Electric measurement of ultra-high dilutions—a blinded controlled experiment

British Homoeopathic Journal January 1998, Vol. 87, pp. 3-12

Electric measurement of ultra-high dilutions - a blinded controlled experiment HARALD WALACH,* TEDJE VAN ASSELDONK,'~ PERICLES BOURKAS,:~ ALEXAND..RA DELINICK,w GALEN IVES,** COSTAS KARRAGIANNOPOULOS,$ RAINER LUDTKE,I't MICHEL VAN WASSENHOVEN,w167 CLAUDIA WITT,*** Abstract

This experiment was designed to test the hypothesis put forward by P. Bourkas, A. Delinick and C. Karragiannopoulos of the National Technical University of Athens (NTUA) that Ultra High Succussed Dilutions (UHSD) can be distinguished from control solutions by an Electric Measurement Device (EMD), developed by the NTUA team.M0 A pre-formulated experimental protocol was followed, measuring in random sequence test solutions of double-distilled and deionised water (aqua injectabile), potentised water (6 cH, 30 cH), Natrum muriaticum (Nat mur) potentised in aqua injectabile (6 cH, 30 cH), either blind or open. The number of measurements was determined by a power analysis based on open pilot readings. While the open pilot trial performed by the NTUA team showed a large difference in readings for the controls and test-solutions, the experimental blind test was negative. The only significant difference observed was between Nat tour 6 cH and Nat mur 30 cH, and the direction of the difference was in the opposite direction from that predicted by theory and found in the pilot experiment. No differences were found between any other conditions, and in particular Nat mur 30 cH and aqua 30 cH could not be distinguished. It was suggested that the failure to detect a difference in the main trial resulted from a different brand of water being used in the main trial; the likelihood of this, and other alternative explanations, is discussed. It was concluded that the EMD is a highly sensitive apparatus for measuring impurities in water. As yet there is no obvious link between the measurement of impurities in water and the purported alteration of solvent in the process of homoeopathic potentisation. Introduction

Homoeopathically prepared substances, Ultra * University of Freiburg, Rehabilitation Psychology, D - 79085 Freiburg; t Institute for Ethnobotany and Zoopharmacognosy, Rijksstraatweg 158, NL 6573 DG Beek/Ubbergen; :~ National Technical University of Athens, Electrical and Computer Engineering Department 42, 28th October St., GR - Athens, 10682; w Center of Homoeopathic Medicine, Pericleous 1, Maroussi, GR - Athens 15122; ** Priority Search, Sheffield Science Park, Arundel Street, GB - Sheffield S1 2NS; t t Institut ftir Medizinische Informationsverarbeitung, Universitat Ttibingen, Westbahnhofstr. 55, D - 72070 Ttibingen; w167Maison de l'Homropathie, 132 chre de Bruxelles, B- 1 1 9 0 Bruxelles; *** Universit~itsklinikum Charitr, Humboldt-Universi~t, Institut fiir Epidemiologie, D - 10098 Berlin.

High Succussed Dilutions (UHSD), are usually prepared stepwise by diluting a remedial substance in the ratio 1:99 in ethanol, water or lactose. The homoeopathic medicine is vigorously shaken, stirred, ground, or otherwise mixed, eg by sonication, II between the dilution steps. UHSDs are usually applied according to the 'law of similars', matching the symptom picture of a patient with the symptoms which U H S D s produce in human volunteers, or which are known to have been cured in sick persons in the past. They can be clinically effective, as some well-conducted trials have shown, 12-17 and can produce reproducible effects in experimental models. 18-~1Some physical theories have been advanced,22 but there is as yet no conclusive evidence. A number of well-conducted clinical trials have given unexpectedly negative results, (eg 23-27), and some prestigious experimental tests have failed

