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Human basophil degranulation triggered by very dilute antiserum against IgE

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When human polymorphonuclear basophils, a type of white blood cell with antibodies of the immunoglobulin E (IgE) type on its surface, are exposed to anti-IgE antibodies, they release histamine from their intracellular granules and change their staining properties. The latter can be demonstrated at dilutions of anti-IgE that range from 1 x 10(2) to 1 x 10(120); over that range, there are successive peaks of degranulation from 40 to 60% of the basophils, despite the calculated absence of any anti-IgE molecules at the highest dilutions. Since dilutions need to be accompanied by vigorous shaking for the effects to be observed, transmission of the biological information could be related to the molecular organization of water.
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NATURE VOL. 333 30 JUNE 1988
Human basophil degranulation triggered by very
dilute antiserum against IgE
E. Dayenas, F. Beauvais, J. Amara*, M. Oberbaum*, B. Robinzon t, A. Miadonna t, A. Tedeschit, B. Pomeranz§,
P. Fortner§, P. Belon, J. Sainte-Laudy, B. Poitevin & J. Benveniste||
INSERM U 200, Universite Paris-Sud, 32 rue des Carnets. 92140 Clamart, France
* Ruth Ben Ari Institute of Clinical Immunology, Kaplan Hospital, Rehovot 76100, Israel
t Department of Animal Sciences, Faculty of Agriculture, PO Box 12, The Hebrew University of Jerusalem, Rehovot 76100, Israel
t Department of Internal Medicine, Infectious Diseases and Immunopathology, University of Milano, Ospedale Maggiore Policlinico,
Milano, Italy
§ Departments of Zoology and Physiology,* Ramsay Wright Zoological Laboratories, University of Toronto. 25 Harbord Street,
Toronto. Ontario M5S 1Al, Canada
To whom correspondence should be addressed.
When, human polymorphonuclear basophils, a type of white blood cell with antibodies of the immunoglobulin E (IgE) type on its
surface, are exposed to anti-IgE antibodies, they release histamine from their intracellular granules and change their staining properties.
The latter can be demonstrated at dilutions of anti-lgE that range from 1 x 1012 to 1 x 10120; over that range, there are successive peaks of
degranulation from 40 to 60% of the basophils, despite the calculated absence of any anti-lgE molecules at the highest dilutions. Since
dilutions need to be accompanied by vigorous shaking for the effects to be observed, transmission of the biological information could be
related to the molecular organization of water.
THE antibodies responsible for human immediate hypersensi-
tivity belong to the IgE isotype1. The most salient feature of IgE
is its capacity to bind to mast cell and polymorphonuclear
basophil membranes through receptors with high affinity".
Human basophils are specifically challenged by immunological
stimuli such as allergens or anti-lgE antiserum that can bridge
IgE molecules in membrane,. This process triggers trans-
membrane and intracellular signals followed by granule
exocytosis with the release of histamine and loss of meta-
chromatic staining of basophil granules by a basic dye such as
toluidine blue. Optical basophil degranulation is well corre-
lated with other in vitro and in vivo procedures for the
diagnosis of allergy4-7.
In preliminary experiments, degranulation of human baso-
phils contained in leukocyte suspensions was induced not only
by the usual concentration of anti-lgE antibody (1 x 103 dilution
of anti-lgE antiserum, corresponding to 2.2 x 10-9 M anti-lgE
antibody in the assay), but also by very low concentrations of
this antibody (2.2 x 10-16/18 M), where the number of IgG anti-
lgE; molecules in the assay is supposedly too low to trigger the
process. We then further explored this phenomenon.
Serial tenfold dilutions of goat anti-human IgE (Fc) anti-
serum (1 mg specific antibody per ml) were prepared in
HEPES-buffered Tyrode's solution containing human serum
albumin (USA) down to 1 x 1060, dilution, corresponding to a
2.2 x l0-66 M theoretical concentration (th) in the assay (see
Fig. 1 legend for methods). The expected basophil degranula-
tion, which was assessed by counting cells with metachromatical
properties, was observed after exposure of leukocyte prepara-
tions to low antiserum dilutions with a maximum at ~ 1 x 103
dilution. Successive peaks of degranulation varying between 40
and 60% were then found down to 1 x 1060 dilution, with periods
of 6 to 9 tenfold dilutions (Fig. 1a). In other experiments, the
antiserum was serially diluted a hundred-fold down to 1 x 10120
(to give 2.2 x l0-126 M th in the assay) and similar results were
obtained (Fig. 16). Degranulation induced by high dilutions of
anti-lgE antiserum was observed in ten experiments on the full
range of dilutions down to 1 x 1060, when at least 70 similar
results were obtained at one or the other part of the high dilution
scale in the participating laboratories (Toronto, preliminary
results). As controls, goat antihuman IgG (Fc) antiserum (Fig.
