Tales of two similar hypotheses: the rise and fall of chemical and radiation hormesis.

This paper compares the historical developments of chemical and radiation hormesis from their respective inceptions in the late 1880's for chemical hormesis and early 1900's for radiation hormesis to the mid 1930's to 1940 during which both hypotheses rose to some prominence but then became marginalized within the scientific community. This analysis documents that there were marked differences in their respective temporal developments, and the direction and maturity of research. In general, the formulation of the chemical hormesis hypothesis displayed an earlier, more-extensive and more sophisticated development than the radiation hormesis hypothesis. It was able to attract prestigious researchers with international reputations from leading institutions, to be the subject of numerous dissertations, to have its findings published in leading journals, and to have its concepts incorporated into leading microbiological texts. While both areas became the object of criticism from leading scientists, the intensity of the challenge was greatest for chemical hormesis due to its more visible association with the medical practice of homeopathy. Despite the presence of legitimate and flawed criticism, the most significant limitations of both chemical and radiation hormesis and their respective ultimate undoing were due to their: (1) lack of development of a coherent dose-response theory using data of low dose stimulation from both the chemical and radiation domains; (2) difficulty in replication of low dose stimulatory responses without an adequate study design especially with respect to an appropriate number and properly spaced doses below the toxic threshold; (3) modest degree of stimulation even under optimal conditions which was difficult to distinguish from normal variation; and (4) lack of appreciation of the practical and/or commercial applications of the concepts of low dose stimulation.

Evaluating homeopathic drugs within a biomedical framework.

The concept of hormesis can provide an evaluation framework for the assessment of homeopathic treatment preparations following a post-conditioning hormesis protocol based on the research of van Wijk and colleagues. This proposal would require that doses of administered drug conform to analytical chemistry requirements for quantification. This developmental framework can provide a scientific 'point of contact' between the homeopathic and biomedical communities, which has long been lacking.

Does homeopathy have anything to contribute to hormesis?

Homeopathy is the best known medical analogue of hormesis, others include hormoligosis and paradoxical pharmacology. Homeopathy is based on the concept Similia similibus curentur ('Let like be cured by like'); the exploitation of secondary effects of drugs, the body's reaction rather than the primary pharmacological action. The most controversial aspect of homeopathy is its use of 'ultramolecular' dilutions in which a single molecule of the starting substance is unlikely to be present. Classical pharmacological actions in vivo have been reported with dilutions as high as 10(-22)mol/L, but homeopathic medicines may be far more dilute than this. There is growing biological evidence including independent reproduction that in vivo effects may occur at such dilutions. In a systematic review, 73% of experiments showed an effect with ultramolecular dilutions including 68% of high-quality experiments. Physical and physico-chemical work suggests that homeopathic preparations contain stable ordered supramolecular structures, gas nanobubbles and dissolved silicates may be involved. Homeopathy may contribute to the generalizability and reproducibility of hormesis effects. It also raises the question of the threshold of hormesis effects.

Hormesis and its relationship with homeopathy.

Homeopathy is an ancient and complex therapeutic method that is rediscovering its scientific foundations. Hormesis is a frequently observed phenomenon that has been rigorously reported with precise dose-response curves. The therapeutic method based on the principle of 'like cures like' should not be confused with hormesis, which has several different implications from those of homeopathy. Yet, because both these approaches to nature and medicine are very broad in scope, they do end up having some points of contact. Thus, the well-established and consolidated field of hormesis can help cast light, through its ideas and research methods, on the possible mechanisms of action of remedies in ultra-low doses.

Testing the hormetic nature of homeopathic interventions through stress response pathways.

The scientific foundations of hormesis are now well established and include various biochemical and molecular criteria for testing the hormetic nature of chemicals and other modulators. In order to claim homeopathy as being hormetic, it is essential that, in addition to the hormetic biphasic dose response, homeopathic remedies should fulfill one or more molecular criteria. Since stress response pathways, such as heat shock response, antioxidative response, autophagic response and unfolded protein response, are integral components of the physiological hormesis, it is important that homeopathic drugs be tested for these pathways if these are to be considered as hormetins and to cause hormesis.