Simple plant models in order to obtain 
a large data samples testing homeopathic treatments

“Lilli Kolisko” research group 

Simple plant models in order to obtain a large data samples testing homeopathic treatments.

Experimental studies testing homeopathic treatments on biological systems are generally very difficult due to the complexity of the system itself and its interaction with the environment. Moreover, as there is no complete theory to explain the action of homeopathic potencies on living matter, it is very hard to deal with the contradictory results sometimes obtained. For this reason in our studies, started in 1990, we sought simple plant models in order to obtain a large data samples for structured statistical analysis and to relate directly any effect to the corresponding treatment. Our research group is multidisciplinary, including biologists, medical doctors, a statistician and a laboratory technician, in order to take account of different aspects of the research.

As a general feature of the in vitro systems, our plant models let overcome main disavantages of clinical trials such as placebo effect, ethical difficulties, consuming of time, low number of replications, and high costs. As peculiar and unique advantages, plant-based bioassays can rely on a very cheap and nearly inexhaustible source of biological material, which can be easily stored and quickly cultured on simple growth media, maintaining a high degree of differentiation in vitro.

The plant models we have studied are:

·         in vitro seed germination and growth (wheat and Arabidopsis thaliana)

·         in vitro pollen germination (apple and kiwifruit)

·         tobacco/tobacco mosaic virus (TMV) interaction

In all our plant models we studied the effects of various decimal potencies of Arsenicum album (As2O3), which was choosen because of its well-known toxic effect on
plant growth until 10-6 dilutions. In some experiments, part of the seeds or of the pollen were previously stressed with a material sublethal dose of As2O3. The purpose of this preliminary poisoning was to establish whether or not there is an amplification of the homeopathic treatment effect.

Wheat model

Experiments on germination and on seedling length were performed. In the first series of experiments, we tested more than 50,000 seeds of Triticum durum L., which
were germinated on sterile sand in Petri dishes in order to record germination values after 4 days. In the second series of experiments, seeds (900 in total) were germinated into plastic/paper envelops in order to periodically evaluate root and stem length after 4 to 7 days of growth.

A certain number of decimal potencies (between 23x and 45x) of As2O3 were used to treat stressed and non-stressed seeds by blind protocol. Four classes of treatments were performed:

-  Merck H2O (control)

- potentised H2O

- highly diluted As2O3

 - highly diluted and potentised As2O3 

By means of different statistical analyses, significant effects of homeopathic treatment on either wheat germination or shoot/root length were repeatedly evidenced. In particular, some As2O3 potencies (40x, 42x, 45x) markedly increased germination in both stressed and non-stressed seeds, the effects being highly significant against control group. By contrast, other As2O3 potencies (27x, 35x) repeatedly induced significant inhibitory effects. Arsenic 30x showed an inhibitory effect in one experiment and a stimulatory effect in another one. Interestingly, the potentisation of water (30x, 42x, 45x)  induced highly significant positive effects on germination, especially in the case of stressed seeds, whereas highly diluted As2O3 did not show any effect at all. When we compared H2O 45x and As2O3 45x, both highly significant vs. control, the difference was generally highly significant in favour of the arsenic. Experiments on wheat plantlets confirmed the stimulating effect of As2O3  45x. Stem length, measured after 4 to 7 day from germination of stressed seeds, resulted in fact significantly enhanced by the homeopathic treatment against control group in both the experiments performed. Moreover, by analyzing the average growth on day 7 in relation to different treatments with potentised water,  diluted arsenic, and potentised arsenic vs. control, an oscillatory trend was observed.

Recently, we performed experiments to evaluate the influence of temperature and ageing on As2O3 45x and H2O 45x effectiveness in stimulating germination of stressed wheat seeds. We have collected 48 sets of data (standard trials), corresponding to 1584 seeds, for each treatment or control group. We have then compared each treatment with the control group corresponding to the same temperature (20°C, 40°C, 70°C and 100°C, respectively). We detected a highly significant stimulating effect (p-value < 0.1%) of As2O3 45x, at 20°C, 40°C and 70°C, and a slightly significant stimulating effect (p-value < 0.1%) at 100°C, which seems to be the “critical point”. When considering potentised water (H2O 45x), we detected a significant stimulating effect only at 20°C, but less significant than As2O3 at the same temperature. We also observed that the effects are more evident in the last experiments when excluding the data taken from the first 12 or 24 experiments out of 48, and all the comparisons considered, with As2O3 45x and with H2O 45x, become significant. These data show that temperature has a greater influence on potentised water than on potentised arsenic, and that ageing significantly increases the effectiveness of homepathic treatments. 