1b, n = 4) or Tyrode's solution containing HSA (n = 5) were
diluted down to 1 x 10120 and 1 x 1030, respectively. Cells
incubated in conditions identical to those with anti-lgE anti-
serum gave no significant degranulation. The repetitive waves of
anti-IgE-induced degranulation were reproducible, but the
peaks of degranulation could shift by one or two dilutions with
every fresh sequential dilution of anti-lgE and depended on the
blood sample. The waves of basophil degranulation were also
seen with substances other than anti-lgE anti-serum at high and
low dilutions, such as monoclonal anti-human IgE antibodies,
specific antigen in allergic patients or in peroxidase-immunized
rabbits, phospholipase A2 from bee venom or porcine pancreas,
the Na+ ionophore monensin (up to 90% degranulation at 1 x
10-30 M th) and the Ca2+ ionophores A23187 and monomycin (1 x
10-38 M th). The specificity of the observed effects at high dilu-
tions (already noted when comparing antiserum against IgE
with antiserum against IgG) was further strikingly illustrated in
the ionophore experiments, because removing the correspon-
ding ion from the cellular environment blunted basophil
Blind experiments: test tubes were randomly coded twice by two independent pairs of observers and assayed. The codes were simultaneously broken at the end of all
experiments. Dilutions of anti-lgE antiserum were performed as described in legend to Fig. 1.
* Uncpded additional tubes for negative (Tyrode's-HSA) or positive (algE 1 x 10 ~*) controls, t Data represent the mean 1 s.e. of basophil number actually counted in
triplicate (see legend to Fig. 1 for methods). % Number in parenthesis indicates percentage degranulation compared with Tyrode's-HSA.
NATURE VOL. 333 30 JUNE 1988
Fig. 1 Human basophil
degranulation induced either
by anti-IgE anti-serum (•)
diluted tenfold from 1 x 102
down to 1 x l060 (a) or
hundredfold down to 1 x
10120 (b) or by anti-IgG anti-
serum (O) diluted hundred-
fold from 1 x 102 down to 1
x 10120 (representatives of
at least 10 experiments for
anti-IgE and 4 experiments
for anti-IgG). The signifi-
cant (P < 0.05) percentage
of degranulation was 15%
(a) and 20% (b). (....) rela-
tion to the number of
counted basophils from
control wells'''.
Methods Goat anti-human
IgE (Fc) antiserum or as a
control, goat anti-human
IgG (Fc) antiserum (Nordic
Immunology, The Nether-
lands) was serially diluted as
indicated above in HEPES-
buffered Tyrode's solution
(in g 1-1 : NaCl, 8; KCl.
Na4. 1.040; glucose, 1
human serum albumin (HSA), 1.0; heparin. 5000 U per 1; pH 7.4). Between each
dilution, the solution was thoroughly mixed for 10 s using a Vortex. Given the
molecular weight of IgG molecules (150,000). the 1 x 1060 and 1 x 10120 dilutions
correspond in the assay to 2.2 x 10-66 M(th)and 2.2x l0-126 M (th) respectively.
Venous blood (20 ml) from healthy donors was collected using heparin (1 U per
ml) and a mixture of 2.5mM EDTA-Na4/2.5 mM EDTA-Na, (final concentrations)
as anticoagulants and allowed to sediment. The leukocyte-rich plasma was
recovered, twice washed by centrifugation (400g, 10 min) and finally resuspended
in an aliquot of HEPES-buffered Tyrode's solution. The cell suspension (10 μl)
was deposited on the bottom of each well of a microtitre plate containing 10 μl
CaCl2, (5 mM final) and 10 μl of either of anti-IgE or anti-IgG antiserum dilutions.
To a control well were added 10 μl CaCl2, and 10 μl Tyrode's but no anti-IgE or
anti-IgG antiserum, plates were then incubated at 37°C for 30 min. Staining
solution (90 ml; HX) mg toluidine blue and 280 μl glacial acetic acid in 100 ml 25%
ethanol, pH 3.2 3.4) was added to each well and the suspension thoroughly
mixed. Specifically redstained basophils (non-degranulated basophils) were
counted under a microscope using a Fuchs-Rosenthal haemocytometer. The
percentage of basophil degranulation was calculated using the following formula:
Basophil no. in control - basophil no. in sample/ basophil no. in control x 100.
