Homeopathy and Evidence-Based Medicine: Back to the Future Part IV

Homeopathy and Science

This week’s entry† is a summary of some of the tests of homeopathy. It is a necessary prelude to a discussion of how homeopaths and their apologists promote the method. Several tenets of homeopathy lend themselves to tests. The doctrine of similia similibus curantur (“like cures like”) was tested by Hahnemann himself, as introduced in Part I of this blog. It is a special case that will be discussed further below. Hahnemann’s second doctrine, “infinitesimals,” suggests laboratory, animal, and clinical studies looking for specific effects of homeopathic preparations.

“Provings,” also called “homeopathic pathogenic trials,” suggest testing “provers” for the ability to distinguish between homeopathic preparations and placebos, and suggest asking homeopaths to identify specific remedies solely by the “symptoms” they elicit in “provers.” The homeopathic interview and prescribing scheme, gathering copious “symptoms” and matching them to the appropriate “remedy” in the Materia Medica, suggests testing homeopaths for consistency in symptom interpretations and prescriptions. The clinical practice suggests outcome studies, both of individual “conditions” (with the caveat that, strictly speaking, homeopathy does not recognize disease categories—only “symptom” complexes) and of the practice as a whole.

Several of these categories overlap. Several have been tested: the results have overwhelmingly failed to confirm homeopathy’s claims. I will mention a few of the more conspicuous examples.

Cinchona Bark: the Sole Test of the “Law of Similars”

Similia similibus curantur is the sine qua non of homeopathy: Hahnemann’s “eternal, infallible law of nature.” In Part I of this series I asserted that it had been “definitively disproved.” A few dissenting comments from readers have convinced me that I did not adequately explain the nature and the limitations of the experimental basis for Hahnemann’s first “law,” and therefore that I had not justified my categorical assertion. What follows is an attempt to remedy that failing.

Hahnemann took cinchona in 1790 believing, as did most of his contemporaries, that it was curative of “intermittent fever” (or “marsh ague”). He wondered how it worked, and hoped that he might learn something by testing it on himself. His reactions, as quoted in Part I of this blog, seemed to him to be similar to (“ordinarily characteristic of”) the symptoms of intermittent fever. Thus Hahnemann had his “eureka moment”: “like cures like,” he decided, must be a universal fact of nature.

Now comes the rub: we know that cinchona actually did cure most cases of intermittent fever, the disease that we call “malaria.” Cinchona was one of the few effective remedies known to European physicians at the time. Thus the first “proving” was partly evidence-based, if only by happy coincidence: in Hahnemann’s “n-of-1” pharmacodynamic trial, he began with the correct assumption that he would study an effective treatment. In all subsequent “provings,” however, he worked in the other direction: he began by assuming the truth of the “law of similars” and sought only to collect “symptoms.” He eventually “proved” the popular “allopathic” medicines of the era, but in doing so he no longer considered what “allopaths” used those medicines for, other than to disparage such uses.

Among the 65 substances listed in Hahnemann’s Materia Medica, cinchona (“china”) was probably the only one that specifically cured a disease*—although Hahnemann could not have known that at the time. Thus even if he had thought that he experienced the “symptoms” of syphilis after taking mercury, for example, it would not have supported his doctrine of “similars”; mercury is not a specific cure for syphilis, although it was prescribed for that at the time. Many substances that Hahnemann “proved”—opium, ipecac, belladonna, digitalis, etc.—had useful physiologic effects but were not curative of diseases per se. In any event Hahnemann disparaged even the few rational uses of those drugs (e.g., digitalis to “diminish the frequency of the quick, irritated pulse”), as he discussed at length in the Introduction to his Organon.

Thus, although Hahnemann and all homeopaths since his time have held that every “proving” is further proof of the doctrine that defines homeopathy, in fact none are so. Only the very first “proving” was even partly based on a medical fact (even if Hahnemann didn’t know it), and is thus the sole test of Hahnemann’s “first law.” The rest of the evidence relevant to that first “proving,” moreover, is not flattering to similia similibus curantur. In 1820 Pelletier and Caventou isolated quinine, the active anti-malarial ingredient of cinchona bark. [1] By the late 19th century, during the flowering of the Germ Theory of disease, Alphonse Laveran had established that malaria is caused by a blood-borne parasite. In the latter part of the 20th century the mechanism of action of quinine and other anti-malarial drugs was largely elucidated, and in each case it involves killing the protozoa that cause the disease. As previously stated, “it has nothing to do with ‘like cures like,’ vitalism, ‘dynamism,’ ‘inducing the self-healing response,’ or any other process proposed by Hahnemann or his followers.”

That is why we in the modern world may assert, with utter confidence, that “the very foundation of homeopathy has been definitively disproved.” There is irony in this history. One might expect, after Hahnemann’s famous encounter with cinchona bark, that homeopaths ought to be particularly adept at curing malaria. They are not. Not only do they frequently prescribe “remedies” that have no known or plausible role in eradicating malaria parasites, but even if they prescribe “cinchona” itself they don’t actually give any; their dilutions see to that. By the time Hahnemann assembled his thoughts for the cinchona entry in his Materia Medica, the therapeutic reality of treating malaria had become unrecognizable.