Arabidopsis thaliana model     

            The plant model system of Arabidopsis thaliana seedlings is the most used in plant physiology and plant molecular biology, due to the unique features of this species such as small genome, small size, short life cycle and easy handling. We propose this plant as a further model for research in homeopathy field.

The first part of the present work consisted in the optimisation of the experimental protocol in order to obtain reliable data. In fact, experiments were carried out to define the minimum culture medium (that is containing as few chemical compounds as possible which could interfere with the various treatments) able to allow a satisfactory percentage of seed germination. Since the seeds had to be pre-treated (stressed) with ponderal amounts of the same principle (Arsenicum album), we showed that As2O3 induced a 31% inhibition of germination but did not affect seedling development. Under these experimental conditions, the model system was shown to be statistically reproducible, and thus the various treatments were performed.

After the preliminary stress-treatment with As2O3, seeds (10 per Petri dish) were soaked in different media containing Phytagar and a homeopathic dilution or Merck water (stressed controls, Cs). A non-stressed control (C) was also prepared in which the preliminary treatment simply consisted in water. The treatments were:

  1. Merck H2O, stressed and non-stressed controls

  2. potentised H2O (23x, 30x, 45x)

  3. highly diluted As2O3 (10-23, 10-30, 10-45)

  4. potentised As2O3 (23x, 30x, 45x)

The following experimental parameters were evaluated:

a)      percentage of germinated seeds per Petri dish at 4, 5, 6, 7, 8 days;

b)      size of 7 day-old cotyledons.

All the experiments were performed “blind” on a total of 2070 seeds. As far as the percentage of seed germination is concerned, statistical analysis indicated a significant inhibitory effect by As2O3 30x compared with stressed-controls (Cs). This effect was present throughout the germination period but exhibited a significantly decreasing trend from day 5 to day 8. Regarding cotyledon size, the inhibitory effect of As2O3 30x was confirmed; this treatment in fact caused a significant reduction in the development of cotyledons compared with Cs. The same effect was observed with water 30x but not with As2O3 10-30. This confirms previous reports indicating a greater influence of the dynamisation compared with the dilution process.

The As2O3 45x treatment was also highly significant, compared with Cs, in inhibiting the growth of cotyledons; on the contrary, in the wheat model system the same dilution always exerted a stimulating effect on seed germination and growth.

Pollen model

The pollen model presents some peculiar features which make it well suited to test homeopathic preparations: easy to obtain, storage at –20°C for several years, test prerformed in a short lapse of time, very high number (several thousands) of individuals tested in each trial, wide range of data for statistical analysis. We are currently using pollen from apple and kiwifruit, performing a liquid mass culture into Petri dishes and recording percent germination (with a semi-automatized procedure) after 3 hour incubation. First results showed a significant stimulatory effect of some As2O3 potencies on germination of pollen preliminarily stressed with a material dose of As2O3.

Tobacco/TMV model

An important difference between this model and others described up to now is that the stress imposed is a biotic one, that is inoculation with the tobacco mosaic virus (TMV). Tobacco plants with the N resistance gene exhibit a hypersensitive response (HR) to TMV that is considered one of the important mechanisms leading to resistance: instead of spreading systemically, the virus is limited to the vicinity of the inoculated cells, many of which undergo a controlled process of cell death (PCD, programmed cell death), resulting in the development of macroscopically visible necrotic lesions: a lower number of hypersensitive lesions involves a faster and more effective defence response.

Nicotiana tabacum cv. Samsun NN plants were used. After TMV inoculation disks were cut from leaves and left floating in Petri dishes containing the different treatments. The working variable was the number of local hypersensitive lesions per leaf disk, counted three days after virus inoculation. As2O3 treatments 5x and 45x induced a significant decrease in the number of hypersensitive lesions vs. controls, whereas 5C and 45C did not show significant effects. These findings seem to agree with the classical point of view of homeopathy, both hahnemannianan and anthroposophical, according to which the centesimal potencies are more related to the psychic world than the decimal ones, so we suppose centesimal potencies could fit better with animal models.

Moreover, since our results showed repeatable effects of As2O3 potencies on hypersensitive reaction, we carried out poisoning tests on healthy tobacco plants with ponderal As2O3 (by analogy with “remedy proving”). The detected symptoms are quite similar, at a macroscopic level, to hypersensitive lesions due to TMV inoculation, whereas poisoning with other inorganic compounds induce very different responses. These preliminary studies, which will be further investigated by microscopic analyses, seem to confirm the law of similarity.