Between 60 arid 120 basophils were counted in cell suspensions from control wells
after incubation either in the absence of anti-IgE antiserum, or in the presence of
anti-IgG antiserum.
To confirm these surprising findings, four blind experiments
were carried out (Table 1). In all cases the results were clear-cut,
with typical bell-shaped degranulations at anti-IgE dilutions
from 1 x 1032 to 1 x 1037. The replicates were usually very close
and of high significance (ANOVA test). In a fifth experiment, 7
control tubes and 3 tubes containing a dilution previously
determined as active (1 x 1034) were counted blind: basophil
degranulation was 7.7 ± 1.4% for the controls, and 44.8, 42.8
and 45.7% for the tubes containing diluted anti-IgE. The
random chance in all these experiments was 2% and therefore
the cumulative results statistically confirm the measured effect.
Two further blind experiments were performed using the
usual dilution procedure: of the 12 tubes used in the first
experiment (Table 2), 2 tubes contained goat anti-human anti-
serum IgE at 1 x 102 and 1 x 103 dilutions, 6 tubes contained
dilutions from 1 x 1032 to l x 1037, and 4 tubes buffer-HSA alone.
The tubes were then randomly coded twice by three parties, one
of which kept the two codes. The 12 tubes were each divided into
4. Three batches of 12 tubes were lyophilized, one of which was
used for gel electrophoresis, one for assay of monoclonal anti-
bodies, and the last (with the unlyophilized sample) for gel
electrophoresis and basophil degranulation. By comparing the
results of the different tests it was easy to identify the tubes
containing IgE at normal concentrations compared with the
tubes containing highly diluted IgE and the control tubes. When
the codes were broken, the actual results exactly fitted those
predicted, but HSA and its aggregates were present in all solu-
tions and complicated interpretation of the gel electrophoresis.
Fig. 2 Electrophoresis (polyacrylamide 7-15%. bands revealed by silver staining):
samples numbered 1 to 5 are standards for the blind experiments a. c. e, h, m, p.
Lane 1. Molecular weight standards for electrophoresis; lane 2, monoclonal IgG
added with human serum albumin; lane 3. Tyrode's buffer without human serum
albumin; lane 4.1 x 102 anti-IgE dilution; lane 5.1 x 103 dilution. Samples tested
Wind: a and c, buffer; e, 1 x 1036 anti-IgE dilution: h. 1 x 102 anti-IgE dilution; m,
1 x 103 anti-IgE dilution; p. 1 x 1035 anti-IgE dilution.
So we performed another almost identical experiment, using 6
tubes containing unlyophilized samples and buffer without
HSA. Pour tubes contained antibody at 1 x 102, 1 x 103, 1 x 1035
and 1 x 1036 dilutions, and 2 contained buffer alone. These
tubes were coded and assayed according to the above protocol.
The decoded results were clear-cut, high basophil degranulation
being obtained with 1 x 102, 103, 1035 and 1036 dilutions, but no
anti-IgE activity or immunoglobulins were detected either in the
control tubes or in assays containing the 1 x 1035 and 1036
dilutions (Tables 2 and 3 and Fig. 2). Thus there is no doubt that
there was basophil degranulation in the absence of any detec-
table anti-IgE molecule.
These results may be related to the recent double-blind
clinical study of Reilly et al.8 which showed a significant reduc-
tion of symptoms in hay-fever patients treated with a high
dilution (1 x 1060) of grass pollen versus placebo, and to our ex
vivo experiments in the mouse". We have extended these
experiments to other biological systems: using the fluorescent
probe fura-2, we recently demonstrated changes in intra-
cellular Ca2+ levels in human platelets in the presence of the
Ca2+ ionophore ionomycin diluted down to 1 x 10-39 M th (F. B.
et al., unpublished results).
