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Biological Agriculture and Horticulture, 1984, Vol. 2, pp. I-SO 0144-8765/84 $5

1984 A B Academic Publishers Printed in Great Britain

Homoeopathy and its Potential Role in Agriculture- A Critical Review

A. M. Scofield

Department of Biochemistry, Physiology and Soil Science, Wye College {University of London), Wye, Ashford, Kent, TN25 5AH, England

ABSTRACT

Homoeopathy is a therapeutic system in which diseases are treated with substances, usually in extreme dilutions, which, when given to healthy individuals, produce the same symptoms as the disease being treated. Homoeopathy is an holistic method of treatment in that the whole organism is treated in an attempt to raise its level of resistance and stimulate its ability to throw off disease. In this respect it is well suited to the holistic concepts of biological agriculture. Because of the extreme dilution of the remedies they are relatively cheap, have little or no ecological side-effects and, on the whole, are harmless. This review introduces the basic principles of homoeopathy, discusses the experimental evidence for the efficacy of homoeopathic treatment of disease and considers its potential role in agriculture. The conclusion is that despite a great deal of experimental and clinical work there is only a little evidence to suggest that homoeopathy is effective. This is because of bad design, execution, reporting or failure to repeat experimental work and not necessarily because of the inefficacy of the system which has yet to be properly tested on a large enough scale. It is suggested that there is sufficient evidence to warrant the execution of well-designed, carefully-controlled experiments, particularly in naturally diseased organisms, to investigate the efficacy of homoeopathy further. Some of the experimental work already done suggests that homoeopathy may be of value in the treatment and prevention of diseases in crops as well as domestic animals.

CONTENTS

Introduction

a.Homoeopathy as a therapeutic method

b.Homoeopathic medicines

Clinical trials

a.Clinical trials with humans

b.Clinical trials with domestic animals

Introduction to experimental work in homoeopathy

Experimental work with plants

a. Normal plants

b. Plant diseases

c. Experimental poisoning

Laboratory trials with animals

a. Normal animals

b. Infections

c. Oedema

d. Erythema

e. Gastric ulceration

f. Diabetes

g. Wound healing

h. Fertility

i. Cancer

j. Physical performances

k. Behaviour

1. Poisoning

Studies with isolated organs and in vitro studies

a. Isolated organs

b. Enzyme activity

c. In vitro cell culture

d. Studies with bacteria

Homoeopathic drug structure and mechanism of action

a. Drug structure

b. Mechanism of remedy action

Discussion

The potential of homoeopathy in agriculture

Conclusions

INTRODUCTION

The control of disease in both man and animals is at present very largely attempted by means of chemotherapy, the use of specific chemical agents or drugs which have been shown to positively influence the course of particular diseases. In the same way the control of plant disease in modern agriculture is attained by the application of specific chemicals in the form of fungicides, insecticides, etc., with the specific intention of destroying the infective organisms. In cases such as these chemotherapy is directed at alleviating the symptoms of the disease or at destroying the bacterial or fungal infections. However, the use of powerful chemical agents may result in negative rather than positive effects; for example, a significant proportion of human disease results as the side effects of drug treatment and is known as iatrogenic (physician-induced) disease. Similar effects may be found in agriculture (Hodges & Scofield, 1983a,b). Alternatives to this allopathic approach to disease treatment have been sought in the system of homoeopathy, a method which attempts to treat the whole organism, enabling it to throw off the disease rather than merely attempting to relieve the specific disease symptoms. Development of the homoeopathic system in agriculture would have considerable ecological advantages since many of the pesticides at present in use are wide-spectrum biocides with widespread ecological effects.

The recommendations for international standards for biological agriculture made by I.F.O.A.M. (International Federation of Organic Agriculture Movements), as well as many national standards, allow the use of homoeopathy in the control of disease. However, there is much ignorance as to the nature of homoeopathy and it is the purpose of this paper to review the subject, with particular emphasis on the evidence for the efficacy of homoeopathic remedies and the potential of this method for disease control in agriculture.

a. Homoeopathy as a therapeutic method

Homoeopathy is a therapeutic method that has as its fundamental tenet 'let likes be cured by likes' (similia similibus curentur). The principle of curing illness by agents that produce similar effects in the healthy body was stated as early as 300-400 B.C. in the Corpus Hippocraticum, the work of Hippocrates and his school. Two Hippocratic principles of cure were recognised. The antagonistic way was said to remove the pains i.e. the symptoms of disease while the cure by likeness was said to restore a diseased individual into à healthy one (Leeser, 1938). These principles are similar to today's practice of allopathic (orthodox) and homoeopathic medicine respectively.

Since the days of Hippocrates the principle of cure by likeness appeared sporadically in medicine. Samuel Hahnemann (1755- 1843), however, was the first person to put therapy on an experimental basis and the observations he made on himself and others led him to enunciate 'similia similibus curentur' and to develop this idea as a new system of medicine for which he coined the name 'homoeopathy'. Hahnemann was born in Meissen in 1755. He was an eminent scholar, was self-taught in chemistry, and spoke several languages. By means of teaching and translating scientific articles he supported himself until qualifying as a doctor of medicine in 1779. He quickly became one of the most distinguished physicians in Germany but eventually became disillusioned at the many faults in medicine as it was then practiced. These included purgings, bleedings and blunderbuss therapies which he felt did more harm than good. This disillusionment led to his giving up the active practice of medicine and he confined himself to translating scientific literature.

While translating Cullen's Materia Medica into German he found himself disagreeing with Cullen's explanation of the action of Cinchona bark (quinine) in the treatment of malaria and he took some himself to observe its action. While taking the bark he found that he developed the symptoms of 'intermittent fever'. The symptoms disappeared when he stopped taking it. So here then was a remedy that was effective in treating a disease which, when given to a healthy person, produced symptoms of the same disease. Hahnemann concluded that it was possible that drugs that induce the symptoms of a disease may be capable also of curing them. So began Hahnemann's life work.

He began by testing the effects of a large number of substances on the human body, using himself and friends. These tests were known as provings. The symptoms produced by 27 drugs were published in 1805. More extensive provings were published subsequently in his Materia Medica Pura. He returned to medical practice and tested the drugs that he was proving on the healthy, on the sick. His thoughts and ideas on the new therapeutic system were published as The Organon of Medicine in 1810 and developed in later editions.

During his experiments Hahnemann observed that after dilution and shaking, to mix the solution thoroughly, the medicine seemed to have a greater effect. He believed that shaking activated the healing principle of the medicine. Hahnemann called the diluted and shaken (succussed) substance a potency.

Not all homoeopaths accept potentization as fundamental to homoeopathy (Guttentag, 1940, 1966) and, in fact, as early as 1836 the national homoeopathic organization of Germany unanimously adopted the tenet that 'the determination as to whether or not a remedy be homoeopathic is derived neither from its amount nor from its form, but solely from its relation to the disease' (Guttentag, 1966).

As would be expected from their different philosophical approaches the criteria used for remedy selection are different for the allopathic and homoeopathic schools of medicine. In homoeopathy the symptoms of the patient are crucial for remedy selection. Homoeopaths look upon symptoms as positive or beneficial phenomena in that they indicate the pathway taken by the organism in an attempt to regain health. By providing remedies, which in provings on healthy subjects produce these symptoms, the homoeopath hopes to aid the body's natural healing processes.

As well as using symptoms the physician employs personal details such as past medical history and, particularly, personality characteristics, to build up as complete a picture of the patient as possible. These details are then matched by one of the drug-pictures of the remedies and the one which matches most closely, known as the similimum, is prescribed. Because the patient is treated, and not the disease, different patients suffering from the same disease may require different remedies.

Many homoeopaths believe that, unlike conventional medicine which lacks any system of coherent principles, homoeopathy possesses a precise set of principles governing diagnosis and treatment (Courter, 1981). Having said this, however, an examination of more advanced texts on homoeopathic prescribing (e.g. Roberts, 1942; Vithoulkas, 1980) reveals that application of these principles is far from simple and open to a great deal of personal interpretation. There is so much variation amongst practitioners in the application of homoeopathy, largely because of its piecemeal evolution, that Campbell (1978) believes that there can be no comprehensive definition of homoeopathy today. He believes that the only valid definition of homoeopathy is "what is practiced by those who call themselves homoeopathic physicians".

The proving of drugs has continued since Hahnemann's day and the results are included in the numerous Materia Medical The symptom-complex characteristics of the remedies form the body of the modern materia medica and they have been derived from a) provings of tinctures of plants, salts, metals, synthetic drugs, animal venoms and extracts etc., b) the toxicology of the substances, c) symptoms which have been helped or cured by a particular remedy in a reasonable number of patients. The effectiveness of certain remedies has also been associated with certain characteristics of the patients (Boyd, 1981).

Provings have traditionally been made at material, although non-toxic doses, and also at relatively high homoeopathic potencies e.g. 30c 10-60 dilution) (see Table I for nomenclature of potencies). However, recent attempts at the Royal London Homoeopathic Hospital to prove remedies at the 30th potency have met with little success and it is believed that only a small category of healthy people are sufficiently sensitive to respond to higher potencies i.e. the greatest dilutions (Scott & McCourt, 1982). The work of Moss et al. (1982) involving in vitro studies of` the effect of remedies on the behaviour of human and guinea pig white blood cells tend to support this conclusion. Thus, although most people may be assumed to be unaffected by taking the wrong remedy, there may be a small minority who will be affected, albeit only transitorily, and it may not be true to say, as many do, that homoeopathic remedies are harmless if the wrong one is taken (Scott & McCourt, 1982).

Since its inception homoeopathy has attracted opposition despite its frequent superiority over conventional medicine in the cholera and typhus epidemics of the last century. In the 1854 cholera epidemic in London the mortality rate at the homoeopathic Golden Square Hospital, in one of the worst affected areas, was 16% compared to the general rate of over 50%. The results were suppressed by John Paris, President of the Royal College of Physicians, and following complaints, a separate Parliamentary Paper was issued repairing the omission.

Even now homoeopathy is opposed by much of the medical establishment in Britain despite the fact that this, and other countries, officially recognize homoeopathy and give it state support. In the veterinary field interest appears to be increasing. A recent symposium on veterinary homoeopathy organized by the British Homoeopathic Association at which over 300 veterinary surgeons attended, was oversubscribed (Anon., 1982) and the British Association for Homoeopathic Veterinary Surgeons was formed in 1981.

Homoeopathy receives more respect, and is practiced more widely, in continental Europe, particularly France, Germany and Switzerland, despite legal problems incurred under Napoleonic Law. In India there are some 200,000 registered Homoeopathic practitioners and 104 Homoeopathic colleges (Fulder & Monro,1981) and homoeopathy is widely practiced despite incessant criticism from the allopathic establishment (Bhardwaj, 1980). The law regarding the practice of homoeopathy and other forms of complementary medicine, and its international aspects, are reviewed by Fulder & Monro (1981).

