The Molecular Mechanisms of Homeopathy.

With the launch of the 1023 campaign against homeopathy, it seems appropriate for me to write a bit on that very subject. But where to start – there are so many blogs that talk about the issues that people have with homeopathy.  The ethical reasons for campaigning against it and the slap in the face that homeopathic “medicine” is to scientific thinking have been subject to in-depth coverage. Recently Prof David Colqhoun has finally gained access to teaching materials for a now-defunct BSc in Homeopathy, via a freedom of information request. He is reviewing them systematically on his excellent DC’s improbable science blog.

So with all this covered by other, more eloquent and seasoned bloggers than myself, I have decided to look at homeopathy from my own niche in science – from a structural/molecular biologist’s point of view.

How medicines work.

To understand the issues that science has with homeopathic “remedies”, one needs to know how conventional drugs work. They work by interacting with another molecule in your body. Generally they will either activate or inhibit the activity of protein molecule that is involved in some sort signal transduction pathway, or in the catalysis of a particular chemical reaction. Structural biology, particularly X-ray crystallography is an immensely powerful tool for understanding the nature of these drug: receptor interactions.  For example, crystallography has revealed the nature of interactions between a bacterial ribosome and the antibiotic chlorampenicol and HINI (Swine flu) neuraminidase interaction with anti-influenza drug, Tamiflu. These structures reveal the nature of the interaction at an atomic level. We can see Electrostatic interactions (negatively charged atoms/groups interacting with positively charged atoms/groups) such as salt bridges and hydrogen bonds. We can see aromatic stacking interactions (aromatic groups stacking alongside each other) and other hydrophobic interactions. We can precisely map out the atomic nature of an interaction.

Such information is invaluable in understanding how a drug works. We don’t have this information for every single drug that is used. But in time we will.

A “conventional” drug, eg Tamiflu, consists of a chemically defined active ingredient at a known and measurable concentration. Each adult dose of Tamiflu contains 75 mgs of Tamiflu. Given that Tamiflu has a molecular weight of 312.4 g/mol, each 75mg dose of Tamiflu contains 1.4×1020 (~140,000,000,000,000,000,000) molecules of Tamiflu (0.075/312.4 * Avogadro’s constant).

Your body takes up a known percentage of this drug – this is known as “bioavailability”. In the case of Tamiflu, the bioavailability is ~60% – so of the 1.4×1020 molecules of Tamiflu that you swallow, only 8.6×1019 get into your blood stream. These then circulate for until broken down/excreted. Tamiflu works by mimicking the natural substrate of influenza virus neuraminidase, sialic acid. By preventing influenza virus neuraminidase binding to endogenous sialic acid presented on the surface of your cells, Tamiflu prevents infection of host cells. Simple.

How Homeopathy works.

Homeopathic remedies are based upon highly dilute samples of a compound that causes a similar effect to the symptoms of a given disease (“like cures like”). For example, if disease X gives me hiccups, and plant extract Y gives me hiccups, I would take a dilute solution of plant extract Y to cure the symptoms of disease X.

We’ll overlook the fact that this is treating a symptom (by causing it?), and not addressing any underlying cause – because homeopathic remedies are “potentised” during their production. The originator of homeopathy was Samuel Hahnemann, who described a process whereby the effect of these cures could be enhanced by serially diluting them until one reached ultra low concentrations. Each dilution step would be accompanied with “succussion” of the solution – ten hard strikes against a soft, often leather-covered object. The wikipedia page on Homeopathy has a good description of this process.

A typical homeopathic remedy has a concentration of 30C, that is to say, 1 part compound in 10030 (so 1060). After Hahnemann first devised homeopathy, Avogadro’s constant (number of molecules in a mole of substance) was calculated, and shown to be roughly 6×1023 (hence 1023 campaign). So in a 1023 or 11.5C solution one might reasonably expect to find 1 molecule of compound. The odds of finding a single molecule of active compound of a 30C homeopathic remedy are very roughly 1 in 10,000,000,000,000,000,000,000,000,000,000,000,000 (10 million million million million million million).

