HOMEOPATHY AND SCIENCE: A CLOSER LOOK* David W. Ramey, DVM*Mahlon Wagner, PhD^ Robert H. Imrie, DVM` Victor Stenger, PhD#   Introduction Since its inception over 200 years ago, homeopathy has fallen in and out of favor. Its apparent resurgence in these times has rekindled the discussion as to whether homeopathic medications are an effective treatment against disease or whether they are no more than an elaborate placebo. The discussion as to whether or not it is an effective therapy is ongoing in human and veterinary medicine; it appears to have devolved into one between proponents of homeopathy and those who rely on firm evidence of effectiveness before adopting any therapy. This review attempts to assess the state of the current evidence regarding homeopathy.   * P.O. Box, 5231, Glendale, CA 91221 ^ Professor Emeritus of Psychology, State University of New York at Oswego ` 448 NE Ravenna Blvd., #106, Seattle, WA 98115-6401 # Professor of Physics and Astronomy, University of Hawaii   History The German physician Samuel Hahnemann (1755-1843) is generally acknowledged to be the founder and developer of homeopathy, although some of his concepts appear very early in medical history.1 Dissatisfied with the state of medicine at the time, which included bleeding, purging, cupping and excessive doses of mercury, he ceased his medical practice in 1782 and began translating medical and chemical texts. It was during this time that he apparently began to seriously question the proposed mechanisms of drug activity of his contemporaries. Hahnemann followed a tradition that viewed disease as a matter of the vital force or spirit. The concept of the vital spirit appears to be one of the earliest speculations in recorded medical history and similar forces form the proposed basis for any number of metaphysical health practices. It is an alleged nonmaterial "force" that sustains life and for which there is no objective evidence.2 According to Hahnemann, "The causes of our maladies cannot be material, since the least foreign material substance, however mild it may appear to us, if introduced into our blood-vessels, is promptly ejected by the vital force, as though it were a poison....no disease, in a word, is caused by any material substance, but that every one is only and always a peculiar, virtual, dynamic derangement of the health."3 Consistent with this philosophy is the belief that it is more important to pay attention to symptoms than to the external causes of disease. Knowing the specific symptoms of illness, treatment is then a matter of finding a substance or substances that induced the same symptoms in a healthy individual. This is the basis of Hahnemann's "Principle of Similars." The work of Pasteur and Koch on inoculations with very small amounts of weakened disease-causing microbes seemed to support this notion at the time.  Hahnemann and his followers went on to test the effects of almost 100 substances on themselves, a process known as "proving." The typical procedure was for a healthy person to ingest a small amount of a particular substance and then attempt to carefully note any reaction or symptom (including emotional or mental reactions) that occurred. By this method, Hahnemann and his followers "proved" that the substance was an effective remedy for a particular symptom. That such a method of determining the effectiveness of a treatment is implausible and at least open to the power of suggestion should be inarguable. In fact, in one controlled study, healthy subjects reported similar symptoms whether given a homeopathic dilution of belladonna or a placebo.4  Nevertheless, the collected experiences of such incidents became the basis for a compendium called the Materia Medica. Because some of the substances tested were toxic (such as poison ivy, strychnine and various snake venoms), during a proving it made sense to ingest minuscule doses. This may be the source or the homeopathic principle of "infinitesimal dilutions" in which the most dilute solutions are alleged to be the most potent.  The origin of the principle of "potentization" is more obscure. Potentization purports to make the diluted, inert substance active by releasing its energy. According to Hahnemann: "Homeopathic potentizations are processes by which the medicinal properties of drugs, which are in a latent state in the crude substance, are excited and enabled to act spiritually upon the vital forces."5 Simple dilution of a drug is insufficient to produce a cure. To achieve potentization, after each successive 1-to-9 ("D") or 1-to-100 ("C") dilution, the solution must be shaken vigorously (the process is known as "succussion"). In the case of a powdered substance, it must be vigorously ground up (trituration). Potentization purports to liberate the energy of the substance being used for treatment and this liberated energy purportedly remains, even in the lowest doses.  