Using the molecular weight of immunoglobulins and
Avogadro's number, we calculate that less than one molecule
of antibody is present in the assay when anti-IgE antiserum is
diluted to 1 x 1014 (corresponding to 2.2 x 10-20 M). But in the
experiments reported here we have detected significant
basophil degranulation down to the 1 x l0120 dilution. Specific
effects have also been triggered by highly diluted agents in
other in vitro and in vivo biological systems8-11, but still remain
unexplained. The valid use of Avogadro's number could be
questioned, but we are dealing with dilutions far below the
Avogadro limit (1 x 10100 and below). It could be argued that
our serial dilution procedure is subject to experimental error,
but this is ruled out because: (1) pipette tips and glass micro-
pipettes were discarded between each dilution (performed
under laminar flow hood). (2) The c.p.m. in tubes containing
serially diluted radioactive compounds decreased in propor-
tion to the degree of dilution down to the background (data
not shown). (3) Contamination would not explain the succes-
sive peaks of activity that evoke a periodic phenomenon and
not a monotonous dose-effect curve, as usually observed when
concentration of an agonist decreases. (4) To eliminate the
possibility of contaminating molecules present in the highly
diluted solutions, we carried out two series of experiments which
can be summarized as follows. An Amicon membrane with
molecular weight cut-off 10K retained the basophil degranu-
lating IgG (150K) present at low dilutions (1 x 102 1 x 103) in
anti-IgE antiserum. By contrast, the activity present at high
dilutions (1 x 1027 1 x 1032) was totally recovered in the 10K
Amicon filtrate. Anion or cation exchange chromatography,
NATURE VOL. 333 30 JUNE 1988
Blind experiments and dilution protocols as in Table 1., Lack of strained
bands. ND, not determined. A faint band corresponding to IgG appeared after
reduction by 2-mercaptoethanol.
* Basophil degranulation tests I, II, III were performed using 3 different blood
samples (see Fig. 1). Percentage basophil degranulation induced by aIgE, as
compared to Tyrode's HSA, was calculated from duplicates.
t Electrophoresis (polyacrylamide 7-15%, revealed by silver staining) was carried
out in Rehovot (A) and at INSERM U 200 (B).
$ Uncoded additional tube for positive control.
§ + +, + Bands correspond to IgG present in large or small amounts.
according to the type of resin used and the pH, did or did not
retain the anti-IgE IgG at low dilutions, whereas the same
activity at high dilution was always excluded from the columns
and fully recovered in the first eluate. These filtration and ion-
exchange experiments demonstrated that the activity of the
antiserum at high dilution cannot result from contamination of
the highly diluted solution with the starting material. They
showed, in addition, that the high-dilution activity does not
present in space the steric conformation of an IgG molecule as it
acts like a 150K charged molecule, but is not retained by the 10K
filter or by a charged chromatography column.
We then investigated the physical chemical nature of the
entity active at high dilution. Our results can be summarized as
follows. (1) The importance of agitation in the transmission of
information was explored by pipetting dilutions up and down ten
times and comparing with the usual 10-s vortexing. Although the
two processes resulted in the same dilution (degranulations at
1 x 102 and 1 x 103 were superimposable whatever the dilution
process), degranulation did not occur at high dilution after
pipetting. Ten-second vortexing was the minimum time
required, but vortexing for longer (30 or 60 s) did not increase
high-dilution activity. So transmission of the information
depended on vigorous agitation, possibly inducing a sub-
molecular organization of water or closely related liquids. (2)
The latter is possible as ethanol and propanol could also support
the phenomenon. In contrast, dilutions in dimethylsulphoxide
did not transmit the information from one dilution to the other,
but increasing the proportion of water in dimethylsulphoxide
resulted in the appearance and increment of the activity at high
dilutions. (3) Heating, freeze-thawing or ultrasonication
suppressed the activity of highly diluted solutions, but not the
activity of several active compounds at high concentrations. A
striking feature was that molecules reacted to heat according to
their distinctive heat sensitivity, whereas all highly diluted solu-
tions ceased to be active between 70 and 80°C. This result
suggests a common mechanism operating at high dilution,
independent of the nature of the starting molecule.
Therefore we propose that none of the starting molecules is
present in the dilutions beyond the Avogadro limit and that
specific information must have been transmitted during the
dilution/shaking process. Water could act as a 'template' for
the molecule, for example by an infinite hydrogen-bonded
network12, or electric and magnetic fields13,14. At present we can
only speculate on the nature of the specific activity present in the
highly diluted solutions. We can affirm that (1) this activity was
established under stringent experimental conditions, such as
blind double-coded procedures involving six laboratories from
four countries; (2) it is specific for the ligand first introduced, as
illustrated when goat antiserum (IgG) anti-human IgE, but not
goat IgG anti-human IgG supported this phenomenon. The link
between high and low anti-IgE dilutions is shown as we could not
detect basophil degranulation at high dilutions if it did not occur
within the classical range. High dilutions of histamine, but not of
its carboxylated precursor histidine, inhibited IgE-dependent
basophil degranulation. Finally, ionophores at high dilution did
not work when the specific ion was removed from the cell
suspension (F.B., unpublished results). (3) Using six bio-
chemical and physical probes, we demonstrated that what
supports the activity at high dilutions is not a molecule. (4)
Whatever its nature, it is capable of 'reproducing, subtle molec-
ular variations, such as the rearrangement of the variable region
of an IgG (anti- versus anti-y) molecule.
