Lo Article Discussion Steven Bittenson, hbittenson@aol.com May 20, 1997 Originally posted to homeopathy@lyteforce.com. (Some corrections and slight revision 11/27/97, 12/26/97) I started writing this for other (educational discussion) purposes, then realized that some folks on the homeopathy mailing list might be interested. I hope you find it useful or at least entertaining. It's quite long. This was not originally intended as a review for a professional scientific audience, but it is written from a technical perspective. My first objective was to talk about the process of research and model- building, using this interesting and likely controversial work as a focus. ************************* PERSONAL PERSPECTIVE To put some perspective on ``where I come from'' in general: I'm both a Western-trained physical scientist** and a long-time student of alternative medicine. There are a few others with this combination of backgrounds I've already learned of on the homeopathy list. It's nice to know you're there. I strive (not always successfully) for balance and flexibility between these sometimes apparently conflicting world-views. I trust and use rigorously the ``scientific method'' where I think it's appropriate, and also have experienced enough of phenomena presently outside of Western science that I'm confident there's a lot right in front of us that's yet to be understood, and difficult to study conventionally. I can't imagine saying either ``Using this technique is wrong because we can't completely understand its fundamental mechanism'' or ``We do it only THIS way because a wise man figured it out correctly hundreds of years ago.'' I really want to gain understanding of what's behind alternative healing methods. From my efforts in that direction, I confess to having developed a lack of patience with ---those ``scientists'' who think that anything they can't already measure doesn't exist (concrete model-bound). ---those ``physicians'' who claim that only large statistical studies can guide the treatment of individuals (liability-bound). ---those ``alternative healers'' who are absolutely convinced that THEIR technique is the only TRUE PATH, bordering on religion and excluding other modalities (but accepting none of the responsibility or liability imposed on allopaths). ---charlatans of all stripes who sell ideas or devices they know are false or ineffective (double-talk, sleight-of-hand). Boy! That sounds pretty cynical. I didn't delete it though; I guess iconoclasts are like that. We all do need firm beliefs and structure in our lives or we can't constructively and enjoyably get anywhere at all, but experience and training don't have to lead to rigidity or deceptiveness (said he rigidly, but honestly). ********************************************************* **My technical background: Ph.D., chemical physics. Since leaving academia in 1983, I've worked mostly as an R&D Manager, Product Development Manager, researcher, and consultant in the laser, medical equipment, electronic capital equipment, and energy/environmental industries. My academic work before jumping ship was mostly in chemical dynamics. I'm always looking for ways to merge my technical professional and alternative medical paths. ********************************************************* REFERENCES: 1. Anomalous State of Ice Shui-Yin Lo, Modern Physics Letters B, Vol.10, No. 19 (1996) 909-919. 2. Physical Properties of Water with Ie Structures Shui-Yin Lo, Angelo Lo, Li Wen Chong, Lin Tianzhang, Li Hui Hua, Xu Geng Modern Physics Letters B, Vol.10, No. 19 (1996) 921-930. ********************************************************** Note in anticipation of some comments: Yes, I have read Bellavite and Signorini's book Homeopathy--A Frontier in Medical Science, and there's a lot of relevant stuff there that we could get into, but this document is too long as it is---maybe another time. ********************************************************** *Quick Outline* (as opposed to critical review) (from my original posting to homeopathy@lyteforce) Summaries of the critical review follow the separate discussions of each article Lo proposes a theoretical framework to explain some unique physical properties he measures of very dilute water solutions of common chemical compounds. These solutions are prepared in a manner similar to potentized remedies (homeopathic word use, not Lo's). Lo's principal claim is that at least some substances dissolved in water can lead to the formation of tiny ice-like crystals which then can exist and grow INDEPENDENTLY of the original substance that induced their formation. This theory predicts that in successively diluted/shaken (succussed?) solutions there is thus a very physical presence which is due to, but does not require any concentration of, the original solute. He estimates that these crystals incorporate up to a few per cent of the water in a solution. Lo uses an assortment of standard analytical chemistry techniques to support his conclusions, including pictures of micrometer-scale structures taken using an electron microscope. Lo chose three common chemicals for this work: sodium chloride (Natrum Mur), nitric acid (Nitricum Acidum), and sodium hydroxide. All three compounds are very soluble and form ions (fundamental charged units) in aqueous solution. To a chemist, they are nicely representative of salt, strong acid, and strong base, respectively. The maximum dilution used in the study was ~13X. Lo's initial argument is interesting, but there are significant issues with his follow-through and support of his conclusions. ********************************************************** We'll look first at paper #1, then at Paper #2 ********************************************************** ICE DISCUSSION: Lo begins by writing briefly about the special forms of ice that can crystallize at room temperature, but only at very elevated pressures starting around 7000 times what we experience in the earth's atmosphere at sea level. This high pressure is