Hahnemann believed that homeopathic remedies must be appropriately prescribed for individual body types and personalities, based on the ancient humoral theories of Galen. According to these theories, there were four body types and personalities, based on which body "humor" predominated: blood (sanguine, warm-hearted and volatile), black bile (melancholic, sad), yellow bile (choleric, quick to anger and to action) and phlegm (phlegmatic, sluggish and apathetic). In addition to describing a few basic body types, he also suggested that there are a corresponding few primary causes of acute and chronic illnesses, which he called "miasms." The first miasm, known as "psora" (itch) refers to a general susceptibility to disease and may be considered the source of all chronic diseases. The other two miasms in homeopathic theory are the venereal diseases syphilis and sycosis (gonorrhea). Together, these three conditions were considered to be the cause of at least 80 per cent of all chronic diseases. Homeopathy has made several important indirect contributions to the practice of medicine. At the time that it was developed, the medical treatments of the time were often more dangerous than the disease that they purported to treat. Indeed, homeopathy may have helped hasten the demise of such treatments. Homeopathy provided the initial idea and source for useful drugs such as nitroglycerin6 and aconite.7 Early scientists such as Joseph Lister and Sidney Ringer stated that they were led to important pharmacological discoveries because of homeopathy.8 Homeopathy has also been given credit for providing early support for clinical trials with control groups, systematic and quantitative procedures and the use of statistics in medicine.9 From the standpoint of veterinary medicine, it is curious that Hahnemann did none of his work on animals. Psora, syphilis and gonorrhea are not conditions recognized in animals. The fallacy of prescribing medications for animals based on how they make people feel seems obvious given interspecies variations between reactions to various pharmacologic substances. The concepts of prescribing medications for body types and personalities would seem to be particularly difficult to apply to animals, as well.  It should be obvious that the premises upon which Hahnemann's work were based are difficult to support based on current knowledge. From a strictly hypothetical standpoint it is possible that Hahnemann came up with the right conclusion from the wrong reasons. However, while criticisms based solely on the origin of the philosophy may not be entirely damning, they are, at least, instructive.     The Physics of Homeopathy If homeopathic remedies are effective, there is a mechanism by which they work. It is a fact that the mechanism of action by which they might work has not been established. If the remedies do work, they must do so in a manner which would appear to violate established principles of physics, chemistry and pharmacology or they must work in a manner which is yet to be discovered. As one early critic of homeopathy wrote, "Either Hahnemann is right, in which case our science and the basis of our thinking is nonsense, or he is wrong, in which case this teaching is nonsense."10  By successively diluting the initial substance, extremely dilute solutions can be made rather quickly. The dilution limit is reached when the volume of the solute is unlikely to contain a single molecule of the solvent. The limit recognizes that there is a large but finite and specific number of atoms or molecules in a mole of substance (a mole is the molecular weight of a substance, expressed in grams). That number of atoms or molecules is 6.022 X 1023, also known as Avogadro's number.  Homeopathic remedies are diluted by either a factor of 10 or 100. "D" dilutions are prepared by serial dilutions of 1:10; "C" dilutions are prepared by serial dilutions of 1:100. Thus, a remedy marked C30 would imply a 1:100 dilution performed 30 times. By simple mathematics, it can be calculated that at dilutions of C12 or D24 or greater, it is not likely that the remedies contain even a single molecule of the original substance.  Since the original substance is not present in extremely dilute homeopathic remedies, explanations for a mechanism of action of homeopathic medications have moved towards speculation. Such proposals include the formation of stable ice crystals, magnetic properties of water or the formation of protein shells in the water mixture.11 Water molecules are highly polarized, a fact that already accounts for much of the special role of water in biology. However, the likelihood that water can maintain a complex ice-like structure under the vigorous shaking that usually accompanies homeopathic preparation has not been demonstrated. Neither has any physical mechanism by which such hypothetical structures can produce the implied biological effects. Some of the hypotheses appear to be completely insupportable. Speculation that the mechanism of action of homeopathic medications is somehow related to biological magnetite have been criticized by the investigator who discovered the substance as lacking any foundation and based on a misunderstanding the structure of magnetite.12 Water is also not ferromagnetic. Structural changes in matter appear to be easily demonstrable in other applications, using such techniques as transmission electron microscopy, spectroscopy, ultraviolet transmission characteristics, X-rays and ultrasound. If they exist, structural changes in the composition of homeopathic remedies should be relatively easy to detect. So far, such changes have