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The Case for Homeopathy

D. Laboratory / in vitro activity of homeopathically-prepared substances

Human Basophil degranulation triggered by a very dilute antiserum against IgE
A well-known immunological reaction involves degranulation (the release) of histamine by basophils with IgE antibodies on their surface, when triggered by anti-IgE-containing antibody serum.

Starting in 1985, Professor Benveniste’s team of bio-chemists at the University of South Paris demonstrated that very dilute solutions of anti-IgE antibodies (10-2 – 10-120) induced this histamine release, creating successive peaks of degranulation (typically representing what is known as a biphasic response) from 40 – 60% of basophils, despite the absence of any anti-IgE molecules at the highest dilutions. They found that the dilutions needed to be accompanied by vigorous shaking for the effects to be observed. One of their inferences was that biological information could be related to the organization of water. Their work was eventually published in Nature in 1988 36. The homeopathic community viewed this as a landmark publication because it provided laboratory proof of a biological effect of ultra-dilute and succussed solutions.

This research was debunked by other scientists when they could not replicate these results. Scientists at London’s University College published their failure to reproduce Benveniste’s work in Nature in 1993. The controversy surrounding Benveniste’s work cost him his laboratory, his funding and his international scientific credibility. Benveniste was undeterred by this, claiming the negative findings occurred because his protocols were not understood and he continued to try and get other laboratories to take up the challenge of testing whether his work was valid or not.

Inhibition of histamine release from basophils activated by anti-IgE antibody, by dilute solutions of histamine It is also well-known that histamine released by activated basophils feeds back negatively on these basophils to inhibit further release of histamine.

A consortium of four independent research laboratories in France, Italy, Belgium, and Holland, led by Professor M. Roberfroid at Belgium's Catholic University of Louvain in Brussels assessed whether ultra-dilute solutions of histamine could inhibit anti-IgE-induced degranulation of basophils. Rigorous double-blind methodology was applied with independent laboratories preparing the test solutions and control solutions, which was co-ordinated by an independent researcher who was not involved in the measurement and analysis phases. Three of the four labs involved in the trial reported a statistically significant inhibition of basophil degranulation by the ultra-dilute histamine solutions (10-30 – 10-38M) compared with the controls. The fourth lab gave a result that was almost significant, so the total result over all four labs was positive for the ultra-dilute histamine solutions.

Professor Madeleine Ennis, a biochemist at Queen’s University, Belfast who is skeptical about the possibility of ultra-dilute solutions exerting any biochemical effects, was part of this team. She took the methodology a step further to exclude the possibility of human error in counting residual stained basophils by hand, after the histamine inhibition reaction: she used a previously developed protocol which tagged activated basophils with a monoclonal antibody that could be observed via fluorescence and measured by machine. Her work was reported in Inflammation Research in April 2001 37 and was the first published confirmation of Benveniste’s experiments.

The findings of the consortium were published in Inflammation Research in May 2004 38: in three different types of experiment they showed that high dilutions of histamine exert an effect on basophil activity, confirmed by flow cytometry. Inhibition of histamine was reversed by Cimetidine (an H2 antagonist).

Lionel Milgrom of the Imperial College of Science, London, made the following comments in the Guardian, a nationally-syndicated U.K. newspaper, in an article on the above work on 15 March 2001: “The consequences for science if Benveniste and Ennis are right could be earth shattering, requiring a complete re-evaluation of how we understand the workings of chemistry, biochemistry, and pharmacology.

One thing seems certain. Either Benveniste will now be brought in from the cold, or Professor Ennis and the rest of the scientists involved in the pan-European experiment could be joining him there.”

Laboratory evidence of activity of homeopathic potencies
Dr. H.W. Boyd lists a number of early laboratory tests showing in vitro effects of homeopathically prepared substances in his excellent book for doctors who are also students of homeopathy, Introduction to Homeopathic Medicine (2nd ed. 1989, Beaconsfield).

