I realize that I’ve said it many times before, but it bears repeating. Homeopathy is the perfect quackery. The reason that homeopathy is so perfect as a form of quackery is because it is quite literally nothing. On second thought, I suppose that it’s not exactly nothing. It is, after all, water or whatever other diluent that homeopaths use (usually ethanol). However, thanks to some basic laws of physics and chemistry and a little thing known as Avogadro’s number, any homeopathic dilution greater than 12C (twelve serial 100-fold dilutions) is incredibly unlikely to contain even a single molecule of starting compound. That unlikeliness reaches truly astonishing levels as we reach the common homeopathic dilution of 30C, which is the equivalent of a 1060-fold dilution. Given that that little thing known as Avogadro’s number, which describes how many molecules of a compound are in a mole, is only approximately 6 x 1023, a 30C dilution is on the order of 1036- to 1037-fold higher than Avogadro’s number. Even assuming that a homeopath started with a mole of remedy before diluting (unlikely, given the high molecular weight of most of the organic compounds that can serve as homeopathic remedies), the odds that a single molecule could remain behind after the serial dilution and succussion process is infinitesimal. Appropriately enough, the “law” in homeopathy that states that diluting a remedy will make it stronger is the law of infinitesimals.
It is also the reason that homeopathy is nothing.
Homeopaths have known these facts for many decades. Anyone who is any sort of a scientist or has an understanding of science, when confronted with these simple, well-established physical laws, might—just might—start to rethink his belief in something that is so utterly implausible from a scientific standpoint. Indeed, homeopathy is about as close to impossible as anything I can imagine, because for it to “work” multiple well-established laws of physics and chemistry would have to be not just wrong, but spectacularly wrong. Yet, as Richard Dawkins famously put it, undeterred, homeopaths bravely paddle up the river of pseudoscience and invent explanations to “explain” how homeopathy could work, the most famous of which is the so-called “memory of water,” in which the water in the homeopathic remedy remembers all the good bits meant to heal but, as Tim Minchin so famously put it, somehow forgets all the poo that’s been in it. Homeopathy is truly magical thinking, which is why I love to use it as an illustrative example of quackery. Not only is it magical thinking, but because it is nothing but water, it’s a very useful educational example for placebo effects and the general types of fallacious arguments quacks and pseudoscientists make. Apparently it’s time for another one.
Not too long ago, I wrote about the National Center for Complementary and Alternative Medicine (NCCAM), specifically how until fairly recently it would fund studies of the ridiculously implausible treatment modality that is homeopathy. I even looked at a couple of these studies to see if they had yielded anything of value. Not surprisingly, they did not, other than some unbelievably awful papers published mostly in bottom-feeding alt-med journals. The principal investigator (PI) of the grants in question, it turns out, is a woman named Iris Bell, who, it further turns out, is faculty at the University of Arizona, home to that godfather of “integrating” quackery into real medicine (i.e., “integrative medicine”), Andrew Weil. Now, it just so happens that I’ve found a “review” article on homeopathy written by this very same person, published in BMC Complementary and Alternative Medicine a little more than a month ago and entitled A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system. Truly, this is an apologetic for homeopathy that could have been written by Dana Ullman or Lionel Milgrom, and it’s appearing in what is turning into one of the foremost journals of quackademic medicine.
Thw quackademia is strong in this one
The central thesis of the paper, which Harriet Hall has discussed before, is the concept that homeopathy works through “nanoparticles.” Of course, like so many things that quacks appropriate for themselves, like quantum theory and epigenetics, nanoparticles are a real phenomenon with many therapeutic promises. Unfortunately, the versions of nanoparticles described by Bell are related to real nanoparticles as scientists currently understand them only by coincidence. So, as you will soon see, what we have here is an NIH-funded investigator (funded through NCCAM) teaming up with Mary Koithan to write a mass of pseudoscience defending homeopathy and proposing a mechanism by which it might work. Think on that a moment as I delve into the actual paper. In fact, even though this paper is open-source (which means that you can read the entire thing for yourself), I think I’ll nonetheless lay down the abstract, because it is truly a thing of quackademic beauty:
This paper proposes a novel model for homeopathic remedy action on living systems. Research indicates that homeopathic remedies (a) contain measurable source and silica nanoparticles heterogeneously dispersed in colloidal solution; (b) act by modulating biological function of the allostatic stress response network (c) evoke biphasic actions on living systems via organism-dependent adaptive and endogenously amplified effects; (d) improve systemic resilience.
