Biological Effects of BELLE Low Level Exposures BELLENEWSLETTER A Publication for the Northeast Regional Environmental Public Health Center, University of Massachusetts, School of Public Health, Amherst, MA 01003 Vol. 16 No. 1, April 2010, ISSN 1092-4736 HORMESIS AND HOMEOPATHY Introduction TABLE OF CONTENTS Introduction Edward J. Calabrese, Ph.D. Edward Calabrese .................................................................................................1 Department of Public Health Environmental Health Sciences Division HOMEOPATHY: CLARIFYING ITS RELATIONSHIP Morrill 1, N344 TO HORMESIS Edward Calabrese and Wayne B. Jonas, M.D. .................................................4 University of Massachusetts Amherst, MA 01003, USA Commentaries Phone: 413-545-3164; Fax: 413-545-4692 HORMESIS AND ITS RELATIONSHIP WITH E-mail: [email protected] HOMEOPATHY: MANUSCRIPT FOR HUMAN EXPERIMENTAL TOXICOLOGY Prof. Paolo Bellavite, M.D. ................................................................................11 This issue of the BELLE Newsletter addresses how, if at all, HOMEOPATHY: CLARIFYING ITS RELATIONSHIP the concepts of hormesis and homeopathy may be related. TO HORMESIS It should be pointed out that in the numerous articles I Simonetta Bernardini .........................................................................................19 DOES HOMEOPATHY HAVE ANYTHING TO have published on hormesis I have never claimed that the CONTRIBUTE TO HORMESIS? two are toxicologically related. I have argued that Hugo Dr Peter Fisher ....................................................................................................21 Schulz, the person given the most credit for discovering the MIASMAS, GERMS, HOMEOPATHY AND HORMESIS: hormesis concept, made a major mistake by thinking that COMMENTARY ON THE RELATIONSHIP BETWEEN HOMEOPATHY AND HORMESIS he had discovered the explanatory principle of homeopa- John R. Moffett, Ph.D. .......................................................................................28 thy. By linking the hormesis concept (not the name) to the HORMESIS AND HOMEOPATHY: BRIDGE OVER medical practice of homeopathy it was my opinion that TROUblED WATERS Dr. Menachem Oberbaum ................................................................................34 this was the equivalent of hormesis receiving a scientific TESTING THE HORMETIC NATURE OF “scarlet letter”. This opinion was based largely on the HOMEOPATHIC INTERVENTIONS THROUGH homeopathic principles associated with extremely high STRESS RESPONSE PATHWAYS Suresh I.S. Rattan, Ph.D.,D.Sc. and Taru Deva, Ph.D. ..................................40 dilution practices. These practices, which go back to the POST-CONDITIONING HORMESIS AND THE HOME thinking of Hahnemann, the founder of homeopathy, are OPATHIC SIMILIA PRINCIPLE: MOLECULAR clearly not related to the concept of hormesis. ASPECTS R. Van Wijk and F.A.C. Wiegant......................................................................45 The major challenge that hormesis has had over the past Summary several decades was to be taken seriously by the scientific EVALUATING HOMEOPATHIC DRUGS WITHIN A community. Over 1,200 articles in the scientific literature BIOMEDICAL FRAMEWORK Edward Calabrese and Wayne B. Jonas, M.D. ...............................................51 have been published on hormesis based on a review of the Web of Science data base. Over 80% of these articles have biological stress responses (Calabrese et al., 2007). I saw been published since 2000. The concept of hormesis has that the research of Wiegant and Van Wijk was concep- become incorporated into the leading toxicological text- tually very similar to the concept of post-conditioning books (Klaassen and Watkins, 2003; Hayes, 2008) as well hormesis which was first described in this paper on a as the object of presentations to the BEIR VII committee common terminology. The findings were extended by of the National Academy of Sciences (Calabrese, 2000), this group in a series of progressively detailed papers the focus of workshops at annual meetings by leading pro- (Ovelgonne et al., 1995; Vanrijn et al., 1995; Wiegant et fessional societies like the US Society of Toxicology, and al., 1998, 1999). Then for unknown reasons they no lon- the object of special issues of journals (e.g. Aging Research ger pursued the question, nor did any other group pick Reviews, 2008; American Journal of Pharmacology and on their interesting findings. Toxicology, 2008) and conference proceedings (e.g. I did complete the initial drafting of my paper but it was Environmental Health Perspectives, Dose Response, now significantly different from the one that I had Critical Reviews Toxicology, Journal of Applied planned. This draft (see finalized