When this was pointed out to the homeopaths (that their remedies had zero active ingredients) they happily discovered that the water in which the active ingredient was dissolved in had a memory and not only remembered the active ingredient (doubtless both its molecular structure and pharmokinetic properties), but the water could also pass this memory on to other water molecules. Cool, huh?

Note – the succussion process allows the water to remember the therapeutic ingredient, but not all the other stuff that the water has seen down the years. And given that a molecule or two of the water currently in the coffee I am drinking were likely to have at sometime been intimately associated with an Ebola virus particle or a molecule of the Ricin toxin – I sincerely hope this is the case. The molecular mechanism of succussion, and how it selects for particular solutes, is currently not understood.

But in order for a homeopathic remedy to work, not only does the water need to retain a memory of the active ingredient, it needs to actually mimic it, so it can then interact with the required target molecule to exert an effect. It has to adopt a similar/identical form.

How water interacts with other (bigger) molecules

Crystallographers can show that molecules such as proteins and DNA interact with solvent water atoms in quite specific ways. I’ve even generated a little picture to show precisely that:

The grey surface represents the molecular surface of a particular protein I’m working on. The red spheres represent ordered water molecules that interact with the suface of the protein.

We see these bound water molecules in pretty much every crystal structure we solve, as the vast majority of crystals are formed from aqueous solutions. Indeed, water molecules can become trapped inside proteins and help them fold correctly and bind substrates or metal ions. Water molecules also participate in chemical reactions – often being split to protenate leaving groups.

So the idea that water adopts a structure around another molecule is not that far fetched. So, being inquisitive, scientists tried to determine if this water structure persisted after the molecule was removed. And to their surprise, it did – but for only ~50 femtoseconds (0.00000000000005 seconds – not very long at all – and not much use for a remedy that’s going to sit on the shop shelf for weeks).

And another thing…

For the sake of further enquiry, let’s assume that the peer-reviewed letter to Nature above is wrong (it isn’t), and water can retain a memory of what’s been dissolved in it for much longer than 50 femtoseconds (it can’t).

This isn’t enough – an empty shell of water molecules around a compound that was once there isn’t going to be enough to interact with and engage protein receptors – they actually have to then rearrange and mimic the chemical and physical properties of the molecule that induced the formation of that shell in the first place.

Not only this – this water structure then has to be robust enough to occupy a protein-binding site and fend off other molecules that might normally bind to that site with a high affinity – molecules that will displace water molecules all the time in order to get into that very binding site. The original therapeutic molecule will not only have a particular shape and form – it will have an inherent stiffness and rigidity – water molecules in solution move relatively freely and will shift to surround any molecules dissolved it them – that is why water is such an excellent solvent. But not homeopathic solutions. Oh no.

In order to circumvent this, the energetics of homeopathic remedies must be amazing – water molecules typically interact with each other via low energy, transient “hydrogen bonds” – each hydrogen bond requires 5-30 kJ/mol to break it (depending upon solvent conditions, temperature, etc), but a permanent “covalent” bond that links atoms in a drug molecule typically requires over 300 kJ/mol to break it – i.e. at least over 10 times stronger. And yet the homeopathic shell of water molecules manages to be as strong as this. Utterly fantastic stuff.

The properties of homeopathic solutions are beyond comprehension – and to think that all this was achieved by diluting something to a point where no original molecules remain whilst periodically banging it on something leathery.

Homeopathy is truly unbelievable.

It is the fantastic and unbelievable nature of homeopathic remedies that leads scientists to question their validity as an effective form of therapy. Experiments to investigate this show that homeopathy is no more effective than placebo. When a therapy has no active ingredient, no conceivable mechanism of action, and cannot be demonstrated to be more effective than a placebo, to claim otherwise is both dangerous and immoral. It certainly has no place whatsoever in a public funded health service like the NHS.

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18 Responses to The Molecular Mechanisms of Homeopathy.