not been demonstrated. One ultrasonographic study failed to show differences between homeopathic remedies and water.13 On an empirical basis, even a homeopathic practitioner and his patients were unable to distinguish between two different homeopathic remedies with "strikingly different properties" over nine years of testing.14  From a physical standpoint, structural changes in the water of extremely dilute solutions seem unlikely. Structural studies of water/alcohol mixtures will show regions of local order. However, these regions are transient; depending on the temperature, they can only last for the briefest of times. For most materials, local order does not persist in the liquid phase (the problem is entropy).15. The exceptions are liquid crystals, whose highly elongated molecules are still not able to move about freely when the liquid phase is reached. There has never been the slightest hint, from theory or experiment, that water can form a liquid crystal. It may also be postulated that there is some sort of biologic effect of homeopathic medications that is independent of known physical laws. Of course, such speculation would be virtually impossible to test and there is no known substance which fits such parameters. Appealing to unknown laws to explain undocumented phenomena simply falls outside the framework of legitimate science.  Further physical difficulties with the concept of homeopathic dilutions relate to the fact that many such remedies come in the form of lactose tablets. In these instances, the homeopathic dilution is applied to the pill, which serves as a carrier. Of course, the diluted liquid must evaporate, which leads to the question of how the information is transferred from liquid to lactose tablet. Other questions include why the diluted mixture would remember only the healing powers of the active substance but forget the side-effects or why the water doesn't remember other things with which it might have been in contact.  The fact that there is no known mechanism by which extremely dilute homeopathic medications should be able to exert a biological effect is indeed a source or concern to proponents of homeopathy. In fact, if proposed mechanisms can be shown to be insupportable, the Director of the Office of Alternative Medicine of the National Institutes of Health has written that, "highly speculative and imaginary [sic] explanations may be necessary."16 As a Nobel Prize winning physicist noted, "The theory of quantum electrodynamics describes Nature as absurd from the point of view of common sense. And it agrees fully with experiment."17 From a mechanistic point of view, however, homeopathy neither makes sense nor agrees with any experiment. Accordingly, most discussions of the possible effects of homeopathy prefer to focus on discussions of results of studies.   In Vitro Studies In 1988, homeopathy was thrust into the forefront of controversy with the first publication of work supporting effects of homeopathic solutions in a mainstream science journal. The authors of the paper suggested that extremely dilute solutions of antiserum against human IgE were able to induce basophil degranulation.18 Although the experimental model chosen is known to be extremely unstable, the journal in which the study was published could find no apparent flaws. Subsequent to publication, however, the journal sent an investigating team to the laboratory which concluded that there were serious flaws in the original investigation.19 That a war of words subsequently commenced is inarguable. More to the point is that at least three separate investigators using identical or similar experimental models have failed to reproduce the results.20, 21, 22 In fact, the only studies which indicate an in vitro effect of homeopathic dilutions come from the same laboratory. The lead investigator of the studies has since gone on to claim that homeopathic information has been digitized and can be transferred by computer disk over the Internet. Furthermore, his immunopharmacology laboratory has been shut down by INSERM, the French medical research agency.23 Finally, a libel claim by the investigator against two French Nobel prize winners who called the investigator a fraud was recently thrown out of French courts.24   Reviews and Meta-Analyses When trying to evaluate the evidence for the effectiveness of homeopathic remedies, it is possible to find investigations in which positive, negative or no results are reported. Evaluation of the literature for any form of therapy is difficult and studies vary as to quality. Such a problem appears to be particularly acute in the evaluation of literature concerning alternative therapies such as homeopathy. For example, investigators in one study categorized all 204 articles in one year's editions of four journals on alternative medicine as positive, neutral or negative. They found 64 per cent of the papers were classified as helpful, 35 per cent as neutral and only 1 per cent as negative. The investigators concluded that there is a strong publication bias in favor of positive conclusions about alternative therapies and that their findings imply that the literature is not objective.25 One way to attempt to answer the question of the effectiveness of homeopathic