Despite official opposition and ridicule, and despite the lack of a scientific explanation for its action, homoeopathy has persisted for the last 150 years and, if the waiting lists of Homoeopathic doctors is any guide, flourishing. The reasons for this are not dissimilar to those that made Hahnemann first give up practicing medicine. Most users of Homoeopathic medicines were found by Avina & Schneidermann (1978) to have previously used conventional medicine but to have found it unsatisfactory for a variety of reasons. These included instances of negative side effects of medicine, lack of nutritional or preventive medical advice and lack of health education. They also disliked the tendency of many conventional doctors to look for psychological explanations for disease. Homoeopaths rarely make such psychiatric diagnoses. Patients also preferred homoeopaths because they tended to spend more time with them than conventional doctors.

b. Homoeopathic medicines

The remedies are derived from the animal, vegetable and mineral kingdoms. They include herbs, botanical medicines, drugs, extracts of animals and minerals. Extracts of diseased tissues are also used (nosodes) e.g. Carcinosin from cancer tissue, as well as substances or organisms responsible for disease (isotherapy or isopathy). Where a disease is suspected of being caused by a deficiency then it may be treated or prevented by prescribing the relevant substance in a potentized form e.g. Calcarea phosphorica and Magnesium phosphoricum can be given prophylactically to prevent milk fever in cows (MacLeod,1981). A treatment such as this is a departure from the traditional definition of homoeopathy. Other variations of the basic Homoeopathic technique are used in continental Europe and include the administration of potencies of organs or cells to treat diseases of the same organs (organotherapy, cytoplasmic therapy).

The concentrated medicines are in the form of liquid mother tinctures prepared by the maceration and extraction of suitable source materials in suitable alcohol/water mixtures. Soluble salts are usually dissolved initially on a wt:wt basis. Insoluble substances are initially ground in a mortar with lactose for the first few potencies before finally making potencies in an alcohol/water mixture. This process of grinding is known as trituration (See Gengoux & Thi, 1978 for details of remedy preparation).

Homoeopathic potencies are prepared by successive dilutions of the mother tincture in a vehicle of alcohol and water (usually 87% ethanol) or sometimes water alone. There are two usual methods of dilution: a decimal (x or D) and centesimal © or cH). In the former the substance is diluted one part by volume in nine of solvent at each stage and in the latter one part in ninety nine. After each dilution the solution is shaken vigorously with impact (succession). Hahnemann believed that succussion activated the remedy and Boyd (1946) emphasized the importance of this activity when he claimed to have shown that at a concentration of cat 5.131 x 10-7 mg.ml-1 HgCI2 prepared by succession produced a statistically significant stimulation of diastase activity whereas microdoses prepared without succession did not. Jones & Jenkins (1981) also claim that the loss of activity of homoeopathic remedies with age may be reversed by resuccussion of the remedy. The nomenclature of homoeopathic dilutions is shown in Table 1. Low potencies are those which have been diluted least.

The manner in which homoeopathic remedies are prescribed varies greatly between doctors and different fields of thought. Normally a limited range of potencies is used, e.g. Ix, 3x, 6x, 12x, 6c, 12c, 30c, 200c, IM, 10M and CM (Scott & McCourt, 1982). Remedies are usually prescribed one at a time and allowed to act before another prescription. Some doctors, particularly on the continent, prescribe low potency cocktails i.e. a mixture of drugs diluted to a relatively small extent. Although the remedies can be prescribed in liquid form they are normally given in the form of sugar granules to which the liquid remedy has been added.

As well as directly treating disease conditions homoeopathic remedies can be used prophylactically to prevent, or reduce, the severity of` a disease. Hahnemann successfully used Belladonna as a prophylactic in a scarlet fever epidemic ( Boyd, 1981).

CLINICAL TRIALS

The homoeopathic literature contains many reports of` the successful use of remedies in the treatment of disease but, whereas these are no doubt of great value to the practicing homoeopath, the majority of reports are not of controlled trials and are of little value in making a scientific assessment of the efficacy of homoeopathy. A few controlled clinical trials have been made but the results have been equivocal, in some cases partly because of poor experimental design.

a. Clinical trials with humans

The best controlled early clinical trial was that conducted during the second world war in London and Glasgow on the prevention and treatment of mustard gas burns (Paterson, 1944). The trials were conducted blind. In the Glasgow trials an isopathic preparation (Mustard gas 30c) was used whilst in London a selection of drugs was used. These were given to volunteers either before or after administration of mustard gas to the skin. The results were submitted to analysis. The conclusions based on the larger London trial were that Rhus toxicodendron 30c, given as a treatment, caused a significant shift in the frequency of deep to medium skin lesions while leaving the incidence of

superficial lesions unaltered and Mustard gas 30c, given prophylactically, resulted in a significant shift in the frequency of both deep and medium lesions, thereby increasing the incidence of superficial lesions. The results of the much smaller Glasgow trial were in accord with the findings of the London trial.

A re-analysis of the data using modern statistical methods by Owen & Ives (1982) showed that the Glasgow experiments did indeed give clear cut results in favour of mustard gas isopathy over placebos whilst in the London trials significant results were obtained in favour of mustard gas potencies, Rhus tax. and Kali bichromicum. All other treatments did not differ significantly from controls.

More recent years have seen the publication of some of the most satisfactory clinical trials (Gibson et al., 1978, 1980a,b). These were double-blind therapeutic trials to test the value of homoeopathic remedies in the treatment of rheumatoid arthritis. A wide range of remedies was used and the relevant ones selected for each individual patient. The first trial, which lasted one year, compared 41 patients treated with high doses of salicylate with 54 patients treated with homoeopathy, who received individually prescribed remedies, and 100 patients who received a placebo (Gibson et al., 1978). They showed that patients who received homoeopathy responded statistically better than those that received salicylates and they suffered no side effects. Moreover, 42% of the patients on homoeopathic therapy were able to discontinue all orthodox therapy during the year. The fact that these patients were allowed to continue their previous orthodox anti-inflammatory therapy whereas the patients who received salicylates had to discontinue their previous anti-inflammatory drugs, and the fact that patients who received homoeopathic treatment were seen by different doctors from those being given salicylate led to criticism of the trial (Huston, 1979).

These criticisms lead to a more rigidly designed double-blind trial (Gibson et al., 1980a,b). In this trial, which lasted for three months, the homoeopathic remedies, of which there were many and which were tailored to the individual patients' symptoms, or placebo, supplemented the patients' conventional therapy of non-steroidal anti-inflammatory drugs. There was a significant improvement in subjective pain, articular index, stiffness and grip strength in those patients receiving homoeopathic remedies whereas there was no significant change in the patients who received placebo. It appeared that homoeopathy was a safer and probably no less effective alternative to present-day second-line drugs in the treatment of rheumatoid arthritis.

A more recent trial (Shipley et al., 1983) used a double-blind, crossover method to compare Rhus tax. 6x with fenoprofen in the treatment of osteoarthritis of the hip and knee. Fenoprofen was shown to have beneficial analgesic and anti-inflammatory effects which differed significantly from those of placebo, whereas Rhus lox. and placebo did not differ significantly.

This trial has been criticised for several reasons. a) the trial only lasted two weeks on each of` the three treatments. Chronic cases such as osteoarthritis need a long time to respond to homoeopathic remedies. Acute conditions would respond more rapidly (Ghosh, 1983; Kennedy, 1983).

b) Only Rhus fox. was prescribed on a very limited symptom picture. The patient's total symptom picture should have been taken into account and a suitable remedy prescribed. In chronic diseases constitutional remedies are invariably indicated (Ghosh, 1983). A test of homoeopathy as a system, rather than a specific remedy, should be done as in the case of Gibson et al. (1978, 1980a,b).

This latter criticism also applies to some other recent clinical trials. Savage & Roe (1977, 1978) conducted double-blind trials using Arnica 30c or M to assess its benefits in acute stroke illness. Both trials failed to demonstrate any significant benefit of the homoeopathic treatment. However' of those patients that presented classical Arnica symptoms (3/40 in the 1977 trial) two made good progress under the treatment. In the 1978 trail only one patient had typical Arnica symptoms and he received placebo!

Also using a double-blind technique Gassinger et al (1981) tested Eupatorium perfoliatum 2x and acetylsalicylic acid in patients suffering from the common cold. Neither subjective complaints, body temperature or laboratory findings showed any significant difference between groups which was taken as evidence that both drugs were equally effective. Unfortunately no placebo group was included in the design

The effect of Arnica on the bruising response of volunteers was tested by Campbell (1976) using blind techniques. Arnica 30c was found to have little effect in reducing bruising whereas Arnica l0M was highly effective. In the latter case the trial was single-blind, although those taking part in it were told that it was double-blind. The patients first all received placebo for the first bruising. For a second bruise, produced later, they were all given Arnica 10M.

The first experiment, which used Arnica 30c, also involved two consecutive trials on separate bruises but in this type of cross-over trial, where in half the volunteers the placebo followed the remedy, it is Impossible to know whether, when the remedy is given first, it is having a carry-over effect on the second bruise.

It is more difficult to assess the significance of trials which have not been conducted double-blind because of the possibility of suggestion or unconscious bias at some stage of the trial. Although the nurses and patients were unaware of the treatment given in a trial of Staphysagria in post-coital cystitis of women the trial was not double-blind with regard to the organizing physician (Ustianowski, 1974). The results showed a definite superiority of the homoeopathic remedy over the placebo and the trial should be repeated under carefully controlled double-blind conditions.

Many of` the clinical reports in the literature are of` individual cases or series of cases and usually do not contain any controls. Even some experimental trials do not contain proper controls. For example, Paterson & Boyd (1941) showed that a homoeopathic potency of alum-precipitated diphtheria toxoid (30c) or Diphtherinum 201c could apparently increase the proportion of` negative Schick tests following an original positive reaction to a greater extent than the normal Schick fluctations. Not only were there no proper controls and no statistical analysis but the percentage of` cases immunized was not sufficient for the authors to justify substitution of` the normal immunizing infection for diphtheria (alum-precipitated toxoid) by homoeopathic treatment where lasting immunity of` the accepted type was desired. Despite these criticisms such experiments are sometimes used as evidence to support the Pact that homoeopathy works (c.g. Stephenson, 1955).

b. Clinical trials with domestic animals

Reports of` well controlled clinical trials on animals are limited. Gaarden (1974, in Frerking & Aehnelt ( 1978)) injected 20 ml Echinacin intramuscularly (i.m.) into cows at the time of` insemination and found that this significantly increased the pregnancy rate over controls in two trials (at first and third insemination; Table 2). Whether the controls were injected is not clear.

Using Caulophyllum (30C), chosen because of its reputation in assisting in all aspects of` parturition, Day (1974) reported a statistically significant reduction ha the rate of stillbirths in a group of` 10 sows given a course of the remedy in their food before farrowing, as compared to an untreated control group.

Although the author recognised that there was no double blind approach, the fact that the animals were allotted alternately to the control and experimental groups and, later, when the whole herd was treated the rate of piglet mortality fell from around 20% to 2.6% during the following four months rising again to 14.9%, two months after treatment ceased would suggest that the work is well worth repeating.

The control heifers of Soni & Parekh (1977) appear not to have been injected whereas the experimental animals were injected with one of several remedies in an attempt to remove warts. Five injections at daily intervals cured sessile and pedunculated warts in all 14 treated animals whereas in the controls the papillomatous growth progressed with an increase in the number and size of warts. As in many trials no indication, unfortunately, is given as to whether the trials were conducted double-blind.