British Homoeopathic Journal

to be reproduced. 28-31 Research into UHSDs would be greatly facilitated once the nature is known of the purported active principle, which is suspected to reside in some structural change in the solvent. 32-36 Measurements with NMR spectroscopy have yielded some promising, albeit equivocal and preliminary results.37, 38 It is therefore of paramount importance to discover whether UHSDs are structurally different from pure or potentised solvent, and whether this difference is stable and independent of context--a prerequisite for establishing a causal link with therapeutic efficacy. A method is required which will demonstrate this reproducibly and independently of both context and investigator, both of which are necessary but not sufficient conditions to establish the homoeopathic potency as a scientific fact. It would therefore be a crucial step forward to find a method of investigating differences in structural or other p r o p e r t i e s b e t w e e n UHSDs and pure or succussed solvents. Such a method has been proposed by P. Bourkas, A. NTDei~nick and C. G. Karagiannopoulos of the National Technical U n i v e r s i t y of Athens (henceforth called the NTUA team), which is both relatively simple and reliable. In previous publications a new Electric Measurement Device (EMD) was introduced for measuring the electrical properties of UHSDs.4. 5, 9 Owing to patent applications in preparation (by PB & CK), the machine was described only as a 'black box', which measures a set of variables such as conductivity, electric field strength, resistance, capacitance, and relative permittivity, and internally computes these into an i n d e x score called the ' H a h n e m a n n ' by the i n v e n t o r s . The ' H a h n e m a n n ' is a new unit without any comparable counterpart. It is meant to quantify the 'energetic' or 'internal structure' of a solution processed according to homoeopathic pharmaceutical practice by vigorously shaking or succussing it. The machine has to be calibrated by system settings to various ranges in order for solutions of different properties to be investigated, including nature and quality of solvent, and volume to be measured. The m a c h i n e ' s p a r a m e t e r s are t h e n set to measure a specific type of solvent of a certain volume. Calibrating the machine can be a lengthy process. The calibration process has to be repeated for every different type

of solvent and for different volumes. Measurement is carried out by placing an electrode, usually made of copper, in a liquid for several minutes, during which time sample readings are taken at predetermined intervals. This results in a series of m e a s u r e m e n t s which are graphically displayed as a curve on the monitor of a notebook computer attached to the EMD via a physical and software interface. After a measuring period of approximately two minutes--the period can be arbitrarily c h o s e n - - a mean reading in Hahnemann units of the solution measured is displayed. The NTUA team carried out a series of preliminary open measurements in which the EMD showed clear differences between several freshly potentised test solutions up to 30 cH, mother tinctures and control solutions. It therefore seemed appropriate to test the hypothesis that the EMD is able to measure homoeopathically potentised substances, and to distinguish them from control solutions such as ethanol or water which are commonly used as solvents. After some discussion, a controlled protocol was developed to test this hypothesis experimentally. After the NTUA team had made the necessary preparations, including a pilot trial for power function calculations, the experiment took place in Athens on February 10-11 1996 at the premises of a local homoeopathic pharmacy that makes their own remedies and is a major supplier of homoeopathic medicines to other pharmacies. Method

Protocol development The protocol was developed in preliminary form and sent out to approximately 40 persons known to be experts in the field or interested in such an experiment (for names of respondents see Acknowledgement). From a wide range of constructive criticism a second version was compiled and re-circulated. Final amendments were made, with some issues discussed personally by phone or letter. A final version, approved by everybody interested in participaring in the trial, was drafted and deposited with the editor of the British Homoeopathic Journal. Some points were added by the NTUA team to clarify certain local aspects (eg potentisation machine used, supplier of material, etc), the major one being that 'measurement values might be different when the experiments are repeated due to the differences in the quality of

Volume 87, January 1998 the solvent used'. All protocol specifications were defined in writing before any experimental procedures, especially measurements, were carded out. The protocol thus represented a consensus of all parties and experts involved. What was left out of the protocol was the specification, which potentisation machine would be used and which supplier of the water, since we presupposed that these parameters would remain the same from pilot to final experiment. Design The design was a completely randomised, 2 by 5 factorial experimental design with 10 cells and n = 6 independent measurements per cell, ie 60 measurements, with blind/open measurements as one factor, and test-solutions as second factor (Table 1). Measurements Open Solutions Nat tour 6/30

Contr I 6/30

Contr II

Blind Solutions Nat mur 6/30

Contr I 6/30

Contr II

TABLE1. Design of the Experiment. Key: Nat tour Natrum muriaticum succussed Contr I Water for injection (aqua injectabile), succussed Control II Water for injection (aqua injectabile), reference control, unsuccussed 6/30 succussion6 cH, 30 cH Each independent measurement per cell was made from a new bottle, ie each measurement represented a flesh bottle. The measurement recorded was the last value of five consecutive measurements. In order to guard against preparation artefacts, two separate lines of preparations (potencies and succussed controls) were made. The procedure was identical for each line, the only difference being that the entire preparation process was repeated, so that half of the preparations were made from a freshly prepared stock bottle. This preparation factor