 

Conclusions

·     Plant model systems used in our laboratories resulted to be sensitive to homoeopathic treatments.

·     The effect of treatments depended on the model, and the dose-response curve showed an oscillatory trend.

·     We succeded in obtaining:

-          low internal variability of our systems

-          good reproducibility of the results

-           a large data base necessary to perform a powerful statistical analysis

-           quickness in performing the trials (4-8 days for seeds; 3 h for pollen; 3 days for leaf disks)

Another aspect which seems particularly interesting came out considering for wheat and tobacco/TMV models the variability parameter: Certain potencies of As2O3 showed a surprisingly constant effect on wheat germination and tobacco hypersensitive response in comparison with control or water potencies. This result can open new perspectives in the interpretation of homeopathic phenomena.

Under the effect of As2O3 potencies, in particular As2O3 D45, both wheat and tobacco/TMV models showed a decreasing of variability of the system. This surprising result seems to be due to a “dilution” of the effect on the “whole” system rather than an effect on the single elements under analysis. If this result will be confirmed, it could be the basis for a “theory of living systems”, more specific and adequate than a theory based on quantum-mechanic models.

 

References

 

1)      Betti L., M. Brizzi, D. Nani, M. Peruzzi, 1994. A pilot statistical study with homoeopathic potencies of Arsenicum album in wheat germination as a simple model. Br. Hom. J. , 83, 195-201.

 

2)      Betti L., M. Brizzi, D. Nani, M. Peruzzi, 1997. Effect of high dilutions of Arsenicum album on wheat seedlings from seed poisoned with the same substance. Br. Hom. J. , 86, 86-89.

 

3)      Nani D., L Betti, M. Brizzi, M. Peruzzi, 1997. High dilution effect in an Arsenicum album/ wheat model: experimental results and hints for basic research. In: Der Merkurstab, Beitrage zu einer Erweiterung der Heilkunst. Tagungsband Wissenschaftlicher Kongreb, Goetheanum, Dornach, 13-15 Juni 1997, pp 46.

 

4)      Brizzi M., L. Betti, D. Nani, M. Peruzzi, 1997. An overall analysis of a series of experiments based on high dilutions in an Arsenicum album/wheat model. In: Omeomed’97, Urbino (Italy), 25-28 Sett. 1997, Abstract Book, pp. 12-13.

 

5)      Brizzi M., L. Betti, D. Nani, M. Peruzzi, 1998. A statistical overview of some recent studies regarding the effects of Arsenicum album high dilutions on wheat germination. In: Unconventional medicine at the beginning of the third millennium, Pavia (Italy), 4-6 Giugno 1998, Abstract Book, pp.136.

 

6)      Betti L, Brizzi M, Calzoni G L, Speranza A, Scaramagli S, Torrigiani P, Vanti M, Viglino D, Cuffiani M, Nani D, Peruzzi M, 1999. Il problema dell’efficacia dell’omeopatia: modelli vegetali complementari agli studi clinici. Cahiers de Bioterapie, 2: 17-26.

 

7)      Brizzi M., L. Betti, 1999. Using statistics for evaluating the effectiveness of homeopathy: analysis of a large collection of data from simple plant models. Atti III Congresso Nazionale della Società Italiana di Biometria, Roma 7-9 luglio 1999, pp. 74-76.

 

8)      Brizzi M., D. Nani, M. Peruzzi, Betti L.,  2000. Statistical analysis of the effect of high dilutions of arsenic in a large dataset from a wheat germination model. Br. Hom. J. , 89: 63-67.

 

9)      Betti L., R. Chattat, A. Brusa, F. Borghini, 2000. L’omeopatia in farmacia. Risposte teorico-sperimentali ad un campione statistico di informazione professionale. Atti Omeopatia italiana a convegno, Milano 18-20 Febbraio 2000, pp. 12-14.

 

10)  Borghini F., L. Betti et al., 2000.  L’omeopatia in farmacia. Presupposti metodologici, teorici e sperimentali alla pratica professionale. Atti Omeopatia italiana a convegno, Milano 18-20 Febbraio 2000, pp. 19-30.

 

 

11)  Betti L, Biondi S, Brizzi M, Calzoni G L, Lazzarato L, Nani D, Peruzzi M, Scaramagli S, Speranza A, Torrigiani P, Trebbi G, 2000. Modelli sperimentali di studio degli effetti biologici delle diluizioni omeopatiche. Atti del convegno: Il medicinale omeopatico-Tra tradizione e realtà farmacoterapica. Milano, mercoledì 27 settembre 2000, 24-48.

