The formic acid process in humans
Formic acid was given by Rudolf Steiner as a "classical example" of anthroposophically extended pharmacognosy.As he put it, formic acid is continually produced from oxalic acid in the human organism. The conversion of matter was stated ultimately to lead to formic acid "everywhere in the body". The final step in this metamorphosis of matter, the conversion of oxalic acid to formic acid, releasing carbon dioxide which is then exhaled, is,according to him, the necessary basis for astral body activity in this organism. (1,2) In aging individuals and also with some pathological conditions,the ability to do this is reduced, and death finally ensues when the ability to produce formic acid ceases altogether.1 With pathological conditions, it would be possible to give either the formic acid, of which too little is produced, or its precursor oxalic acid. Rudolf Steiner said that it was not the substance itself that mattered in this, but the activity, the process, of producing it.
In the 1920s this did not conflict with current knowledge of physiology.All kinds of organic acids were known to occur with the degradation of carbohydrates, fats and proteins in the human metabolism. On the other hand, the question as to how the carbon dioxide we exhale was produced was then one of the great unsolved questions in biochemistry. (5) A hypothesison the degradation of carbohydrates and fats offered by Thunberg in 1920that was taken up by others does not differ greatly from Steiner's description.According to Thunberg, acetic rather than formic acid was produced in addition to carbon dioxide; this comes next in the series of carboxylic acids.Analogous to this, Thunberg's precursor was not oxalic but pyruvic acid.Other variations on the same theme were postulated for the degradation of various amino acids, which means that the production of formic acid from oxalic acid might well have been considered another possibility.
The situation is very different today. Full details of how carbon dioxide develops in the human body and which acids are involved in the process have been known for a long time. Conversion of oxalic to formic acid has not been confirmed. In fact, one of the reasons why oxalic acid is toxic is that unlike various plants and bacteria, humans are evidently unable in principle to metabolize it. Even if a low degree of such activity were to be demonstrated, anyone taking the scientific view would be unable to accept the statement that everywhere in the human organism the conversion of matter ultimately leads to this process, and that this would be a physiological process of such fundamental importance that it is a matter of life or death.
If we simply repeat the statements Steiner made in the 1920s today, we are clearly going against established knowledge in the field of physiology,which obviously would not have been Rudolf Steiner's intention. (6,7) In this particular case he expressly hoped that the things he spoke of would also discovered in "modern physiology". (2) He said this would not be possible,however, for as long as processes within the human being were regarded in the same way as "external processes", like the laboratory experiment he himself gave as an example. According to him, the process is different inhuman beings than it is in a retort, and it was not the substances mentioned that mattered but the process he characterized.
Below it will be shown that research in biochemistry and physiology has actually discovered this "formic acid process" a long time ago and sorted out many of the details. (8) This resolves an apparent conflict between conventional medical research and its anthroposophically extended form.
How is carbon dioxide produced in humans?
By far the most important sources for carbon dioxide in human metabolism are the three oxidative decarboxylation processes, as they are called, in the citric acid cycle (Deviating from current usage the names of the acids are used in this context and not those of their salts, i.e. citric acid rather than citrate, pyruvic acid rather than pyruvate, etc.) and glycolysis. All the carbon dioxide produced in the conversion of carbohydrates, fats and most amino acids arises with decarboxylation, when acid or carboxyl functions (COOH groups) are split off asCO2. Another decarboxylation process that goes in exactly the same way occurs in the degradation of the branched-chain amino acids valine, leucine and isoleucine. The only minor deviation is the first decarboxylation to breakdown the aromatic amino acids phenylalanine and tyrosine, which will be considered later.
Apart from this in anabolic processes.(9) This happens most intensively in connection with fatty acid synthesis in fatty tissue. The reduction equivalents needed are obtained by breaking down sugars by the pentose phosphate pathway. Carbon dioxide is again the result of decarboxylation. Compared to oxidative conversion, however, no oxygen is used in this case. Other CO2sources of very minor significance in terms of quantity are the biosynthesis of porphyrin (hem) and of cholesterol, in both cases with special decarboxylation processes. For the sake of completeness let me also mention the decarboxylation processes involved in fatty acid synthesis as such and in gluconeogenesis. These merely release the carbon dioxide which immediately before was bound by carboxylation. Then there is also the spontaneous decarboxylation of the "ketone body" acetoacetate to give acetone. This occurs only with starvation and in diabetics.