The precise nature of this phenomenon remains unex
plained. It was critical that we should first establish the reality
of biological effects in the physical absence of molecules.
The entities supporting this 'metamolecular' biology can only
be explored by physical investigation of agitation causing inter-
action between the original molecules and water, thus yielding
activity capable of specifically imitating the native molecules,
though any such hypothesis is unsubstantiated at present.
We thank Professor Z. Bentwich from Ruth Ben Ari Insti-
tute for supervision of experiments conducted in Rehovot. The
participation of J. Geen (Univ. Toronto), B. Descours and
C. Hieblot (INSERM U 200) in experiments and of V. Besso in
editing is gratefully acknowledged. This work is dedicated to the
late Michel Aubin, who played a decisive role in initiating it.
Received 24 August 1987; accepted 13 June 1988.
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6. Pirotzky. E. eial. Lancet i. 35&-361 (1982).
7. Yeung-Laiwah, A. C. Patel. K R . Seenan. A K. Galloway. E. & McCulloch. W. Clin
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8. Reilly.D.T. Taylor. M A , McSharry.C. & Aitchison.T. Lancet ii. 881 -886 (1986).
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12. Stanley, H. E . Teixeira. J. Geiger. A. & Blumherg. R L Physics 106A. 260-277 (1981).
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Editorial reservation
READERS of this article may share the incredulity of the many referees
who have commented on several versions of it during the past several
months. The essence of the result is that an aqueous solution of an
antibody retains its ability to evoke a biological response even when
diluted to such an extent that there is a negligible chance of there being a
single molecule in any sample. There is rfo physical basis for such an
activity. With the kind collaboration of Professor Benveniste, Nature
has therefore arranged for independent investigators to observe repeti-
tions of the experiments. A report of this investigation will appear
... polémiques intenses. Et bien que l'idée ait été émise à la suite d'une publication dans une revue scientifique renommée [1] et portée par un chercheur et médecin de réputation internationale, le Dr Jacques Benveniste, elle reste actuellement dans l'histoire des sciences comme un affaire trouble, ravivant les conflits autour de l'homéopathie et autour de laquelle rôde le fantôme de la fraude. Ayant été à l'origine de ces travaux pour les médicaments homéopathiques en 1980 [2] dans l'Unité U200 de l'Inserm dirigée par Jacques Benveniste où je suis resté jusqu'en 1991, j'ai ensuite essayé de les prolonger jusqu'en 1997 au sein des laboratoires homéopathiques, puis seul jusqu'au déremboursement de l'homéopathie en 2020. ...
... L' « affaire » médiatique a connu de nombreux rebondissements : après la publication dans Nature [1], et la contrepublication assez incroyable de la commission d'enquête [3], la mémoire de l'eau a été décrite sous l'angle du mystère [2,4], de la vérité [3,5], et de l'imposture [6]. Cet aspect tient naturellement au fait qu'elle impliquait l'homéopathie, mais est aussi en lien avec la personnalité et le parcours de J. Benveniste, biologiste réputé qui faisait partie des scientifiques nobélisables au début des années 80. Dans les années 90, son opposition en France aux Prix Nobel de physique (Georges Charpak) ou de biologie (François Jacob), l'implication très forte de Nature, le suivi et l'organisation d'une partie du débat par le journal Le Monde [7,8] ont contribué au caractère sensationnel de ce qui est ainsi devenu une « affaire ». ...
... Ce modèle avait à ses yeux l'avantage de se dérouler en un seul temps, ce qui facilitait son étude par d'autres laboratoires, contrairement aux études d'inhibition qui nécessitaient d'abord l'activation par un agoniste approprié (allergène ou anticorps anti-IgE), puis mise en présence des cellules et du médicament ou de son contrôle. De plus, il n'était pas question directement d'homéopathie, même si des références à son évaluation sont faites dans l'article de Nature [1]. ...
Résumé La controverse à propos de la “mémoire de l’eau” ne peut se comprendre que si le volet médiatique de cette “affaire” est dissocié des publications scientifiques sur ce sujet et des sources médicales homéopathiques qui en ont été à l’origine. Si l’aspect médiatique a été excessivement développé, la répétabilité des travaux scientifiques s’est avérée insuffisante, les efforts faits par la communauté homéopathique ayant été limités. Ceci a eu des conséquences sur l’évolution de la recherche en homéopathie et indirectement sur l’arrêt du remboursement de l’homéopathie par la Sécurité sociale en France.