The proposed active components of homeopathic remedies are nanoparticles of source substance in water-based colloidal solution, not bulk-form drugs. Nanoparticles have unique biological and physico-chemical properties, including increased catalytic reactivity, protein and DNA adsorption, bioavailability, dose-sparing, electromagnetic, and quantum effects different from bulk-form materials. Trituration and/or liquid succussions during classical remedy preparation create “top-down” nanostructures. Plants can biosynthesize remedytemplated silica nanostructures. Nanoparticles stimulate hormesis, a beneficial low-dose adaptive response. Homeopathic remedies prescribed in low doses spaced intermittently over time act as biological signals that stimulate the organism’s allostatic biological stress response network, evoking nonlinear modulatory, self-organizing change. Potential mechanisms include time-dependent sensitization (TDS), a type of adaptive plasticity/metaplasticity involving progressive amplification of host responses, which reverse direction and oscillate at physiological limits. To mobilize hormesis and TDS, the remedy must be appraised as a salient, but low level, novel threat, stressor, or homeostatic disruption for the whole organism. Silica nanoparticles adsorb remedy source and amplify effects. Properly-timed remedy dosing elicits disease-primed compensatory reversal in direction of maladaptive dynamics of the allostatic network, thus promoting resilience and recovery from disease.
Homeopathic remedies are proposed as source nanoparticles that mobilize hormesis and time-dependent sensitization via non-pharmacological effects on specific biological adaptive and amplification mechanisms. The nanoparticle nature of remedies would distinguish them from conventional bulk drugs in structure, morphology, and functional properties. Outcomes would depend upon the ability of the organism to respond to the remedy as a novel stressor or heterotypic biological threat, initiating reversals of cumulative, cross-adapted biological maladaptations underlying disease in the allostatic stress response network. Systemic resilience would improve. This model provides a foundation for theory-driven research on the role of nanomaterials in living systems, mechanisms of homeopathic remedy actions and translational uses in nanomedicine.
Ah, I do so love me some good technobabble, and the above is some of the best, as I said before, on par with Lionel Milgrom’s quantum homeopathy or his visualization of quantum entanglement at a macroscopic level between practitioner, remedy, and patient. (Never mind that quantum entanglement doesn’t work that way. Never let reality or science get in the way of brilliant-sounding science-y blather that impresses the rubes.)
Let’s deconstruct a bit, shall we? First, Bell is saying that “research indicates” that there are measurable source and silica nanoparticles in homeopathic remedies. Hmmmm. I wonder where silica nanoparticles could come from, if in fact they have actually been detected in homeopathic remedies. It couldn’t have anything to do with the fact that most homeopathic dilutions are made in glass vials, could it? Perish the thought! In any case, if you delve into the introduction, which says essentially the same thing as the abstract, only longer and with a lot of nonsensical references, you’ll find that one of the references that purports to claim that there are “nanoparticles” in homeopathic remedies is the very same paper that our very own Harriet discussed. personally, even though the paper is two years old, I can’t resist taking a crack at it myself, because it is such an incredible joke that it has to be seen.
Back to the future, or: you should really check your solutions more carefully
The article to which I’m referring was an article by Prashant Satish Chikramane and his colleagues at Department of Chemical Engineering, Indian Institute of Technology (IIT), Bombay, India. Entitled Extreme homeopathic dilutions retain starting materials: A nanoparticulate perspective. Basically, the investigators…well, it’s too easy to give away the results in a sentence or two; so let me pontificate a little more before I do.