Testing the “Law of Infinitesimals”: the Benveniste Affair

Modern homeopaths grant that most of their “remedies” contain none of the original substances, but claim that since they “work” there must be a reason, as yet unexplained by science. Some of their favorite explanatory candidates are “spirit-like essence” and “water memory.” The latter is the explanation that homeopaths most commonly ascribe to a series of highly publicized experiments in the 1980s by the late Frenchman Jacques Benveniste, who reported persistence of biological activity of certain antibodies even after diluting them far past the point at which any could have remained in the solution.

Benveniste’s claims were not actually consistent with homeopathy per se: the activity that he reported did not increase progressively with each new dilution, as “potentizing” would have predicted, but sputtered in a series of peaks and troughs, never exceeding the potency of the original, most concentrated sample. The qualitative biological activity, moreover, remained the same whatever the dilution—whereas homeopathy’s “like cures like” doctrine would have predicted a very different, roughly opposite effect at high dilutions (“potencies”).

Nevertheless, any biological activity referable to a substance no longer in a preparation diluted 10^120-fold would have been news, had it been convincing. The journal Nature, with admitted trepidation, published Benveniste’s paper in 1988 after he had satisfied various requirements of reviewers. Subsequently, a three-person team visited Benveniste’s lab to give him the opportunity to repeat his experiments under their observation. The team included John Maddox, the editor of Nature; Walter Stewart, an expert in scientific error and fraud; and James (“The Amazing”) Randi, a professional magician and investigator of paranormal claims. The three found multiple flaws in the project, including a lack of checks against contamination, inadequate controls, a “disregard for statistical principles,” previously undisclosed sponsorship by a supplier of homeopathic medicines, a general belief among all in the laboratory, bordering on religious fervor, in the truth of their claims, no attempts to control for observer bias, lack of blinding in general, and no consideration of even the possibility of sampling errors.

Most importantly, the observers found that Benveniste’s results were not reproducible even when performed by his own group under lax controls, and that the experiments were a complete failure when performed under strict, double-blind conditions. Later, at least three other European labs were also unable to replicate Benveniste’s results.

In spite of these problems, or more likely because of them, Benveniste became a legend in “alternative medicine” circles. Thus Daniel Eskinazi of Columbia University’s Rosenthal Center for Complementary and Alternative Medicine complained in the JAMA “Complementary, Alternative, and Integrative Medicine” series of November, 1998, that “established academic researchers have been discredited and have had difficulties when attempting to conduct alternative medicine research,” citing Benveniste as an example. But the discrediting of Benveniste was entirely justified, as reviewers of Eskinazi’s manuscript could have easily discovered. Benveniste was later the recipient of two “Ig Nobel” prizes, the first in 1991 for the project just discussed, and the second in 1998 after he had claimed to “digitize” biological messages from homeopathic dilutions and transmit them over the Internet. He died in 2004.

Other “Pre-Clinical” Tests…

…, at least until 1999, have suffered from “a lack of independent replication of any pre-clinical research in homoeopathy. In the few instances where a research team has set out to replicate the work of another, either the results were negative or the methodology was questionable.”

Clinical Tests: “Provings,” “Symptoms,” and Outcomes

As previously cited, several tests of “provings” have failed to demonstrate what homeopaths claim. Homeopaths also demonstrate poor “inter-rater reliability” in evaluating symptom diaries. Outcome studies of homeopathic treatments have not provided real evidence for specific effects. Two “meta-analyses” are worth mentioning only because they have been touted as supporting the claims of homeopaths. The first, in 1991, concluded: “The amount of positive evidence even among the best studies came as a surprise to us. Based on this evidence we would be ready to accept that homoeopathy can be efficacious, if only the mechanism of action were more plausible.” The second, in 1997, 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.”

Subsequent reviews of those and other reports found that when corrections were made for publication bias and other method flaws, the apparent findings disappeared. Two projects involving trials of homeopathy for specific conditions are worth mentioning because they, too, are touted by proponents: the first is the series by David Reilly, mentioned at the beginning of this series. As stated, the results were “inconsistent and largely subjective.” The second was a trial of “individualized” homeopathic “remedies” for childhood diarrhea. It reported a slight, but statistically significant, reduction in the number and duration of loose stools. Subsequently our fellow blogger Wally Sampson, with co-author William London, wrote a damning critique of the diarrhea paper.

Next week: Homeopathy and Evidence-Based Medicine

* The modern reader will recognize that Bismuthum may also be able to make that claim, but that wouldn’t have been known to Hahnemann.

[1] Tracy JW and Webster LT. Drugs used in the chemotherapy of protozoal infections: malaria. In: Hardman JG, Limbird LE, Gilman AG. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 10^thEdition. McGraw-Hill, New York 2001. pp. 1069-1095

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†The Homeopathy Series:

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Kimball Atwood

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