reasonably compared with the squeeze under a 6 kilometer (4 mile) tall column of lead at the Earth's surface. Special laboratory apparatus is normally required to make and stabilize tiny amounts of such materials. Ice is taken here to mean any solid phase form of water. In his papers Lo proposes and develops a model for a new ice of this sort he calls ``Ie'' (Ice formed by Electric field forces), formed around and due to the forces exerted by the electric fields around individual ions in very dilute water solution. This Ie (if real) has not been previously characterized, but probably has a crystal structure different from known types of ice, so quantitative predictions of its properties (e.g., the pressure required to form it, structural guesses) are approximate at best. Lo attempts to extend the current models of high-pressure ice formation to answer the questions: * Is there a solid theoretical basis for the existence of ``Ie'' ice? * Can we find experimental evidence for the existence and properties of Ie ice? The purpose of our discussion is * to outline Lo's model, to evaluate its sensibility, * to develop an opinion of whether Lo has experimentally demonstrated phenomena which support the existence of Ie, * to look for additional activities which would clarify any questions that arise, * to explore some of the implications of Lo's proposal, particularly for homeopathy. NOTE: Lo labels his proposed crystals ``IE'' (Upper case ``I'', upper case subscript ``E'') I use ``Ie'' here because subscripting sometimes get lost in electronic transmission. ******************************************************* MODEL-BUILDING AND MOTIVATION Learning about high pressure phases of water such as ice VI or ice VII (to which Lo compares his Ie) has helped researchers understand the properties of water, crystals, phase transitions, and chemistry under unusual conditions, and there is a body of literature in this field. These rare phases of water (or of other substances) are usually represented in books and articles in the form of interesting and complex ``phase diagrams'' which show graphically the temperatures and pressures at which these various forms change into one another. Lo draws on this body of information to create his model. Model-making is a type of challenge that scientists find useful and stimulating, and models help us answer our questions about how things work. We fine-tune our models as necessary, and occasionally trade them in for better ones as more information becomes available. Dependence on a particular model can also hold back new understanding, so it's good to be flexible enough not to confuse a model with TRUTH. Although Lo uses no homeopathic language at all in his articles, I suspect that his driving question is one that undoubtedly occurs to nearly any scientist who acknowledges that homeopathy is more than a placebo effect: ``What's IN a potentized homeopathic remedy?-----there's got to be SOMETHING there!!---What model of how things work might lead us to PREDICT the possibility of homeopathic effects?'' Can existing models help us, or do we need an entirely new one here? Lo is probably wise not to advertise overtly this sort of goal, but the thought does appear to lead his measurements. A model that consistently pulls together things which already have been observed can be very handy. You can build a pretty neat model of how the universe moves in little curliques around the earth at its center, and you can organize useful tables of observations on that basis. Some early astronomers did precisely this. Researchers or other practitioners can bury themselves in such things for a long time. The REAL test of a model, however, is how it predicts new ranges of behavior or whole new phenomena. It is such PREDICTIVE modeling that to many people describes real science at work. Trading in their epicycles for orbital mechanics was a tough sell to some folks in the astronomical community of a few hundred years ago, but the predictive power of the new model won out over viewing the earth as the center of the universe. *********************************************************** LO'S MODEL, principal points: 1. Start with an isolated ion in aqueous solution. This ion has around it an electric field which decreases rapidly with distance (Large electric field gradient). 2. Water molecules have an electric dipole moment, or internal distribution of charge so that the molecules are somewhat polarized: opposite ``ends'' of the molecule are effectively oppositely charged (+ and -), though the molecule as a whole has no net charge. Such electric dipoles are attracted by the electric field GRADIENT of the ion. 3. This attractive force may be interpreted as a `pressure', usually expressed in units of force/area. Lo estimates (rough calculation) this pressure to be greater than 7000 bar out to about 3 layers of water molecules around a singly charged ion. 4. By comparison with known high pressure ices, Lo takes 7000 bar as a likely minimum pressure of formation of a new form of ice which grows closely around the ion, but only as far out as the high pressure reaches. He acknowledges that the structure of Ie isn't known, and that because of the spherical distribution (decrease with radius) of pressure around an ion, it's likely not a regular lattice like that of a known ice, e.g., ice VI. 5. If other ions get too close, the effective electric field gradient (and ``pressure'') around the first ion decreases, and the ice ``melts.'' These proposed ice crystals are thus stable only in very dilute ionic solutions. Based on known average rates of ice crystal growth, opposed by known average rates of approach of molecules to each other in aqueous solution, Lo estimates that the MAXIMUM concentration of ions permitting stable Ie crystals to form is 10^-5 (1E-5) moles/liter (Moles/liter=Molar=M), to keep all the Ie from melting. COMMENTS: This starts out pretty reasonably. Ions in aqueous solution are well known to attract water molecules around