was not taken as an experimental factor in the design, as it was not deemed to be essential, but rather a control procedure to minimise effects of contamination. Material, preparation, methods Fresh materials were used for the experiment, as is normal for the preparation of homoeopathic substances for sale. Preparation was carried out in the homoeopathic pharmacy of George Korres, Athens, by Arhontoula Hatzilazarou, a qualified pharmacist who prepares homoeopathic remedies for therapeutic use in the course of her daily work. All preparation procedures were carried out in the presence of, and were supervised by, members of the research group. No odorific substances were allowed in the laboratory - no coffee, soap or perfume, and hands were washed with ethanol. The laboratory is situated on the first floor, reached from behind the counter area of the pharmacy. Preparation and coding was carried out in the laboratory itself, while the measurements were carried out downstairs. During the preparations of the test solutions, PB, CK and AD prepared for the measurements downstairs by calibrating the EMD. Test substances were prepared following the same procedure as had been used to produce the pilot measurements: Excess sodium chloride (Aldrich Chemicals, random crystals, 99.99% purity, 1,000 g, closed and sterile bottle, batch No. XXII) was d i s s o l v e d in 20 ml of water ( a q u a injectabile, injectable water, double distilled, deionized and purified, prepared by Chropi Co., hereafter referred to as 'water') taken from a fresh, sealed bottle. The supernatant saturated solution was used as the starting material. Bottles used for potentisation were commercial, dark brown glass bottles (10 and 30 ml) of identical appearance, heated in an autoclave at 100~ C, and slowly cooled to room temperature over night. 10 ml bottles were used for intermediate potencies, containing 2 ml of each solution; 20 ml of the final potency to be measured was made in 30 ml bottles. Potentisation was carried out on a commercial p o t e n t i s a t i o n m a c h i n e ( D y n a m a t 50 C, Belgium), set at a shaking force of 95 units on the machine's scale, counting 100• shakes. Bottles were taken from the autoclave by TvA and prelabelled with numbered stickers. 2 ml of water was placed in each of a series

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of 10 ml bottles by GI, to which 0.02 ml of saturated sodium chloride was added with a micropipette (Eppendorf). This was potentised on the potentisation machine, allowed to settle briefly, and labeled N a t m u r cH1. From this, 0.02 ml was taken using a new, clean tip on the micropipette, and added to 2 ml of water in a fresh bottle. T h i s process was repeated five times to yield N a t m u r 5 cH. From this solution, 2 ml was added to 19.8 ml in a 30 ml bottle, again potentised to yield N a t m u r 6 cH. From this potency, the process was continued up to N a t m u r 30 cH, again using 10 ml bottles containing 2 ml of liquid for intermediate steps and 30 ml bottles containing 20 ml of liquid for the final step. Two different control substances were prepared. Control I was diluted and succussed in exactly the same way as the N a t m u r potencies, except that the starting solution was 0.02 ml of water in 2 ml of water. Control II was unsuccussed water from the same stock bottle. After the first set of potencies and controls had been prepared, the entire procedure was repeated a second time, using the same starting material and preparing fresh stock solutions. This p r o c e s s resulted in two 30 ml bottles of each of N a t m u r 6cH, N a t m u r 30 cH, a q u a i n j e c t a b i l e 6cH, aqua injectabile 30 cH, and one sample of unsuccussed water. From each of these stocks of test solutions, 2 ml was pipetted into 12 bottles (10 ml), six from each production line, such that six bottles contained 2 ml of N a t m u r 6cH from the first production line, and another six contained N a t m u r 6 cH from the second production line, and so forth. The measuring bottles were filled immediately after preparation. The resulting 60 bottles were closed and placed separately about 1.5 m away from the production area and 15 cm apart from each other, to avoid the possibility of 'energetic contamination'. This precaution was observed at all times when handling the test bottles and test material. Bottles were labelled with r e m o v a b l e labels; different colours were used for the respective potencies, and the two production lines were noted on the labels as 'A' and 'B'.

Randomisation and blinding A f t e r all m a t e r i a l s had b e e n p r e p a r e d , everybody concerned with preparation of test substances and measurement left the laboratory except for RL and the pharmacist AH, who

together coded the bottles. The code numbers, which had been generated in advance by RL using the 'ranuni' random number generator provided by SAS, randomised the sequence of blind and open measurements, as well as that of the test solutions. The protocol required that the bottles be freshly labelled, the labels carrying only numbers. Separate data sheets, which were distributed before measurements began, carried the substance names of the 30 open measurements, and code numbers only for the 30 blind measurements. No member of the measurement team was present during the coding of the bottles, and those who had performed the coding left the pharmacy and remained outside the building while the measurements were carried out. During the coding of the bottles, RL discovered a minor flaw in the labelling of the bottles--in the N a t tour 30cH series, nine bottles were classified as having come from the first production line, with only three from the second. For this reason a planned post-hoc analysis on differences in production lines could be completed only partially. This in no way invalidates the data, however, since the bottles had been clearly labelled as N a t tour 30cH by coloured labels. The error might have occurred while the original labelling was done, mistaking the colour of the original stickers, or else when the original labels were replaced by the blinding labels. After the error had been detected, RL conferred with MvW to discuss the matter, and they decided to withhold this information until the end of the experiment in order not to exacerbate an already somewhat tense atmosphere.