medications is to look at reviews and meta-analyses (studies of studies). Of course, whether by review or by meta-analysis, attempts at reviewing any medical literature are not without their own problems. Reviews have been criticized as being subject to the bias of the reviewer. On the other hand, meta-analyses, which attempt to gather information and draw conclusions by pooling various reports have been much criticized for using many "weak" studies to arrive at a "strong" conclusion and for relying on the subjective opinions of the authors to determine which studies are worthy of inclusion, among other reasons.26 Further concern about the validity of meta-analysis comes from recent work which indicates disagreement between meta-analysis and subsequent large, randomized, controlled clinical trials in as many as 35 per cent of the cases studied.27 Nevertheless, several reviews and meta-analyses on homeopathy have been performed. Apparently, their results are open to some interpretation. That interpretation may, at first glance, seem to be no more than a "glass half-empty or half-full" argument between proponents of homeopathy and those of evidence-based medicine. Thus, for the purposes of review, it seems most useful to quote the conclusions of the studies rather than take individual bits of data out of them. The authors were able to find four meta-analyses and six reviews of the effects of homeopathic medications. Three of the reviews specifically relate to veterinary medicine.  In 1985, a chapter on veterinary homeopathy concluded that, "Contrary to what you hear or read too often, rigorous scientific demonstration of the therapeutic effect of homeopathic remedies in veterinary medicine has not yet been done. Although it may seem exaggerated to conclude that homeopathy has absolutely no place, from a pragmatic point of view (and relative among animal owners...), in veterinary medicine, it is obvious that future works will have to bend to the new modern methodologies in order to be able to take away the firm beliefs of stern minds."28  A 1990 review of 40 published randomized trials of homeopathy in human medicine found that most of the studies had major methodological flaws and concluded that, "the results do not provide acceptable evidence that homeopathic treatments are effective."29  A 1991 meta-analysis of homeopathy in human medicine concluded, "At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homeopathy, but only by means of well performed trials." The investigators also noted that, "Critical people who do not believe in the efficacy of homeopathy before reading the evidence presented here probably will still not be convinced; people who were more ambivalent in advance will perhaps have a more optimistic view now, whereas people who already believed in the efficacy of homeopathy might at this moment be almost certain that homeopathy works."30 In a later letter, the authors noted that, "The results of our review would probably be interpreted differently if laboratory studies showed convincing evidence that there is some action of high potencies."31  A 1992 German review of homeopathy concluded that, "Due to the advance of alternative medicine a critical synopsis by means of the comparison between scientific medicine (clinical medicine) and homeopathy is warranted. The review of studies carried out according to current scientific criteria revealed - at best - a placebo effect of homeopathy. Until now there is no proven mechanism for the mode of action of homeopathy. Sometimes so-called "alternative medicine" prevents effective curative measures. In spite of the justified criticism concerning the technical over-estimation of classical medicine, scientific research should remain the basis of clinical work."32  A 1993 German review of homeopathy in veterinary medicine makes several conclusions:  * "Doctor and veterinarian are similarly obligated to apply the therapeutic measure that prevailing opinions deem most effective. Where there is for particular definite illnesses a particularly effective and generally recognized treatment, in such cases the supporters of homeopathy may not disregard the better successes from their own differing direction."  * It is undisputed that homeopathy in the area of stronger potency can achieve effects pharmacologically and toxicologically; the superiority of homeopathy as a therapeutic measure in comparison with conventional therapy methods is at this point not verified. Moreover, the harmlessness of homeopathy in stronger potency is for the most part not verified.  * The effectiveness of homeopathy in middle and high potencies is up to now not verified. It is undisputed that with the help of homeopathy, not insignificant placebo effects can be achieved. In veterinary medicine, giving an animal an 'active' placebo and another a 'passive' can play a significant role and influence the owner."33  A 1994 review and meta-analysis of serial agitated dilutions (SAD) in experimental toxicology stated that, "As with clinical studies, the overall quality of toxicology research using SAD preparations is low. The majority of studies either could not be reevaluated by the reviewers or were of such low quality that their likelihood of validity is doubtful. The number of methodologically sound, independently reproduced studies is too small to make any definitive conclusions regarding the effect of SAD preparations in toxicology."34  A 1996 review of homeopathy, concluded that:  * "No one should ignore the role of non-specific factors in therapeutic efficacy, such as the natural history of a given disease and the placebo effect. Indeed, these factors can be used to therapeutic advantage."  * "As homeopathic treatments are generally used in conditions with variable outcome or showing spontaneous recovery (hence their placebo responsiveness), these treatments are widely considered to have an effect in some patients."  * "However, despite the large number of comparative trials carried out to date there is no evidence that homeopathy is any more effective than placebo therapy given in identical conditions."  * "We believe that homeopathic preparations should not be used to treat serious diseases when other drugs are known to be both effective and safe."  * "Pending further evidence, homeopathy remains a form of placebo therapy."35  A 1997 meta-analysis concluded, "The results of our meta-analysis are not compatible with the hypothesis that the clinical effects of homeopathy are completely due to placebo. However, we found insufficient evidence from these studies that homeopathy is clearly efficacious for any single clinical condition." Furthermore, "Our study has no major implications for clinical practice because we found little evidence of effectiveness of any single homeopathic approach on any single clinical condition." The authors concluded by calling for more research, "providing it is rigorous and systematic."36 One critic of the study cautioned that when the best trials were examined, the odds of a positive effect of the therapy were distinctly lower than in the overall study.37 Another critic suggested further caution in interpreting the results of this study by noting that negative trials may have been less likely to be published, which may have skewed the analysis. 38  Another meta-analysis conducted in 1997 examined the use of homeopathy for the treatment of postoperative ileus, measured by the time to first flatus. The investigators concluded that their analyses "do not provide evidence for the use of a particular homeopathic remedy or for a combination of remedies for postoperative ileus. Several drawbacks inherent in the original studies and in the methodology of meta-analysis preclude a firm conclusion." Given those caveats, the study also suggested that homeopathic dilutions less than 12C (those which may contain some of the original substance) had a significant effect, whereas dilutions greater than 12C had none.39  A 1998 review of homeopathic treatment in animals suggested approaching homeopathy with an "open mind." As evidence for the effectiveness of homeopathic treatment in animals, the study cites 3 studies in which some clinical evidence of effectiveness was seen, 7 in which the results were difficult to interpret for various reasons and 6 in which there was no response to treatment or worsening of the condition. Several of the studies cited were performed on healthy animals. In one of the studies in which the condition of sick animals worsened, the worsening of the animal's health is taken as possible evidence of treatment effectiveness, according to "Herring's Law."13 Critics would note that such a "law" or "healing crisis" would mean that one can't lose when administering homeopathic medications because whether the patient improves or gets worse, the treatment may be viewed as being successful. Very few, if any, of the researchers conducting animal and in vitro studies on homeopathy have been rigorously conducted. Properly blinded, randomized experiments with high dilution homeopathic preparations and both a placebo group and a known effective treatment group with a large number of animals and predefined outcome variables that examine the effect on diseases (rather than production efficiency) are absent in veterinary homeopathy. In addition, researchers have been guilty of not reporting differences (if such existed) between the homeopath and placebo groups.33 While the animals (and tissue preparations) may not be susceptible to suggestibility, clearly the researcher making the critical observations could be influenced. One would hope that animals researchers would also be aware of the pioneering work of Pavlov showing that animals are often responding to any change in their environment which could obviously be confused with a response to homeopathic medication.40  Subsequent to submission of the most recent meta-analysis in human medicine, several good trials of homeopathic medications have been conducted in human medicine. Randomized, placebo-controlled double blind studies have shown homeopathic remedies to be ineffective in the treatment of adenoid vegetations in children,41 for control of pain and infection after total abdominal hysterectomy42 and for prophylaxis of migraine headache.43, 44 Furthermore, to date, no single study of homeopathy showing positive results has been successfully replicated.  