Oxidative decarboxylation processes
The principle of oxidative decarboxylation is most easily shown with the decarboxylation of pyruvic acid, an intermediate product of glycolysis. The process was suspected by Thunberg and has been confirmed since the 1940s.The acid function of pyruvic acid, its carboxyl or COOH group, is released asCO2. This decarboxylation process is coupled with the oxidation of the neighboring functional group, a keto or carbonyl function (C = 0) to give anew carboxyl function. The result is that the process yields another acid as well as carbon dioxide, in this special case acetic acid, or rather acetyl-CoA, abound form of acetic acid. (Mere decarboxylation without oxidation would yield acetaldehyde.)
The process is exactly the same with the decarboxylation of alpha-keto-glutaric acid in the citric acid cycle and the special decarboxylation processes in the degradation of the branched-chain ammo acids. In all these cases the carboxyl function which has been removed is immediately replaced by a new one in the process of oxidation. Even the enzymes and co-factors involved in the process are always very similar if not identical. (10)
As already mentioned, the first decarboxylation in aromatic amino acid degradation takes a slightly different course. The above-mentioned decarboxylation processes can only be called oxidative in formal terms in so far as aketo function gains a higher oxidation level and becomes a carboxyl function.As with most biological "oxidations," it involves the withdrawal of hydrogen instead (dehydrogenation), in conjunction with the addition of water. The degradation of aromatic amino acids on the other hand is a case of genuine oxygenation, with oxygen added directly. This is a general characteristic of aromatic substance degradation.(9) In this case the effect is the same, however,as in the previous cases. The split off carboxyl function is immediately replaced by a new one as the neighboring keto function is oxidized.
A special feature of a different kind may be seen in the other decarboxylation process in the citric acid cycle, which we have not yet considered - isocitric acid. In this case, oxidation (or rather dehydrogenation) takes place but there is no new carboxyl function. This is, however, only a very minor change from the decarboxylation processes discussed so far. With them, the starting material was always an alpha-keto acid, i.e. a carboxylic acid with a keto function immediately adjacent to the affected carboxyl function. In a way this is also the case with isocitric acid decarboxylation. Here, too, an alpha-keto acid is initially produced - oxaloacetic acid. This is not decarboxylated immediately, however, but only after binding an acetyl group to the alpha-keto function. Here substance is brought into the citric acid cycle between the production and decarboxylation of the keto acid, with the result that the cycle is maintained in spite of losses due to decarboxylation. Binding of the acetyl group means that the keto function cannot be oxidized to become a carboxyl function, but the acetyl group (= acetic acid) adds a further carboxyl function.Oxidation then leads to a new alpha-keto function instead, and the next oxidative decarboxylation step can follow immediately. Apart from these peculiarities, which are connected with the cyclic nature of the whole process,this oxidative decarboxylation is completely the same as the others that have been mentioned.
The last decarboxylation process to be considered is the one in the pentose phosphate pathway. As already mentioned, this is also oxidative, at least in formal terms, but does not even involve indirect oxygen consumption. In the citric acid cycle, glycolysis and amino acid degradation dehydrogenation causes the hydrogen which is withdrawn to be added to the respiratory chain as a reduction equivalent and hence indirectly to the oxygen. In the pentose phosphate pathway it is retained and used in reductive biosyntheses. Another particular characteristic is that no keto acid is decarboxylated- not even indirectly as in the case of isocitric acid - but a saccharic acid. The product of this oxidative decarboxylation thus is not an acid but a sugar. This process may also be cyclic, when the sugar (a pentose) reduced in length by degradation is through a series of conversions at the sugar level converted back to the original substance (a hexose).
All these decarboxylation processes may evidently be seen as variations of one single process. The most important differences have to do with the relationship to oxygen. If it is merely a matter of providing reduction equivalents for reductive biosynthesis, oxygen is not involved at all, with the cycle remaining at the relatively much reduced sugar level (pentose phosphate cycle). This process, by the way, is similar to the citric acid one in its processual details,(9) - the addition of substances to the citric acid reflecting the involvement of an anabolic aspect. On the other hand oxygen is used directly as an oxidizing agent in the synthesis of aromatics, a group of substances that characteristically show particular persistence and resistance to degradation. (Thus lignin can only be degraded by special micro organisms; other examples are tannins and sporopollenin, the most persistent of all biogenic substances.) The greater majority of oxidative decarboxylations are, however, only made possible by the indirect involvement of oxygen.