  1. Saintpete says:

    We all its nonsense but its very nice to have the science spelled out so well!!

  2. SFScience says:

    Oh, but you didn’t mention Einstein, or how little mass there is in the Universe – too much science and not enough woo!

  3. MarcCallinan says:

    Excellent explanation of the science proving homeopathy is bogus

  4. bazzargh says:

    Another astounding claim homeopaths make is that it can work in vapour form (in Hahneman’s Organon: “medicines may be administered through the nose and respiratory organs which, by means of olfaction and inhalation through the mouth, are especially receptive”). Hahneman’s observation is true of medicines with an active ingredient, since individual molecules will exist in the gas, but when the only supposed active ingredient in the liquid form is a memory of structure – which cannot exist when the water evaporates – what on earth do homeopaths think is happening here?(I’m even more flummoxed by the dry sugar pillules – what’s that supposed to be – a memory of a memory of water?)

  5. Dave says:

    @bazzargh – I hadn’t come across the vapour phase route of administration. That is… just astounding. Wow.Re: sugar pills – the water (that remembers) tells the sugar what it saw, so it can also remember (apparently).

  6. Sastry.M says:

    Mind is associated with psyche and definition is related to perceptions from sensory organs of body(soma).While sesory experiences such as vision,hearing,smell,taste,touch etc.are the result of rational stimuli, as for example from a rose flower, the perceptions of integrating mind to color,fragrance,form etc. resulting in psychic reaction as a response varies from person to person. The majority appreciate in favor but an odd one may react with allergy. While the majority response is taken for granted the odd one presents a challenge. Judging from human resposes to various phenomenal stimuli of external world we observe that the energies impinging upon receptive organs such as a minimum intesity of light required to enable seeing,the density of diffused molecules to catch smell or pressure of sound to become audible should satisfy thresholds of minimum levels for experiencing. This requirement defines magnitude of impinging energy of a particular stimulus. The second relates to qualifying characteristics for discerning and differentiating such as color,fragrance,taste,sonority etc.These two requirements coexist for all worldly objects.Since the range of sesory perceptions of average persons are limited scientific instruments help greatly extend them both in real time cognition or by sampled transformation and recognition.However scientific instruments are the result of human sub creation and also require defined thesholds of sensitivity as well as domains of charecteristc ranges such as frequencies,bandwidths etc as relavent to working processes.Now making human personalty as the primary and an augmenting scientific instrument as a secondary one the threshold settings of the latter are within the range of mental prowess of its creator while the primary human body itself is not readily amenable to certain judiciously selected preset values of defintion.The malfunction of a machine relates to disease of its creator with deranged health.The mind operates as a CPU of an intelligent machine which is activated by consciousness and interfaced to sensory organs with psyche.The psychic thresholds to external stimuli vary with individual sensitivities and hence the personal response to a given magnitude of external stimulus also varies and has to be individually established. Therefore rational and defintive scientific observations cannot be readiy applied to human beings. Psyche reacts to characteristics while body responds to magnitudes. The response of body is related to both magnitude or intensity of impinging energy physically as well as characteristics of its stimulus. Therefore material concentration of a medicine of scientifaically measurable molecular diffusion and observable biological reaction many not vochsafe prolonged bodily reaction by the Priciple of Duality although nullifying disease syndrom with active mimicking by fighting with toxic effects may render relief for a short period. Indeed if we closely observe ourselves we find that our psyche reacts to both context and content although the latter may not contain any material information. A sudden recolection of a nausating experience such as cleaning sewage pipes during morning hours while sitting at a dinner table will be sufficient to add churning to a suffering stomach with hunger even without one molecule of the stench! Other members sitting at the dining table may not believe the reaction of distress of the effected one in the presence of appealing aroma of laid out food nor the sufferer dare spoil the apptite of others by his disclosure. If we try to believe everything only with scietific support we need not attribute ethics to homeopathic dispensations because ethics belong to spirituality of purely mental domain including beliefs and morals while the homeo therapeutic applications render relief from acute agonies and cure to chronic sufferings in a psycho-somatic manner as experienced directly and reported authentically by many people.