Measuring apparatus and measurements The measuring device was the same equipment that had been used on previous occasions. After preliminary calibrating experiments before the start of the trial, it had been decided to set the machine to the following starting parameters: energy = 32 (range 1-1,020), mobility = 1,000 (range 1-19,531), number of measures = 1,000, sampling period = 1 second, samples = 5. Sixty freshly prepared copper electrodes, manufactured to fit neatly into the opening of the bottles, were rinsed with 60% ethanol and allowed to air dry. A fresh electrode was used for each measurement, and the used electrodes were kept separately. Measurement was carried

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out by PB and CK, and witnessed by the others. The displayed measurements were announced by AD and immediately entered on the preprinted data forms by everyone present, the master form being completed by AD in the immediate vicinity of the computer display. The bottles were brought down one by one from the laboratory by MvW, while the persons who prepared the codes and carried out the randomisation waited outside the building. The label was read aloud and compared with the prepared data sheet, the bottle was opened, and the measuring electrode immersed. Recording was initiated immediately, and after the final reading was reached and the Hahnemann value displayed, this was announced and recorded. Data handling and statistical analysis

The number of measurements ~per cell had been determined according to a power function calculation based on the values reported in the

Test solution Water (unsuccussed) Water (succussed) Nat tour 6 cH Nat tour 30 cH

No. observ. 14 16 24 29

pilot trial, yielding a power well over = 0.9. After all the measurements had been written down, a volunteer entered the data on a notebook computer into the SAS system, which had previously been set up to accept the randomised data. Data entry was then repeated by a second person, and this double entry ensured that no entry errors occurred. Analysis was performed immediately, once the data had been verified, u s i n g a 2 by 5 f u l l y s a t u r a t e d f a c t o r i a l A N O V A procedure in SAS.

Results Results are shown for the pilot trial and the main experiment separately. A full report of the statistical analysis of the main experiment can be obtained from H W or RL, and this is also deposited with the editor of the B r i t i s h H o m o e o p a t h i c J o u r n a l . T h e results shown in Table 2 are those provided by the NTUA team following the pilot experiment, Tables 3 and 4

Median Score 4.900 4.801 1.957 3.475

SD 0.1737 0.2831 0.1377 0.4176

Mean Score

SD

Range

0.55 0.47 0,45 0.48 0.73

2.24-3.68 1.73-3.04 2.36-3.47 1.67-3.00 1.25-3.20

SD 0.41 0.58 0.30 0.39 0.39

Range 1.78-2.84 1.76-3.29 2.37-3.10 2.07-2.96 1.54-2.58

TABLE2. Result from pilot experiments, Test solution

No. observ.

Water (unsuccussed) 6 2.76 Water 6 cH 6 2.21 Nat mur 6 cH 6 2.79 Water 30 cH 6 2.55 Nat rnur 30 cH 6 2.08 TABLE3. Result from main experiment---open condition. Test solution Water (unsuccussed) Water 6 cH Nat mur 6 cH Water 30 cH Nat mur 30 cH

No. observ. 6 6 6 6 6

Mean Score 2.27 2.47 2.79 2.47 2.00

TABLE4. Result from main experiment--blind condition: no. of observations, mean Hahnemann value,, standard deviation and range.

British Homoeopathic Journal

give the results for the experimental test, Figure 1 summarises the results graphically. 5.,_

I + ~

I

.

0,15 0

I v~lm" oCH

I NjmurG(~l

I WdBI" ~ C H

I klat mur 30CH

FIGURE 1. Summary of Results from Pilot* and Main Experiment--Hahnemann Units for Water (non potentised), Water 6 cH, Water 30 cH, N a t m u r 6 cH, N a t m u r 30 cH *Pilot experiments scores represent median H-values, and only values for potentised water have been provided. Therefore, scores for the potentised water of the pilot experiment have been extrapolated both to Water 6 cH and Water 30 cH It is apparent from the above mean values and standard deviations that none of the large differences reported in the pilot trial were observed in the main experiment. There was also no difference between open and blind measurements. These findings were confirmed by the analysis of variance: there is a moderate model fit which explains 28% of the variance; there is no main effect on the blindness factor (F 1/59 = 0.41; p = 0.52), a main effect on the group factor (F 4/56 = 3.83; p = 0.009) and no significant interaction (F 4/56 = 0.93; p = 0.45). Pairwise post-hoc comparisons between groups (Ryan-Einot-Gabriel-Welsch multiple range test) showed that the main effect in the group factor is due to the difference between N a t t o u r 6 cH and N a t t o u r 30 cH. No difference can be shown between any of the other possible pairs, and especially not Test solution

No. observ.