Homoeopathic preparations, instead of` antibiotics, are used by a cooperative at Morlaix, France to control mastitis in cows (Perrot, 1980). The recommended treatment with four products (one intramammary, two intramuscular and one oral) was too complex for the farmers and they settled for intramammary treatment alone. The treatment was reported to be effective in 96% of a series of 173 cases when treatment commenced immediately after onset of mastitis but in only 52% of 86 cases when treatment was begun 24-48 h after the first signs of illness and only 24% of 45 cases when treatment was delayed longer. Homoeopathic treatment led to slower recovery than after antibiotic treatment and was not effective against chronic and conform mastitis. No remedy details, statistics or practical details arc given in the report.

INTRODUCTION TO EXPERIMENTAL WORK

Research in homoeopathy has been reviewed by Stephenson (1955), Wurmser (1967), Pirtkien(1976),Unger(1970)and Pedersen(1972).Kollerstrom(1982) reviewed the experimental literature that concerned plants, micro-organisms and in vitro experiments and concluded that only three works stood up to critical scrutiny. These were Boyd (1941, 1942, 1954), Pelikan & Anger (1971) and Mansvelt & Amons (1975).

Much of the experimental work m homoeopathy is open to a number of criticisms which will be discussed in this paper. One which must be mentioned here is the choice of remedy used in the various test systems. Although the choice is sometimes obvious e.g. the use of isopathic preparations in the relevant cases, or a remedy prescribed for conditions in humans is used under experimental conditions with similar symptoms or aetiology, in many cases the reason for choosing a particular remedy is neither stated nor obvious.

In the following section a wide selection of experimental work is presented and discussed. The . papers have, of necessity, been selected from those normally accessible in the U.K. The inclusion of a large number of papers in this review does not imply that there is a strong body of evidence supporting the experimental demonstration of homoeopathic action. The justification of including so many papers is that they provide an indication of the wide range of experimental approaches and, by highlighting their shortcomings, it is hoped that future experiments may be conducted which will avoid the problems that dog so much of this work. In assessing the work it became clear to me that the words of the leading German homoeopathic physician of earlier this century, H. Wapler: "Our literature is our greatest enemy." (from Guttentag, 1966) is as true today as it was then.

EXPERIMENTAL WORK WITH PLANTS

a. Normal plants

The stimulus for much of the work on the effect of homoeopathic potencies on the growth of plants was provided by the Koliskos whose studies are summarized in English by Kolisko & Kolisko (1978). The rationale behind the work was that the homoeopathic remedies replaced missing elements or deficiencies of them. Although many tables are given no statistics are presented and the data are insufficient to make a proper assessment of the work.

The work of` Koffler (1965) and Wannamaker (1966, 1968) on the effect of potencies of sulphur or boron on the growth of onions is also difficult to assess. In Wannamaker's work masses of figures, but no statistics, are given and there is no indication of the rationale behind the work. She claims that both sulphur and boron potencies affect the weight and length of plants as well as the mineral content. Koffler (1965), in a blind trial, also demonstrated great differences in the growth and sulphur content of` seedlings grown in soil treated with sulphur potencies compared to those treated with placebo. A great mass of figures is again presented but with little discussion.

The Koliskos' experiments stimulated a very detailed study by Pelikan & Unger ( 1971)of the effect of potentized silver nitrate (AgNO3) on the growth of` wheat seedlings. This was a well conducted and analyzed experiment involving a series of`40 growth trials repeated six times. Each series exhibited the same type of` curve, a three part growth curve rising from potencies 8x to 14x, falling to 16x and then rising again. Basold ( 1968) conducted a similar experiment but, although he claimed significant differences in the growth of` wheat seedlings treated with various potencies of` AgNO3, the statistical analysis is faulty, an opinion confirmed by Burkhardt (in Kollerstrom, 1982).

The pattern of growth response to the increasing the same as in Pelikan & Unger's work.

This work from Dornach stimulated Jones & Jenkins (1981) to undertake a similar study using potencies of other substances as well as AgNO3. Very small, but significant, changes in growth were found with some of the potencies and in the two trials with AgNO3 similar curves of`changes in growth with increasing potency were obtained. It is unfortunate that Jones & Jenkins (1981) used centesimal potencies whereas Pelikan & Unger (1971) and Basold (1968) used decimal potencies as a comparison of the curves from these works would have been valuable, because, as has already been emphasized, it is important for the validation of homoeopathic action that comparable results are obtained by different workers in well controlled trials.

In a more recent work Jones & Jenkins (1983) compared the potential of` yeast and wheat seedlings as models for testing homoeopathic remedies in the laboratory. Using Pulsatilla they found that some potencies inhibited growth whilst others stimulated it, and the pattern of change with increasing potency was similar for both organisms and, although no indication of variance was given, they claim the variations were statistically significant. No explanation is given for choosing Pulsatilla. Steven (1983) in a well designed, controlled and analyzed trial has repeated the work of Jones & Jenkins (1983) using the yeast Schizosaccharomyces pombe. He failed to demonstrate any effect on yeast growth of` potencies of AgNO3, Pulsatilla, Silica, Prunus spinoza or Bryophyllum.

The work by the Koliskos and Pelikan & Unger also stimulated studies by Bockemuhl (1968) on the effects of serial dilutions of iron pyrites on the growth of cress seeds. In two trials using 4x--22x potencies of iron pyrites he observed rhythmic variations in growth with increasing potency. He concluded that the variations were significant but in a letter to Kollerstrom (1982) he writes "unfortunately the effects of` our experiments with potentized (i.e. serial dilution with shaking) FeS on cress have not proved as statistically significant as we had first considered."

The potential importance of rhythmic variations in growth was suggested by Netien & Graviou (1978) working with Lepidium sativum (cress). They claim to have found rhythms of growth, the magnitude of which depended on the time of day at which the seeds were germinated. These rhythms, they claimed, changed when the growth medium contained copper sulphate (CuSO4) 15c. The implications of the work are important but it needs to be repeated in carefully controlled trials with more sophisticated statistical evaluation. The data presented in the paper are insufficient to make an independent assessment of their claims.

The failure to present a statistical analysis of the results is also a shortcoming of the work of Roy (1932) who claimed to obtain regular rhythms of stimulation and inhibition of` the growth of barley seedlings under the influence of` different potencies of` barley stalks, and of` studies on the respiration of` wheat coleoptiles treated with low potencies of` the poisons sodium arsenate (Na2HAsO4) (Boron & Zervudacki, 1962) or cobalt chloride (Netien, 1962). In both studies some potencies were claimed to stimulate, some to inhibit while others had no effect on respiration.

Some work has been conducted on the effects of homoeopathic remedies on fungi. Bertrand (1912) observed a stimulatory effect of low concentrations (unsuccussed) (10-8_10-10 by weight) of manganese in the culture medium on the development and formation of conidia of Aspergillus niger. Narodetzki (1938) used higher succussed dilutions of` sodium borate and mercuric chloride (HgCl2) (up to 30c) to study the mycelial growth of`Aspergillus niger in culture. Some potencies decreased the output of mycelia but in one case a potency (18c), which inhibited production in three series, increased it in another. The data from this thesis presented by Stephenson (1955) or Netien & Girardet (1965) does not allow a proper assessment of` the work.

A statistical analysis was not employed in a much more recent work by Misra et al. (1980) to assess the et`lect of` 14 homoeopathic drugs at the 200th potency on aflatoxin production and mycelial growth of` Aspergillus parasiticus in a liquid rice-flour medium. Some drugs stimulated, some inhibited and one had no effect. Replicates were very small (3).

b. Plant diseases

Some trials have been conducted, mainly by Indian workers, on the control of` fungal and viral diseases of plants. Khanna & Chandra (1976b, 1977a, 1978) have published the results of` a series of` trials on the control, using homoeopathic preparations, of fruit rots caused by fungi. Their results are summarized in Table 3. The experimental method first involved testing a large number of different potencies of a variety of remedies to determine whether they would inhibit germination of the relevant fungal spores in hanging drop preparations. The remedies chosen were drugs normally used to treat human fungal diseases Those remedies, at the potencies which completely inhibited spore germination in vitro, were then tested on fruits inflected with the fungus, either before or after homoeopathic treatment. Some significant results were obtained. Many of the potencies that provided positive results were not those commonly used by homoeopathic physicians who tend to use a very limited range Although these experiments provide useful pointers to practical application in the field of agriculture they need to be repeated as independent experiments a number of times before the efficacy of` the method can be accepted. As only some potencies produced positive results, it is essential that these potencies consistently produce the expected results, or practical application of the method would he virtually impossible.

Khanna & Chandra (1976a, 1977b) have also used the hanging drop technique to study the effect of` various remedies on the inhibition of spore germination of Alternaria alternaria, a fungus causing leaf blight of wheat. Certain potencies of some drugs were found to cause inhibition of spore germination and these were tested in viva by spraying wheat plants 24 h prior to infection with the fungus (Khanna & Chandra, 1977b). When examined 20 days later a 41% and 59% control of the disease was found with Arsenicum album 199c and Kali iodide 200c respectively, while the other seven remedies selected from the hanging drop trials were ineffective. The same caveat can be applied to this work as to the fruit rot studies described above.

The hanging drop technique was also used by Chaube et al ( 1978) to assess the fungotoxicity of the 30th and 200th centesimal potencies of a number of homoeopathic remedies against Helminthosporium oryzae, Fusarium solani and Penicillium decumbens. Some remedies were found to inhibit spore germination whilst others accelerated it. The work involved only three replicates of each treatment and there was no statistical analysis. Work of` this nature can only serve as a guide to larger well controlled trials in the future.

Various workers have tested the effect of` homoeopathic drugs controlling or preventing virus inflections in plants. Verma et al. ( 1969) tested a variety of`drugs, selected from those used in human medicine for the treatment of diseases whose symptoms are suspected to be caused by viruses, against the symptoms caused by tobacco mosaic virus (TMV) in local lesion and systemic hosts. A variety of drugs were claimed to have an inhibitory effect on virus multiplication rate and local lesion production. However, the number of` replicates is not given and no statistics are presented. Again using TM V Singh et al (1980) claimed that some homoeopathic drugs inhibited lesion production in the host, Nicotiana glutinosa, but the same criticisms apply to this work as to the former work on TMV.

No statistical analysis is presented in the work of Khurana (1971) who tested the effect of homoeopathic remedies on the response of` host plants to three papaya viruses and cucumber mosaic virus. Moreover the groups were small. He claimed that homoeopathic treatment was more effective used prophylactically than as a treatment of`infected plants. It was also clawed to be more effective on systemic hosts than on local lesion hosts. Prophylactic treatment with some homoeopathic drugs was also claimed to be more effective than post-infection treatment in reducing the severity of symptoms and delaying their appearance in distortion ring spot virus infection of papaya seedlings (Abidi et al., 1977). Again this work involved a small number of replicates and no statistical analysis.

Shukla & Joshi (1982) tested the ability of various homoeopathic remedies to inhibit the pathological effects of sugarcane mosaic virus in sorghum. Inhibition was claimed with some of the drugs tested but the trial was small, there was no statistical analysis and flew practical details were given.

