The Dark Ages Illuminated: The “Humorless” Remedies of Pseudo-Apuleius
- Stata Norton, PhD
During the Dark Ages, many of the medical traditions established by the early Greeks and Romans were not lost but were continued, and, in some cases, improved upon. Evidence for this is provided by a major treatise in the materia medica of the period, the Pseudo-Apuleius herbal, a pharmacopoeia first prepared in the sixth century and revised continuously until the Renaissance. One remedy in this treatise is mandrake (Mandragora officinarum), which had been used for thousands of years to treat skin disorders arising from various infections (1) and continued to be used throughout the Dark Ages for the same pathological conditions. Mandrake is an example of a medical treatment that combined three principles of medieval therapeutics: tradition, established efficacy, and magical properties. Rather than hindering the advancement of the medical sciences, establishment of these principles of treatment helped prepare the way for the introduction of alchemy, the advent of chemistry and the rise of modern pharmacology.
Background
The Middle Ages the period of European history spanning the invasion of Rome by the Goths in the fifth century CE to the beginning of the Renaissance (about 1400) has been called the Dark Ages because the period is typically viewed as marked by cultural stagnation. This millennium was one of considerable political unrest, with various groups vying to control those parts of the former Roman Empire that encircled the Mediterranean. Trade between Europe, the Middle East, and Asia languished and commerce among the coastal cities of Europe and Africa declined, defining the culture of the period (2).
In considering the evolution of modern therapeutics, it is often assumed that Greek and Roman medicine was reintroduced in Europe in the early Renaissance. Alchemy, the embryo of modern chemistry, arrived from the Arabian peninsula during the Renaissance [(3) and see (4, 5)], making it appear as though pharmacotherapeutics had disappeared with the Roman legions. Extant texts indicate, however, that medieval Europeans were well aware of Greco-Roman pharmacopoeias, and utilized as therapies the natural products available to them that were originally catalogued by the ancients. Thus, there was no need to reintroduce these ideas at the end of the Middle Ages. Rather, the early Renaissance was characterized by a re-emergence of the writings of Galen and of the Hippocratic school of medicine that emphasized an approach to drug selection based on a hypothetical mechanism of action.
Materia Medicaof the Middle Ages
Although social and economic conditions were markedly different from conditions during Roman control of the Mediterranean, the Middle Ages did not lack in the production of remedies intended to alleviate suffering. Throughout the Middle Ages, one primary written source for medical remedies was a compilation of several treatises, comprising a materia medica. Nearly fifty manuscripts of this materia medica are extant, from the sixth century, when it was originally written, until the sixteenth century. The most extensive treatise in the manuscripts is the herbal of Pseudo-Apuleius (Box 1). Several copies of this herbal are available in facsimile, including one in a manuscript known as the Medicina Antiqua (Codex Vindobonensis 93) (6), produced in southern Italy (ca. 1225 CE) and containing many interesting illustrations. Another copy available in facsimile and transcription is the ninth century Pseudo-Apuleius manuscript in Monte Cassino, Italy (7). The definitive edition of the Pseudo- Apuleius treatise has been published, based on twelve manuscripts dating from the seventh to the fifteenth centuries (8).
The Materia Medica of the Middle Ages
Throughout the period of the Middle Ages, beginning in the sixth century, there is one major materia medica, a compilation of treatises put into one manuscript that was copied over the centuries into the Renaissance with minor variations. About fifty copies survive. The manuscript is comprised of two treatises on plants and one on animal remedies plus some shorter pieces. The longest text, covering about 130 herbal remedies, is attributed in the text to “Apuleius Platonicus,” who is known by historians as “Pseudo-Apuleius,” to distinguish the unknown author from the known Roman author, Apuleius. Medicina Antiqua (Codex Vindobonensis 93), the name given to one of the surviving manuscripts, is a fine example of the compilation and the published facsimile (6) is used here as a major source of information from the Pseudo-Apuleius treatise.
The texts of the different Pseudo-Apuleius manuscripts are very similar and contain information derived, sometimes almost verbatim, from first century writings on remedies, Pliny’s Natural History (9) and the Materia Medica of Dioscorides (10). The texts often contain annotations added by subsequent authors from their own experiences with these remedies.