them. The proposed possibility of crystallization at low concentration is novel and intriguing. The size of the Ie crystals would be limited to roughly 2 nanometers, based on Lo's pressure calculations. This is pretty small; many molecules (especially biomolecules) are much larger. In addition, as Lo describes, no other ion could get near one of these Ie bodies without melting it, while new ones form around newly isolated ions. The concentration of, e.g., salt in our bodies is orders of magnitude higher than the 1E-5 M Lo proposes as the maximum allowed ionic concentration for Ie stability, so the theory outlined above is incomplete if the objective is to lead us toward homeopathy (Ie thus proposed could not persist (exist?) in a human body). We'll talk below about how he attempts to complete the model. Lo does not put ranges (minima and maxima) on most of his estimates. I'm uncomfortable with this omission. His intuition might be good here, but his estimates can only suggest that it's conceivable such a structure might form. Any reality may be several orders of magnitude away in either direction from the 1E-5 figure which sems to fit so well with his experimental data. Another item Lo should discuss explicitly is the role of self-dissociation of water into positively and negatively charged ions, (nominally hydrogen+ and hydroxide- for the purpose of this discussion) at ~ 1e-7 M (this is the origin of pH 7 as neutral with regard to acid versus base). Along this line, since the pressure drops with distance, there should be an interestingly structured transition region where the ice fades and more usual hydrogen-bonded liquid takes over. A lot of work has been done over the years regarding the interactions of ions with surrounding water molecules. Does Lo's theory dovetail into e.g. classical treatment of transport of solvated ions? How about well-known properties of ionic solutions extrapolated to zero concentration? None of this sort of analysis appears in the publication. ****************************************************** ANALYTICAL WORK, LO'S INTERPRETATION AND MODEL EXTENSION Lo looks for measurable properties of dilute ionic solutions, seeking evidence for the presence of Ie. He uses NaCl (sodium chloride, table salt), NaOH (sodium hydroxide, also lye or caustic soda), and HNO3 (nitric acid) as his test chemicals. All three are ionic in solution, and representative of a salt, a strong base, and a strong acid, respectively. Ultraviolet light absorbance: This is one of two analytical approaches discussed in this paper. The second paper reports on some other techniques. Lo measured how much 190 nm wavelength light is transmitted by solutions of his test chemicals as he successively diluted them with pure water (purified by reverse osmosis). At this ultraviolet wavelength, water itself absorbs some of the light. In addition, the attenuation of 190 nm light passing through a sample is very sensitive to the presence of most dissolved or light-scattering substances. The measurement technique simultaneously sends light through the test solution and a separate reference cell of pure water, comparing the magnitudes of transmitted light. In Lo's measurements, as the solutions get very dilute, the relative light attenuation in the test cell does not drop to zero as we might expect, but begins to level out at about 1% (at around 1E-5 M concentration) with the optical absorbance increasing and decreasing with successive dilutions in an apparently cyclical fashion around the nominal 1%. COMMENTS: Classically viewed, this is very odd behavior. The relative absorbance of the test solution SHOULD go to zero with great dilution unless something is either propagating itself dilution-to-dilution, or if there's some experimental contamination going on. Lo is convinced it's the former. I think he needs additional tests to adequately support this position. The cyclical nature of the effect with dilution also requires multiple repetitions of his experimental measurements to support. There are a few fairly simple measurements which could make the data and the story more convincing. a) Make the absorption path longer. I suspect his absorbance cell is at most ~10 cm long. If the absorbance scales with longer path length, the measurements would be better supported. Variations in a nominal 1% decrease in a signal are difficult to validate. Certainly more sophisticated spectroscopic measurement would reveal more. b) Show an example of a solution which DOES drop to zero absorbance with successive dilution in the same apparatus. Without such a comparison, his pure water versus dilute solution data are pretty disconnected, and the reader can't tell whether or not there's a peculiar experimental problem confusing the results. Also start with pure water and ``dilute'' it in the same manner as the test sample: this might uncover systematic experimental errors. c) Carry the dilutions to the obvious (homeopathic) limit. Lo carried his dilutions out to ~1E-13M. If the ions are really unnecessary to maintain Ie, the dilutions should be carried out AT LEAST to 1E-24M (roughly equivalent to >12C potentized remedy) to show this. He was already more than halfway there; why stop? d) Detail and carefully control the experimental procedure. Lo does not detail his method of successive dilution adequately to determine if surface effects (interior of the dilution vessels) are important. Were the same vessels used each time? what size(surface-to-volume ratio) and how were vessels cleaned between dilutions? He does discuss cleaning of the ultraviolet absorption cell ``....carefully wash...'', but this isn't nearly enough information to allow someone else to reproduce his work. e) Measure light scattering. Lo notes that the spectrometer he uses will show decreases in transmitted light through the cell if light is scattered as well as if it's absorbed. Light scattering of this magnitude is quite measurable, and would INCREASE with dilution if Ie crystals are forming. This could