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  Understanding The Active Principles of Mistletoe
  

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By: Armin Scheffler, Ph.D.
(Original title: Zum Verstaendnis der Mistelarzneistoffe. Der Merkurstab 1996; 49: 97-100. English by A. R. Meuss, HL, MTA)

The background to this paper is the connection between the processes that lead to cancer and the processes of mistletoe development. This is intended as a basis for understanding the active principles of the plant. Aspects considered are "embryonic quality"(1,2) "time shift in developmental processes",(3) and "sense organs developing in the wrong site"(4) in both humans and mistletoe.

To treat cancer, the proliferating etheric principle,(5) elsewhere called a "revolution of physical forces" by Rudolf Steiner,(6) must be removed, using a natural activity. When this obstacle in the physical body has been removed, the next step is to encourage the human ether body to act in the direction of the tumor site. This means that I and astral body are activated again in the human metabolic sphere by giving mistletoe. The aim is to create a mantle of warmth. This will restore the balance, creating healthy alternating reactions between upper and lower human being in the metabolic sphere. This is often connected with biographic characteristics.

We know today that mistletoe toxins are able to cause natural cell death (apoptosis) in growth-activated tissue, which includes tumor tissue.(7) The process is connected with the mistletoe lectins, the most powerful mistletoe toxins, and one sees a definite reaction when mistletoe lectins are given to patients. Antibodies to the lectins develop within a few weeks. In vitro studies have shown that the antibodies neutralize the cytotoxicity of the lectins.(8) However, when the human ether body needs to be involved in the site of the tumor process again in the second phase, a second process develops which is clearly connected with other mistletoe constituents. Characterization of a substance derived from the live sphere of the mistletoe is the main aim of this paper.

We generally differentiate among three groups of substances in the sphere of organic life: those related to fat, those that are sugar-like, and proteins. Here, a substance from among the fat-related mistletoe compounds will be presented, signs of tumor activity from this group having been extraordinarily sparse until now.

There are three different types of fat-related compounds. Cutins and waxes on one hand and fats on the other are deposited, whereas membrane lipids always remain part of the vital process concerned.

Cutins create a membrane of polymeric hydroxy fatty acids (polyesters) on the surface of every non-aquatic plant. Waxes are normally deposited within or on cutins. In terms of the generative organism, cutins and waxes are substances that have reached the end of the road. Higher animals are unable to digest them.

The second group to be withdrawn from the vital process, at least temporarily, is the fats. They are typical storage compounds deposited inside cells in droplet form. They are utilized above all for the energy metabolism of future processes, be it in the plant itself or for other organisms. We may thus speak of fats having future potential.

Here, the membrane lipids of mistletoe are of special interest. Small in quantity, they are extremely important in functional terms. Forming double layers (membranes) they set the limits everywhere to different functional spheres. What is more, the biological membrane itself supports numerous physiological functions. Every biological membrane is always fully adapted to existing conditions of life. If the outside temperature changes, the lipid composition of the membranes also changes. Processes of uptake or secretion are induced when substances approach a membrane. Being the border between different functional spheres, every membrane has an electrical potential that must be actively maintained in physiology. The best known are the potentials of cell membranes themselves which depend on the potassium and sodium concentration. Membrane lipids are therefore the most vital in this group of substances.

In mistletoe, almost all organs of which are green, the densely packed membrane systems of chlorophyll-containing chloroplasts are particularly numerous. When fresh mistletoe is triturated in an aqueous system for pharmaceutical production, the different membranes of the plant tissue are torn open and spontaneously change into small hollow spheres in the medium. These are called vesicles. Working with Prof. Kabelitz's group in Langen, we were able to show that membrane vesicles obtained from fresh mistletoe grown on apple trees can stimulate the release of tumor necrosis factor alpha and of interieukin beta from blood monocytes. Cytokine release causes activation of inflammatory processes that are desirable for tumor resistance.

A second discovery is that membrane vesicles in particular are able to stimulate lymphocytes of mistletoe-treated patients. This was demonstrated as follows. Breast cancer patients were treated with Abnobaviscum Mali 4. Before and 1,4 and 12 weeks after starting treatment, their blood lymphocytes were assessed to see if growth could be stimulated by the mistletoe preparation used and the vesicles. Before and after 1 week's treatment the lymphocytes could not be stimulated in vitro. However, after 4 and 12 weeks' treatment, spontaneous proliferation was increased by a factor of c. 15 on exhibition of mistletoe. Stimulation was distinctly better if isolated vesicles were used. In this case, the increase in proliferation rate was by a factor of c. 45.