Comparing Pseudo-Apuleius to Galen and the Hippocratic School
Medical schools during the Renaissance began to adopt the medical writings of Galen and of the school of Hippocrates, resulting in a loss of interest in the Pseudo-Apuleius and other treatises from the Middle Ages. There are three major differences between the old tradition represented by the Pseudo-Apuleius and the reintroduction of Hippocrates and Galen.
Availability of Remedies
The author of the Pseudo-Apuleius herbal deleted all medicinal plants described by Pliny and Dioscorides that could not be found growing in southern Europe. Any plant or plant product obtained through Mediterranean trade such as myrrh from Damascus, opium from Egypt, terebinth from the island of Chios or aloe from Sucotra was not included because it was not available in Europe during the Middle Ages. Of the hundreds of plants discussed as remedies by Pliny and Dioscorides, approximately 130 are found in the Pseudo-Apuleius manuscripts. They are used to treat 150 defined medical conditions, ranging from minor aches and pains (i.e., toothache and headache) to serious medical conditions (i.e., malaria and epilepsy). When, during the Renaissance, Mediterranean trade was again established, the remedies used by Galen became available once more.
Hypothetical Basis for Therapy
Galen promoted the Hippocratic idea that all disease was the consequence of an imbalance of four basic humors relating to four body fluids: blood (hot and wet), phlegm (cold and wet), black bile (cold and dry), and yellow bile (hot and dry) (11). Therapeutic plants were also classified as hot, wet, cold or dry in quality. In addition these qualities were sometimes quantified as one to four degrees in increasing effectiveness. Thus the choice of plants for treating a specific disease was based on the supposed humoral imbalance and the qualities of the plants. For example, fever was treated with plants that had a cold quality. This disease-treatment concept contrasted markedly with the ways remedies were selected for use in the Middle Ages. The word “humor” is rarely mentioned in the Pseudo-Apuleius herbal and even then not as cause of disease. In addition, in the Pseudo-Apuleius, plants are not described as having hot, cold, wet, or dry attributes. Where the use of a remedy is based on empirical evidence of successful treatment of a medical condition, no hypothetical justification is required. In the Pseudo-Apuleius, the evidence supporting medicinal value may be obtained either directly by observation or from tradition both seem to have operated in the Pseudo-Apuleius herbal. That is, the author appears to have selected remedies based on traditional information obtained from texts by Pliny and Dioscorides. Subsequently, the author and subsequent contributors modified and added information based on their own observations. This is seen in the various copies of the Pseudo-Apuleius treatise compiled by Howald and Sigerist (8).
Galenical Mixtures as Remedies
The Hippocratic humoral concept of disease, carried over to therapy, resulted in the use of mixtures of several plants for one medical condition. If one cold plant was not effective in a fever, the logical therapeutic action under that hypothesis was to add other cold plants. This concept is lacking in the Pseudo-Apuleius herbal. Mixtures of plants are rarely used as remedies. The most common phrase introducing a plant as a remedy is: “This [name of herb] by itself is a cure for [medical condition].” Of the 131 plants in the Medicina Antiqua copy of Pseudo-Apuleius, nearly one-third are used only for one medical condition. Another one-third are used for two medical conditions, often related. For example, juice from species of Ranunculus (Herb #8) is proposed first to relieve ulcers. The second use is as a remedy to open abscesses to allow pus to exude. The use of a single plant and not mixtures for one condition or related conditions is a major difference in selection of therapies between the Middle Ages and the Renaissance, when the Hippocratic-Galenic writings were reintroduced.
Description of the Pseudo-Apuleius Treatise
The minor differences in the various copies throughout the Middle Ages do not prevent a general description. A drawing of each of the approximately 130 plants in the copies of the Pseudo-Apuleius herbal is followed by a list of names used for the plant, including Greek, Roman and Italian, and often additional names including Egyptian, Dacian, and Gallic names. This list is usually followed by a brief description of the habitat of the plant. One or more of its medicinal uses is provided, accompanied by a description of the portion of the plant to be used, method of extraction in wine, water or vinegar for oral consumption or method of grinding in fat or oil for use as an unguent. The drawings of the plants vary in quality from poor to good: the most-stylized drawings are barely recognizable cartoons whereas the best appear to be drawn from life. For example, the blackberry (Rubus fruticosus, Herb #89) in the herbal is very recognizable. The illustrations of the plants are presumably included as aids to identification, although it is questionable if a person familiar with gathering herbs would need any guide beyond the plant name. Other drawings illustrate uses of the plants. For example, a remedy for seasickness (an extract of pennyroyal, Mentha pulegium, Herb #94) is accompanied by a drawing of a boat with oarsman, sail, and four passengers. The number and quality of illustrations in the treatises in the Medicina Antiqua is unique and the manuscript has been described as the final efflorescence of the materia medica of the Middle Ages (7).