First off, this article appears in the journal Homeopathy. Yes, there is indeed a journal called Homeopathy. Given the level of pseudoscience that must be within the pages of a journal called Homeopathy, I fear a block hole of woo, which will suck all real science into its event horizon, leaving nothing behind but more woo. Personally, though, I like to think of Homeopathy as one of those fake journals designed to put a patina of science in the form of science-y sounding jargon and the appearance of using the scientific method but without actual science. Either that, or the articles within do actually adhere to the scientific method, but in the end they are nothing more than what Harriet Hall likes to call “tooth fairy science.” Given that homeopathy violates several known physical laws and that, for homeopathy to work, not only would scientists have to be wrong about huge swaths of well-characterized science they’d have to be spectacularly wrong.
So let’s see how Chikramane et al try to justify homeopathy. After all, I love reading introductions to homeopathy papers. After having declared homeopathy to have “stood the test of time,” Chikramane et al then go on to level this howler:
However, a major lacuna has been the lack of evidence of physical existence of the starting material. The main difficulty in arriving at a rational explanation stems from the fact that homeopathic medicines are used in extreme dilutions, including dilution factors exceeding Avogadro’s number by several orders of magnitude, in which one would not expect any measurable remnant of the starting material to be present. In clinical practice, homeopathic potencies of 30c and 200c having dilution factors of 1060 and 10400 respectively, far beyond Avogadro’s number of 6.023 Ã 1023 molecules in one mole, are routinely used.
Many hypotheses have been postulated to justify and elucidate their mechanisms of action. While some hypotheses such as the theory of water memory,formation of clathrates, and epitaxy are conjectural in nature, others such as those based on the quantum physical aspects of the solutions and have not been sufficiently tested, either due to complexity in validating the hypothesis or due to non-reproducible results. The ‘silica hypothesis’ is the only model that proposes the presence of physical entities such as siloxanes or silicates resulting from leaching from the glass containers. Following a dearth of credible and testable hypotheses to identify any physical entity responsible for medicinal activity, most modern scientists continue to believe that homeopathy at best provides a placebo effect.
This being all science-y and all, there should be a testable hypothesis, and apparently the authors did have what appears to be a testable hypothesis. In any case, the apparent hypothesis is that there would be structural differences in the homeopathic remedies. So our intrepid investigators went out and obtained a bunch of homeopathic remedies from various Indian manufacturers of homeopathic remedies at three different potencies (how I hate ot use that word in this context), including 6C, 12C, and 30C, all of them in 90% ethanol. They then analyzed these physico-chemical aspects:
- The presence of the physical entities in nanoparticle form and their size by Transmission Electron Microscopy (TEM) by bright-field and dark-field imaging.
- Their identification by matching the Selected Area Electron Diffraction (SAED) patterns against literature standards for the corresponding known crystals.
- Estimation of the levels of starting metals by a 500-fold concentration of medicines, followed by chemical analysis using Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES).
The homeopathic remedies were chosen to have been based on various metals “so chosen that the metals would not arise either as impurities or as contaminants.”
Did the investigators think that metals couldn’t find their way into these homeopathic remedies somewhere along the way in the manufacturing process? Another problem with the paper is that the investigators used as their control HPLC-grade ethanol and Milli-Q water. How on earth did they know that the manufacturers were so fastidious as to use HPLC-grade ethanol and Milli-Q water, the latter of which is distilled, highly filtered, and then deionized to a ridiculously high electrical resistance? I use Milli-Q water all the time for molecular biology experiments because it is so pure and free of electrolytes. So, right off the bat, we see the investigators using a dubious control that isn’t equivalent to their manufactured homeopathic remedies purchased from “reputable” firms, meaning that any differences they observe can’t necessarily be attributed to the homeopathic dilutions of the metals. Not surprisingly, the investigators found differences, and, their being believers in homeopathy, they immediately made all sorts of ridiculous conclusions:
Zincum met, Aurum met, Stannum met and Cuprum met 30c and 200c were analyzed by TEM. The results are given as photomicrographs (Figure 1(a)e(p)), which clearly demonstrate the presence of nanoparticles and their aggregates. Due to extreme dilution often only a single nanoparticle or a large aggregate is seen. Hereafter, the term ‘particles’ collectively refers to the nanoparticles and their aggregates. We noted a high polydispersity of the particles in the solutions.