be a really key supporting measurement. f) Measure ultraviolet attenuation as a quantitative function of shaking the sample. Lo makes the argument that the variations in UV absorbance with successive dilutions is a ``random'' process due to variations in ``shaking, breaking and then growing'' Ie crystals. I have trouble with this argument. First of all, I see nothing in Lo's model that suggests that these Ie crystals could be broken up (by shaking!) and reformed without the ion to provide the electric field gradient. Second, why would such ``random'' variations create a periodic effect with dilution? Third, Lo suggests that fragments of broken crystals would have a dipole moment which would create a field gradient in which Ie could regrow. Why don't such fragments simply ``melt'', especially with other fragments nearby? Lo's argument implies to me that Ie is independently stable at room temperature without the aid of an applied field gradient due to aqueous ions. I'll reserve judgment for now because some of Lo's data does suggest that something's really going on here, but his model does at this point get a bit reminiscent to me of Kurt Vonnegut's ``Ice nine''--a stable high temperature ice which causes a disaster in his novel ``Cat's Cradle.'' Question: Have any of you experienced homeopaths ever succussed a high potency remedy until it solidified in the bottle?(humor) My suggestion here to Lo is to do more carefully controlled measurements both in shaking and diluting; perhaps diluting in multiple bottles and then remixing. As in a) above, use a longer cell to reduce random variations due to measurement limits. g) Use infrared rather than ultraviolet spectroscopy. Lo observes that the ultraviolet spectrum of his various chemical compounds look the same as each other at high dilution, and he suggests that this is because all form the same sort of ice crystals. Perhaps this is so, but if the spectrum is due largely to light scattering, and with the relatively small amount of light lost, it's hard to tell what's going on except that something's there. Other spectroscopic techniques might be much more useful here. Infrared or Raman spectroscopy, for example, might let us see characteristic vibrational modes associated with Ie structures. Most types of fluorescence spectroscopy would be a lot more sensitive (assuming the probe light doesn't ``melt'' the crystals). Lo does get a little further into experimental/analytical work in his next paper. The suggestion that a ~3 water molecule-radius Ie crystal can be broken into stable fragments by shaking, and then can then regenerate and grow (larger than the original?!) is a particularly tough one to support. I estimate that a three water molecule radius Ie crystal around a simple ion as proposed by Lo would likely contain fewer than 400 water molecules. Since there's a rapid gradient of ``pressure'' with proximity to the ion, I suspect that any fragmentation would be more like a ``peeling'' of the outer layer(s), leaving just some water molecules in perhaps some initial relative orientation, but unlikely to breed bigger ``chunks.'' More likely they would be quickly equilibrated with the ambient liquid. I suggest that HERE is an area to focus a proof of principle test key to support Lo's theory. ****************************************** ADDITIVES TO ENHANCE Ie PRESENCE Lo adds a ``dielectric material with a high boiling point'' to (theoretically) enhance the growth of Ie to larger structures, but he doesn't tell us what it is (patent disclosure in process?, proprietary?). The mechanism of Ie formation proposed earlier is the interaction of water molecules with the electric field GRADIENT around an ion, which rapidly decreases with increasing distance. How does the unidentified dielectric substance enhance the gradient far from or independent of the central ion? Is there some confusion between electric field and electric field gradient in the paper? I have some trouble understanding his argument here. Lo sees dramatically increased UV light attenuation in the solution with the ``dielectric material'' added to ``several parts per million.'' Without knowing what the substance is, it's difficult to tell if this is significant as it bears on Ie formation. Many chemical compounds absorb ultraviolet light very strongly. He then distills some of the solution (low temperature evaporator) and sees SOME of the increased UV attenuation carried over into the distillate (not all, from his published spectra). His claim is that the dielectric material, which has a boiling point of 350 degrees C, will not distill over at 67 degrees C. In general this is a pretty reliable statement, but without knowing what the dielectric material is, It's difficult to comment constructively here (What's the vapor pressure curve? pure versus a mixture? chemical properties? interaction with water? dielectric constant) Even with that knowledge, more reported experimental detail would help. If I understand Lo's points here correctly, he's saying that: --the Ie structures (nominally positively or negatively charged) are attracted to and collect around molecules of the dielectric material --the overall structure now looks like dipoles of Ie with a dielectric molecule(s) somewhere in the middle, controlling the charge distribution --these Ie structures maintain integrity in the gas phase and have a vapor pressure similar to that of water. I'd like to know why the distillation wasn't done at the usual 100 degrees C and what results might have been at that temperature. Is there information in there? Are molecules of the dielectric carried over in the gas phase with the Ie structures? If so, can the distillate be reconcentrated, recovering the spectrum of the dielectric substance? ******************************************** ELECTRON MICROSCOPY Lo sees micrometer-scale, rod-like structures which he associates with Ie, using electron microscopy. He also states that these structures can be seen with an optical microscope, but doesn't