Boat with passengers illustrating the use of pennyroyal (Mentha pulegium) for seasickness. Used with permission of the ONB.
Treatments Discussed in Pseudo-Apuleius
Although many of the remedies are used to treat pain associated with conditions such as headache or kidney stone, some ailments are identified by specific pathological signs, such as jaundice. The following are examples of treatments.
Ignis Sacer
The medical condition called ignis sacer (“holy fire”) in the Pseudo-Apuleius herbal refers to one or more conditions in which the primary signs are little blisters on the skin, associated with the sensations of burning and itching. Both erysipelas (i.e., red skin caused by streptococcal infection of the dermis) and shingles are included in the term and perhaps some similar conditions. A primary remedy was mandrake root, ground with vinegar and placed on the irritated skin with linen bandages (Herb #132). Both Pliny (XXVI, 121) and Dioscorides recommended mandrake for ignis sacer. Dioscorides had specified that the root should be ground with vinegar (IV, 75). A second remedy, winter cherry (Physalis alkekengi, Herb #75) like mandrake, a member of the Solanaceae family was used to treat this condition as well. The expressed juice of the herb put on linen was said, by itself, to cure ignis sacer “to an amazing degree.” Pliny did not recommend this plant as a remedy, describing the effects, when taken orally, as dangerous (XXI, 180). Dioscorides stated that its juice was good for erysipelas and shingles as an unguent combined with other ingredients (IV, 71).
Both mandrake and winter cherry contain the three belladonna alkaloids: atropine, scopolamine, and hyoscyamine. The pharmacological actions of these alkaloids on the central and autonomic nervous systems have been extensively studied and their use continues to this day. Although their utility as topical treatments for irritated skin or mucous membranes has been superceded by cocaine and other local anesthetics, this action of the belladonna alkaloids was medically important (12) and belladonna liniment was officially listed until 1947 in the United States Pharmacopoeia (USP) for relief of pain. Presumably, the local anesthetic action of the juice of the belladonna alkaloids is responsible for some of the effectiveness in ignis sacer.
Although both herbs relieved the pain of ignis sacer, there was a marked difference in the two plants relative to the difficulty associated with their procurement. Collection of winter cherry was, like most of the herbs, a simple problem of finding and collecting the plant which grew wild in southern Europe. On the other hand, a legend had grown up around mandrake. The root was described as having a human form and harvesting it was said to pose great risk to the procurer. Pliny offered a mild version of the legend, suggesting only that the procurer should stand with his face to the wind since the odor was soporific (XXV, 148). In the Middle Ages the legend assumed major proportions. When the mandrake root was pulled out of the ground, it would emit a frightening scream and whoever pulled up the plant would die. Therefore the actual pulling was done by a dog tied to the stem of the plant. Interestingly, this supposed magical property of mandrake was not a part of its therapeutic efficacy. The legend may have been useful in increasing the cost of mandrake for the benefit of the supplier. It is recorded that unscrupulous persons carved bryony roots into human form and substituted them for mandrake root for purchase by the unwary practitioner (13).
Atropa belladonna may have been another source of the belladonna alkaloids in the Middle Ages. Its root could have been substituted readily for mandrake. Also, it is possible that the two plants, Atropa belladonna and Mandragora officinarum, were confused as the same plant, as has been suggested for both Pliny’s and Theophrastus’ writings. The plants are closely related species and in the first year of growth have a similar appearance, and both grow wild in southern Europe.