between water 30 cH and N a t m u r 30 cH. An additional A N O V A which included production lines as additional factor (with only four groups owing to the coding error in the N a t m u r 30 cH group) confirmed that there were no relevant differences between the solutions produced in separate production lines. F-values were small to negligible, none coming close to significance. It could be hypothesised that since the production process took roughly three hours, coding approximately 30 minutes, and measurement followed immediately afterwards, the lack of effect could be due to an ageing of the test solutions. An analysis of covariance was therefore carried out with sequence number as a covariate, thus controlling for time. There was no uniform time trend; values for controls tended to decrease slightly over time, values for N a t m u r bottles tended to increase slightly. No overall time effect was thus confirmed. The results of the pilot trial were therefore not supported by the main experiment. The NTUA team suggested that this negative result may have been due to alterations in protocol from pilot to main trial, in particular the use o f a different brand o f water for injection. The water used in the pilot had given a higher reading in its pure state than the water used in the main experiment. It was therefore agreed to carry out another experiment with a simpler design, omitting the blindness factor and reduced to a one-factorial design with five levels. The same procedures were used as in the first experiment, with two exceptions: Water from the brand used in the pilot ( a q u a i n j e c t a b i l e , Cooper) was used, obtaining this from the only available source which was a stock bottle which had already been opened. Since insufficient new test bottles were available, bottles which had been used in the main experiment were rinsed with tap water and dried in the autoclave. This re-use

Score

Water (non potentised) 10 2.34 Water 6 cH 10 1.86 N a t tour 6 cH 10 1.74 Water 30 cH 10 1.80 N a t m u r 30 cH 10 1.83 TABLE5 Results from additional experiment--blind condition. -

SD

Range

0.34 0.33 0.17 0.22 0.17

1.73-2.81 1.47-2.49 1.56-2.10 1.44-2.10 1.63-2.08

Volume 87, January 1998

of bottles, however, only came to light after the experiment had been completed, and had it been known in advance the experiment would not have been carried out. Ten measurements were made per cell, and the results are given in Table 5. As is apparent from the data, and confirmed by ANOVA, the only significant difference is between reference control (unsuccussed water) and all other test solutions. No other group shows any statistically significant difference. In this experiment, an Analysis of Covariance with time as covariate shows a significant time effect (F 1/49 = 5.43; p = 0.024) - the Hahnemann value reduces consistently over time, indicating that the substances show some ageing effect. Following the discovery that bottles had been re-used in this experiment, and moreover rinsed with tap water which would undoubtedly introduce contaminants, it was agreed to carry out one further experiment. This used a fresh sample water for injection which gave an acceptably high initial reading, and new bottles prepared as for the main experiment. Open measurements were made as soon as each test substance was ready; it soon became obvious that results very similar to those shown in Table 5 were being obtained, with only the unsuccussed control differing significantly, and the experiment was abandoned.

Discussion Although the first additional experiment is not valid from an experimental point of view because of the re-use of the bottles, it nevertheless gives some information. The only obvious effect in this additional experiment is that between unsuccussed control and all other conditions. The water used in the second experiment was placed in some of the few remaining new bottles for calibration, and these readings came close to the value found in the pilot experiment, although the bottle had by then been opened for more than four weeks. However, the readings obtained in the experiment were much lower, perhaps because of contamination. This clearly shows that the EMD does measure something, namely contamination, in this case. The discovery after the experiment that bottles rinsed with tap water had been used suggests that the EMD is very sensitive to ionic impurities in water. The question remains whether it measures

9 anything other than impurities, and whether there was any other reason for the inability of the main experiment to detect any systematic difference between U H S D s and controls. Several parameters were different in the main experiment from the pilot, such as the brand of the injectable water used (Cooper vs. Chropi), the volume of the potentised material (100 ml vs. 20 ml), and the potentisation machine used ( H o m e o k i t D y n a HV1 vs. Dynamat 50C). It is also of note that in the pilot experiments rigorous controls such as randomisation, blinding, and perhaps other factors, were absent. Furthermore, in open calibration readings of the same type of water in 10 different bottles with the same electrode we found quite a variation of measurements (the 10 different readings were: 2.04, 2.74, 3.11, 2.45, 3.33, 2.85, 3.09, 2.98, 2.21, 2.68 with a standard deviation of 0.41), which may point to the fact that already the different bottles introduce quite a large variation. (This is not due to the electrodes, since calibration readings with different electrodes and multiple measurements with one and the same electrodes gave much the same results). The water used for the main experiment came from a new, sealed bottle. Whilst it was a different brand (Chropi as opposed to Cooper), it was nevertheless aqua injectabile. The baseline reading for pure water (Cooper) in the pilot study was 4.9, while in the main experiment this was 2.51, although during calibration pure water was measured several times well over 3.5 H. It could therefore have been that the water used in the main experiment was slightly contaminated with ions, despite it being aqua injectabile. But if this were the sole reason, it is strange to see that in the main experiment the highest Hahnemann v a l u e - representing as it were the measurement with the least impurity, and recalling that in the pilot experiment the highest value observed was for pure, u n s u c c u s s e d w a t e r - - w a s obtained for Nat m u r 6 cH. This solution clearly carries the largest number of ions of the samples, regardless of whether the baseline water is itself slightly contaminated. Therefore, if the water had been the only p r o b l e m , one w o u l d h a v e e x p e c t e d the Hahnemann values for the measurement of pure water to be quite low--as they were in this e x p e r i m e n t . But in c o n t r a s t to the observed data, one would also have expected