Dr. Boyd listed laboratory studies showing the effects of the following potencies:
- 30C mercuric chloride on starch-diastase and frog heart experiments (W.E. Boyd, 1954)
- 10-19g/ml acetyl choline on sensitized frog hearts (I.A. Boyd).
- D3 – D19 disodium hydrogen arsenate on the respiration of wheat coleoptiles (Boiron & Zervudacki 1963–7)
- 15C copper sulphate on plants poisoned by copper sulphate (Boiron et al 1966)
- 9C Alloxan on the diabetogenic action of alloxan in mice (Cier et al 1967)
- 5C, 7C, 15C solutions of copper sulphate on the respiration of Salvinia natans (Boiron 1973)
- Plumbum metallicum increased excretion of lead in rats poisoned with lead (Fisher 1982)
- Hypericum demonstrated an analgesic effect in mice, possibly by acting on opiate receptors or by releasing endorphins / enkephalins (Keysell 1984)
- 10-11- 10-19 dilutions of silica increased mouse peritoneal macrophage activity. Normally silica is toxic to macrophages. (Devenas, Poitevin and Benveniste 1987)
- 10-22 potencies of Apis (bee venom) inhibited basophil degranulation. Apis is normally toxic to basophils. (Devenas et al 1988)

As the work by Devenas, Ennis and Roberfroid in the pan-European histamine – basophil experiments show, laboratory investigation into the effects of homeopathically-prepared substances are ongoing. Other publications:
- Diluent influences the effect of highly diluted histamine on basophil activation 39 (Lorenz, 2003)
- Ultra-high dilutions of nux vomica reduces voluntary ethanol intake in rats 40 (Sukul 2001)
- Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo 41 (Bonamin 2001)

Meta-analysis of laboratory studies
In 1994 Professor Linde undertook a meta-analysis of 105 laboratory studies of homeopathically-prepared substances 42. He found that the high quality studies were more likely to show positive effects.

Auto-regulatory effects of homeopathy possibly occurs via cellular effects
Homeopathic researchers have not yet defined the precise mechanism of action of homeopathic medicines. Dr. Taylor-Reilly M.R.C.P., lead-consultant at the Glasgow Homeopathic Hospital hypothesised that homeopathy pursues a third therapeutic avenue, that of facilitating auto-regulatory responses, rather than the two modes of pharmaceutical intervention (blocking reactions or substituting for the bodies’ response), in his review of research conducted during a fellowship with the Department of Internal Medicine at Glasgow in the mid-1980’s 43.

This auto-regulatory effect probably takes place via cellular mechanisms. There are heartening studies showing the effect of homeopathic potencies at a cellular level 44, 45.

References

36. Davenas E. et al Human basophil degranulation triggered by very dilute antiserum against IgE. Nature 1988 333 816-18

37. Brown M. and Ennis V. Flow-cytometric analysis of basophil activation: inhibition by histamine at conventional and homeopathic concentrations Inflamm.Res. 2001 50, S2 547-548

38. Belon P. et al Histamine dilutions modulate basophil activation Inflamm Res 2004 53 181-8

39. Lorenz I. et al Influence of the diluent on the effect of highly diluted histamine on basophil activation Homeopathy 2003 92:11-18

40. Sukul S.C. et al Strychnos nux-vomica extract and its ultra-high dilution reduce voluntary ethanol intake in rats J Altern Complement Med 2001 7(2):187-93

41. Bonamin L.V. et al Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo. Br Homeopath J 2001 90(4):198-203

42.Linde, K. et. al. Critical review and meta-analysis of serial agitated dilutions in experimental toxicology. Human & Experimental Toxicology 1994; 13: 481-492

43. Taylor-Reilly D., Taylor M. The difficulty with homeopathy. A brief review of principles, methods and research Compl Med Res 1988 3(1)72

44. Heine, H. and Schmolz, M. Induction of the Immunological Bystander Reaction by Plant Extracts.
Biological Medicine. 1998. 2. 12-14.

45. Chirumbolo, S. et al. Effects of Podophyllum peltatum compounds in various preparations and dilutions on human neutrophil functions in vitro. Brit. Hom. J. 1997

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