And this is what they saw:
Perhaps an inorganic chemist out there can tell me if I’m wrong, but there doesnt’ appear to be any thing particularly special appearing about these particles. Looking at them, it also just occurred to me that there’s another possible explanation for these particles, one in which it is the authors themselves who introduced them into the homeopathic remedies:
The residues of Cuprum met, Stannum met, and Zincum met were acidified to solubilize the particles of their respective starting metals by addition of concentrated nitric acid. Similarly, aqua regia (concentrated nitric acid and concentrated hydrochloric acid in the ratio 1:3) was added to residues of Aurum met, Argentum met, and Platinum met.
I was a chemistry major, and, even though it was nearly 30 years ago, I still remember that concentrated nitric acid contained a fair number of heavy metal impurities. For instance, it can have 5 ppm iron and 10 ppm heavy metals. That’s a lot more heavy metal than a homeopathic dose. On the other hand, the authors report that their analyses were consistent with the metals used in the starting materials. This leads them to conclude:
The confirmed presence of these crystalline species of starting materials or those derived from them (as evident from the SAED patterns) despite the ultra-high dilutions such as 30c and 200c was astounding, proving that the starting materials were retained even with extremely high dilutions.
Actually, I’m a bit less than astounded. An alternative, more plausible, explanation, particularly given the propensity for ayruvedic herbs and other “alternative” medicines produced in India to be contaminated with heavy metals is that the manufacturing plants were thoroughly contaminated with the heavy metals that were supposedly the original starting material for the homeopathic remedies that they manufacture.
Of course, I haven’t even gotten to the most howlingly hilarious flaw in the whole study is where the authors:
During our analyses we also noted the plateauing effect of the concentrations of the starting metals per se in a particular concentration range in potencies 6c, 30c and 200c, in spite of 30c and 200c potencies being 1048 and 10388 respectively more dilute than 6c. It is interesting to note that the plateau for non-noble metals showed a higher metal content than for noble metals. Our ICP-AES results suggested that the asymptote effect commences around 6c potency.
Did it ever occur to the investigators that the reason the asymptotic effect occurs is because maybe, just maybe, that’s about the level of contaminants that are naturally in the plant and/or the water being used to dilute and succuss the homepathic remedy at each step? That maybe, just maybe, it’s impossible to figure out whether those particles they detected were there all along as contaminants in the diluent water used? The authors don’t even consider that possibility, nor do they do any experiments to test for it. Rather, they simply assume that the manufacturers got it right and that these particles are truly a result of the homepathic dilution and succussion process. They speculate wildly about “nanobubbles” and “nanobubble-nanoparticle complexes” as keeping the metal particles from being diluted and succussed way to nothing through 30 100-fold dilutions. Even if this were true, there is no explanation how these particles could have any biological effect. Rather, it is merely assumed that they do and that their very existence somehow validates the woo that is homeopathy, so that the authors conclude:
We have found that the concentrations reach a plateau at the 6c potency and beyond. Further, we have shown that despite large differences in the degree of dilution from 6c to 200c (1012 to 10400), there were no major differences in the nature of the particles (shape and size) of the starting material and their absolute concentrations (in pg/ml).
I can’t help but again ask the authors if they ever considered that the reason tha tthe concentration of nanoparticles didn’t change in concentration or appearance was that they are natural contaminants of the water used to produce the homoepathic dilutions. Apparently not. In the end, it’s truly amusing how a group of homeopaths can take a result that almost certainly is nothing more than detecting heavy metal contamination in homeopathic remedies manufactured in India, a country known for having heavy metal conatmination in herbal remedies and ayruvedic medicines it manufactures and then run with it straight off the end of the plank into a sea of woo. And this is but one quackademic paper cited by Bell to justify her hypothesis. So let’s move on and see what that hypothesis is.
Nanoparticles, hormesis, and allostatic stress response networks, oh my!