10 even lower values, possibly the lowest, for N a t m u r 6 cH, with the other values lying between. If this argument holds true, one would also expect that the potentisation process, which inevitably dissolves ions out of the glass wall of the bottle, would override the a l l e g e d l y finely tuned p r o c e s s of homoeopathic information multiplication. The 30 cH potencies should thus be quite close, especially when the starting substance is already contaminated with ions which would also enter into the amplification effect of succussion. If impurities in the water caused the departure from the pilot results, one would expect water 30 cH and N a t tour 30 cH to be quite close together, lower than water itself and certainly higher than N a t m u r 6 cH, which contains a sufficient concentration of ions to give a substantial effect. The opposite is true: While a q u a i n j e c t a b i l e 30 cH has the same value, 2.51 H (and an even smaller standard deviation) as the reference control, N a t tour 30 cH has the lowest value. It is obvious from our results that the failure to detect an effect is not an issue of power. The experiments were designed to yield a power well above the conventional .90-level, had the effect reported in the pilot study been present. (And although we discovered only after the experiment that the original standard deviations given for the pilot experiment were wrong, power remained above .90 even with the correctly calculated standard deviations.) It is the completely different structure of the data that poses the problem. The pattern of the data clearly does not fit a simple theory of contamination of the baseline water, the completely different structure of the data poses problems, and we do not have clearcut explanations for these phenomena. It was the NTUA team's opinion that the setting of the machine to a Hahnemann value of 4.9 from the outset hampered the experiment, which started off with baseline readings of 2.51 H, due to the different brand of water. It was this team's firm conviction that had the machine been set to measure the quality of Chropi water, the same type of result would have been obtained as in the pilot trial. Whether the procedural variances from the pilot experiment (potentisation machine, volume potentised) have a substantial bearing on the results could only be determined by further studies. The experiment confirms that

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whatever the EMD measures is independent of the awareness or biases of the person conducting the measurements, since there was no difference between readings made under open and blind conditions. The fact that nothing is known about the internal construction of the EMD, due to pending patents, does not invalidate the experiment, since if it measures whatever it is meant to measure in a reliable way, the exact knowledge of the nature of the parameters measured is not at issue at all. A recent series of experiments carried out by one of us 39 used a device similar to the EMD, and additionally measuring impurities by inductively coupled mass spectroscopy, the most sensitive procedure currently available. This showed that effects observed in potencies prepared in glass vanished when potencies were prepared and succussed in polyethylene, and that a considerable amount of ionic impurities were dissolved from the wails of glass bottles. It is therefore unclear to what extent the results so far are measurements of impurities or of structural differences pertaining to the homoeopathic potency. It can be concluded that: 1. The apparently clearcut effects of the pilot experiment could not be reproduced under rigorously controlled conditions. Neither could the initial readings for the reference control be reproduced, and the structure of the data was different from that observed in the pilot. 2. The data give no indication that potentised Natrurn m u r i a t i c u m differs from reference control or potentised water. 3. A difference was observed between N a t m u r 6 cH and N a t m u r 30 cH, and in the additional experiment between unsuccussed solvent and all succussed solutions. This shows that the EMD is a highly sensitive measuring device for dissolved impurities. 4. Whether the results of the pilot study resulted from structural changes in the U H S D or other, random or systematic factors, cannot be determined from this experiment. At present there is no evidence that the readings of the EMD have any s y s t e m a t i c correlation with p u r p o r t e d changes in UHSDs. 5. Future experiments, if deemed feasible, should first of all establish a firm baseline of reference control readings against which

Volume 87, January 1998 to test e x p e r i m e n t a l effects. In order for these effects to be c o n v i n c i n g l y shown, such experiments must use a random and blinded measurement sequence.