A statistical analysis was used by Verma & Awasthi (1978), as well as using groups of 15 replicates, to test the effects of the 12 Schùssler tissue salts (at 6x) (believed by Schùssler to be the basic constituents of the human body) on preventing or treating infection of local lesion hosts with TMV. A variety of stimulatory and inhibitory effects were observed. All 12 tissues salts had significant effects on some of` the three hosts used both before and after inoculation! As with other experiments the work must be repeated a number of times with similar results to gain any credibility. The work should also be done blind or double-blind. It is not clear in the work reported above whether this was part of the experimental method.

c. Experimental poisoning

Experiments have been conducted by a number of workers to study the possible protective or curative effects of potentized CuSO4 on plants partially poisoned by the chemical. Netien and colleagues were among the first to use this model and in an English summary of their work (Netien et al., 1966), they claimed that in one trial pea seedlings originating from plants partially poisoned by CuSO4 grew better in CuSO4 15c than in distilled water. In another trial, however, this was not confirmed. Some of their subsequent work claimed that rhythms could be detected in the growth of seedlings and that these were altered by poisoning or by treatment with CuSO4 15c. The papers are difficult to follow and often make no attempt at statistical analysis (Netien el al., 1972; Netien & Graviou, 1978, 1979).

Graviou & Biron (1971 a) also claim to have demonstrated temporal rhythms of rootlet growth 36-72 h post germination using normal Lepidium grown in either distilled water or CuSO4 15c. The growth rhythms were apparently different for the two treatments but the variances in the results were too great to allow a proper statistical evaluation!

The concept of temporal variations in growth capacity was used by Graviou (1981) to explain the contradictory results he obtained on the effects of CuSO4 15c on rootlet growth of Phaseolus vulgaris germinated in CuSO4 solution. Neither this experiment nor that of Boiron et al(l978) presented a statistical analysis. The latter workers measured «-amylase activity of seedlings grown from grains of wheat placed before germination in CuSO4 solution. They were subsequently grown in distilled water or potentized CuSO4. They claimed that a-amylase levels in the grains placed in CuSO4 15c had risen to control levels (that of unpoisoned grains) by 36 h post germination whilst the levels in those germinated in distilled water remained low.

The most recent, and also the best controlled and analyzed, experiments on the action of homoeopathic CuSO4 on the growth of seedings from grains previously immersed in CuSO4 solutions are those of Auquière & Moens (1981) and Auquière et al. (1982) using mustard and wheat. Their results were very variable and they could not confirm the claims of some of the previous workers that homoeopathic CuSO4 reversed the deleterious effects of pretreatment of the grains with the chemical.

The alga, Chlorella vulgaris, has also been used in a system to test the effects of homoeopathic CuSO4 on the growth of the organism alter poisoning with CuSO4. Graviou & Biron (1971 b) measured chlorophyll production, respiration and growth of the poisoned alga grown in a variety of media including potentized CuSO4 and claimed that all three parameters were augmented by the homoeopathic remedy when compared to a control group. (The identical paper was published by Boron & Marin in 1978!). Although they claimed that the results were statistically significant no statistical data were presented and the number of replicates was not given. In a well controlled and analyzed experiment Moss et al. (1977) failed to confirm the findings of Graviou & Biron (1971b).

Variability of results in repeated experiments was also found by Flemming (1974) who studied the effect of cupric chloride (CUCl2) 30x on the growth of rootless of cress seedlings after partial poisoning by growing for 7 days in a solution of 10-3 g.l-1 CuCI2. Initial experiments gave statistically significant results but later experiments did not. In a personal communication to Kollerstrom (1982) he concluded that "an insight into the relationship between substance, process and potency is not to be gained by this type of experimentation".

LABORATORY TRIALS WITH ANIMALS

a. Normal animals

It is possible that at low potencies some, at least, of the results obtained in homoeopathic research may be seen as examples of the Arndt-Schulz law or hormesis (see later). The work of Heintz on the attraction of fishes (Heintz 1958a,b, 1962) and Daphnia (Heintz, 1964c) to a variety of chemical stimuli, including extracts of t`ish skin, used a series of doses which would be considered low potencies by homoeopathic standards. These were prepared by serial dilution but the extent of succusion is not indicated although any serial dilution must involve some mechanical agitation for mixing. Although the concentration at which attraction or repulsion occurred varied between the different substances tested there was no effect. of any below a concentration of about 10-15--10-16 g.l-1 (Heintz, 1962). Attraction was a characteristic of the lower concentrations while repulsion occurred at higher concentrations and Heintz (1964c) suggested that attraction was due to hydration of` ions whilst repulsion was principally due to the ordinary chemical properties of the ions. These experiments were reviewed by Heintz (1971).

Much of the early work which claimed to demonstrate an effect of homoeopathic remedies on normal animals was not statistically analyzed and ~s not presented in a way suitable for a proper scientific assessment e.g. Junker's (1928) work on the daily changes in the growth of cultures of Paramecium containing homoeopathic concentrations of a variety of substances Konig (1927) grew tadpoles of Rana fusca in potencies of the nitrates of silver and lead and found that some doses stimulated premature metamorphosis whilst others killed. High dilutions (24x--29x) of both substances killed. Vondracek (1929) did similar work with tadpoles of Rana temporalis with dilutions of gold chloride up to 10-21 g.l-1. The mortalities throughout the series of dilutions fluctuated. Like Junker and Konig he obtained a sinusoidal curve of the function tested with increasing dilutions.

Normal mammals have also been used to observe the effects of homoeopathic potencies. Stearns (1925) treated guinea pigs with potencies of NaCI equivalent to dilutions of 10-60--10-2000 and found that the animals exhibited various signs of ill health. Krawkow (1923) recorded the effects of microdilutions of various substances on the flow of blood in isolated ears of rabbits and on the pigmentation of the skin of frogs. Some changes from control levels were found but, as in all the work described in the last two paragraphs, the results were not subjected to critical analysis and may well not be significant.

Statistical analysis was applied by Soberon Castellanos (1977) to the results he obtained on the blood counts from cows injected at parturition with a complex homoeopathic preparation (Pulsatilla miniplex). Blood counts were made 1-3 days post partum and, although the groups were very large, there were no significant differences between treated and control groups.

b. Infections

Jeannes et al. ( 1972) reported that FSH 9c (Follicle stimulating hormone) was effective in treating the crisis induced in guinea pigs and rabbits infected with colibacillus. There was no statistical analysis in this or in the work of Baranger & Filer (1971) who claimed success with potentized Geraniol in the treatment of chicks infected with a virus.

Nasi et al (1982) studied the effect of` homoeopathic remedies on the parasitaemia and life span of mice infected with the protozoan blood parasite Trypanosoma cruzi. They claimed that a nosode prepared from the blood of inflected mice and given for 10 days before inflection reduced parasitaemia and protected the mice from the lethal effects of the infection. All control mice died. A variety of treatment regimes was tried but the nosode given at other times was not effective.

A nosode prepared from T. cruzi itself was also effective in reducing parasitaemia and prolonging the like of mice but only when given before or at the same time as infection. Unfortunately no statistical analysis of the data was made. In view of the fact that one treated group had no parasites in the blood and no deaths, whilst at the same time controls had a heavy parasitaemia and ultimately died, the work should be repeated.

c. Oedema

In a small trial Niebauer et al. ( 1977) induced oedema in rats' paws by injecting formaldehyde or carageen. The efficacy of homoeopathic Apis in reducing the oedema was compared with cortisone which was always effective. Apis 4x reduced formaldehyde-induced oedema and Apis 30x carageen-induced oedema.

This test was used in a larger trial by Niebauer et al. (1978) when they compared the efficacy of Apis 30x, cortisone and placebo. Some slight effect of Apis was found, compared to the placebo, but the trial was marred because differences were found between the electrolyte content, and thus possible antiinflammatory effects, of the placebo and Apis diluents.

d. Erythema

A French group has also studied the potential of homoeopathic remedies in reducing inflammation induced in the skin, this time by ultra-violet irradiation of guinea pigs. Bastide et al. (1975) claimed that Apis 7c given before and/or after u.v. irradiation gave some protection against the development of erythema. Aubin et al ( 1978a, b) extended these studies and also used Calendula 4c effectively. The data were not statistically analyzed and the degree of` erythema was subjectively assessed on a points scale. No statement was made as to whether the work was conducted blind or double-blind which would be particularly important where a subjective assessment of the results is made.

e. Gastric ulceration

Guillemain et al. (1982) induced hyperaemia and ulceration of the gastric mucosa in rats by oral administration of polymyxine B. Histamine 4c was compared with cimetidine as a protective agent against the effects of the chemical The remedies were given 10 min before polymyxine B and the rats killed 2 h later when the extent of the damage was scored. Histamine 4c gave 43.9% protection and cimetidine 68.4% and the authors concluded that Histamine 4c partially opposed the effects of` polymyxine B. The results were statistically analyzed.

f. Diabetes

Mice treated with alloxan develop diabetes with its hyperglycaemia. French workers have studied the potential of potentized alloxan in preventing diabetes or reducing the hyperglycaemia. Cier et al ( 1967) found that Alloxan 9c given to mice before alloxan administration appeared to reduce the number of mice becoming diabetic and also reduced hyperglycaemia. When used as a curative after alloxan injection it was less successful although there was a reduction in the hyperglycaemia. The experiment contained good replication but no statistical analysis. The prophylactic properties of homoeopathic Alloxan were apparently confirmed in later trials by Boron & Cier (1971) and Boron (1972) but again the data were not statistically analyzed.

g. Wound healing

The efficacy of Arnica 12x, Solcoseryl and a placebo in stimulating wound healing in rats were compared and reported by Pfeil (1978) and Niebauer et al. (1980). Wound healing was assessed 6,12 and 18 days after wounding and the results were statistically analyzed. Only at 12 days was wound healing in the Arnica group significantly more advanced than the placebo group and comparable to healing induced by Solcoseryl.

h. Fertility

Both (1980) claimed that after treatment of non-cycling female pigs over 7 ½ months old with potencies of Ovarium compositum or Aristolochia clematis most of the animals showed heat or became pregnant. There were no controls and my own experience with this type of pig suggested that stress, in this case possibly induced by injection, may be sufficient to start the animals undergoing oestrous cycles (Scofield, 1975).

Depression of reproductive activity was reported by Stearns (1925) after treatment of guinea pigs with NaCl potencies equivalent to dilutions of 10-60--10-2000. All 16 female controls became pregnant whilst only 31% of 48 experimental animals conceived. It is not clear from the summary by Stephenson (1955) how the controls were treated.

Prasad & Chandrasekhar (1977, 1978) administered daily to rats Pulsatilla 30c or 200c or the progestational drug, lutocyclin. Significant changes were found in the weight of the ovaries, the rate of follicular atresia, the diameter of the corpora lutea and various uterine and thyroid parameters which suggested that potentized Pulsatilla possessed progestogenic activity. The homoeopathically induced changes were similar to those found with 1.25 mg doses of lutocyclin. These experiments were controlled and analyzed and are worthy of repetition.