    • xtaldave says:

      Wow. Well done for writing so much. And congrats for being my first commenter now that I am on wordpress.

      However, I have to take issue with what you are saying – the central tenet of your argument (such that it is) seems to be that:

      Therefore rational and defintive scientific observations cannot be readiy applied to human beings.

      Which, I am afraid, is utter nonsense.
      (and I think I’ll leave it at that for now)

  7. Sastry.M says:

    Thanks xtaldave for your crucial observation and comment. Indeed all scientific pursuits are to make sense out of an incoherent conglomerate of all natural phenomena. What I mean by your obsrvation is that the working of human mind is transcendental and tends to be irrational in the interpretation of natural phenomena and hence accepted methods of logical reasoning and rational obsevations have to be ingrained to train the mind in a disciplined manner which is science. Thus Mendelef could predict some elements of periodic table far in advance of their actual discovery. But human response to a bar of iron and a bar of gold of the same size would be different although the full elemental structures are well known scientifically.

    • xtaldave says:

      Enough of the sarcasm! That’s my job!

      1. Indeed all scientific pursuits are to make sense out of an incoherent conglomerate of all natural phenomena.
      2. Not merely to make sense of it, but to understand how and why it happens, the mechanism of natural phenomena.

      3. working of human mind is transcendental
      4. Transcendental means “beyond ordinary human experience” – if you really mean this, then I disagree – just because we don’t currently understand the minutiae of the workings of the human brain, doesn’t mean we can’t ever hope to understand them/it.

        Either this is an “appeal to ignorance” type of logical fallacy along the lines of “we don’t understand the precise mechanisms of the human brain, therefore homeopathy works”

        Or you are trying to invoke a “soul” or “spirit” to describe how homeopathy works. Which is just plain wrong.
        I am afraid that your thoughts, your memories, all that you ever were, are or can be, are defined by the arrangements of neurons in your brain, and their chemical reactions and molecular interactions. Sorry if you find this in any way unedifying, but hey, that’s life!

      5. human mind … tends to be irrational in the interpretation of natural phenomena and hence accepted methods of logical reasoning and rational obsevations have to be ingrained to train the mind in a disciplined manner which is science.
      6. You seem to be making my point for me here – homeopathy is an irrational interpretation of natural phenomena, and logical reasoning and rational observations have repeatedly demonstrated that homeopathy doesn’t work / has no mechanism / has no effect / “there’s nothing in it”.

      7. Thus Mendelef could predict some elements of periodic table far in advance of their actual discovery.
      8. Yep – he was a clever fellow – no arguments from me.

      9. But human response to a bar of iron and a bar of gold of the same size would be different although the full elemental structures are well known scientifically.
      10. Yes. Of course Iron and Gold are different. Atoms/ions of Iron and Gold have different numbers of neutrons, different radii, different electron configurations, etc. Therefore they will and do have different effects on humans. These different effects will have different molecular mechanisms – due to differential binding to various proteins or inhibition of various reactions. Again, I’m really not sure of what point you are trying to make here? Are you trying to invoke Alchemy? Iron and Gold are different, therefore homeopathy works?

    • batarista says:

      Sastry.M

      On the one hand you claim that…

      “… the working of human mind is transcendental and tends to be irrational in the interpretation of natural phenomena”,

      …yet you are happy to rely on anecdote…

      “… homeo therapeutic applications render relief from acute agonies and cure to chronic sufferings in a psycho-somatic manner as experienced directly and reported authentically by many people.”

      How then, do you distinguish irrational interpretation from “authentic” report? Science tends to prefer multiple, independent, repeatable observations, controlled for many well-known human biases.