... Nature [21]. The paper reported the results of a simple bench experiment. ...
... After the publication of Ref. [21], Nature set up a team to oversee replications. These Field Theory is the appropriate framework to describe the interaction between photons and dipoles [24]. ...
Full-text available
Water is present in all of its three phases in our natural world. It carves the landscapes on our planet, it is the solvent for biological activity, and it is central in humankind’s physical and intellectual existence. We summarize how water’s properties as a liquid and as a solvent are a consequence of the molecule being a strong dipole subject to Brownian motion. Short-lived hydrogen bridges between neighboring water molecules set up a flexible tetrahedral network. Convoluted pseudoscientific theories have been formulated about water. Many of these theories involve elaborate forms of higher organization and quantum physics. Some such theories have been used as a basis for scams and quackeries. We discuss of few of these excesses.
... This hypothesis has already been suggested by Davenas et al. 41 and also by other researchers in liquid systems, 39,40,42 in which water would be responsible for the changes in their physicochemical properties. 33,41,43,44 These different models suggest NPs formation, as well as NBs generation, due to the mechanical energy promoted by dynamization. Also, the succussion of substances performed under electromagnetic field conditions seems to induce the generation of domains composed of water polar molecules, which bear the signature of the dissolved solute. ...
Background Recent experimental results supporting the dynamization process show modification in the characteristics of solid mixtures. Objective The present work aims to evaluate the physicochemical properties of metallic zinc and lactose, evidencing the interactions between all chemical components presented in dynamized solid mixtures by analytical techniques. Methods Mixtures of zinc and lactose (1:9 w/w) were successively triturated at the same proportion according to the Brazilian Homeopathic Pharmacopoeia, receiving the designation of 10−1 – 10−6 (1dH – 6dH). All samples were submitted to the following characterization techniques: Atomic Absorption Spectrometry (AAS), Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), and Raman Spectroscopy (RS). Results AAS results detected 97.0% of zinc in the raw material, and the triturated zinc lactose system (ZnMet) presented mean values similar to those expected for the physical mixtures: i.e., 9.94%, 1.23%, and 0.11% in the three first proportions (10−1, 10−2, 10−3), respectively. SEM images showed particle size reduction due to the trituration process. The XRD assays of ZnMet 10−3 and 10−6 indicated peak changes at 12.3° and 43.26°, probably associated with modifications of inter-atomic crystalline spacing. The thermal analysis results of dynamized samples suggest modifications in the chemical interaction between zinc and lactose induced by the physical forces applied. RS experiments showed variation in vibration frequencies due to the dynamization procedure, in which marked ZnMet 10−6 spectral modifications were detected at 357, 477, 1086 and 1142 cm−1, and in the wavelength range 860–920 cm−1. Conclusion These results highlight the importance of applying suitable characterization methods to improve our understanding of the properties of homeopathic solid mixtures, whereas the uses of sensitive tools evidence the influence of trituration on the crystalline properties and in the enthalpy variation of dynamized samples.
... The controversy emerged in 1988 after the publication of an article of Benveniste's team and other scientists in the journal Nature [5]. The experiments described in the article suggested that water kept information of biologically-active molecules that had been so diluted that no molecule could be present in test samples. ...
Full-text available
Background: Benveniste’s biology experiments suggested the existence of molecular-like effects without molecules (“memory of water”). In this article, it is proposed that these disputed experiments could have been the consequence of a previously unnoticed and non-conventional experimenter effect. Methods: A probabilistic modelling is built in order to describe an elementary laboratory experiment. A biological system is modelled with two possible states (“resting” and “activated”) and exposed to two experimental conditions labelled “control” and “test”, but both biologically inactive. The modelling takes into account not only the biological system, but also the experimenters. In addition, an outsider standpoint is adopted to describe the experimental situation. Results: A classical approach suggests that, after experiment completion, the “control” and “test” labels of biologically-inactive conditions should be both associated with “resting” state (i.e. no significant relationship between labels and system states). However, if the fluctuations of the biological system are also considered, a quantum-like relationship emerges and connects labels and system states (analogous to a biological “effect” without molecules). Conclusions: No hypotheses about water properties or other exotic explanations are needed to describe Benveniste’s experiments, including their unusual features. This modelling could be extended to other experimental situations in biology, medicine and psychology.