Curiously, the lack of good evidence of effectiveness of homeopathic remedies may be irrelevant to supporters of homeopathy. One leading advocate asserts that proving the effectiveness of homeopathy through scientific research is not important and suggests that personal experience is more important that any number of carefully controlled studies.45 Positive expectations and beliefs of patients and healers have historically resulted in reports of excellent or good outcomes in more than 70 per cent of cases even though the treatments given are now known to have been worthless.46   Is homeopathy safe? Safety is, of course, vital to the discussion of any form of therapy. In fact, most conclusions are that homeopathic remedies are largely safe. Such a finding would, of course, not be unexpected were the remedy to contain only a water and/or alcohol solvent (that is, that the solution would contain none of the original substance).  However, while infrequent, there are reports of adverse reactions to homeopathic medications. Adverse reactions have been reported ranging from pruritis and a measles-like skin rash to anaphylactic shock,47 from pancreatitis48 to contact dermatitis.49 In regards to the safety of homeopathic remedies, the previously cited 1996 review stated that, "Serious adverse effects have been reported with low dilutions (<4CH) given parenterally or orally. However, high dilutions (>5CH) administered orally or sublingually appear to be entirely safe. We believe that homeopathic preparations should not be used to treat serious diseases when other drugs are known to be both effective and safe. In addition, regardless of the condition treated, dilution below 5CH (e.g. 3 or 4CH and especially decimal dilutions or mother tinctures) must not only be considered as having no proven efficacy but also as having potential dangers."33  Further concerns as to safety arise from the apparent attitude against immunization by practitioners of homeopathic therapy. In human medicine, several surveys have demonstrated that homeopathic practitioners routinely advise their clients against immunization.50, 51, 52, 53 Such an attitude would appear to be completely insupportable in light of the tremendous advances made in the protection from disease that vaccination clearly and reliably affords. The origin of homeopathic antipathy to vaccination is unknown; there is nothing in Hahnemann's writings against immunization.54 It may arise from a general hostility towards modern medicine that, according to studies, appears to be prevalent within complementary medicine in general.55, 56  Homeopathic practitioners may also employ the use of "homeopathic vaccines" or "nosodes" prepared from high dilutions of infectious agents, material such as vomitus, discharges or fecal matter or infected tissues. Curiously, nosodes are not prepared according to homeopathic principles, rather, they would be more properly described as being isopathy. Hahnemann himself decried the use of such preparations. 57 There is no evidence at all to suggest that such "immunizations" have any effectiveness.58 There is one case reported in the human literature where a patient followed her homeopath's advice and took a homeopathic immunization against malaria before traveling to an endemic area. The patient promptly got malaria.59 Homeopathic nosodes have failed to protect dogs from death due to parvoviral enteritis.60 Even given the concerns regarding potential problems with immunization in animals, it is virtually inconceivable that an ethical medical practitioner would recommend against the use of proven effective vaccine prophylaxis for diseases such as rabies, parvoviral enteritis or viral encephalitis (to name a few). Vaccination arguably constitutes the single most successful public health measure in human history.   Ethics Any discussion of homeopathy also entails consideration of ethical issues. As homeopathy is unquestionably unproven, it seems clearly unethical to merely give the therapy to an animal and its trusting owner and wait and see what happens.61 Furthermore, social morality would demand that the client be fully informed of the experimental nature of the therapy and consent to it before it is provided. It would also seem clearly unethical to employ an unproven therapy such as homeopathy in cases where an acceptable and effective treatment already exists or where the patient is at risk for greater suffering if the unproven therapy fails.62 Further ethical considerations require that proof of effectiveness be established if safety and efficacy questions have not been documented, as is the case with homeopathy. It would also seem reasonable to expect that if a professional community intends to employ an unproven remedy, said community has the ethical obligation to engage in proper clinical research to help establish or disprove the effectiveness of that remedy.63     Discussion It is difficult to precisely determine what homeopathy is today. Homeopathy as a single, unified school of thought simply does not exist.64 One report has noted that, "There are as many homeopathies as there are homeopaths.65 Furthermore, the ready availability of mass-marketed, non-prescription homeopathic remedies would appear to violate Hahnemann's principle of individualizing therapy based on the symptoms of each patient.56 Additionally, the mere fact that homeopathy is a