By administering Caulophyllum 200c or 10,000c to adult female rats Kumar et al. (1981) found that the 200th potency caused uterine changes that were compatible with estrogenic activity. They claimed that the ovarian changes observed suggested a gonadotrophin releasing hormone blockade. Again the work was statistically analyzed.

i. Cancer

One of the earliest studies on the control of cancer by means of homoeopathic remedies was that of Stearns & Stark (1925). In a large series of experiments they found that some cultures of male fruit flies with an inherited fatal tumour responded successfully to Arsenic 30c and potencies of the tumour and survived, whereas all susceptible males normally died. The work was not statistically analyzed and insufficient data are given to make a proper assessment. The work appears never to have been repeated.

It is only much more recently that homoeopathic scientists have again turned their attention to the problem of cancer, or at least have published papers in the field. Boron et al. (1979) artificially induced either liver tumours with 2-acetylaminofluorene (AAF) or mammary tumours with dimethylbenazanthracene in rats. DNA/RNA 5, 9 or 15c was given before treatment with carcinogen and throughout the experiment, and various histochemical and biochemical measurements were made. The authors claimed that survival in the liver tumour group was significantly better after treatment with DNA/RNA 9c and 15c when compared with controls but no statistics are given. They also claim that homoeopathic treatment for 15 weeks retarded the development of the tumours. Pretreatment with the remedy did not prevent development of mammary tumours.

In a very large trial with rats treated with AAF to induce liver tumours and phenobarbital to promote their development, groups of animals were treated with either RNA 9c, AAF9c, Phenobarbital 9c or H2O 9c (Boron et al., 1982c). In the Phenobarbital-treated group there was a reduction in the percentage of benign and malignant liver tumours and hepatocyte damage. The authors claim to have statistically analyzed the data but no details are given.

Choudhury (1980) obtained surprisingly dramatic results from injecting mice intra-peritoneally with Kalium phosphoricum, Calcarea phosphorica or Ferrum phosphoricum 30x 12 days after transplantation of fibrosarcoma. Of 77 mice 52% were cured and survived more than one year whereas all of the 77 control mice died within 10-15 days.

j. Physical performance

The swimming performance of rats and mice was tested by Boron & Maillot (1973) after treatment with Zinc sarcolactate 6x, sodium phosphocreatine and distilled water. Both drugs significantly improved swimming performance in mice. The performance of rats was also significantly improved after homoeopathic drug treatment.

k. Behaviour

In separate tests of the exploratory and evasive behaviour of mice Binsard (1978) claimed to have shown that Ignatia 3c, chosen because of its effects on the nervous system, augmented the former activity and caused a sedative effect in connection with the latter behaviour. Ignatia 7c and 30c had no effect on behaviour. No statistical analysis was presented.

In a later paper Binsard (1979) used a blind trial technique and tested the effects of Gelsemium 3c, 4c and 5c and Ignatia 3c, 4c and 5c as well as conventional drugs on the behaviour of mice. The results were vary variable. In a second experiment using rats in a blind trial Gelsemium 3c and 5c and Ignatia 4c showed a sedative action. A statistical analysis was used for this trial although, curiously, not for the trial with mice.

1. Poisoning

Guillemain et al ( 1981) gave mice a dose of strychnine that was 100% fatal in normal animals. Experimental animals were given Ignatia 3x, 3c,5c,7c or 12c one hour before the strychnine and the authors claim that the 3x and 5c potencies significantly delayed the time at which death occurred. No effect was observed when the remedy was given 24 h before strychnine, or when administered over one or several days. No data were given in this paper.

A reduction in the mortality of mice following a dose of HgCI2 after prophylactic treatment with Mercurius corrosivus 5c or 9c was claimed by Cambar et al. ( 1983). However, no analysis of the data were attempted and the significance of the results is, therefore, unclear.

Several groups of workers have studied the effect of potentized metals on the elimination of the same substance from animals poisoned with it. Mouriquand et al. (1959) injected pigeons i.m. with sodium arsenate (Na2HAsO4) and 6 weeks later gave three consecutive daily doses at` Na2HAsO4 7c. Arsenic excretion and the degree of vestibular chronaxie were measured. Arsenic excretion appeared to cease 5-6 days after injection but when the Na2HAsO4 7c was given further elimination occurred No elimination occurred in the control group at this time but these animals were not injected with anything when the remedy was given to the experimental group. Vestibular chronaxie also rapidly decreased after the remedy but rook longer in the controls. Although the results look interesting no statistical analysis is presented and no indication of sample size or variance is given.

Similar studies using rats were conducted by Lapp et al. ( 1955) and Boron & Cier (1962a) and they also reported a resumption of arsenic elimination in the urine after injection of homoeopathic sodium arsenate after the initial excretion of arsenic had ceased. Both groups extended their work to include similar trials with rats injected with either an antimony salt (Boron & Cier, 1962a) or a bismuth salt (Lapp et al., 1958) with similar results. The same criticisms apply to these papers as to Mouriquand et al. (1959).

The work on arsenic excretion in rats was extended to study the effect of an isopathic preparation on the resumption of arsenic elimination (Boron & Cier, 1962b). The isopathic preparations were made by potentizing blood from the experimental animals after injection of the arsenic salt. This preparation was claimed to provoke a further small excretion of arsenic after the initial excretion had ceased. The preparations were only effective when injected into the rats from which they were prepared and had only a very slight effect when injected into another rat. Again there is no statistical analysis.

More recently Boron et al. (1982a) have used radioactive tracers to study the effect of`homoeopathic arsenic on the accumulation and elimination of the metal from poisoned rats. They suggest that in some cases Arsenicum album 7c may speed up elimination. Although the experiment is well controlled no statistical analysis is presented.

Elimination of antimony from poisoned pigeons was also studied by Mouriquand et al ( 1961). Potentized antimony or a placebo were given to the animals 11, 12 and 13 days after injection of radioactive potassium antimony tartrate and the radioactivity in the organs and its excretion subsequently measured. The authors stated that their results showed a wide variation which cautioned a prudent interpretation but they nevertheless claimed that antimony elimination was provoked by the homoeopathic remedy. However, no figures are given and there is no statistical analysis.

The work of` Fisher (1982) on lead intoxication of Rats, however, was statistically analyzed. Rats poisoned with lead were treated for 7 days with Phumbum metallicum 200c or penicillamine (a chelating agent). Lead excretion was monitored for 14 days. There was little excretion in controls but both treated groups showed very similar marked and regular excretion of the metal which was significantly greater than in the controls.

In view of the increasing concern regarding heavy metal poisoning Prom environmental contamination the potential of homoeopathic remedies in stimulating the body's excretion of these metals and possibly even reducing their initial uptake should be further investigated.

Experimental liver damage. A French group has published a number of papers on the protective effects of homoeopathic remedies against carbon tetrachloride (CCl4) induced liver damage in rats Unfortunately the papers do not contain statistical analyses and often the most interesting results are those that were obtained subjectively i.e structural changes, although in at least one trial (Bildet et al. 1977) the design was double-blind. Where measurements were made of liver enzymes, changes in these were usually only slight or non-existent. Indeed, in one of' the earliest trials (Cier et al. 1963) homoeopathic remedies were found to have no effect on blood SCOT (glutamic-oxalacetic transaminase) levels, which are an indicator of liver damage, at various times at ter liver damage had been induced in rats and mice with bromobenzene or CCl4. These authors admit that the choice of a suitable homoeopathic remedy in this type of` trial is difficult.

Most of` the work used Phosphorus 7c or 15c before and/or after CCl4 injection and all papers claim some effects of the remedies in protection against CCl4-induced liver damage (Bildet et al. 1975, 1976, 1977; Aubin et al, 1979,1980). Bildet et al. (1978b) used complex mixtures of homoeopathic remedies and claimed that some exerted a protective effect on liver histology but, again, they had no effect on liver enzymes

Other potentized substances have been tried as protective agents against CCl4-induced liver damage. Bildet et al (1978a) used Amanita phalloides 7c and 15c. The results were very variable and, although histological changes were claimed to be less with the 15c remedy than in controls, there was no statistical analysis. Bildet et al. (198 la) used CCl4 5c,7c and 15c for three days before intoxication of rats with CCI4. Again the main difference claimed between groups was the subjective one of histological features.

None of` the work convincingly demonstrates a protective effect of' homoeopathic remedies against CCl4 intoxication in the rat. A comparison is sometimes made with conventional studies which do show a protective effect of small doses of CCI4 against liver damage induced by normally toxic doses of CCI4, dimethylnitrosamine or other compounds (e.g. Ugazio et al., 1973; Pound & Lawson, 1975). In these pharmacological studies the protective doses of` CCl4 are quite high (of the order of` 0.01--0.6 mg.kg-1) and the protective effect decreases with decreasing dose level (Pound & Lawson, 1975). The protective effect lasts for only a few days and is related to the reduction in the activity of the liver drug-metabolising enzyme system. The toxic effects of dimethylnitrosamine are believed to be mediated through metabolic activation by microsomal enzymes. Resistant and non-resistant animals initially undergo similar pathological changes in the liver. However, in protected rats the changes are reversible whereas in susceptible rats the observed changes increase until the death of the animal (Ugazio et al., 1973). It may well be worthwhile to use this well-tested pharmacological model to compare the protective activity of` confirmed pharmacological doses with homoeopathic remedies and at the same time make the relevant biochemical measurements.

STUDIES WITH ISOLATED ORGANS AND IN VITRO STUDIES

a. Isolated organs

The activity of isolated organs has been used as a technique in attempts to demonstrate the activity of potentized remedies. Wurmser (1947) measured the contractions of isolated rat intestine in the presence of various dilutions of butelline. She found that high dilutions acted in the same way as strong doses of the chemical but with lesser intensity. The dose levels used were relatively high in homoeopathic terms i.e. 10-10 dilution was a high dilution, and they would still contain molecules of the original substance.

Perfusion of hearts with solutions containing homoeopathic potencies was tried by Jarricot (1951, in Coulter, 1981) and Pennec et al. (1981). Again the latter authors found diminution or stimulation of cardiac frequency depending, in this case, on the dose level of aconitine (unsuccussed). They also claimed that the augmentation of heart rate by 10-5 M solution (unsuccussed), which was normally irreversible, could be reversed by 9c Aconitine. Statistics are presented but the data are not given in a way that allows a proper assessment.

Boyd (1953) has also presented data on the effect of` low potencies (i.e. 10-6--10-11 dilution) on the effect of`various drugs on heart rate. Higher potencies (e.g. 32c potency) were used by Boyd (1954) of` .Strophantus sarmentosus and he found a greater number of frogs reacted to the potentized substance than to distilled water. These were preliminary results with no statistical analysis and further, more definitive, studies do not appear to have been published.

b. Enzyme activity

The work of` Boyd on the effect of` HgCI2 potencies on the activity of diastase is considered by many to be a classic of homoeopathic research. It involved meticulous cleanliness, lengthy technician training and all stages of the work were regularly checked and many variables monitored and, where possible, controlled. The statistical analysis of` the data was also extensive. As Kollerstrom (1982) has pointed out, the finances required to repeat Boyd's work in the same precise, well-controlled manner would be enormous. The first study (Boyd, 1941) involved two series of tests to measure the effect of potencies of HOCK on the activity of diastase in digesting starch. Some potencies were found to have a significant inhibitory effect whilst others had an activating effect. However, potentized solutions of` nominally the same order of` dilution did not give identical results in each series and Boyd suggested that the pattern of molecular or ionic distribution of the solute, which would still be present at the low dilutions used throughout the diluent may have differed.