make it clear whether he's actually made this type of observation. He also refers to additional analytic techniques he's used, to be published separately. He sets up a mathematical model of the expected shapes of agglomerations of the dipoles he expects to see, and indeed the observed oblong shapes are very consistent with the model. This is an interesting result. I look forward to seeing the additional measurements Lo refers to in the paper. It would be nice here again to know what the dielectric material is, to help get a sense of relative scale of the structures. (the electron micrographs published include 100 nm scale internal substructures). Some electron micrographs shown are of 1E-11 M solutions without added dielectric, and others have the dielectric added. It's not clear from the publication how much more concentrated the structures are in the dielectric case (how pure was the water in the first place?), but the in the pictures, the Ie structures with dielectric present look more robust. ********************************************** SUMMARY Lo proposes a model in which microscopic ice crystals form around ions in very dilute water solution at room temperature. The addition of dielectric materials is then predicted to lead to agglomeration of these crystals into larger structures which can self-propagate without the presence of the original ions. The weakest point in the model---which will require very careful experimental substantiation--- appears to be the suggestion that mechanical shaking can break up the nanometer-scale structures, which then re- grow without the presence of the original ions. Suggestive but very incomplete experimental evidence for the presence of the predicted structures is provided, with the promise of more evidence to come. Lo's apparent reluctance to reveal the nature of an additive he uses to stabilize the Ie structures makes it particularly difficult to evaluate the significance of his spectroscopic data or photomicrographs. I admire the author's attempt to build and support a concrete model which might contribute to an understanding of potentized (homeopathic) remedies. The initial premise is a clever extension of how an ion interacts with its local ``atmosphere'' of water molecules, other ions, (and high dielectric materials?). It would strengthen the author's position if he described the relationship of the proposed model to conventional treatments of ion solvation. A personal note: ``Secret ingredients'' in publications are best left to advertising brochures from companies with proprietary interests which require such protection to ensure profitability. Learned journals are not the best place to practice this approach to disseminating your work. Publish it, or keep it secret---your choice. Otherwise don't be surprised if there are some negative attitudes out there toward you, whatever the topic. ********************************************************** Now let's look at Paper #2 ********************************************************** Lo and associates looked at some properties of water they have prepared to contain the proposed Ie structures. Using their terminology, the authors look at: 1. Dielectric constant 2. Electromotive force using two identical electrodes 3. Electrical resistivity 4. Fluorescence 5. Stability as a function of temperature The authors describe the solutions used for these measurements as having been prepared as discussed in the first paper. It's not clear whether this includes the unspecified ``dielectric substance,'' or other specific details of preparation. 1. Dielectric constant. The authors state that they expect an increase in the measured dielectric constant of water with Ie structures present. Instead they report without comment a 20% decrease. 2. Electromotive force using two identical electrodes. They put stainless steel electrodes in the Ie solution and observe a small but easily measurable voltage generated between the two electrodes. This voltage lasts for an hour or so. They explain the effect as due to the accumulation of some of the Ie dipoles on the electrodes in a somewhat non-random fashion once the first few have (randomly) attached. The polarity is described as being in either direction and, can be disturbed by stirring the sample. This is a curious bit of measurement which I've not previously seen used as evidence for any particular phenomenon, though I remember noticing something like it while fooling around as a graduate student, teaching an undergraduate chemistry lab. This is not, however, an area in which I've done a lot of work--if someone knows more about this, I'd appreciate learning more from you. The authors provide a plot of voltage versus time from immersion of the electrodes, for a number of experimental sample runs. I'm curious as to why the polarity in their plot is not random but mostly starts in the same direction, then changes in the same sense. Unless there is some systematic problem in the voltmeter, hidden asymmetry in the experimental apparatus, compositional difference between the two electrodes, or perhaps some undetected magnetic fields influencing the measurement, the polarity of any measured voltage should be entirely random. Also: is this a plotting convenience (flipping the sign of some data), is it due to the type of metering used (not purely passive)? The authors list in this section some reasons for data to be inconsistent, mostly because the solutions are inconsistently prepared. They include comments about the effect of surface interactions of Ie structures, confusing their information about concentrations and the effects of successive dilutions. I suggest that the authors could easily improve their control over their sample preparation technique. At least the inconsistency argument would probably disappear. 