 

 

12)  Betti L., S. Biondi, M. Brizzi, G.L. Calzoni, L. Lazzarato, D. Nani, M. Peruzzi, S. Scaramagli, A. Speranza, P. Torrigiani, G. Trebbi, 2000. Modelli vegetali per studiare le basi scientifiche dell’omeopatia. Atti Medicina alternativa e medicina scientifica, Padova 28 Ottobre 2000, in press

 

 

13)  Betti L., S. Biondi, M. Brizzi, G.L. Calzoni, L. Lazzarato, D. Nani, M. Peruzzi, S. Scaramagli, A. Speranza, P. Torrigiani, G. Trebbi, 2000. Plant model systems to study the biological effects of homeopathic dilutions. Proceedings General Meeting European Commitee Homeopathy, Bruxelles 10-12 November 2000, pp. 10-21.

 

 

14)  Betti L., S. Biondi, M. Brizzi, G.L. Calzoni, L. Lazzarato, D. Nani, M. Peruzzi, S. Scaramagli, A. Speranza, P. Torrigiani, G. Trebbi, 2000. Ricerca di base in omeopatia: studio degli effetti biologici di soluzioni estremamente diluite e dinamizzate su modelli vegetali. Atti Medicine non convenzionali. Evidenze clinico-sperimentali, aspetti legislativi e diffusione in Italia, Bologna 2 Dicembre 2000, in press

 

15)  Betti L., S. Biondi, M. Brizzi, G. L. Calzoni, A. Canova, L. Lazzarato, D. Nani, M. Peruzzi, S. Scaramagli, P. Torrigiani, G. Trebbi, 2001. Plant model systems to study the biological effects of ultra high dilutions. International scientific conference on Complementary, alternative and integrative medicine research, San Francisco 17-19 May 2001, pubbl. in Alternative Therapies in Health and Medicine, 7(3): S5

 

16)  Betti L., M. Brizzi, G. L. Calzoni, L. Lazzarato, G. Trebbi, D. Nani, M. Peruzzi, 2001. Effetti di preparati omeopatici su modelli vegetali. Atti  convegno: Agricoltura biodinamica: perché. Sabaudia 29 Novembre-1 Dicembre 2001, in press

 

17)  Betti L., Brizzi M., Calzoni G.L., Lazzarato L., Nani D., Peruzzi M., 2001. Testing “Similarity Law Like” And Quantitative Effects Of Ultra High Dilutions On Plant Model Systems. General Meeting European Commitee Homeopathy, Parigi 10 December 2001

 

 

18)  Brizzi M., C. Biondi, L. Lazzarato, L. Betti, 2002. Analisi esplorativa dell’effetto di soluzioni ultramolecolari di triossido di arsenico sullo sviluppo vegetativo in vitro di plantule di grano. Rivista statistica, in press.

 

 

19)  Betti L., Nani D., Brizzi M., Lazzarato L., Peruzzi M., Trebbi G., Calzoni G.L., 2002. An analysis of the “similarity law like” and quantitative effects of ultra high dilutions on plant model systems. International scientific conference on Complementary, alternative and integrative medicine research, Boston 12-14 April 2002

 

20)  Betti L., Calzoni G.L., Brizzi M., Lazzarato L., Trebbi G., Nani D., 2002. Effetti biologici di diluizioni-dinamizzazioni di As2O3 su diversi modelli vegetali. Atti convegno: Ricerca e sperimentazione in agricoltura biologica. Cesena, 9 maggio 2002, pp. 11-13.

 

 

Research Group

 

Betti Lucietta, Lazzarato Lisa, Trebbi Grazia

Dipartimento di Scienze e Tecnologie Agroambientali, Università di Bologna

 

Brizzi Maurizio

Dipartimento di Scienze Statistiche “Paolo Fortunati”, Università di Bologna

         

Calzoni Gian Lorenzo, Scaramagli Sonia, Biondi Stefania, Torrigiani Patrizia

Dipartimento di Biologia Evoluzionistica Sperimentale, Università di Bologna

 

Nani Daniele (Medical Doctor), Peruzzi Maurizio (Laboratory technician)

Gruppo Medico Antroposofico Italiano, Milano
Borghini Francesco (Medical Doctor)

Tutor For. Com., Consorzio interuniversitario, Roma

        per maggiori informazioni scrivere a: 
     info@omeopatia-kolisko.com