Comparison with the descriptions given by Rudolf Steiner
In humans, oxidative decarboxylation continually produces carbon dioxide in all live tissues. All organic matter, except any that is eliminated or irreversibly deposited, will enter into this process at some stage. In conjunction with the processes in the mitochondrial membrane, known to consist in electron transport and oxidative phosphorylation, this is a catabolic process which provides the basis for the life of humans and all ensouled organisms -cell respiration. It is thus evidently an essential basis for astral body activity.Numerous recent investigations have shown that around midlife the function of cell respiration begins to be reduced in vital organs such as the brain, heart and liver, gradually getting less and less.11 When it ceases completely, death ensues very quickly. Cell respiration thus has exactly the physiological role which Steiner ascribed to the formic acid process; the connection with the astral body is also the same.
Chemically, organic acids are decarboxylated in both cases, with acids produced as well as carbon dioxide. There is a difference, however, in that oxalic acid is not a keto acid and its decarboxylation is not oxidative. Yet as Steiner himself said, the process is not exactly the same in humans as in the laboratory experiment which he gave for comparison. Considering the laboratory facilities and skills then available, the experiments actually could not have been done at the time using the keto acids physiologists now consider to be the "right" ones. Pyruvic acid, the simplest alpha-keto acid,would be sufficiently stable chemically, but one could only obtain either acetic acid or carbon dioxide from it by simple chemical means, i.e. without enzymes, and not both at the same time. One would also lose the impressive qualitative aspect of a volatile, pungent fluid and a gas evolving from crystalline oxalic acid that is practically insoluble, pyruvic acid in itself being a pungent fluid. Oxalo acetic acid, which would be the nearest alternative, is already so unstable that it cannot exist as dead matter outside the vital chemical processes.
The kind of comparison we are making here only has meaning if we take account of one fundamental difference between spiritual and conventional scientific research. Conventional science first of all goes into detail; this provides the basis for the elucidation of progressively more complex situations. The spiritual science of Rudolf Steiner, (This refers specifically to spiritual science based on a training that is of the present day, and not to remnants of ancient clairvoyance, where the situation would be different.) (12) on the other hand starts with the greatest and most comprehensive whole picture and may then progress from these to increasingly more complex details. (12,13) Thus going in opposite directions, the two approaches may meet, but cannot take each other's place.It thus shows misunderstanding (sadly common) of the situation when contents presented out of the science of the spirit are treated like findings made in conventional science or even taken in their stead. Things that are accessible to the modern empirical scientific approach, like the details of human biochemistry, for instance, cannot be investigated with anything but the methods of conventional science. (7,13) Conversely, the contents presented by the spiritual scientist must be taken to be what he himself declared them to be- descriptions of events and processes that can only be presented in images.
Might cell respiration thus be the physiological process to which Steiner wanted to refer? The answer should come if we compare the given situations.Steiner chose formic acid as an example to indicate that for anthroposophically extended pharmacology it will be necessary to "perceive the mission substances have in the world". (3) He characterized the world mission of formic acid to be such that it makes aging and decomposing matter that has dropped out of the living context available again for further development. We therefore need to examine if this also describes the world mission of cell respiration and oxidative decarboxylation respectively, or, in a wider context, if the position formic acid has in the world - it was described in detail to the workers building the Goetheanum (1) - is also that of cell respiration . We shall have to limit ourselves to the central aspects. (8)
The world mission of formic acid
Steiner characterized oxalic acid as a substance produced mainly in plants but also in humans and in all organisms altogether. Plant metabolism, he said,only went as far as oxalic acid if left to itself, but interaction with the insect world also produced formic acid, a substance essential for the continued existence of the plant world. Formic acid was particularly in evidence in ants,but was present in all life forms and thanks to the activities of ants also entered into the soil. There it was needed for the healthy decomposition of dying plant matter, so that new life might arise. This also reflected its significance in humans, according to Steiner, something we have already discussed.
Let us now consider each of these in turn in relation to our hypothesis.Oxalic acid is in fact a typical plant substance found in most plants, though usually only in very small amounts. (14) Something to be noted quite generally is that plant saps always contain organic acids in high concentration, compared to human blood. It is however only rarely, in quite specific plants, that oxalic acid really stands out. The most common plant acids are malic and citric acid, two intermediates in the citric acid cycle. In their case it is true that they are also produced in humans and (after minor changes) decarboxylated.