... These pharmacologically active remedies elicit change within the body, both on a biological and physiological level. 9,10 Homeopathy uses several potency scales, 2 of which are D or X (decimal scale 1:10) and the cH (centesimal dilutions 1:100). When potencies beyond 24X or 12cH are reached, the process of preparing homeopathic remedies through potentization leads to the dilution of a raw or bulk form of starting materials beyond Avogadro's number-the number of units in one mole of any substance. ...
Context: Nanomedicine is a rapidly expanding field in which nanoparticles play an integral part. They have 2 distinct characteristics, namely a small size and large surface area, which influence a drug's permeability, solubility, and bioavailability. The trituration technique used in the preparation of certain homeopathic remedies is similar to some processes used to manufacture nanoparticles. New research has confirmed the presence of nanoparticles in homeopathic remedies. The majority of these studies use transmission electron microscopy (TEM), alone or in combination with other methods, to characterize the nanoparticles. Objectives: The study intended to evaluate the use, efficacy, and application of 5 characterization techniques for investigating the presence and size of nanoparticles in Ferrum phosphoricum (iron phosphate) in 2X, 4X and 6X potencies. Design: Quantitative experimental study. Setting: The study took place in the Department of Biotechnology and Food Technology, and the Department of Chemistry (Central Analytical facility and UJ Spectrum facility) at the University of Johannesburg in Johannesburg, South Africa. Outcome measures: The study analyzed 2X, 4X, and 6X potencies of Ferrum phosphoricum using: (1) ultraviolet-visible spectroscopy (UV-vis), (2) Fourier transform infrared spectroscopy (FTIR), (3) dynamic light scattering (DLS), (14) scanning electron microscopy (SEM) for energy-dispersive X-ray spectroscopy (EDX), and (5) transmission electron microscopy (TEM). Data were generated through imaging and the software programs of the equipment. Results: All 5 procedures confirmed the presence of Ferrum phosphoricum nanoparticles and nanofibers for all 3 potencies. Using all 5 techniques permitted characterization of different aspects of the particles, such as functional groups, elemental iron, concentration base, and size distribution. Conclusions: Although all 5 techniques used in the study showed the presence of iron phosphate nanoparticles in the 2X, 4X and 6X potencies of Ferrum phosphoricum, making them essential tools in determining the presence of nanoparticles, UV-vis, FTIR, and TEM analysis were best suited for the analysis of nanoparticles in high-dilution preparations such as homeopathic remedies, due to the limitations of DLS and EDX.
... The water memory controversy supporting the homeopathy industry or the false link between autism and vaccination published by Wakefield, et al., have been highly discussed and publicized. 81 Despite this, the involvement of industrial sponsors of scientific research, particularly in clinical trial research, has increased exponentially. In 1980, 32 % of all biomedical research was funded by industry; this figure increased to 62 % in 2000. ...
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The independence of science was long seen as of prime importance. This position has become less common today. The perception of scientific research as a public service has led to the opinion that it must be accountable to citizens and produce knowledge and innovation that meet their expectations. Numerous authors have voiced the need for anticipatory ethical control of innovation focusing on the scientific research process. This control is considered as the must-have guarantee for “good science.” The current article attempts to trace the ideological origins of the ethical control of innovation, examines its effectiveness against the challenge of globalization and technology-derived major threats and its compatibility with scientific methodology. It also suggests ways to both regulate the innovation process and preserve the independence of science. On the whole, we conclude that truly effective ethical regulation of innovation, i.e. one that protects the greatest number from its adverse effects, is achieved first and foremost by questioning our liberal economic model and the place given to science in our societies.
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The present paper reviews various studies envisaging the role of homoeopathy as an immune modulator. Homeopathic medicine and immunology both are conceptually linked. Homoeopathy is evidentially suggestive of beneficial in boosting the immunological responses in conditions from allergies to neoplasms. Homoeopathic treatment suggest to have stimulatory and co-stimulatory effects in immunological processes including hematological parameters like total and differential leukocyte count proliferation, hemoglobin count with hematopoietic parameters like bone marrow cellularity, inflammatory processes, CRP value, phagocytosis, fibrosis, CD4+ & CD8+ count along with boost in immunoglobulin titers. Various research experiments suggest homoeopathic immunotherapies to have an immune modulatory effect of endogenous substances like thymulin, cytokines, histamines, and immunoglobulins (endoisotherapy). Also homoeopathic preparations from common allergens, agents causing influenza, Leptospirosis, Tuberculosis, Vibrio parahemolyticus and Vibrio alginolyticus, cancer cells have been observed to be effective in generating an Immune modulating response. Homoeopathic medicines causes immune modulating changes through gene expression modulation, stimulation of macrophages, chemotaxis of polymorph nuclear cells and production of cytokines.