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Acknowledgements The following persons gave helpful advice in the process of finalising the protocol: Dr Roland Brandmaier, Biometrisches Zentrum, D-Mtinchen, Dr M. D. Dicke, VSM Geneesmiddelen, NLAlkmaar, Dr John English, GB-Salisbury. Dr Peter Fisher, Royal London Homoeopathic Hospital, GBLondon, Dr Wayne B. Jonas, OAM, NIH, USA-Bethesda, Dr Dick Koster, NL-Leiden, Dr Klaus Linde, D-Mtinchen, Dr Herbert Schwabl, cHZollikon, Dr Joachim Siebenwirth, TU Miinchen, D-Mtinchen, Dr Otto Weingartner, D-Bensheim. We are indebted to the Karl-und-Veronica-Carstens Foundation, Germany, (HW, RL, CW), and to the Blackie Research Foundation (GI) for sponsoring the travel costs. We are especially grateful to George Korres and Arhontoula Hatzilazarou for their personal effort and involvement with the experiment.

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References 1 Delinick AN. A new medical model of the organism and its pathology. The Berlin Journal on Research in Homoeopathy 1991; 1: 243-8. 2 D e l i n i c k AN. A hypothesis on how homeopathic remedies work on the organism. The Berlin Journal on Research in Homoeopathy 1991; 1: 249-53. 3 Bourkas PD, Ouzounoglou N. Biomedical Technology and Specific Hospital Installations. Athens: Simeion Publications 1989. 4 Delinick AN, Bourkas PD, Karagiannopoulos CG. Potency measurements of homoeopathic remedies. Abstracts of the 7th GIRl Meeting, Montpellier, 1993. 5 Delinick AN, Bourkas PD, Karagiannopoulos CG. Experimental evaluation of the results of the potentisation o f homoeopathic dilutions. Abstracts of the 20th Panhellenic Congress of the Medical Society of Athens, Greece, May 1994. 6 Delinick AN. A possible explanation why like cures like in biomagnetism. The International Proceedings of Interdisciplinary Congress in Biomagnetism and Medicine. Kefallonia, Greece, May 1993, 19-24. 7 Antonchenko V, Delinick AN, Ilyin V. Physical properties o f water and how they relate to homeopathic preparations. Proceedings of the

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9th Hellenic Medical Homeopathic Conference, Athens, May 1993, 26--33. Delinick AN. Are pathological symptoms selforganization phenomena? Proceedings of the 48th LIGA Congress of the International Homoeopathic League. Wien: Maudrich, 1993, 111-7. Bourkas PD. The measurement of the homeopathic remedies. European Journal of Classical Homoeopathy 1995; 1: 34--41. Delinick AN. On what primary level of the organism does the homoepathic remedy act upon. European Journal o f Classical Homoeopathy 1995; 1: 42-9. Sukul NC, Ghosh S, Sinha Babu SP. Dosedependent suppression of haloperidol-induced catalepsy by potentised Agaricus muscarius. BrHom J 1996; 85: 141-4. Linde K. Proving the Unbelievable? 7th Blackie Memorial Lecture. British Homoeopathy Research Group. Communications 1996; 24: 54--66. Reilly D, Taylor MA, Beattie NGM, Campbell JH, McSharry C, et al. Is evidence for homoeopathy reproducible? Lancet 1994; 344: 1601-6. Reilly DT, Taylor MA, McSharry C, Aitchinson T. Is homoeopathy a placebo response? Controlled trial of homoeopathic potency with pollen in hayfever as a model. Lancet 1986; 18: 881-6. Reilly DT, Taylor MA. Potent placebo or potency? Br Hom J 1985; 74: 65-75. Jacobs J, Jiminez LM, Gloyd S, Carares FE, Gaitan MP, Crothers. Homoeopathic treatment of acute childhood diarrhoea. Br Horn J 1993; 82: 83-6. Jacobs J, Jimenez LM, Gloyd SS, Gale, Crothers D. Treatment of acute childhood diarrhea with homeopathic medicine: a randomized clinical trial in Nicaragua. Pediatrics 1994; 93: 719-25. Linde K, Jonas WB, Melchart D, Worku F, Wagner H, Eitel F. Critical review and metaanalysis of serial agitated dilutions in e x p e r i m e n t a l t o x i c o l o g y . Human and Experimental Toxicology 1994; 13: 481-92. Youbicier-Simo BJ, Boudard F, Mekaouche M, Bastide M, BayM JD. Effects of embryonic bursectomy and in ovo administration of highly diluted bursin on adrenocorticotropic and immune responses of chickens. International Journal oflmmunotherapy 1993; 9: 169-80. Poitevin B. Mechanism of action of homoeopathic medicines: Recent findings and