  8. Sastry.M says:

    Mr.batarista
    By ‘transcendetal’ I do not refer to spirituality but to mathematical logic.Trigonometric functions are said to be transcendental because ‘1’can be substituted directly for multiples or squared sums as for example:sine(x).cosec(x)=1; sin^2(x)+cos^2(x)=1 etc.,and so for viarious trigonometric ratios.The separate squared sine and cos ratios are summed up to unity which is not possible with algebraic calculatios except a number multiplied with its inverse or both raised to an equal degree.Practically we mean grouping together instead of following exhaustive reasoning which is a unique faculty of human mind. For each chess move a computer exhaustively performs all possibilities within its artificially embedded intelligence to arrive at an optimum move setting while a human-Kasparov-transcends many such by grouping together with his intellectual reasoning which machine does not possess and hence the human won eight out of ten plays. Regarding ‘irrational interpretation of natural phenomena’ initially I beg to be excused to exclude sacasm and any lewd refence to my practical obsevation of a natural phenomenon concerning we human beings ourselves. Human mind only possess consciousness related to the concept of time and commensurately the human body grows in stages of statuture from child hood ‘baby form’to adolescent ‘hairy form’at reaching an average age of puberty and catered to gender requirements.These natural developments are taken for granted in general but appearance is aspired for an aesthetic look by beauty Parlour ads recommending treatments for hair growth on head and depeleting feminine oriented unwanted hairs as if Nature has transgressed aesthetic human rights by doing so. If we men have scietifically succeeded interpreting natural phenomena rationally and manufacturing mutitudes of products in factories the ‘women’ bodies who have conceived and delivered our own male forms as part of a universal process of procreation are not rationally interpreted as to their practical intent of natural hairy form. Some other blog commented to this quiry by saying simply ” o.k. stink if you wish!”

  9. Sastry.M says:

    xtaldave-Sir,
    I am grateful to you for showing keen interest in reading my round about rhetorics patiently and commenting on relavent points to keep my attention on topic. I submit my ‘predicament’ as follows. I am an Indian with great reverence to the profound wisdom of Advaita(Monistic)Philosophy and an electronics engineer by profession with application to signal processing systems.As my profession warrants I have the greatest admiration to the Western scientific Genius and practical wisdom in interpreting Natural phenomena with dynamics of mind conceptually propounding theoretical philosophies supported by rational obsevations and practical expermental provings.To this end I have to rack my brains to get clear understanding of electro-magnetic principles and assume conceptual models for practical applications. I can perceive flow of electical energy or its electromagnetic radiative effects only with the help of instruments.I have a friend of mech.engg. who is an expert in hydraulic instrumentations by profession and an ardent supporter of Advaita philosophy and its scriptural injunctions of learning. He too appreciates the western genius as far as his machines are concerned but does not lean upo it as I do because of my preferred requirements.To him and friends of his like I am a ‘brown skinned westerner’and I admit the view by saying that only eyes perceive colours superficially but the differentiating intellect is the same in all.I am of the same view as your comment about effects on brain caused by the presence of small gold and iron bars whose different elemental latticed structures produce different responses of molecular reactions in brain resulting in relative personal responses. If I refer such a view to my mech.engg. friend he accepts it ‘in proviso’with the broadness of his Monistic Philosophy which I also appreciate but disapproves too much scientific adherence by saying that ‘you would end up in such critical pursuits without ever attempting to know intrincically who you are as the advaita philosophy implores to realize individually’ True but I cannot relent upon my effort to bridge the gap between his/ my revered spiritual philosophy and the practical scientific ones which supported our living in employment.For example advaita philosophy says ” you can directly see the world around you during day and and view the cosmos during night but cannot see the very instrument(eyes)with which you are so doing” Such assertions make one to be more open and realistic especially with the rational back ground of scietific Philosophy.This is the first part of my predicament. The second one is I never relied on homeopathy till 35y of my age with its humbug infinitesimal doses “quacked up” to increasing potencies from 6’th to CM centismal dilutions . Having suffered with ring worms around groines and treated with classical medication for the previous 17 years with periodic reliefs I was implored by friends to try homeopathy. I honestly admit relief within 6 months of treatment although my rational scientific perspective did not admit me to bring myself around to accept the mechanisms of working at least at the molecular levels of common perception. That was in 1977 when my mech.engg. monistic spiritual friend had given me some books to study of his philosophy. I could realize something in forming my own views bringing the broad spirituality to admit my relief from suffering with a scientific perspective which may be out of place in this blog whose kind concern as shown by above comments is a great relief to my unclear views.