treatment philosophy based exclusively on the recognition and treatment of symptoms would seem to contradict claims made by advocates that homeopathy treats the whole patient, whereas "traditional" medicine is merely treats the symptoms of disease.1  It is interesting to compare the course of progress between medications such as aspirin and homeopathy. It was known for many hundreds of years that chewing on willow bark helped relieve pain and inflammation. The active component of aspirin, initially called salicin, was isolated in 1823, not long after the advent of homeopathy. In 1899, a derivative of salicin, acetylsalicylic acid, was developed and marketed for the first time. The mechanism of action of aspirin began to be uncovered about fifty years later. From this basic information, a proliferation of useful non-steroidal anti-inflammatory drugs developed, leading to the most recent advancements of so-called Cox-2 inhibitors. This process of development has been advanced through the contributions of innumerable investigators, starting with Bayer and continuing today.  Contrast that situation with that of homeopathy. After over two hundred years, there is no single condition for which homeopathy is proven to be effective. The mechanism of action is unknown. The principles of therapy have remained unchanged since it was discovered by its founder and individuals who employ the therapy have added little to the original tenets. If homeopathy is science, it appears not to be advancing.  One simple explanation for the purported effects of homeopathy would be that it is a placebo. Such an explanation would answer the many various questions regarding the therapy. Were homeopathic medications placebo, no physical mechanism by which they could have an effect would be expected to be found. The results of clinical trials would be expected to be frequently confusing, disappointing and/or irreproducible if such trials were in fact comparing one placebo to another. Higher dilution medications would certainly be expected to be safe if they were merely water, water/alcohol mixtures or lactose tablets. Such an explanation, while understandably objectionable to proponents of the therapy, also appears to be reasonable, adequate and sufficient, given the current state of research. Were homeopathy to prove an effective therapy, it would be irrational for any legitimate medical practitioner to ignore or fail to employ it. Given the apparent lack of adverse effects from high dilution homeopathic remedies, such a therapy should be readily embraced if it were effective. Indeed, open-mindedness is one of the hallmarks of science and the rapid assimilation of new therapies and technologies has been a consistent characteristic of scientific medicine. In fact, studies have shown that practitioners of mainstream medicine are less dogmatic than those of its alternatives.66, 67 To quote the late Dr. Carl Sagan, "...at the heart of science is an essential balance between two seemingly contradictory attitudes -- an openness to new ideas, no matter how bizarre or counterintuitive, and the most ruthlessly skeptical scrutiny of all ideas, old and new. This is how deep truths are winnowed from deep nonsense."68 There is nothing wrong with the hypothesis that homeopathic remedies, no matter how implausible, are effective. However, such a hypothesis is amenable to scientific testing. Proper trials of homeopathic remedies should be easy to conduct. However, whether they are evaluated by review, by meta-analysis or by postulated physical mechanism, there is no good evidence to date that homeopathic remedies are effective treatments for any condition in human or in veterinary medicine. Nor is there evidence that they are superior to already established therapies. Every practitioner of medicine requires faith in his or her methods in order to be confident. However, faith is not a legitimate foundation on which to build a practice of scientific medicine. Furthermore, in order for people to change their minds, they must have a good reason to do so; mere faith is not such a reason. Advocates of ethical medicine and veterinary science demand reliable evidence of both efficacy and safety before employing therapies to treat their patients. Thus, the question remains; if homeopathic remedies are safe and effective, why have its practitioners and proponents been unwilling or unable to conduct the proper trials and research required to prove it?     References 1 Ullman, D. Homeopathic Medicine: Principles and Research, in Complementary and Alternative Veterinary Medicine, Principles and Practice, Schoen, A and Wynn, S, eds., Mosby, Inc., St. Louis, MO, 1998, 469-484.  2 Raso, J. The Expanded Dictionary of Metaphysical Healthcare: Alternative medicine, paranormal healing and related methods. The Georgia Council Against Health Fraud, 1998, 136. 3 Hahnemann, S. Organon of medicine, 6th ed. Calcutta: M. Bhattacharyya & Co.; 1960: 7-288.  4 Wallach, H. Does a highly diluted homeopathic drug act as a placebo in healthy volunteers? Experimental study of Belladonna 30C in a double blind crossover design - a pilot study. J Psychosomatic Res 1993; 37(8): 851-860.  5 Hahnemann, S. The Chronic Diseases. 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