paper published in this Toxicology). It has been the object of several books issue as Calabrese and Jonas, 2010) now was proposing (Luckey 1980, 1991; Mattson and Calabrese, 2010; that some types of homeopathic treatment may in fact be Sanders, 2010). Of particular importance is that several examples of post-conditioning hormesis. It made me ini- major studies have indicated that the hormetic dose tially think that I was becoming part of the problem for response far outperforms the long revered threshold and hormesis, now a century or more after Schulz created the linear at low dose models used by regulatory agencies problem. So I put the manuscript aside for several (Calabrese and Baldwin, 2001, 2003; Calabrese et al months, and re-read it and all the cited references again. 2006, 2008, 2010). The key point is that the concept of I still thought what I wrote was accurate. I repeated this hormesis is now established in the scientific domain, process again to the same result. I then decided to seek out growing rapidly in interest and influence, being seen as a a few objective critics who agreed with the analysis but basic biological concept. who were concerned that this may hurt the chances of As editor of the BELLE Newsletter I was not inclined to hormesis concept being accepted in the scientific commu- revisit the issue of homeopathy and hormesis. Hormesis nity since homeopathy was considered something like was finally shedding the historical misgiving of Hugo witchcraft. I stressed to these critics that very high dilu- Schulz. Furthermore, since I was convinced that the dis- tion homeopathy may well be a totally wrong concept but coveries of Schulz were not even remotely related to home- that there was “low” dilution school within the broader opathy, I had decided to write an historical article on homeopathic community in which concentrations of med- hormesis and homeopathy in which I would further ical treatments are routinely measured, a group that is decouple any possible historical association of hormesis actually as dismissive of high dilution homeopathy as we with homeopathy. In this article, I planned to make the are. That is, homeopathy was not monolethic and to case that Schulz’s ground breaking research was misinter- characterize it as such was factually incorrect (Calabrese, preted by him, leading to the confused historical linking of 2005, 2008). these two concepts. In the course of this research I came After several months I decided to send the manuscript to across a research initiative by researchers in The Dr. Wayne Jonas of the Samueli Institute and former Netherlands, highly expert in the study of heat shock pro- director of the NIH’s National Center for Complementary teins, which was explicitly designed to test certain alleged and Alternative Medicine, since he has a detailed and concepts of homeopathy within a standard experimental unique understanding of homeopathy and hormesis. Dr. based modern molecular framework. The timing of the Jonas was strongly supportive of the article but suggested discovery of their research occurred when I was co- ways it could be improved. At that point I invited him to authoring a paper with 57 other scientists on the develop- become a co-author. After the manuscript was completed, ment of an hormetically-based common terminology of 2 BELLE Newsletter we decided to send it to The Lancet for publication con- Calabrese, E.J., Hoffmann, G.R., Stanek III, E.J., and sideration. This submission failed to generate interest Nascarella, M.A. (2010). Evidence of hormesis in and it was returned without having received a peer high-throughput screening of antibacterial compounds review. I then suggested to Dr. Jonas that we develop a in E. coli. Hum. Exper. Toxic. (in press). BELLE Newsletter around the paper which would involve Hayes, A.W. (Editor) (2008). Principles and methods inviting a number of experts on the topic to write expert of Toxicology, Fifth Edition, Taylor and Francis Group. commentaries about the article. Boca Raton, FL, pp. 2270. I now invite you to read the manuscript that Dr. Jonas and I co-authored and the expert commentaries, along Klaassen, C.D., and Watkins III, J.B. (2003). Casarett with our response to the commentaries and Doull’s Essential of Toxicology. McGraw-Hill Companies. New York, NY, pp. 533. REFERENCES Luckey, T.D. (1980). Hormesis with Ionizing Radiation. CRC Press, Inc. Boca Raton, FL. Calabrese, E.J. (2000). Radiation Hormesis. BEIR VII Committee meeting. National Academy of Sciences, Luckey, T.D. (1991). Radiation Hormesis. CRC Press, Washington, DC. September 20, 2000. Inc. Boca Raton, FL. Calabrese, E.J. (2005). Historical blunders: how toxi- Mattson, M.P., and Calabrese, E.J. (Editors). (2010). cology got the dose-response