The two above discoveries are meant to serve as examples, showing that exhibition of mistletoe stimulates a cancer patient's potential for inflammatory reaction. In anthroposophical terms this may be seen as activation of the astral body and of the I in the ether body. This agrees with Rudolf Steiner's statement that the astral body can be stimulated by exhibiting live matter, the forces of the ether body by exhibiting matter of animal origin.(5) In the present context, it is important, therefore, that a pharmacological effect is produced not only by the toxic constituents of mistletoe. As already mentioned, toxic substances can influence proliferative etheric principles. Yet pharmacological actions can also be obtained with non-toxic substances such as the membrane lipids, and these are particularly important in the second phase of tumor treatment.

The discoveries were made with isolated substances. In the treatment of cancer it is, however, important to utilize the whole range of mistletoe actions. This should also be reflected in the pharmaceutical process. We have therefore done a more detailed study of interaction between lectins and vesicles. This seemed indicated because membrane vesicles carry galactose on their surfaces that are capable of binding lectins. Distinct interactions were indeed found to take place between lectins and vesicles; these are shown in Fig. 1.
Lectin activity was defined in terms of their capacity for hemagglutination. The method is to make a series of lectin dilutions (1/2, 1/4, 1/8, ...) and determine which still effects agglutination. With the lectins used, this was the case up to the 1/64 dilution. Using another analytical method (AC ELISA and BC ELISA) the lectin concentration was found to be 87 /ug/ml. This is shown as the first set of bars. The third set shows that simply mixing vesicles and mistletoe lectin I means that after an incubation period of 3 days the agglutination titer is surprisingly increased by a factor of 4-8, whereas only a fraction of the lectin content is found using the two ELISA methods. The conclusion is that lectins do not bond to the vesicles through sugars, as expected, but by being incorporated in the vesicle membrane.

To see if the lectins are, indeed, firmly bound to the vesicles, an attempt was made to remove them by means of the usual affinity chromatography. The 4th set shows that this only proved possible to a limited extent. Following affinity chromatography, the vesicles still showed markedly elevated hemagglutination compared to the pure lectins. The ELISA readings were reduced by a further 2/3. The fifth set of bars shows that after incubation with the vesicles only 1/5 of the lectins used could be separated from the vesicles by affinity chromatography. If one also considers that cytotoxicity studies have shown that the acute cytotoxicity of lectins is reduced by about two



powers of ten by binding them to vesicles, the interaction not only points to bonding of these two mistletoe substances but also shows that all available analytical methods show marked changes in mistletoe lectin activity in the presence of vesicles consisting of mistletoe membrane systems. The discovery may initially be taken simply as a scientific phenomenon. Other work done on membrane systems nevertheless leads one to expect that the immuno-logical effects in particular are markedly changed when mistletoe substances are incorporated in membrane lipid vesicles.(9)

These investigations to gain understanding of mistletoe constituents encourage the clinical approach that distinction should be made between different phases of treatment. The beginning of mistletoe treatment is the phase wherein mistletoe toxins can have powerful cytotoxic actions. Adequate dosage is a precondition for this. The organism is able to neutralize cytotoxic lectins and viscotoxins within a few weeks by producing antibodies. In the second phase, therefore, we need to stimulate the patient's capacity for inflammatory reactions. This will restore the potential for interaction within the equilibrium of the I organization that is necessary for the human individuality. Additonally, biographic work is required so that genuine healing may be achieved.

References
1 Kipp FA. Die Evolution des Menschen im Hinblick auf seine lange Jugendzeit. Stuttgart: Freies Geistesleben 1980.
2 Gcebel T. Erdenseele und Landschaftsgeist - Gestaltwirkungen geistiger Wesen im Pflanzenreich und in der Mistel. Persephone 6. Dornach: Verlag am Goetheanum 1994.
3 Sterner R. Spiritual Science and Medicine (GA 312), lecture of 27 March 1920. Tr. not known. London: Rudolf Steiner Press 1975.
4 Steiner R. What can the Art of Healing Gain through Spiritual Science? (in GA 319). Amhem, lecture of 24 July 1924. Tr. G. Kamow. Spring Valley: Mercury 1986.
5 Sterner R. An Outline of Medical Research. Report of lecture of 29 August 1924. (in GA 319). Tr. not known. London: Rudolf Sterner Press 1939.
6 Steiner R. Spiritual Science and Medicine (GA 312), lecture of 2 April 1920.
7 Janssen 0, Scheffler A, Kabelitz D. In vitro effects of mistletoe extracts and mistletoe lectins: cytotoxicity towards tumor cells due to the induction of programmed cell death (apoptosis). Arzneim Forsch/Drug Res 1993; 43:1221-7.
8 Stettin A, Schultze JL, Stechemesser E, Berg PA. Anti-mistletoe lectin antibodies are produced in patients during therapy with an aqueous mistletoe extract derived from Viscum album L. and neutralize lectin-induced cytotoxicity in vitro. Klin Wochenschr 1990; 68:896-900.
9 Bergers JJ. l-iposomes as vehicles for proteins. Mode of protein association and application in tumour immunology. Dissertation, Utrecht University 1992.





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