Homeopathy (2015) 104, 67e68
Ó 2015 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.homp.2015.03.002, available online at http://www.sciencedirect.com
EDITORIAL
Homeopathy, hormesis, nanoparticles and
nanostructures
This issue of Homeopathy is an ambitious attempt to
bring together emerging concepts in biological, toxicolog-
ical, medical and materials science which have important
implications for the theoretical basis of homeopathy.
Hormesis
We start with a series of papers from Prof Edward Calabr-
ese of the University of Massachusetts, who gives a masterly
overview of the field in three papers on principles and appli-
cations, history and mechanisms of hormesis. In fact horm-
esis is not new, nor is its relationship to homeopathy new,
although it is often known by its name in a former incarna-
tion: the Arndt-Schulz law. Calabrese’s first paper reviews
the principles and applications of hormesis: the paradoxical
beneficial or stimulatory effect of low doses of toxins, with a
U or J shaped dose response as opposed to the conventional
sigmoid, S shaped curve assumed in conventional pharma-
cology. As Calabrese points, large-scale data shows hor-
metic dose response curves are more common than
sigmoid. This is very challenging to the toxicology and reg-
ulatory community since it has major implications for
assessment of toxicological and environmental risk.1
Some readers may be surprised by the statement, in his pa-
per on the historical foundations of hormesis that ‘the histor-
ical dispute between homeopathy and traditional medicine
has long since subsided’.2 Finally in his paper on mecha-
nisms, Calabrese points out that although many specific
mechanisms of hormesis involving different receptor/signal-
ling pathways have been documented, the quantitative fea-
tures of the hormetic dose response are independent of
mechanism.3
Menachem Oberbaum, Michael Frass and Cornelius
Gropp then take a sceptical view of the relationship be-
tween hormesis and homeopathy, casting them as unequal
brothers with homeopathy as the underachieving sibling,
clinging to hormesis for scientific vindication. They point
out major differences between the two paradigms,
including the greater specificity of homeopathy and the
greater effect size when the specific homeopathic medicine
is applied.4 Although this does not preclude the possibility
that hormesis and homeopathy are both members of a
larger set of phenomena characterised by reverse or bene-
ficial effects as a function of dose, time or idiosyncracy.
Nanobubbles and microarrays
We then move on to empirical data. Jean-Louis Deman-
geat reviews his many years of work studying nanobubbles
with nuclear magnetic resonance spectroscopy. Homeo-
pathic manufacturing procedures generate nanobubbles,
these have many unusual properties including low buoy-
ancy, longevity and high energy is released when they burst
or collapse. They are associated with superstructures which
seemed to increase with size with increasing dilutions well
into the ‘ultramolecular’ range. Demangeat presents new
experimental evidence about the superstructures which
form around them.5
Andrea Dei and Simonetta Bernadini review the results of
experiments, including their own, using modern methodol-
ogy, DNA micro-arrays, to investigate the influence of
extremely dilute solutions on gene expression. Results
with a number of substances including copper sulphate, Gel-
semium and Apis show concentration-dependent, hormetic
inversion of gene expression.6 As usual with such assays
the results are complex showing up-regulation and down
regulation of different gene groups. But they provide the
exciting perspective of optimising the clinical use of high di-
lutions.