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Serially diluted succussed solutions of a suitable drug/toxic substance can exhibit physicochemical and biological properties even far beyond Avogadro’s limit defying conventional wisdom. They can show hormesis, and homeopathy uses them as medicines. Many studies confirm that they can have an impact on gene expression different than controls. Water in the exclusion zone phase can have memory but for a short period. However, the nanoparticle as the physical substrate can hold information. Nanoparticle and exclusion zone duo as nanoparticle-exclusion zone shell can provide a prolonged memory. The Nanoparticle-Exclusion Zone Shell Model may be an important step toward explaining the nature and bioactivity of serially diluted succussed solutions used as homeopathic medicines. This model may also provide insight into the workings of hormesis. Hormesis is the primary phenomenon through which homeopathic phenomenon may have evolved exhibiting the principle of similars. Hahnemann exploited it to establish homeopathy. The nanoparticle-exclusion zone shells present in the remedy, selected on the principle of similars, can be patient-specific nanoparticles in a symptom syndrome-specific manner. They can carry the drug-specific information for safer clinical applications in an amplified form for high yielding. It suggests homeopathy is a type of nanopharmacology.
Conference Paper
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Le concept moderne d'objectivité, qui se caractérise par son opposition à la subjectivité, est le fruit d'une évolution intellectuelle dont le principal point d'inflexion se situe au XVII° siècle. Et les différentes définitions du concept qui jusqu'à aujourd'hui se sont succédées correspondent à différentes modalités de cette subjectivité qui, les unes après les autres, sont devenues « suspectes ». Mais la compréhension que la science moderne a d'elle-même est solidaire de sa conception de l'objectivité et du réel ; or la "conception du monde" est ce qui caractérise l'activité d'une subjectivité dont on crédite l'avènement à la modernité. Nous essaierons de montrer que la Modernité, tout en balayant certains présupposés des précédentes conceptions du monde, en a conservé d'autres que nous retrouvons dans les caractéristiques pour nous évidentes de l'objectivité et de la réalité, et que les sources de ce sentiment d'évidence plongent leurs racines, entre autres, dans un fond théologico-politique qui n'a pas grand chose à voir avec l'investigation rationnelle sur la nature de la réalité. Comme dit Hans Blumenberg, « Descartes a soigneusement effacé et nié les traces de son héritage historique pour constituer le mythe du commencement radical de la raison. » Autrement dit, la légitimité du discours scientifique s'est construite sur des fondements qu'aujourd'hui nous considérons illégitimes et récusons. A partir de quelques exemples, nous verrons que certains des préjugés qui, au XVII° siècle, ont servi à constituer le modèle des sciences de la nature, sont encore en vigueur aujourd'hui. Et bien que ces préjugés soient hautement problématiques pour les sciences humaines, dans la mesure où ils fondent l'objectivité sur une négation du sujet, ils ont pourtant été indirectement adoptés par celles-ci.
Moral issues concerning the use and abuse of science are broached in this chapter. Scientists have responsibilities to conduct their research in such a way as to respect and acknowledge the contributions of others and to present their work honestly and without seeking to avoid criticism by misleadingly overestimating random error. The onus on scientists of a wider social responsibility for informing the public and guiding decision makers is also discussed, together with the reciprocal responsibilities of decision makers to ensure that they are informed and able to understand the bearing of new knowledge.
The basophil degranulation test (BDT) has failed to gain popular acceptance as a test of immediate-type hypersensitivity since its introduction in clinical medicine in 1961. Recent modification of this technique, however, seemed to have increased its reliability. We have studied a group of twenty-five hay-fever sufferers and a similar age- and sex-matched group of healthy controls to compare the sensitivity of a newly available commercial BDT kit (Baso-kit, Laboratoire des Stallergenes) with specific serum IgE levels and skin-prick tests to meadow-grass pollen. A quantitative correlation was found between the positive BDT (greater than 30% degranulation) and the skin tests, whereas only a qualitative relationship was obtained with specific IgE concentrations. The BDT also identified two subpopulations of responders and non-responders among a third group of hay-fever subjects who had previously been hyposensitized to mixed grass pollen. We conclude that the modified BDT provides a worthwhile addition to the in vitro testing of immediate-type hypersensitivity states.
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