3. Electrical resistivity. The authors discuss their data as if they measure an increase in the electrical resistivity of Ie water above that of pure water, but their plotted data shows a maximum sample resistivity of 0.95 Megohm-cm, versus 18 Megohm-cm expected for pure water. The resistivity they measure does increases with the duration of the measurement for half an hour or so from starting. Their interpretation is interesting: that the water with Ie structures is behaving more like a dielectric material than pure water, and that the 100Hz A.C. signal applied at around 1 volt to do the measurement simulates mechanical shaking to break up and reform the Ie crystals, stimulating their growth. The more Ie, the higher the resistivity, up to some limiting concentration. If the breaking up and reforming of Ie structures is real, this explanation could fit the data. Some additional data is needed here: Does the resistivity drop off again between measurements if the applied voltage is turned off for a while, or if the solution is stirred or heated or cooled? Does the increase occur in previously well-shaken (succussed) samples? Is this dependent on container size (surface-to-volume ratio)? How does their measurement apparatus actually respond to a few other, non-Ie solutions. Does their solution have ``dielectric material'' in it or not? With additional dilutions to get rid of the rest of the ions does the resistivity indeed exceed that of pure water? Do they add more dielectric after dilution? Is there any chemical change in the electrode or the solution due to the applied current? Is the chemical composition of the electrode important to the measurement? 4. Fluorescence. They see some. This section is really frustrating to interpret. Is there or is there not the ``dielectric material'' in their Ie solutions? Fluorescence spectroscopy is a very sensitive technique for identifying small concentrations of chemicals. It would surprise me if this ``dielectric material'' did NOT give a nice fluorescence spectrum of its own in ppm level concentrations (especially in the ``RU''--this means random units, I assume-- reported). The action spectra shown in the paper indicate the presence of an emitting spectral band near 300 nm. There are a lot of chemical compounds with this characteristic. Certain ultraviolet-emitting dyes used in the laser industry are good examples, but there are many others. For example, there's a strong hydroxyl (O-H) spectral band around there, but we don't know what's really in the sample. 5. Stability as a function of temperature. There are apparently some typing or clerical errors in this section, confusing the data reporting, but interpreting the result as positively as possible, the Ie samples show evidence of being stable between 30 and 80 degrees C. The authors also report having heated a sample to 121 degrees C (at elevated pressure), then cooled it back down without loss of the ultraviolet absorption that they suggest is characteristic of Ie. If the spectrum is actually a property of the high boiling point dielectric additive, there's no surprise (or information) here. The authors use their temperature-dependent ultraviolet absorbance data to calculate a fractional presence (indirect concentration measurement) of Ie structure in the sample. They do this by comparison between measurements for pure water versus multiple Ie samples. I didn't try to repeat their numerical analysis, but I didn't see any immediate issue with the approach. If we assume this is OK, they get up to around 4% concentration (3.79%--3 significant figures?) of Ie or whatever it is in their most concentrated sample. I have not thought through whether this result might be different if the light is scattered versus absorbed by Ie, and it's not clear from the text how their calculation `counts' Ie: as a fraction of water molecules in the Ie structures, or as the number of Ie structures as a fraction of the number of water molecules? Their last step in this analysis is to measure the boiling point elevation of Ie samples versus pure water. This is a classic technique for estimating the molecular weight of dissolved substances, and in this case, the 1.0 degree C elevation measured, in combination with the mole fraction measurement above, suggests 17.5 grams/mole as the molecular weight of the Ie---essentially the same as water (18 grams/mole). They take this to mean that Ie is made up of water. Aside: I'd really feel more comfortable if these folks would put some MPE's (Maximum Probable Error information) around their data, even just to know they're thinking about it. In the case of this final measurement, I estimate it to be at least +/- 20% (~15-22 g/mole range, assuming the calculation is sound), but hard to pin down from the information available. The reader shouldn't have to do this for them. Question: I'm not sure how to interpret this section. If the calculated molecular weight is ~18g/mole, that implies that this is the molecular weight of a SOLUTE. Is Ie a solute or a suspended solid, and if it can be treated as a solute, isn't its effective molecular weight as a whole in the hundreds or thousands for a substantial Ie structure? How does this relate to the UV absorbance-based concentration measurement? I'd like to see the authors discuss this. If the solute is water, why is the boiling point changing from that of water solvent? The authors finish with some additional measurements: that after 2 years the apparent Ie structures are unchanged, that HPLC (chromatography) detected <0.2ppm of their ``dielectric material,'' that atomic emission spectroscopy showed <0.1 ppm of the original metal ion (sodium, I presume) in the Ie sample. I interpret these numbers as lower limits of detectivity for the instruments used. It would be nice to know how this particular sample was prepared, and whether ppm here means by weight or by mole ratio. If I assume they've got 0.1 ppm sodium (molar concentration) in the sample, there could be, e.g., 6E-6M NaCl in there---similar to Lo's original estimate for the MAXIMUM ion concentration for Ie formation! Two final suggestions based on the last part of the paper: Measure freezing point depression in addition