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26

27

28

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hypotheses l: Physicochemical mechanisms. Br Horn J 1995; 84: 32-9. Endler PC, Pongratz W, Kastberger. The effect of highly diluted agitated thyroxine on the climbing activity of frogs. Veterinary and Human Toxicology 1994; 36: 56-9. Endler PC, Schulte J. (Eds) Ultra High Dilution. Physiology and Physics. Dordrecht: Kluwer Academic Publishers, 1994. De Lange De Klerk ESM, Blommers J, Kuik DJ, B e z e m e r PD, Feenstra L. Effect of homoeopathic medicines on daily burden of symptoms in children with recurrent upper respiratory tract infections. Br Horn J t994; 309: 1329-32. Walach H, Haag G, Gaus W. KlassischHom6opathische Therapie bei chronischen Kopfschmerzen--Eine randomisierte D o p p e l b l i n d s t u d i e . Abstract Deutscher Schmerzkongreb, Heidelberg. Der Schmerz 1995; 9, Suppl. l: $9. Labrecque M, Audet D, Latulippe CG, Drouin J. Homeopathic treatment of plantar warts. Canadian Medical Association Journal 1992; 146: 1749-53. L6kken P, Straumsheim PA, Tveiten D, S k j e l b r e d P, Borchgrevink. Effect of homoeopathy on pain and other events after acute trauma: placebo controlled trial with bilateral oral surgery. Br Med J 1995; 310: 1439-42. Whitmarsh TE, Coleston DM, Steiner TJ. H o m o e o p a t h i c p r o p h y l a x i s of migraine. Cephalgagia 1993; 13, Suppl. 13: 254. Davenas E, Beauvais F, Amara J, Benveniste J, et al. Human basophile degranulation triggered by very dilute antiserum against IgE. Nature 1988; 333: 816-8. Benveniste J, Davenas E, Ducot B, Cornillet B, Poitevin B, Spira A. L'agitation de solutions hautement dilu6es n'induit pas d'activit6 biologique sp6cifique. Comptes Rendus de l'Academie des Sciences Paris 1991; 312/II: 461-6. Hirst SJ, Hayes NA, Burridgc J, Pearce FL,

Address f o r correspondence Harald Walach, PhD University of Freiburg Rehabilitation Psychology D - 79085 Freiburg Tel. +49-761-203-3055 Fax -3101 email: walach @ psychologie.uni-freiburg.de

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Foreman JC. Human basophil degranulation is not triggered by very dilute antiserum against human IgE. Nature 1993; 366: 525-7. Ovelg6nne JH, Bol A, Hop WCJ, van Wijk R. Mechanical agitation of very dilute antiserum against IgE has no effect on basophil staining properties. Experientia 1992; 48: 504-8. Anagnostatos GS, Vithoulkas G, Garzonis P, Tavouxoglou C. A working hypothesis for homoeopathic microdiluted remedies. The Berlin Journal on Research in Homoeopathy 1991; 1: 141-7. Anagnostatos GS, Pissis P, Viras K. Possible water cluster formation by dilution and succussions. In: Anagnostatos GS, von Oertzen W, editors. Atomic and Nuclear Clusters. Heidelberg, Berlin: Springer, 1995: 215-7. Viras K, Soutzidou M, Pissis P, Anagnostatos GS, Paschali D. Water clusters in methanolwater solutions. 8th International Symposium on Small Particles and Inorganic Clusters ISSPIC 8, Copenhagen, 1-6 July 1996; 3.1 Abstract. Pissis P, Anagnostatos GS, Paschali D, Viras K, Soutzidou M. Multiplication effect of water clusters in methanol-water solutions. 8th International Symposium on Small Particles and Inorganic Clusters ISSPIC 8, Copenhagen, 1-6 July 1996; 3.2 Abstract. Anagnostatos GS, Paschali D, Viras K, Soutzidou M, Pissis P. Detection of water clusters in infinite methanol-water solutions. 8th International S y m p o s i u m on Small Particles and Inorganic Clusters ISSPIC 8, Copenhagen, 1-6 July 1996; 3.2 Abstract. Weing~irtner O. Homo'opathische Potenzen. Wunsch und Wirklichkeit bei der Suche nach der therapeutisch wirksamen Komponente. 1992; Berlin, Heidelberg: Springer. Demangeat JL, D e m a n g e a t D, Gries P, Poitevin B, Constantinesco. Modification des temps de relaxation RMN h 4 MHz des protons du solvant dans les tr~s hautes dilutions salines de silice/lactose. Journal de Medecine Nucleaire et Biophysique 1992; 16: 135-45. Witt C. Versuch der Messung einer nichtstofflichen Information. In: Albrecht H, FriJhwald M, editors. Jahrbuch der Karl und Veronica Carstens-Stiftung. Stuttgart: Hippokrates, 1996: 153-65.