In the flowering region of plants anabolism based on photosynthesis is less, with cell respiration taking its place. Here the plant is quite evidently coming closer to animal nature - directly so with pollination, but also in many ways in the morphology and physiognomy and in the physiology.
Anabolic metabolism in the green leaves correlates with high-level accumulation of different plant acids, and the lamina is characteristically the part of the plant with the highest concentration of acids. Acid levels go down as one moves to the floral region, reaching a minimum in the seed. (15) Actual conversion of oxalic into formic acid has not been observed in this case either.On the other hand there is a definite connection with reproduction, new varieties arising by foreign pollination and the plant world thus ultimately maintained and developing further.
Cell respiration is the process in which organic matter is taken back to its most general, most open original form - carbon dioxide. The significance which carbon dioxide has for the development potential of life, quite apart from photosynthesis, is evident from the fact that the development of young organs in plants, animals and humans often occurs in a milieu with noticeably high carbon dioxide levels, being actively promoted by it. An example would be our own embryonic development. (16,17) In global terms (leaving aside the oceans which have their own circulation) most CO2 is produced in and on the soil in the decomposition brought about by lower animals, fungi and bacteria. It is generally known today that ants play an important role in this. (Steiner, by the way, repeatedly spoke in the same breath of formic acid and the venom of bees and wasps, saying this was related to formic acid and served the same function, only more with regard to flowers, whilst the ants were more concerned with the soil. (1) This is remarkable in so far as bee venom does not contain any formic acid but is, on the contrary,highly basic. (18) A common feature of both poisons is that they are markedly lytic, a property both strong acids and bases have in the inorganic sphere. Here it emerges quite clearly that Steiner was not concerned with formic acid as a substance but with a processual element.)
We need not limit ourselves to the complete decomposition of organic matter, however. Recent work has shown that particularly in woodlands,which Rudolf Steiner was speaking of when talking about ants, a considerable proportion of decomposing material becomes part of the plant sphere again whilst still at the organic level; the mediators for this are soil fungi which on the one hand bring about decomposition and on the other live in close symbiosis with higher plants and supply their needs. (19) In the same way glycolysis in humans not only brings about complete oxidation of the substances, but these processes also provide the versatile starting material for a large number of biosyntheses. The synthesis of non-essential amino acids basically starts from the three alpha-keto acids available here; glucogenesis specially from oxaloacetic acid, whilst almost all the other intermediate products enter into other biosyntheses. There is thus constant renewal of organic substance in humans, it being degraded to the level of these acids and then partly resynthesized again.
There surely can no longer be any doubt but that cell respiration is the physiological process to which Steiner was referring when he said that something similar to the decarboxylation of oxalic acid under laboratory conditions also took place in humans. In view of the extensive agreement between the relevant situations in man as well as in the world of nature outside man, it seems of little importance that the substances involved in the physiology are slightly different from those which Steiner told his listeners he was only presenting as an image for comparison. It seems that at the time,oxalic acid and formic acid made it easiest to demonstrate the principle of a process the physiological and chemical details of which were not yet fully known.
Consequences and prospects
What are the fruits of these deliberations? One immediate consequence is that we should no longer say formic acid is produced from oxalic acid in humans,for that is not the case. Rudolf Steiner himself did not say so either, if we consider everything he said on the subject in context and not take individual statements that may be misunderstood if considered on their own. (Steiner, by the way, repeatedly spoke in the same breath of formic acid and the venom of bees and wasps, saying this was related to formic acid and served the same function, only more with regard to flowers, whilst the ants were more concerned with the soil. (1) This is remarkable in so far as bee venom does not contain any formic acid but is, on the contrary,highly basic. (18) A common feature of both poisons is that they are markedly lytic, a property both strong acids and bases have in the inorganic sphere. Here it emerges quite clearly that Steiner was not concerned with formic acid as a substance but with a processual element.)
Another consequence may well be that we should not literally think of the substance but of the process that was being characterized whenever Rudolf Steiner spoke or wrote of formic acid as a substance occurring in the human body. The question as to whether this process may be fully equated with cell respiration at the physiological level or if something else comes into this as well, needs to be investigated.