    • xtaldave says:

      Basically, my major issues with Homeopathy can be summarised as:

      1) Plausibility – as an advocate of Advaita, you will hopefully appreciate the cause and effect problem inherent in homeopathy – there is nothing in a homeopathic remedy to cause an effect.

      2) Honesty – a practitioner of homeopathy must either lie to patients, or believe that lie themselves. The former is bad practice, the latter displays a lack of critical thinking incompatible with the role of physician.

      3) Danger – most homeopaths are not trained a physicians – relying on homeopathy means that a patient is not getting proper medical scrutiny. People die because of this.

      • Sastry.M says:

        Thanks for the sumary.I would like to express my views in light of Advaita regarding ‘plausibility’ leaving the rest to your personal opinion.To substantiate my scientific perspective I have to rely upon two factors,viz.something known before hand to use as a stimulus to seek a response from an un known (eg.an electronic black box with a pair of each i/p and o/p terminals)entity which is a direct process of obsevation or given the response of an entity to seek the probable causative factors to substantiate effect. In either factor there is a classification between something known and un known. According to Advaita there are four types of Causative Factors.
        1)Sentient Cause: The cause of self defining consciousness-embedded in many highly developed ‘Life Forms’ with the greatest exposition in highest evolved ‘Human Form’on Earth.
        2)Efficient Cause: The cause relating to knowledge-Eg.the knowledge of making an earthen pot, a golden ornament etc. We can also say that efficiency relates practically to ‘perfection’ in human endeavours while the same “Signifies” harmony’ in natural creation.
        3)Material Cause: The substantiating cause. This cause relates to material substantiation in the form of various basic elements and all other extensions in support of physical forms. Thus clay relates to making of pot and gold to ornaments etc.
        4)Instrumental Cause: This cause relates to the making up of an instrument in support of a defined purpose.The whole creation evolves around this cause augmented by the above three. It also includes what we human beings ‘sub-create’ to support our scietific pursuites as well as basic necessities such as weaving cloth for making garments, themometers for measuring temparatures etc.
        We observe that the first and second relate to the subtle while the third and fourth to the physical world. In all of our scientific pursuites we ‘depend’ upon the 3’rd and 4’th while the 1’st and 2’nd form the basis of all creativity. For example the sentient cause creates a consciousness of human life form and the efficient cause creates knowledge in support of human life. Having thus initiated creativity the physical form substantiated by the 3’rd and the 4’th implies a definition of purpose such as the various professions of service and learning.
        In science we explicitly depend on the third and fourth causes to explain Cause-effect relationship while implicitly accept the process of creativity as such for exmple the existence of mercury as a natural liquid metal whose thermal epansive properties are made use of in making thermometers and therapeutic properties in medicines. While the former property may support a secondary instrument such as the thermometer the latter therapeutic property may cause a known primary effect but not necessarily a known bodily reaction after its cessation. This is because the sentient and efficient causes create with “Signatures” of descernable and definable “Characteristics” into a more dependable material and instrumental cases such as the Periodic Table and Various scientific instruments. Therefore we may surmise that the charactritic signtures of various medicines transferred to the medium of alcohol and globules by the process of spurtive shocks of succussion may be sufficient for the psyche in spite of material absence to recognize the similarity of symptoms thrown up in fighting a disease and hence parametrically augment the vital force immensely in producing neuro/ biological reactions in overcoming the disease force and restoring health.

  10. Neuroskeptic says:

    Great post, and nice blog!

  11. […] yet joined up the dots from ERK1/2 activation to inhibition of serotonin reuptake, the mechanistically implausible affront to rational thinking that is homeopathy works, right? Wrong. (I should mention here that we […]

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