Dropsy
Although considered a disease in the Middle Ages, dropsy is any condition associated with generalized accumulation of fluid and edema. Edema is symptomatic of heart, lymphatic system, and kidney diseases, among others. During the Middle Ages, dropsy was treated with several different herbs. One herb, squill (Urginea maritima, Herb #43), was especially recommended for dropsy. The squill bulbs were ground, extracted in hot water, and given to the patient to drink with a mixture of honey and vinegar. According to the text, the “dropsy is evacuated through the urine.” Alternatively, some of the herb could be placed under the tongue to achieve the result. Both of these methods were given by Pliny for the treatment of dropsy (XX, 100). Dioscorides recommended baked squill bulb for treating edema (II, 171). Squill contains several cardioactive glycosides similar in action to digitalis (14) and the bulb has been used for centuries for its action on the heart and to relieve dropsy. Squill bulb and “vinegar of squill” were official in the USP in the twentieth century (15).
Physician offering a patient a remedy for dropsy. Used with permission of the ONB.
Another treatment for dropsy was very unusual in that it was a defined mixture of herbs, in contrast to the usual use of a single herb as a remedy. This remedy was a combination of equal weights of four herbs: white chameleon thistle (Atractylis gummifera, Herb #26), wall germander (Teucrium chamaedrys, Herb #25), yellow bugle (Ajuga chamaepitys, Herb #27) and periwinkle (Vinca herbacea, Herb #28). The four plants were ground together very finely and drunk with wine. Unusually, the given dosage of the remedy was carefully specified: adult men, five tablespoons; women and minors, three tablespoons; children, one tablespoon. This is the only remedy in the Pseudo-Apuleius herbal specifying dose to this degree. A drawing in the Medicina Antiqua (Folio 44v) shows a patient receiving a potion of this mixture for dropsy. Each of these plants was considered by Pliny a diuretic useful for dropsy (XXII, 46; XXIV, 30, 131, 132), but the combination of these herbs was not mentioned by him. Although Dioscorides described white chameleon thistle and wall germander as useful for dropsy (III, 8, 98), he did not mention periwinkle and yellow bugle in this context.
Any diuretic action of these four herbs is not currently of pharmacologic interest but other effects are being investigated. The hepatotoxicity of the white chameleon thistle is well known (16) and the toxicity has been proposed to arise from the content of diterpenoid glucosides (17). Wall germander contains neoclerodane diterpenoids reported to cause liver damage through metabolic oxidation (18). Although yellow bugle contains neoclerodane diterpenoids (19), the plant has not been implicated in causing hepatotoxicity. Some alkaloids in various periwinkles, such as vincristine from Vinca rosea, cause cell death through inhibition of tubulin filament formation; however, this alkaloid has also been reported to interact with some other cytotoxic chemicals to inhibit apoptosis (20). The alkaloids in Vinca herbacea have not been reported to inhibit tubulin filament formation. A possible reason for the unusual combination of these four plants in the Pseudo-Apuleius herbal is that the combination reduced the amount taken of each plant, thereby reducing toxicity. It is also possible that some constituents in the four plants might reduce the formation of reactive metabolites, as has been suggested for various plant components (21). If the four plants used in this remedy were combined and the doses were specified in an attempt to reduce the toxicity, the author of the remedy had made empirical observations beyond the information available in the writings of Pliny and Dioscorides.
Angina Pectoris
Chest pain (probably referring to angina pectoris) was recognized in the Middle Ages as a specific condition. One recommended treatment was pennyroyal (Mentha pulegium, Herb #94), ground in water or vinegar and given orally. Pennyroyal was given as a remedy for various painful conditions. Monoterpenes, such as nepetalactone (22) and pulegone (23) in pennyroyal have been reported to have analgesic actions that might relate to the use of pennyroyal to alleviate pain, although other effects of ingestion of the essential oil might limit the dose. Pennyroyal was also considered effective in nausea, including seasickness, as noted above. These two uses of the herb echoed Pliny’s recommendations of pennyroyal for pains in the chest and for nausea (XX, 153) and Dioscorides’ advice that it be used to relieve nausea (IV, 38).