Questions also arise in connection with medical and pharmaceutical aspects. Steiner did on several occasions state very clearly that human beings should be given the substance which they are not able to produce in adequate amounts themselves, and depending on the given situation either formic acic or oxalic acid. (1,3,4) This would mean that in the light of present knowledge on<would have to give suitable intermediates from the citric acid cycle or from glycolysis, or also other substances that will easily convert to these. Sucl preparations are in fact available and reported to have proved effective. Suclan interpretation also seems obvious in the light of the comment that it is not the substances that matter but the process, for we give these substances in order to stimulate the process. Even the statement that we need to know the mission substances have in the world if we are to judge their actions are humans does not conflict with this, for this was expressly given as a suggestion for conventional scientific research, saying that this should no longer be limited to the chemical analysis of isolated substances, which was then still very much the custom, but that we must also consider the biochemical and physiological processes in man and nature. (3)
Does this mean that Steiner's statements concerning formic and oxalic acid were erroneous? That would be the case if one was considering only the"material" actions of these substances and they had in fact proved ineffective on the indications given in this context. The medicinal use of ants has been known from antiquity if not earlier, and in the case of oxalic acid, too, Steiner was apparently able to base himself on positive experience, as is especially apparent from the following: "A situation may exist where the organism puts up direct resistance to the direct application of formic acid, but where the organism is very much inclined to produce its own formic acid from oxalic acid if one increases its oxalic acid levels. In cases where one does not get anywhere with formic acid, it is often necessary to give a course of oxalic acid treatment, because oxalic acid becomes formic acid in the human organism. (3)In the light of this we would need to correct not the details given about the medicinal agents but only the physiological and chemical interpretation of their mode of action from the present-day point of view.
Another question is, of course, how specific Steiner's suggestions for medicines were meant to be. As already mentioned. he would often speak of formic acid as almost synonymous with the venom of bees and wasps. The source for oxalic acid he gave was not only wood sorrel but also"clover altogether, as it grows in the fields". (1) Steiner's "oxalic acid" thus cannot simply be equated with chemically identified oxalic acid, for fodder plants such as the clovers grown for this purpose (botanically unrelated with sorrel) generally have only low levels of an acid which is poisonous to browsing animals. Steiner clearly used the term "oxalic acid" more to represent plant acids altogether; it was merely that at the time very much more was known about oxalic acid than others, it being relatively easy to detect. (14)
This indicates some of the issues on which further work may be done. It is quite evident that in speaking about oxalic and formic acid Steiner was not primarily intending to refer to specific medicinal agents nor present any kind of complete research findings. His example was given, as he said, as "merely an indication of how necessary it is to get to know not only the firmly defined organs but also the humoral, the fluid process, both in the cosmos out there and within the human organism, and this in every detail." (3) He wanted to encourage "a different science" as the basis for pharmacognosy. One aspect of this, the detailed study of the "humoral processes" in the organism, was still in its very beginnings at the time, but has since been taken very much further. (7) The extensive investigations Hans Adolf Krebs, a young assistant physician, started at Freiburg University and continued in England after his enforced emigration, seem almost a direct application of he suggestion made by Rudolf Steiner. (5) They led to the elucidation of the citric acid or Krebs cycle for which he received the Nobel Prize for Medicine in 1953.
The other aspect, something Rudolf Steiner spoke of as "taking the macroscopic view, (3,30) is needed all the more at the present time. It is a matter of looking for connections of the kind briefly mentioned above when speaking of "mission in the world." Made the be-all and end-all, analytical processes going down to smaller and smaller levels will lead away from life("not, of course, as regards reality, but for gaining insight" 21), even if once is convinced to be hot on the trail of the mystery of life. The findings of the"analysts" must therefore always be brought back to the reality of life by looking for a macroscopic perspective. The opposite bias, taking the macroscopic view without adequate knowledge of details, easily leads to vagueness or even illusion. Thus a "macroscopist" in his turn depends on the work of the "analysts" who provide him with the material he needs. Conventional biochemical research thus calls for the methodological expansion encouraged by the anthroposophical approach just as this in turn will need the other if it is to be properly grounded. Science will only be "complete", as Steiner once put it, if the two approaches complement one another. (13) This is why it is so important to resolve apparent contradictions between them, for these can only arise from lack of understanding.
The work has been supported by Weleda AG, Schwaebisch-Gmiiend, Germany.
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