than me in this area but I wanted to do something. Hopefully something that wasn’t too antagonistic, but which might, just, give a tiny pause for thought.

  3. Bob O'Hara says:

    bq. “Gone in 10-to-the-minus-13 seconds”.
    Sounds like it’s homeopathic on the temporal scale too.

  4. Marianne Baker says:

    Brilliant post, Stephen.
    Great point about the complexity of antibodies – having been shocked to find colleagues (working with immunohistochemistry in the lab!) who believe homeopathy works because of ‘physics’ etc., it’s really nice to see a properly thorough (though as you say, still greatly simplified!) scientific approach to the claim of ‘water memory’.

  5. Andreas Forster says:

    Great post, Stephen. Evolution does really explain everything, doesn’t it?

  6. Brian Clegg says:

    Stephen – it’s interesting that if this were a post on evolution, you would be very wary of taking this kind of humorous statement of the unscientific (before shooting it down), because some creationist/ID person would cherry pick the nice bits and quote you as supporting their cause.
    Perhaps with the collapse of the BCA case and the House of Commons committee laying into homeopathy we will soon find that supporters of CAM will similarly start finding posts like yours and will say, ‘Well, Professor Curry says that homeopathy is “an amazing phenomenon” that “echoes the body’s natural healing process.”‘ Mmm! Want some of that.

  7. Austin Elliott says:

    Yes, there is always a danger, with gentle satire, that the people you are satirising think you are being serious.
    The thing that annoys me about homeopaths (in common with many other Unreality enthusiasts of various kinds) is that they can’t grasp the implications of the old saying:
    bq. _”Extraordinary claims require extraordinary evidence”_
    One could certainly call what the immune system does _”extraordinary”_ – but after the last century’s worth of research we actually have an extraordinary amount of data/knowledge as to how it does it – down sometimes to the molecular level, as Stephen describes. This understanding is necessarily incomplete, and evolving. But it’s there.
    In contrast, the other lot simply make ridiculous claims (like _”water has memory”_) and then get huffy if you ask them to prove it, or to rule out the obvious _lacunae._ An approach that sadly extends to even supposedly “peer reviewed” journals of Unreality. See, for instance, “here (which, if you read to the end, recalls one of James Randi’s best lines).”:http://draust.wordpress.com/2007/11/15/journals-of-alternative-medicine-insufficient-scepticism-cargo-cult-science/

  8. Stephen Curry says:

    Was about to comment but then we lost contact with the internet. I was about to say:
    Actually Bob, 10^-13 sec is quite a lot, time-wise. More that enough, if I understand correctly to start a universe!
    Thanks Marianne – I too have come across homeopathic devotees in labs, though that was in France where these ridiculous remedies are more commonly used.
    I’m not sure about everything Andreas but I do see it as biology’s “Grand Unification Theory”. The interesting thing is that homeopathy and Darwin’s theory, give or take a few decades, are of a similar vintage. Where they differ is that the evidence accumulated since then has only served to buttress and expand evolution by natural selection whereas homeopathy has been left high and dry.
    The only remaining wonder is why so many still fall for it.

  9. Stephen Curry says:

    You make an interesting point Brian but I’m not about to start editing myself to accommodate the possibility that the loonier devotees will start quoting me. If they do and trackbacks start to kick in, I will at least get the chance to give a riposte.
    Not that that is likely to have so much effect. You only have to read the unscholarly rantings of someone like Dana Ullmann to get a depressing notion of the staying power of the proponents of homeopathy.
    I guess I was partly trying to ensure that someone who chanced upon this post via some pro-homeopathy link might get most or all of the way through it before realising about the ‘punch-line’.
    But as Austin knows only too well, there are plenty of ‘believers’ out there for whom no amount of evidence or common sense, even, will suffice.

  10. Austin Elliott says:

    Dana Ullman, the homeopathic salesman, is more familiarly known online as “DUllman”, which sums him up nicely. But he is certainly indefatigable.
    Years ago when I was first commenting on Internet bad science forums I used to liken homeopathy to a religion with a central dogma _”justified by faith”_, and I still think that is the best explanation for why the adherents are so impervious to any argument. Slightly edited version of one such comment:
    bq. “Apart from the priesthood (the homeopaths) and the adherents, and working entirely through faith, [homeopathy] also has an ancient sacred book which cannot be questioned (Hahnemann’s _Organon_), plus other sacred writings which give instructions (Hahnemann’s other writings and the works of one or two of his followers)… plus (best of all, IMHO) the magical transformation of mundane materials into something special to be taken by the faithful, which happens through prescribed ritual carried out by the priest-figure/homeopath.”