I must give Iris Bell credit. She is imaginative. Of course, although imagination is a good thing in science, there is a difference between imagination and just making stuff up, and Bell’s review article definitely falls into the latter category. Given that she is a homeopath, this is perhaps not surprising. What helped me get through her article was to view it as a work of fiction, in which the wildest flight of fancy wins, particularly if one can put a nice homeopathic science-y sounding sheen on it, which Bell does with aplomb. What you need to know to understand why homeopaths have latched on to nanoparticles is that (1) even homeopaths know that physics and chemistry as we understand them render homeopathy physically impossible and (2) they need to change the game if they are to put a chink in the dam of science holding back their river of woo. In other words, having conceded that those nasty reductionist scientists are right when they point out that homeopathy is water and cannot work they way homeopaths claim, homeopaths need to reclaim plausibility, no matter how much they have to abuse other sciences to do it.
For example, after pointing out that under “conventional” science homeopathy is impossible, Bell then opines:
These points are seemingly valid, if the underlying assumptions are valid – i.e., that homeopathic medicines are ordinary, dissolved and diluted bulk-form chemical drugs in true solution that could only act pharmacologically  with linear dose–response relationships. However, the trituration and succussion procedures in classical homeopathic remedy preparation may actually be crude manual methods that generate “top down” nanoparticles of source material. Nanoparticles range in size from 1 nanometer (nm) on a side up to 1000 nm or more, though much nanoscience research focuses on special acquired properties of small nanoparticles below 100 nm . Trituration with mortar and pestle is a manual method for mechanical grinding or milling, similar to ball milling used in modern nanotechnology [49,50]. Like modern nanotechnology methods of microfluidization [51,52], sonication [53,54], and vortexing , manual succussions introduce intense turbulence, particle collisions, and shear forces into solution that break off smaller and smaller particles of remedy source material as well as silica from the walls of the glass containers or vials . The combined impact of these mechanical nanosizing procedures  would be to modify the properties of the remedy [26,30,32], generating remedy source nanoparticles [2,3], as well as silica crystals and amorphous nanoparticles [3,4,32].
Got that? According to Bell, all that grinding and succussion generates nanoparticles, and these nanoparticles do things. All sorts of things. Magical things. Like homeopathy things. They can even emit electrical signals! Oh, wait. The paper Bell cites to justify that claim is the infamous paper by Nobel Laureate Luc Montagnier, who, unfortunately, appears to have fallen prey to the Nobel Disease and become a crank. Indeed, that particular paper was roundly criticized for its poor methodology and conclusions not supported by its data, and these days Montagnier is subjecting autistic children to long term antibiotic treatment and appearing at quack conferences like Autism One, along with women who think that giving autistic children bleach enemas is a good way to treat autism. In other words, as sad as it makes me to say it, Montagnier is no longer a good scientist, and I wouldn’t trust anything he publishes these days any more than I trust what Dana Ullman publishes—or, for that matter, Iris Bell.
Let’s take a look at the four parts of Bell’s model. Here’s the first part:
Homeopathic remedies are highly reactive source and/or remedy-modified silica (or polymer) nanoparticles, not bulk-form drugs [2,3];
This is utter nonsense, as I explained when I discussed one of the papers used to support this assertion. These “nanoparticles” are almost certainly nothing more than contaminants and show no real evidence of being “highly-reactive” or “remedy-modified.” More importantly, they show no evidence of actually doing anything therapeutic.
Remedy nanoparticles stimulate a complex adaptive response in the organism that begins in the allostatic stress response network, with cascading indirect consequences over time across the entire self-organizing organism. The homeopathic simillimum (clinically optimal) remedy nanoparticles  serve as low level, but highly salient novel stressors, i.e., specific biological signals for the overall organism ;
Boiled down to its essence, this says something along the lines of: Like, the human body is really complicated, you know? And these nanoparticles do something just as complicated, you know? It’s so complicated that we don’t know what it is and can’t prove that it happens. But it sure is fun to speculate!