to boiling point elevation Measure viscosity. at 4% concentration there might be a measurable effect. ****************************************************** SUMMARY I began reading this paper excited to see how Lo substantiates his claims/model developed in his first paper on this subject. I'm left with a bit of a hollow feeling both because of his choice of measurements to report and because of relatively low overall data quality. I'm not convinced that there's nothing there, but it's hard to get really enthusiastic about what's been concretely reported so far. I won't be going out of my way to share these results in detail with physical scientist associates who are snidely skeptical of homeopathy, although I'd love to be able to do so, and maybe it will work out later. Does Ie exist and contribute to a technical picture of homeopathy? We'll have to leave that as a question until this work is better substantiated or reported. Lo's electron micrographs look interesting, and I'd really like to see the atomic force microscopy results he promises in the reference section of the paper (say, for 15C nat mur without the secret ingredient). Especially with research as controversial as anything that might support a physical basis for potentized (homeopathic) remedies, authors should work hard to be sure that what they publish in professional scientific journals is well nailed down. I don't think that this is the case with this publication, though I wish the authors the best if they continue this work. ********************************************************* SOME IMPLICATIONS IF LO'S WORK IS SUBSTANTIATED Now it's my turn to venture to the edge. Following are some of the implications I see for homeopathy if Lo's findings are corroborated and extended by other researchers. Some of what's written/suggested below has shown up in discussions and a writeups I've seen about homeopathy, but I'll let this stand on its own for now. 1. If Lo's crystal theory is correct, and if potentized remedies really work through the presence of these crystals, then beyond ~12C, succussion is vastly more important than dilution for potency, since succussion can only bring the crystals up to a limiting concentration, and this limit will be the same for any high dilution. This could influence approaches to dosing or at least help us understand differences. Past 12C, dilution might be like waving your hand over the right doorpost, while succussion is the light switch. (see Steve's soapbox, below) 2 Lo predicts and demonstrates qualitatively that some chemical additives in part-per-million concentrations can enhance the concentrations of ``crystals'' in the potentized solution. If proven, this might yield VERY potent ``remedies'', or accidental enhancements due to certain low level impurities. Is this his big secret about the additive he uses, and has anyone done a proving of it? Maybe lactose does this. 3. If there really are visible crystals with measurable properties related to a ``parent'' reagent in homeopathic remedies, then it's conceivable that homeopathy will be seen as a real chemical treatment by regulatory agencies such as the FDA, leading to closer scrutiny and/or or greater co-opting by the allopathic community. Scary, especially to the non-MD practitioner. 4. Lo's model suggests to me that potentization would be more effective at low temperature--perhaps near water freezing temperature. Are there any comments you experienced folks have on potency versus (preparation) temperature? Can you potentize near freezing to increase potency, then warm it up? 5. Even with this model, the question is still quite open of what happens to the crystals when dry pellets are prepared from solutions, then dissolved in the mouth. Is there loss of structure? Is it recovered with redissolution? Do the crystals get more concentrated? Does this provide evidence that/why liquid and dry potencies cannot be directly compared? 6. Lo's data shows a periodicity in some (spectroscopic) properties of his solutions versus dilution (Alternating high versus low absorption of ultraviolet light with successive dilutions). If this effect is real, then successive X, C, LM dilutions may or may not increase potency. This also tends to support the idea that these different scales require different approaches to dosing, and that a single approach might be devised that gets us wherever we want. 7. Lo's electrical conductivity measurement implies that applying an AC electric field to a remedy might be the equivalent of succussion. A potential (no pun intended) means of homeopathic standardization? What about magnetic field effects? 8. Since the Ie crystals would ``melt'' immediately upon exposure to the normal ionic content of human body fluids, the implication is that homeopathic action is an EXTREMELY immediate stimulus on exposure. This also suggests that one of the differences between liquid and dry dosing is that the liquid will provide an immediate exposure over a large surface area and then it's all over, while pillules will continue to expose the patient at a lower level until they dissolve. 9. Food for thought: If the electric field gradient mechanism Lo proposes is correct, then what about all the non-ionic substances that comprise most of the materia medica? are there two or more mechanisms of homeopathic action? Does sugar play the role of Lo's secret ingredient? *************************************************************** RELEVANT ANECDOTE The theoretician is walking down the hall when the experimentalist runs up to him, very excited, and says: ``I DID IT, I finally DID IT!! I just got data in the lab showing that `A' is greater than `B'!!!'' The theoretician is quiet for a while, then begins thoughtfully: ``A is greater than B? Hmmmm... A is greater than B.'' Then with great certainty and burning gaze: ``YES, YES, I can prove that! I can PROVE that A is greater than B!!'' ``OH!,'' says the experimentalist, ``Did I say A is greater than B? It must be all this excitement. I'm