The work was extended to higher potencies (up to 30c) (Boyd, 1942) and again he found that some potencies activated enzyme activity, some inhibited it and some half no effect. He also again found that solutions of nominally the same order of dilution did not give identical results ha different series of` tests. He tended to explain results on material quantities of` solute remaining. A significant result was found at a dilution of the original material to 10-56, which is well beyond the Avogadro number, but he was unable to explain it and accepted the result as preliminary and in need of confirmation by further work.

In the last paper of` the series Boyd (1954) presented ha great detail the methodology and results of several years meticulous investigation on the effect of high potencies (32c and greater) of` HgCI2 on diastase activity. Experiments were conducted in three years and all series Rave significant results. with various potencies stimulating the hydrolysis of starch when compared to distilled water controls.

Boyd's studies were stimulated by the work of' Persson (1933, 1938) who tested the effect of' various potentized substances on enzyme activity. Although various effects were claimed the results were not statistically analyzed. Again, in a more recent study by Kraus of al. (1981), in which pyruvate kinase activity was measured in the presence or absence of` Phosphorus in potencies from 3-15c, the data were not statistically analyzed. As in other homoeopathic studies a sinusoidal curve of activity with increasing potentization was produced with some doses inhibiting and some activating the process. Without statistical analysis the significance of' such curves must remain in doubt.

c. In vitro cell culture

The activity of` lymphocytes in culture can be influenced by various chemicals and this system has been used by various workers to study the potential of substances in homoeopathic potencies to modify these effects. In a well controlled and analyzed experiment Mansvelt & Amons (1975) studied the dose-effect relationship of' HgCI2 on the proliferation of murine lymphoblasts. Three separate series were done with culture solution concentrations of HgCI2 in ranges from 0.9 x 10-5 - 0.9 X 10-18 M; 0.9 x 10-12 - 0.9 x 10-25 and 0.9 x 10-15 - 0.9 x 10-21 M. These were prepared by serial dilution with extensive shaking. In the first range concentrations of 0.9 x 10-5M and 0.9 x 10-6 M proved toxic as expected. However, 0.9 x 10-16 M and 0.9x 10-17 M also appeared to be growth inhibiting, the latter result being confirmed in the second and third series. The results were statistically significant. The authors pout out that with prolonged dilution one would expect ultimately a flat dose response curve but this study shows that this is not necessarily the case.

Kollerstrom and colleagues have repeated some aspects of this work but their results were not significant ( Kollerstrom, 1982). They tested HgCI2 in the range 0.9 x 10-10 0.9 x 10-18 M but failed to find any effect on the growth of` murine lymphoblasts in culture.

Some lectins e.g. phytohaemagglutinin ( PHA) from Phaseolus and pokeweed mitogen can induce the transformation of lymphocytes into dividing lymphoblasts in cell culture. The potential of Phylolacca(pokeweed) h1 homoeopathic potency to modify the action of` mitogens on lymphocyte activity has been studied by French workers. Colas at al. ( 1975) found that of Phytolaca 5c, 7c, 9c and 15c added to cultures of lymphocytes 15 min before the addition of PHA, the 9c and 15c potencies resulted in a reduction in lymphocyte transformation. No statistical analysis or estimate of` variance was given.

When given 15 min after addition of` PHA Phytolaca 7c but not 15c was found to result in a significant inhibition of` lymphocyte stimulation (Bildet et al., 1981b). The data were analyzed by t-test but no standard errors were presented.

The effect of' homoeopathic potencies on the responses Mother white blood cells in culture to various chemical stimuli has also been studied. Boiron el al. (1982b) tested the effects of` homoeopathic Histamine and Apis on basophil degranulation induced by a variety of allergens. Although no statistics are presented the results suggest that there was a significant effect of both substances in preventing degranulation in the presence of an allergen.

Poitevin et al. ( 1983) studied the effect of 5c and 9c Belladonna and Ferrum phosphoricum on the liberation of' free oxygen radicals from neutrophils from healthy human donors. These are implicated in the inflammatory response. They found significant inhibition of radical release by the drugs which was comparable to the inhibition induced by the anti-inflammatory drugs indomethacin (10-4 M) and dexamethasone (10-5 M). They claimed that certain subjects were more sensitive to the homoeopathic drugs than others. Although the data were statistically analyzed insufficient details of the experimental protocol are given (e.g. number of replicates, how the controls were organized) to allow a critical assessment of the work. Failure to include essential methodological details is a shortcoming of much of the published work in homoeopathy.

Moss At al. (1982b) tested the effect of five homoeopathic remedies, normally used in treating mild bacterial infections, in the range 2 x 10-7 to 10-13, g.l-1 on the movement of guinea pig macrophages or human leucocytes in vitro. In four series of experiments 47/533 tests showed a statistically significant modification of cell movement. With human leucocytes 5/50 tests from four subjects were significant. In some experiments movement was facilitated whilst in others it was inhibited. The largest effects were obtained with a few sensitive guinea pigs and one human. The magnitude and direction of the effect appeared to depend on the batch of animals being treated rather than the set of remedies used. These results suggest, like those of Poitevin et al. (1983), therefore, that the effectiveness of homoeopathic remedies may well be influenced by the sensitivity of the individual. The incidence of significant results in these experiments was low but Moss el al. (1982b) point out that homoeopathic remedies would normally be used to treat ill subjects who would be expected to have a higher sensitivity to the remedy than healthy subjects, such as were used in the experiments.

Cells other than blood cells have been used in culture as test systems for homoeopathic remedies. Boiron el al. (1981) cultured epithelial cells and fibroblasts in vitro in the presence of concentrations of HgCl2 which depressed the mitotic index. Protection against the depressing effect of the chemical was found for HgCl2, 5c but not for 15c. The experiment was statistically analyzed.

d. Studies with bacteria

Noiret & Glaude (1977) used CuSO4 3c, 4c, 5c, 6c, 15c or 27c as part of the culture medium for Enterobacter cloacae, Listeria monocytogenes, Streptococcus bovis (group 1) and Edvardsiella tarda. Potencies 6c, 15c and 27c were always found to stimulate growth, 3c to inhibit growth, whilst the results with potencies 4c and 5c were variable. This work was statistically analyzed and appears worthy of repetition.

HOMOEOPATHIC DRUG STRUCTURE AND MECHANISM OF ACTION

a. Drug structure

Until the 1960s many workers concentrated on demonstrating the presence of the original solute in the remedy using low potencies and used these findings as evidence that at least these potencies could work because of` the presence of' some of`the solute molecules (e.g. Boyd, 1936). Many physiological processes are certainly controlled or affected by minute quantities of substances which may act either directly on a target process (e.g. nerve poisons) or by initiating a form of cascade action (e.g. factors in the blood clotting process). However, this does not explain the action of potencies diluted beyond the Avogadro number when the likelihood of finding a single molecule of the original solute becomes progressively more remote as the dilution Creases. The extensive use of high potencies, in which none of the original solute exists, has proved a major stumbling block to acceptance of homoeopathy by the scientific and medical establishment and has been the cause of much derisory literature. However, should the effectiveness of homoeopathy be scientifically proved then one may have to face up to the fort that some form of energy, the nature of' which we know nothing, is being generated during potentization. The understanding of such energy might be compared to what the Greeks knew shout electricity when they observed that they could pick up straws with amber after rubbing it.

This problem has been approached by recent workers by suggesting that the therapeutic properties of the remedy lie in the vehicle (i.e. the solvent and, presumably. the sugar to which the liquid remedy is often added to make pills--but see later). Various techniques have been employed to demonstrate that there are physical differences between potentized dilutions and the vehicle, whether potentized or not (see Stephenson, 1955; Wurmser, 1967). These studies have included the use of u.v. spectra, conductivity measurements and i.r. analysis (Heintz, 1941), surface tension measurements Kumar & Jussal, 1979), NMR spectroscopy (Smith & Boericke. 1966~ 1968; Young, 1975), dielectric strength measurement (Brucato & Stephenson, 1966), Raman-Laser spectroscopy (Luu-D-Vinh, 1975; Boiron & Luu-D-Vinh, 1980) and other methods (Heintz, 1964a,b, 1972). Much of this work claimed to demonstrate regular peaks and troughs in activity with progressive dilution end Heintz (1964c) ho claimed that these peaks correspond to maximum effects found in the biological systems reported in his earlier work.

The results of such work are generally not presented in a form which is suitable for scientific assessment. No statistics are presented and it is often impossible to determine if more than one replicate at each dilution was made. The claim made in many works that a sinusoidal curve of the parameter measured was obtained with increasing dilution is, therefore, difficult to confirm. The sensitivity of the equipment used in the earlier work would also lead one to suspect that much of the fluctuation observed may lie in the techniques used. In fact Heintz (1942) retracted his claims of 1941, when he reported rhythmic variations in the i.r. spectra and conductivity of remedies with increasing potentization on the grounds that there were inaccuracies in measurement, evaporation of`solutions and distortion of the mica plates of the i.r. cells. Young (1975) in a relatively recent work using an NMR, in which there is no satisfactory statistical analysis, recognizes that "the analysis is preliminary and that many checks and rechecks should be made before the evidence is conclusive." Reproducibility is crucial in all scientific research but appears to be a rare commodity in homoeopathic trials. Whether this is simply the result of a failure to repeat work, or is due to the failure to reproduce the positive results of a previous trial is impossible to say.

Although hinted at by earlier workers (e.g. Gay, 1949, 1952, in Wurmser, 1967) it was Barnard (1965) who developed the idea of the solvent carrying the informational content of the original solute and acting as the remedy, rather than the original solute. He believed that water polymers were formed by succession, structure of which was determined by the original structure of the solute which caused spatial changes in the solvent. These polymers were believed to be induced to grow and split by the energy provided by succession. These solvent polymers could impregnate further succussed solutions and act as templates for the generation of more polymers. This would lead to an increasing population density of longer and longer polymer chains up to a limiting length at which they would fracture. Gibson (1968) has suggested that the peaks in physical measurements claimed at various potencies by some authors (see above) may correspond to fracture of the water polymers induced at critical lengths by succession. The idea of the solvent carrying the informational content of the solute has been suggested and developed by other authors since Barnard (Smith & Boericke, 1966; Barnard & Stephenson, 1967, 1969; Gibson, 1968; Unger, 1970; Rawson, 1974; Kumar & Jussal, 1979; Boiron & Luu, 1981; Jones & Jenkins, 1981). The importance of succession in providing energy to propagate the information content through successive dilutions has been emphasized by many authors (Gibson, 1968; Jones & Jenkins, 1981).

The extremely complex structure of water with its continuously variable hydrogen bonding has led to the suggestion by a number of authors that it may take up a great variety of forms under the influence of the different homoeopathic templates, although this has yet to be proved in practice. Although Barnard (1965) suggested that the formation of long chain water polymers may be occurring during potentization other possibilities are available. Jones & Jenkins (1981), after considering recent work on the structure of water, have suggested that water polymers may occur not as long chains but as closed chains of cyclic clusters of two to six molecules. Their three-dimensional structures could be maintained by bonding forces acting over relatively long distances and would be sensitive to electrical forces as might be imposed on them by neighbouring molecules, perhaps of solute. Mechanical agitation would alter the molecular relationships within the solution and fresh electrical situations may occur. As in Barnard's theory these short chain three-dimensional polymers would act as templates passing information onto subsequent dilutions.