  11. Stephen Curry says:

    Amen, brother!

  12. Mike Fowler says:

    Nice post Stephen!
    bq. _The only remaining wonder is why so many still fall for it._
    I suspect this is one of the few (if not only) aspects of homeopathy that can be explained: _desperation_.
    When nothing else seems to work, a little blind faith can offer comforting hope.

  13. Stephen Curry says:

    Actually, Mike I suspect desperation has little to do with it (though that may be a selling point of other CAMs for some).
    Many just believe, having rather blind faith in homeopathic practitioners. Many probably experience what they perceive to be a genuine benefit of treatment, being unable to distinguish it from placebo.

  14. Lee Turnpenny says:

    Homepathy as a belief system – yeah, I’ve been considering that. Which perhaps places the “You have to respect people’s beliefs” mantra-ing followers of other psychologically-cuddly, anecdote-driven, faith-based systems who criticise it on somewhat rocky ground, unless they’re prepared to tolerate criticism of their own. Or do its scientific pretensions make it different – kind of a pseudoscientific cult thing?

  15. Peter B says:

    FYI femtosecond = 10^(-15) second
    Think powers of 10 in multiples of 3

  16. Stephen Curry says:

    Lee – it may seem kind of cultish but most practitioners seem to me to want to dress up in the white coat of science. Which means of course that they are deserving of nothing short of the severest scrutiny. Respect doesn’t come into it.
    Thank you for the clarification Peter B – and welcome to NN. I’m pretty sure Bob knows that 10^-13 secs is 100 fsecs but you are correct to remind us of the need to be vigilant and precise in our language!

  17. Zack Domike says:

    What might be like the “memory of water?” An example: the solar system as an analogy of the water molecule, at another scale: Earth spins on an axis averaging 23* off the ecliptic plane, and so creates annual seasons.
    Would you call it “memory of water” if the homeopathic mix applies a consistent spin to certain electrons in the water molecules?
    This is a plausible physical explanation for the difference between mixes that make homeopathy. Who has a laboratory to measure these differences – test that to scrutinize materials. Note: you will have to invent some very sensitive machinery, similar to an immune system perhaps?

  18. Stephen Curry says:

    Hi Zack. Goodness, where to start?
    The solar system is not a relevant analogy. It consists of massive objects that interact via gravitational forces. A water molecule is a miniscule object that, even at room temperature, is constantly bombarded with other molecules. The thermal energy of the water system is sufficient to ensure that the arrangement of water molecules is constantly randomised. This property of the system provides a plausible explanation for the observed behaviour or water as a shapeless liquid.
    What plausible mechanism is there for a ‘homeopathic mix’ to apply a ‘consistent spin to certain electrons in the water molecule’?
    In science, while one must of course remain open minded, we are only likely to make progress if we have a good understanding of the known properties of the systems under investigation. This allows us to detect anomalies, which can lead to new insights or refinements of theory.
    I suggest that your ‘hypothesis’ fails to reach this standard.
    Need I add that, given the observation that RCTs repeatly demonstrate that homeopathic preparations have no effect beyond placebo in patients (e.g. see here, there is nothing to investigate mechanistically in the first place.

  19. Lee Turnpenny says:

    Wow, Zack! Err, so Heisenberg’s Uncertainty Principle actually allows for a plausible physical explanation for… homeopathy? Unfalsifiably brilliant! So all one needs is people _believing_ it works. One’s gotta admit that’s good, eh?

  20. Mike Fowler says:

    Heh, just ask the cat which way the electrons in water are spinning. Whether it’s alive of dead will have no bearing on it’s answer.
    Stephen, just to clarify, I can sympathise with folk who suffer from ailments that have no (highly) reliable medical cure, that then seek comfort in untested/unproven ‘remedies’. I’ve even gone through acupuncture in a bid to relieve excruciating back pain. It didn’t work, but the big pharma muscle relaxants did the trick!
    Those people that proffer and profit from untested/unproven ‘remedies’, especially those that are consistently shown to be shams or are no better than a placebo, deserve nothing but scorn and regulation. And possibly to be hung, drawn and quartered. Or perhaps diluted and succussed.

  21. Stephen Curry says:

    Completely agree Mike.
    And, speaking of “Those people that proffer and profit from untested/unproven ‘remedies'”, there was a great critique of the ‘work’ of DUllman — mentioned above — at Respectful Insolence earlier today.

  22. Austin Elliott says:

    Link in that last comment is broken, Stephen.
    PS Can I plug my new post on:
    “Critical analysis: homeopathic quantum flapdoodle”:http://blogs.nature.com/austinelliott/2010/04/20/quantum-homeopathic-flapdoodle
    Test your power to distinguish spoof quantum bollocks from the sincerely crazy variety.
    I know Stephen has visited already, but it might amuse some others too.

