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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