It has been suggested by Kollerstrom (1983, personal communication) that there are fundamental features of these theories that have yet to be considered in detail such as the stability of the induced water polymers and, even if they are found to maintain their integrity for any length of time, how the information is passed to and stored in the sugar granules on which the vehicle will evaporate.

b. Mechanism of remedy action

But if the information-carrying solvent polymers, possibly in a wide variety of three-dimensional shapes, are the remedies how do they work within the body? Barnard & Stephenson (1967) suggested that bacteria and other substances may produce polymers in the body fluids and the remedies may act by neutralizing these polymers. A similar system was suggested by Gibson et al. (1980a) who compared it to the antibody-antigen reaction and suggested that the effect of a remedy on a metabolic block or deflect may therefore be analogous to a lock and key. An esoteric action has been suggested by Barnard & Stephenson (1969) in which they consider that in disease large excursions in entropy occur. The homoeopathic remedy would provide informational content which would somehow act in an anti-entropic manner.

Other authors, presumably in recognizing the difficulty of` explaining the action of homoeopathic medicines within a conventional materialistic framework, have proposed that health is maintained by some energy field that permeates or surrounds the body (c.g. Roberts, 1942; Vithoulkas, 1980). Deviations in this energy field, the exact description and name of`which varies between authors, give rise to disease and homoeopathic remedies, it is proposed, effect a cure by virtue of their inherent energy patterns which correct the distorted energy field of`the body. Explanations at this, or even at a spiritual level. a concept suggested by Hahnemann himself`, are virtually impossible to prove or disprove. This, however, does not mean that they are wrong. As Helmholz cautioned us: "I beg of you not to forget that even materialism is a metaphysical hypothesis, an hypothesis that proved very fruitful indeed in the field of the natural sciences, but nevertheless is always an hypothesis." (from Guttentag, 1940).

There is as yet no evidence to suggest that any of these proposals is valid. Indeed, despite the publication of a number of papers on the physical structure of` potentized remedies these are, on the whole, so poorly presented that it would be fair to say that there is little good evidence that there are significant reproducible differences between specific remedy potencies and their vehicle. With the equipment now available statistically sound scientific investigation in this field can be performed. Nevertheless, although it is interesting to demonstrate that physical changes occur in potentized remedies this is not sufficient.. They must be shown to have an effect on the sick organism. In this context the words of Virchow "The possibility of an explanation is no scientific criterion" (from Guttentag, 1966) are very apt.

The Arndt-Schulz law. The Arndt-Schulz law has been used as one of the scientific explanations in support of homoeopathic medicine in spite of the fact that the law does not contain any explanation as to its activity. This law, also known as Hueppe's Rule, states that substances which inhibit biological processes at sublethal levels may be expected to stimulate them at lower levels. The phenomenon was first described for the growth and respiration of yeast by Schulz (1888) and later Hueppe (1896) demonstrated that bacteria behave in the same way.

Throughout this century numerous examples of the activity of` the Arndt Schulz law on a variety of biological phenomena in a wide variety of` organisms have been published (Stabbing, 1982). Kon (1978) has drawn attention to the dangers of assuming a monotonic (i.e. linear) dose-response relationship of an organism to drugs in the safety testing of food additives. He suggests that a number of additives, although safe at the high levels usually used in drug safety evaluation, may in fact represent a hazard at the low concentrations at which they are normally used. He provides evidence to suggest that they exhibit paradoxical effects in that their dose response does not obey the monotonicity rule.

The phenomenon of` paradoxical responses has also been investigated extensively by Wilder (1957) who formulated the "Law of Initial Value". This law states that "there is a specific inverse relation between the intensity and direction of a response to a stimulus on one hand, and the pre-experimental level of` a function tested on the other". Thus, for example, benzedrine or caffeine may prove stimulatory to normal people yet act as a sedative in those already stimulated e.g. restless and agitated children. Numerous physiological, neurological and psychological examples are given by Wilder (1957) in support of the law. The recognition of` such a property of biological systems is of obvious significance to homoeopathy where a substance which causes a specific symptom in a healthy organism is given to alleviate the symptom in a sick one. The initial value of the symptom in the sick organism is obviously at a much higher level than in a healthy organism which does not exhibit the symptom or exhibits it only at a very low level. Under these circumstances, Wilder's law may be of significance in remedy action, although Wilder's law is not so dependent on dose level as on the initial value of the function being tested. The Arndt-Schulz law, on the other hand, is directly related to dose level and the paradoxical responses are produced at low dose levels, which is characteristic of homoeopathy.

The Arndt-Schulz law forms the basis of the phenomenon of hormesis, a term first proposed by Southam & Ehrlich (1943) to describe "a stimulatory effect of subinhibitory concentrations of` any toxic substance on any organism." In his review of hormesis Stebbing (1982) presents numerous examples of growth stimulation in a wide variety of organisms by substances which are toxic to growth at higher levels. He discusses the various suggestions put forward to explain this effect but tends to the view that a single explanation may suffice rather than different ones for each specific substance. He argues that the effect is at the level of the biosynthetic control mechanisms. At high levels the toxicant will inhibit these mechanism and reduce growth etc.

At low levels he suggests that the toxicant may exert the same effect but the organism is capable of correcting at the biosynthetic level. He suggests, however, that the biosynthetic mechanisms tend to overcorrect over a limited range of subinhibitory concentrations of toxicants and this results in hormesis. In Stebbing's words "This interpretation suggests that the increased growth is not in itself an adaptation to minimise the effects of` growth inhibitors, even though this might be expected to reduce tissue concentrations, but rather it is a consequence of the adaptive behaviour of rate sensitive control mechanisms." Although Stebbing concentrates on growth hormesis the term is not restricted to growth alone.

In the many examples given by Stebbing hormesis only occurs at levels of` toxicant which would, by homoeopathic standards, be high and represent very low potencies. The lowest concentration of any substance that demonstrated growth hormesis was of the order of 10-5 - 10-6 g.l-1 which is equivalent to a homoeopathic dilution of only about 4c, or even lower if the diluting effect of the body is taken into account. Moreover, the difference between dose level resulting in hormesis and that resulting in growth retardation is often of a single order of magnitude (i.e. 10x) which would only represent one decimal potency! It seems, therefore. that although the Arndt-Schulz law may, on cursory examination, be a useful start for a scientific explanation of homoeopathic activity it could only hold water at low potencies, and, in view of what has been said above, it is extremely doubtful whether the Arndt-Schulz law could even operate at these potencies. At the potency levels normally used in homoeopathic medicine the Arndt-Schulz law as an explanation of homoeopathic action is a non-starter.

DISCUSSION

It is obvious from the comments made during this review that much of` the experimental work is open to a number of criticisms. In this section the main criticisms will be considered and suggestions made on how they may be overcome in the future.

Many of the papers considered above did not make any statistical analysis of the data. In other work where analysis of the data was claimed the data were often not presented in a way that allows an independent assessment of the authors' claims, e.g. no indication as to sample size or variance is given. It must be said that the impression was gained that statistical analyses were sometimes used where a positive result was to be gained whilst it was ignored in cases of negative results and general conclusions were derived from the data which would not be supported by a proper analysis. In many papers other methodological details, essential both for a critical assessment and for repeating the work, are missing, e.g. precisely how the controls were organized.

The bulk of the papers for these reasons alone, would not be accepted for publication in a conventional scientific journal such as Biological Agriculture and Horticulture.

Even when positive results were obtained in well-controlled and well analyzed experiments these results often stand alone. Often no repetition of the experiment appears to have been made--or at least it has not been published--and it is unfortunate that in most of the cases where promising work has been repeated independently, and the results published, these have been negative. In conventional science repeatability of a phenomenon is essential for its general acceptance and this is particularly important in homoeopathy if its validity is to be accepted by the scientific community at large.

Kollerstrom (1982) has discussed the problem of non-repeatability and has pointed out that even one positive result, if statistically satisfactorily proven, then has to be fitted into some framework of explanation as a "fact". She suggests that the role of` the experimenter ("experimenter effect") should be considered in these cases. Such phenomena as non-repeatable positive results are not, of course, confined to homoeopathic research and occur not uncommonly in conventional scientific experiments. Such observations often pass with little comment as they are assumed to be due to various, often obscure, uncontrolled factors which, if recognised and controlled, would lead to the desired result.

In many experiments no hypothesis was being tested. Indeed, in some cases, no indication at all is given as to why the experiment was performed! This state of affairs is particularly surprising as there is a view amongst some homoeopaths that homoeopathy is the only truly scientific branch of medicine (but see Campbell, 1978 for further discussion of this)! A testable hypothesis should, thus, easily be framed. The failure to clearly identify the rationale of the experiment is a particularly damning criticism of much of the work.

In some trials where a large range of potencies was tested and positive results were obtained these have often been at potencies that are not normally used by homoeopaths. It is also unfortunate that in one of the best series of trials Boyd often found that potencies of HgCI2 that significantly stimulated diastase activity in one series of tests would inhibit them in another. Causes of such variations between trials have sometimes been attributed to differences in the composition of the remedy or to changes associated with the time of the month or year. If such observations were shown to be valid, and they have yet to be, then it would be almost impossible to practise homoeopathy satisfactorily.

Some of the trials were frankly badly designed. This is particularly true of some clinical trials where a remedy, rather than the system, was tested. Homoeopathy is essentially an holistic therapy and can only truly be tested as such. I do not believe that this makes it particularly non-amenable to double blind trials as Monro (1983) suggests. To date the best clinical research which demonstrates the effectiveness of homoeopathy (Gibson et al., 1980a, b) used a double-blind design incorporating individual prescribing.

Double-blind techniques can be applied to laboratory experimentation more easily than to clinical trials. Here a limited number of`remedies are being tested in a systematic way, often in a simplified, highly controlled system. Despite the amenability of the laboratory situation to the blind technique it appears to have been infrequently used, or if it has been it was not stated. Admittedly, the double-blind technique is frequently not used in conventional science but, providing the results do not affect the fundamental tenets of the particular field, few people worry. Homoeopathic research is a threat to conventional wisdom as it cannot be understood in conventional terms and thus the smallest detail may become open to criticism in an attempt to discredit the unexplainable. Greater caution is thus required in the design and execution of experiments than in conventional science if the results are to gain any credence with the scientific community. Unfortunately, the way in which much homoeopathic research has been reported is slipshod and does not inspire confidence in the reader.

In my opinion it could be argued that the controlled laboratory experiment hears little resemblance to homoeopathy in its broad conception and it is questionable to extrapolate any results thus obtained to the clinical situation. Indeed, even in 1922 Faber (Guttentag, 1940) had stated with regard to bacteriological therapy that "the artificially induced disease is not the same as the spontaneously occurring infectious disease." Many of the laboratory experiments used artificially induced diseases or experimental poisonings as test systems. Such procedures lay emphasis on the importance of the causative organisms or chemicals and not, as homoeopathy would have us believe, on the susceptibility of the organisms to disease which is caused by other, often unknown, factors. It is this susceptibility to disease, as a reflection of the disturbed equilibrium of the organism, that is being treated by homoeopathy. In a recent letter to Kollerstrom (1982) Flemming colluded that the experiments involving artificial poisoning of cress seedlings, and their subsequent treatment with the potentized poison, would not lead to an understanding of the action of homoeopathy.