sorry, I meant to say that B is greater than A!'' The theoretician ponders this for only a moment, then says ``AHA!! Even easier'' (Thanks to Oded Kafri for this one many years ago) *************************************************************** STEVE'S SOAPBOX I read a science fiction story some years ago about a primitive society in which a universal religion directed that every time a person entered a room, they must first make a ritual sign over the wall space to the right of the doorway. It was sacrilege not to do so, and children were carried through doorways until old enough to learn: the tale was told that you'd lose your eyesight if you ignored the ritual and if God was in a bad mood. The tribal Elders developed arcane doctrinal explanations for the ritual, and these were woven into the fabric of the civilization over the generations. It turned out in the story that these people were the descendants of marooned survivors of a spaceship crash, and the ancestral civilization usually put their electric light switches on the wall to the right of doorways. It would be dark inside if you forgot to turn on the switch: thus the blindness legend. Doctrine prevented enlightening research until another spaceship landed. I've seen arguments among posters to the homeopathy list over whether double blind studies are possible, appropriate, practical, important, or imperative in homeopathy. At the other end of the universe I've heard arguments from allopaths that all evidence is worthless UNLESS it's been multiply verified by large double blind studies. I think we've got to strike a better balance here. Most knowledge starts out wobbly. Scientists understand and accept this premise (well, mostly---this can challenge the ego or the patent position): we seek review, corroboration, and consultation with others trained in the field to see what we may have missed. Clear communication is important if you really want to disseminate information or if you want constructive feedback. The careful accumulation and organization of data in forms that others can interpret for themselves is critical to this process. Documentation of homeopathic provings are good examples here--- ``I'd like to know how these guys in Australia in 1990 really did this proving for remedy `A' versus those guys in France in 1991 for remedy `B.' Did one group know about the other, and how should all this influence repertorization for my patient who needs reliable help in Canada today?'' The more I know, the better. The more consistently the data was taken, the less I have to go to the original sources over and over again to figure out what really happened and what's relevant to my case. This is part of why we have a ``scientific method,'' a discipline which facilitates changing data into useful information, then maturing it into knowledge. Without some reasonably consistent process in place to assist, you have mostly folk tales and rituals, often ultimately becoming religion, especially as uncertain original details fade from memory. It's nice to have some religious rituals: they form an accepted foundation of behavior. On the other hand, maybe if I'm left-handed I should make a sign over the left side of the doorway? Will my vision improve if I use BOTH hands? What if the door is really wide and I can't reach both sides simultaneously? If only I knew WHY I'm supposed to make this hand sign in the first place, maybe I wouldn't worry so much, or drop the groceries because I stuck my hands out reflexively at the door. Following rituals without a fundamental understanding is like walking along a narrow path with blinders on: you don't know what you'll land in if you miss a step, so you train yourself to more and more rigidly follow the rituals. Part of the job of religious priests is to make following the path easy enough, and the penalties for straying severe enough, that the blinders become a comfort rather than a restriction. Eventually the blinders are irrelevant--you can't see in new directions anyway. I find this state very Uncomfortable, and particularly worrisome when it is indulged by my physician. I can barely handle it in an automobile mechanic, but you know, the ones who work that way charge less, and their work is sometimes OK. (I admit that this approach is great for some forms of basic societal training ---10 commandments and all that). A simple example of why I'd like to see something like Lo's work succeed: I've read many differing opinions in the homeopathy list regarding the use of LM's, M's, C's, alternating remedies, split dose, ascending dose, ....it goes on. A theoretical basis for the action of remedies, or even just understanding how potentization works, might resolve much of this discussion. Such a basis would also garner respect from practitioners of other healing modalities, if that's what homeopathy and homeopaths really want. A final ramble: As a professional scientist, I know there can be many interpretations of a set of data. More than once in my career I've had to rethink something I was certain I KNEW was true for a long time. Each time this happened it was through seeing evidence that I could interpret for myself. These events teach a flexible strength. Building and maintaining this sort of strength is a significant part of the work and joy that goes into being a scientist worthy of the label, something I always strive for. Danger lies in either too much rigidity or in blowing too freely with the wind. Deification of Hahnemann makes me just as queasy as does ill-considered simultaneous-multi-modality mixopathy, or modern allopathic overprescription of nth generation antibiotics (with maybe a little yogurt). Our society is moving very quickly on a number of fronts and it's easy to get left behind. I'd rather help bring homeopathy as a whole along into the next century than deal with divisive infighting among homeopathic subspecialties---the latter is a path to obscurity. *End of soapbox* **********************************************************