Allosteryandallostasis
We conclude with two complex and closely argued theo-
retical papers from Iris Bell and Gary Schwartz and from
Paolo Bellavite and colleagues which examine the issues
raised by homeopathy in the context of current concepts
in biological science. Bell and Schwartz look at the impli-
cations of recent developments in nanotechnology science
for homeopathy. They point out that homeopathic
manufacturing methods, particularly trituration, are essen-
tially the same as some nanotechnology preparation
methods. Nanoparticles have dramatically different prop-
erties from the same substances in crude form. Bell and
Schwartz discuss these in the context of stochastic reso-
nance, complex adaptive systems and time dependent
sensitisation.7 Bellavite et al discuss the ‘protein energy
landscape’ which plots conformations of a protein against
free energy. Viewed from this perspective the main aim of
the ‘vital force’ is to achieve optimal energy utilisation, a
valley in the energy landscape. This model accounts, for
instance, for homeopathic ‘aggravations’.8
The terms allostery and allostasis are central to the the-
ories of Bellavite and Bell respectively and should not be
confused. ‘Allostery’ means the regulation of protein by
conformational change through binding at a site which is
not its active site. This is in contrast to orthostasis, binding
to an active site which is the dominant concept in modern
 Editorial
P. Fisher
68
conventional pharmacology, the paradigm for the action of
agonist, antagonist and blocking drugs. ‘Allostasis’, central
to Bell and Schwartz’s Nano-Particle-Cross-Adaptation-
Sensitisation (NPCAS) model is the process of restoring
homeostasis in response to stress. In the NPCAS model ho-
meopathic medicines trigger adaptive responses to stress
through stochastic resonance.
Although these two groups approach the question of how
homeopathic medicines might act from different perspec-
tives, their results are compatible. For instance allostasis
can be seen as the process of restoring optimal energy uti-
lisation in the energy landscape. While allostery is likely to
be involved in the adaptive processes triggered by nanopar-
ticles in the NPCAS model.
Much work is needed to understand the practical and
therapeutic implications of these models and to draw out
experimentally-testable hypotheses. Nevertheless taken
together the papers in this special issue mark a major theo-
retical advance in the understanding of homeopathy and a
major step to overcoming plausibility bias: the prejudice
that homeopathy ‘does not work because it cannot work’.9
Homeopathy (2015) 104, 68
Ó 2015 Published by Elsevier Ltd on behalf of The Faculty of Homeopathy.
http://dx.doi.org/10.1016/j.homp.2015.03.001, available online at http://www.sciencedirect.com
Corrigendum to “Editorial: Animals and
memory” [Homeopathy 104 (2015) 1e2]
The Editorial ‘Animals and Memory’ which appeared in the last issue of Homeopathy (2015) 104, 1e2, included an error. It
referred to: ‘38 trials identified in the previous bibliometric study, 18 were published in the peer-reviewed literature.’. This
should have read ‘38 trials identified in the previous bibliometric study, 18 were placebo-controlled.’. I apologise to Robert
Mathie and Jűrgen Clausen for this error.
Dr Peter Fisher, Editor-in-Chief, Homeopathy.
DOI of original article: http://dx.doi.org/10.1016/j.homp.2014.12.001.
Homeopathy
References
1 Calabrese E. Hormesis: principles and applications. Homp 2015;
104: 69e82.
2 Calabrese E. Historical foundations of hormesis. Homp 2015; 104:
83e89.
3 Calabrese E. Hormesis within a mechanistic context. Homp 2015;
104: 90e96.
4 Oberbaum M, Frass M, Gropp C. Unequal brothers. Homp 2015; 104:
97e100.
5 Demangeat J-L. Gas nanobubbles and aqueous nanostructures: the
crucial role of dynamization. Homp 2015; 104: 101e115.
6 Dei A, Bernadini S. Hormetic effects of extremely diluted solutions
on gene expression. Homp 2015; 104: 116e122.
7 Bell I, Schwartz G. Enhancement of adaptive biological effects by
nanotechnology preparation methods in homeopathic medicines.
Homp 2015; 104: 123e138.
8 Bellavite P, Signorini A, Marzotto M, Moratti E, Bonafini C,
Olioso D. Cell sensitivity, non linearity and inverse effects. Homp
2015; 104: 139e160.
9 Rutten L, Mathie RT, Fisher P, Goossens M, van Wassenhoven M.
Evidence and plausibility: the case of homeopathy. Med Health
Care Philos 2012; http://dx.doi.org/10.1007/s11019-012-9413-9.
Peter Fisher
Editor-in-Chief
E-mail: peter.fisher@uclh.nhs.uk