Many experiments have attempted to demonstrate some effect of homoeopathic remedies on normal organisms, although the reasons for doing this are rarely obvious. How are we to interpret any positive results that this work proves? Does it mean that all normal plants and animals are in some way out of balance so that they are capable of responding to homoeopathic remedies, sometimes in a positive, but also sometimes in a negative manner? Or are some normal organisms sufficiently sensitive that they are capable of having their normal equilibrium disturbed by homoeopathic remedies, as suggested by Hahnemann? I quail at the implications of some of the work reported above which claims that high potencies of various substances are capable of causing ill-health and even death in normal animals (e.g. Stearns, 1925; Konig, 1927; Vondracek, 1929). This work has never been confirmed, and I suspect that it will not be, but if it is how then are we to regard the safety of homoeopathic prescribing? In view of the potential safety problems of incorrect prescribing or free public access to remedies the possible effects of remedies on normal organisms should be a priority of extensive investigation. The work of Moss et al. (1982) suggests that only a minority of normal subjects are sensitive to remedies and, if confirmed, the work done on normal organisms is not easy to interpret and can hardly be expected to lead very far. Also the rationale of studies which attempt to demonstrate deleterious effects on entire disease organisms e.g. bacteria or fungi in vitro is surely suspect within the holistic framework of` homoeopathy. Although the ability to destroy specific pest and disease organisms using homoeopathic remedies would be a boon to biological agriculture the concept of wholesale destruction or interference with reproduction is anathema to the concept of homoeopathy which is surely aimed at making the affected organism more resistant to infection rather than the destruction of some potential disease organism.

It has not been my intention in this review to be destructively critical of the work conducted in homoeopathy. Much of the work condemns itself. There is some experimental evidence to suggest that homoeopathy could be effective and a large number of reports of successful clinical experience which suggests that despite the general failure of scientific investigation to support homoeopathy something is afoot that is worthy of proper investigation. As Stoff (1983) has aptly put it "It is a highly questionable scientific practice to dismiss a body of significant empirical evidence (such as homoeopathy) simply because the underlying philosophy, which rationally interprets such results, assumes premises foreign to those currently accepted".

The research reported in this review certainly does not disprove the efficacy of homoeopathy; rather, because of its poor design or execution or reporting,or because of its incompleteness it does little to prove that homoeopathy works. And when this therapeutic system is opposed and disbelieved by the bulk of the scientific and medical establishment the onus is upon the system to prove itself. It is, unfortunately, judged guilty until proven innocent. I do not believe that homoeopathy is not amenable to scientific demonstration. It does, however, require careful consideration of what it is that you are testing and I believe that the most convincing test of homoeopathy will be as a system on sick or susceptible organisms and not on isolated parts of the system under highly artificial conditions. An hypothesis must be framed and tested by very carefully designed and executed experiments. The hypothesis must be such that it can be disproved. As Popper (1972) has stated, the criterion of the scientific status of a theory is its falsifiability, or refutability, or testability. It is possible that the entrance of personality, both of the physician and the patient is of crucial importance in the treatment. Even in 1926 Krehl (Guttentag, 1940) suggested that the further development of medicine lay in the entrance of personality as an object of research and evaluation. Such a concept is recognized as important in fundamental particle physics. Nevertheless, I do not believe that this renders double-blind trials impotent as Monro (1983) suggests. But they certainly need careful design.

Some of the problems involved in conducting research in homoeopathy, particularly of a clinical nature, was discussed in a recent paper by Ives (1983). He also suggests lines of future research and criticizes many of the published investigations in the field for reasons similar to those presented in this review.

THE POTENTIAL OF HOMOEOPATHY IN AGRICULTURE

The concept of homoeopathy as an holistic system of medicine which attempts to raise the level of resistance of an organism to disease or to stimulate its inherent ability to throw off disease is compatible with the wider concepts of biological agriculture. Homoeopathy is generally thought to be a safe method even when applied wrongly, although this point needs some clarification, it is non-polluting both of the environment and of the food product, and the medicines are much less expensive than conventional drugs. As this review emphasizes, however, its efficacy in the treatment of disease has yet to be satisfactorily, scientifically, demonstrated.

The role of homoeopathy in the treatment of animal diseases is clear and is similar to its place in the treatment of human diseases. Interest in this field is increasing (Anon., 1982) as more practitioners recognize the limitations and potential dangers of conventional, allopathic medicine and search for safer, effective alternatives. The homoeopathic veterinary materia medica is based on the human materia medica, provings having been made on humans rather than on animals. The materia medica is supplemented with material gained from experience with clinical cases. The toxicology of a number of substances that are used to make homoeopathic remedies is different in domestic animals than in man e.g. Nux vomica, aconite, belladonna (Scott & McCourt, 1982) and need to be specifically dealt with in a veterinary materia medica. Obviously, as animals cannot describe their symptoms the vet must rely on what he can observe and the symptoms available on which to base the selection of the similimum are much more limited than in the case of human patients. Possibly as a result of these limitations a wide range of nosodes has been developed in veterinary homoeopathy to treat and prevent specific diseases (MacLeod, 1983).

The possibility of using homoeopathic remedies prophylactically is probably much stronger in the veterinary field than with humans, as the concentration of animals with modern production methods allows relatively easy treatment. Many of the most important animal diseases are, in fact, a consequence of modern production methods, they very often occur on a herd, rather than an individual basis, and their aetiology is often clearly defined Hodges & Scofield, 1983a, b). Because the predisposing causes may often be clearer than in human medicine remedy selection may be facilitated and the disadvantages of the lack of subjective symptoms for similimum selection may be offset to a certain extent. When used prophylactically, of course, the selection of remedy does not depend on symptoms, which will not have appeared, and the choice of a suitable remedy can, therefore, be reduced to a narrow range. It is in the field of veterinary prophylaxis that Elm Farm search Research Centre, in conjunction with Wye College (University of London) and the University of Kassel have begun a double-blind trial of the efficacy of homoeopathic prophylaxis in the prevention of milk fever in cattle.

The work reported by various Indian teams on fungal and viral diseases in plants leads to the exciting possibility that plant diseases may be controlled by the use of homoeopathy. The most obvious successes in this field, and indeed in many of the experiments with animals, has been with the prophylactic use of the remedies to prevent or reduce the severity of disease. There is no materia medica for plants and a great deal of careful thought and intuition will be required to select the correct remedies unless one resorts to isopathic methods with nosodes.

Very little homoeopathic work has, as yet, been conducted on diseased plants under natural conditions and it is too early to assess the potential of homoeopathy in the control of crop diseases, although the work reviewed would suggest that this is an area that could warrant further investigation. How homoeopathy could be used in the control of pests of crops is open to conjecture. Without killing the pests, which seems hardly commensurate with homoeopathic philosophy, the only conceivable ways in which the therapy could be of some use is to strengthen the resistance of the plants to the effects of pest attack, make them less attractive to pests, or to stimulate the reduction of predators.

Finally, as homoeopathy is aimed at producing a bodily state that is not conducive to the development or support of disease the possibility arises of treating the soil, which may well have been imbalanced by agricultural practices (Hodges & Scofield, 1983a, b), to prevent the development of disease in those organisms that rely upon it for their sustenance. Such a philosophy is part of Biodynamic farming and the soil is sprayed with a preparation (No.500)which is a high dilution of cow manure (Pfeiffer, 1947; Koepf, 1976)and it claimed to have a beneficial effect on the subsequent crops.

CONCLUSIONS

It is obvious from this review that, despite much experimental and clinical work, there is only a little evidence to suggest that homoeopathy is effective. This is because of bad design, execution, reporting, analysis and, particularly, failure to repeat promising experimental work and not necessarily because of the inefficacy of the system which has yet to be properly tested on a large enough scale. There is sufficient evidence to warrant the execution of well designed, carefully-controlled experiments to investigate the efficacy of homoeopathy further. In view of the holistic conceptual framework of homoeopathy it seems to me that the most valid experimental approach would be to test the system on naturally diseased or susceptible animals rather than isolating and testing parts of systems in the laboratory, or artificially inducing disorders and concentrating on the causative organisms or factors. Included in the susceptible category could well be studies on poisoning, particularly with heavy metals, a situation that is increasingly relevant in today's industrial society, and its prevention and treatment with isopathic remedies. Moreover, instead of proliferating experimental models, as this review has clearly shown to be the case up to now, and frequently only using them once, it is desirable that two or three conceptually sound test systems should be developed which should be used over and over again in different laboratories in an attempt to demonstrate that any homoeopathic phenomena are repeatable.

Although homoeopathy has most certainly not been disproved it is hardly surprising, in view of the quality of much of the experimental work as well as its philosophical framework, that this system of medicine is not accepted by the medical and scientific community at large. Certainly, should sufficient evidence accumulate to suggest that homoeopathy is effective then one's views, not only of disease, but also of the nature of man, may have to be radically reviewed.

At present, however, there may be some justification in the orthodox school treating homoeopathy with suspicion although hardly with the unscientific criticism that it frequently publishes. Apart from the evidence not proving homoeopathy's case a number of observations have been made which appear inconsistent with the views of many homoeopaths and need to be clarified. For example, the question of safety of homoeopathic remedies when incorrectly used needs urgent consideration. The observations that homoeopathic remedies may potentially affect normal organisms and indeed, may be used at the 30th potency in provings, is inconsistent with the often quoted remarks that at least homoeopathy will do no harm even if it does no good! Anyway, a placebo effect is hardly justification for an entire system of medicine!

Another area of fundamental importance, particularly from a point of view of practice, is that of sensitivity. There is some evidence that not all organisms are sensitive to homoeopathic remedies. It is absolutely essential that this be clarified and, if found to be true, tests must be developed to identify those responsive to homoeopathic remedies. If this is not done then, although one may eventually demonstrate that homoeopathy is a statistically effective form of treatment, unless its success rate approaches that of orthodox therapy it is unlikely ever to make much impact, except largely as a therapy of last resort. Indeed, unless a substantial programme of investigation by trained scientists is undertaken on a continuing basis this is what homoeopathy may remain.

ACKNOWLEDGEMENTS

I should like to thank Dr. Linda Fellows, Dr. Jean Kollerstrom and Dr. David Hodges for their helpful comments during the preparation of` this review.

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Pelikan, W. & Unger, G. (1971). The activity of potentized substances. Experiments on plant growth and statistical evaluation. British Homoeopathic Journal 60, 233-266.

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Stoff, J.A. (1983). Homoeopathy--a clinical science. British Homoeopathic Journal 71 148- 151.

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Verma, H.N., Verma, G.S., Verma, V.K., Krishna, R. & Srivastava, K.M. (1969). Homoeopathic and pharmacopoeia! drugs as inhibitors of tobacco mosaic virus. Indian Phytopathology 22 188-193.

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Wannamaker, A.K. (1968). Further work with boron dilutions and dynamizations. Journal of the American Institute of Homeopathy, 61, 28-29.

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(Received :25th November 1983)

Copyright © 1984 A B Academic Publishers. Reprinted with permission. All rights reserved.


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