  23. Stephen Curry says:

    Thanks for the tip-off Austin – I have fixed the link in my comment above.
    And people – please do have a look at Austin’s blog: the quantum bollocks really has to be seen to be believed!

  24. Stephen Curry says:

    And I have just come across this briliant riposte to a recent Ullman article in the Huffington Post by David Brenders, Prof. of Communication, who completely dismantles his specious arguments.
    Well worth a look.

  25. Zack Domike says:

    From experience with other blogs, clearly some people prefer to completely dismantle other’s specious arguments. My suggestion about a possible analogy is given as a way that might help describe a mechanism for the memory of water. Stephen, you say we must remain open minded, and so cannot wait for all known properties of each system.
    There are several plausible mechanisms for a ‘homeopathic mix’ to apply a ‘consistent spin to certain electrons in the water molecule.’ One analogy is to the earth’s tilt in the solar system, but this is in a different scale. Perhaps you can imagine a mechanism for homeopathic water to retain a tiny chemical signature in some molecules, not enough for us to measure at this time; this signature creates anomalies that distinguish homeopathic from other dilutions. If not chemical, perhaps the signature is related to some other particle within the water that we cannot yet track; where is your measurement of bosons, quarks and interacting neutrinos? No need to limit our molecule properties to only electrons!
    Like you, I have been a mechanistic quantifier conversing with like-minded people to confirm my knowledge. But I do believe that we have an enormous task ahead of us – to invent some very sensitive machinery, to test minute effects around us. In the meantime, I will try to keep my mind open to possibilities, similar to my immune system perhaps?

  26. Stephen Curry says:

    Zack we don’t seem to share a common understanding of the word ‘plausible’. None of your suggested ‘mechanisms’ is remotely realistic or based our our current understanding of how the world works. Indeed the invocation of sub-atomic particles to explain medical processes suggests a detachment from the realities of physics, chemistry and biology that is often seen in the proponents of homeopathy.
    But all this talk of mechanism is premature, or rather, pointless since 200 years of investigation have failed to demonstrate any beneficial effect of homeopathy beyond the placebo effect. If you can point me to one systematic review of the literature that had concluded homeopathic remedies have a significant effect, we can restart the discussion.
    But for now, I am with the regulatory body for pharmacists in Northern Ireland (my home country) who have concluded that it is important to make their customers aware that homeopathy is “not an efficacious form of treatment”.

  27. Zack Domike says:

    To clarify this theme, I am interested in the topic “Memory of Water,” not defending homeopathic remedies. On the other hand, I am very excited by mechanisms that are not remotely realistic based on our current understanding of the way the universe works.
    History of science has demonstrated many shifts in these paradigms. At present rates of expansion of our capabilities for investigation, I hope you live long enough to see mechanisms for the memory of water.

  28. Stephen Curry says:

    The history of science has been punctuated by paradigm shifts. But these are not so frequent and only occur after long-standing investigations have thrown up problems with existing theories that cannot be resolved in the old framework of understanding and demand a true revolution. The obvious examples are the discovery of oxygen, Einstein’s theories of relativity and the advent of quantum mechanics.
    But as for the topic of the ‘Memory of Water’, I see nothing to discuss. There is nothing in current science to suggest that the topic even arises. There are no difficulties in present theories of nature that seem likely to benefit from such a bizarre hypothesis.
    Science proceeds from the data, from the evidence. The imagination is certainly important when formulating new theories but if allowed too free a rein, it wanders off in to fantasy.

  29. Lee Turnpenny says:

    Does the ‘topic’ “Memory of Water” ever arise in connection with anything other than discussion of _homeopathic remedies_ (an oxymoronic term)…?

  30. Ken Doyle says:

    Oh yes. Well, almost.

  31. Zack Domike says:

    Here is another avenue that may explain the “Memory of Water,” the wobble.
    From Wikipedia, see Libration – In physics and chemistry, there are some situations where a molecule (or other group of atoms) within a larger system can undergo
    libration. For example, in liquid water, any given water molecule is attracted to neighboring molecules, so that it has a preferred orientation and cannot freely rotate. (Of course, over time, the neighboring molecules move around and the preferred orientation changes.)
    So among the billions and billions of water molecules and the quasi-random assemblage of ingredients means that a huge diversity of Librations are created. These are wobbles that change the character of water, which can be called memory!

  32. Stephen Curry says:

    Zack – 10/10 for persistence. 0/10 for understanding. How many femtoseconds would any such structure last? More than one? Please – do us a favour and go and learn some physics.

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