Then we have:
The adaptive plasticity processes that underlie the direction and magnitude of remedy effects on living systems involve nonlinear physiological phenomena such as hormesis, cross-adaptation, time-dependent sensitization and cross-sensitization/oscillation. As a low intensity stressor, remedy nanoparticles stimulate changes in the opposite direction to those of the higher intensity stressors that fostered the original development of disease [16,97,98]. The disease-related maladaptations prime the system [10,39]. Then the correct remedy in low dose elicits reversal of direction of the maladapted responses.
Did I say that the human body was complicated? I’ll say it again. It’s really, really complicated, and these homeopathic nanoparticles do things even more complicated than what I said before. For example, they don’t even do normal dose-response curves; they’re more powerful at lower doses, just like Hahnemann said! And they oscillate. Or something. Disease maladaptations (nice word, eh?) get the system ready for these wondrous particles, which can then reverse the maladaptation. All of this is a bit odd, though, given that homeopathy is explicitly designed to treat symptoms, not the underlying cause. After all, the very principle of “like cures like” is based on symptoms, not biology.
None of which stops Bell from writing:
The adaptive changes that the remedy evokes ultimately strengthen systemic resilience. The successfully treated individual can resist and rebound from subsequent challenges from higher intensity homeostatic disruptors of the organism as a complex network, at global and local levels of organizational scale .
Damn, I wish I could write word salad this tasty. As I read this passage, I started to wonder whether I was the victim of a Sokal-style hoax here or whether Bell wrote her paper the way that David Bowie used to like to write songs: By cutting up newspaper and magazine articles and randomly splicing the words back together. In this case, it seems as though Bell cut up a bunch of nanoparticle papers and some homeopathy literature and then threw them together to produce much of this paper.
Here’s what I mean. This whole paper sounds very impressive, but when you analyze individual passages you quickly realize that it means nothing. It’s a whole lot of blatant speculation. Now, blatant speculation in science is not necessarily a bad thing, but only when it is at least somewhat plausible and, more importantly, when its limitations are clearly acknowledged. None of this applies here. Bell claims that homeopathic remedies are an example of hormesis, which is ridiculous. She goes on at length about the phenomenon of cross-adaptation, in which widely different stressors can affect the same intermediary pathway, blithely asserting that homeopathic remedies work through cross-sensitization without presenting any convincing evidence that this is so. She does the same thing for other phenomenon, in which homeopathic remedies apparently exhibit metaplasticity and time-dependent sensitization, which Bell uses as a rationale for why “pulsing” homeopathic remedies is a good idea, concluding that these remedies somehow “strengthen systemic resilience,” whatever that means. It sounds all too much like the generic quack claim of being able to “boost the immune system.”
Perhaps the most hilarious part of the entire article is Table 1: Parallels between homeopathic and modern scientific research literatures. Examples include comparisons of the “homeopathic literature” and real science, with the real science being tortured into agreeing with the homeopathic literature. For instance, one of items states that disease is the “dynamic mistunement” of the living system (i.e., life force). In the real scientific literature, according to Bell, disease is “the current manifestation of failure to adapt or compensate for allostatic overload from convergence of biological, chemical, physical, and psychological stressors on the nonlinear adaptive stress response network, which is embedded within the larger complex network of the overall organism.” I get it! they’re totally the same! Hahnemann apparently foresaw scientific developments over two hundred years into the future!
I’ll conclude with this comparison. From the homeopathic literature:
Higher potencies (more dilution and succussion steps) have longer lasting effects on living systems  (succussion involves intense mechanical shaking of the solution by pounding the glass container against a hard elastic surface).
Now from the real scientific literature:
Succussion, like modern microfluidization techniques , introduces cycles of fluid acceleration and turbulence with repeated changes in the direction of flow, producing the potential for particle collision and shear forces to break off smaller and smaller particles. These procedures, while different from each other and from sonication as a technique for agitating solutions and producing nanoparticles, share the ability to create nanobubbles and shear forces. Nanoparticle research suggests that there are nonlinear relationships between the number of microfluidization cycles or sonication time and variations in the sizes, morphologies, and physico-chemical properties of the “same” bulk-form material substance [52,53,244].
Again, can’t you see how they’re totally the same? No? Neither can I.
She currently is still the PI on a training grant held by the University of Arizona to teach woo to medical trainees.