Anti-inflammatory Remedies
Plants with anti-inflammatory properties were used for a variety of conditions in which redness, swelling, and pain developed in a tissue. Although it would be centuries before Koch’s postulates defined the role of bacteria in infection, the concept of inflammation was well known. About 400 BCE, Theophrastus used the Greek word “aphlegmanton” (anti-inflammatory), to describe the use of a mixture of plant gum resins with medicinal properties that relieved the inflammation caused by any wound (24). These specific plants are not found in the Pseudo-Apuleius herbal because they were not available. Instead, European plants with anti-inflammatory properties are recommended. Although the usual preference in the Pseudo-Apuleius is to list one plant for one medical condition, multiple uses for plants with anti-inflammatory properties are provided. Two plants used to check inflammation are plantain (Plantago major, Herb #2) and vervain (Verbena officinalis, Herb #4).
Of the twenty-two uses given for plantain, at least eight were for conditions associated with inflammation, such as wounds, for swelling of the parotid glands, for pain and swelling of the area following blood-letting, for those who were spitting blood and pus, and for ulcers in the mouth. The plantain leaves were ground and the expressed juice was taken orally or applied locally, depending on the condition. Sometimes both methods of administration were recommended. Because pain and swelling were associated also with venomous bites from snakes, scorpions, and even bites from mad dogs, these conditions were treated with plantain. Without knowledge of the difference in the cause of inflammation owing to infection or to venoms, a difference in therapy was not made.
Vervain was prepared in much the same way as plantain. Of the twelve uses of vervain, four were for ulcers, wounds, or fistulas. It was noted under another description of the plant that drinking the powdered plant removed all poisons from the body through the feces. Like plantain, vervain was recommended for treating snake bite and the bite of a mad dog. The use of extracts of anti-inflammatory herbs to alleviate the effects of venoms and other poisons was common in the writings of Pliny and Dioscorides. Pliny noted that both plantain and vervain were useful for venomous bites as well as for ulcers and wounds (XXV, 108, 119, 122, 125) as did Dioscorides (II, 126; IV, 60).
In agreement with the use of these two plants in conditions with inflammation and pain, several recent studies on plantain extracts have shown that extracts of the plant have immunomodulatory activity (25) and also inhibit COX-2-catalyzed prostaglandin synthesis (26). Vervain also has marked anti-inflammatory actions (27, 28).
Magical Remedies
Magical effects were ascribed to some herbs in the Middle Ages even when the same plant was recommended also for more mundane uses, and these different types of action (i.e., pharmacological vs magical), incompatible from a modern viewpoint, were simply different modalities as viewed by the practitioners in the Middle Ages. Ironwort (Sideritis romana, Herb #74) is a member of the mint family, and the juice has antibacterial (29) and anti-inflammatory properties (30). These actions may have been the reason the herb was used to clear dimness of vision in the condition called albugo (white spot on the cornea). Its magical use was based on a fable that may have developed around the Greek name for the plant, sideritis, (sideros is Greek for iron). If a traveler carried a plant of iron-wort on a journey, the traveler would appear magically to be accompanied by several armed men, frightening off any robbers. This fable is illustrated in the Pseudo-Apuleius treatise of the Medicina Antiqua (Folio 78v). Although Pliny recommended ironwort for albugo (XXV, 142), the fable does not appear in his writings. Dioscorides mentioned only that the leaves of ironwort controlled inflammation (IV, 33).
A traveler (on left) carrying a plant of ironwort appearing to be protected by armed men. On the right, robbers hide in fear. Used with permission of the ONB.
Discussion
The medical practitioner in the Middle Ages was faced with the collapse of Mediterranean economy that made it impossible to obtain many of the therapeutic remedies previously employed in the Greco-Roman world. Nevertheless, the traditional remedies that had been written down by Pliny and Dioscorides during the first century CE were not lost. Rather, by the sixth century, from these manuscripts the author of the Pseudo-Apuleius treatise drew much information. Combined with several other shorter treatises, this treatise became the dominant materia medica of Europe until the Renaissance. The remarkable stability of the information retained in the numerous versions of the Pseudo-Apuleius herbal reflects the poor economic conditions of the Middle Ages and the lack of opportunity for innovation. An important point, however, regarding the therapeutic tradition of the Middle Ages is that the medical practitioners were not averse to modifying remedies based on empirical evidence of effectiveness. Indeed, because the underlying concept was that a single herb could be used to cure a specific medical condition without reference to any humoral imbalance, modifications based on empirical evidence alone were readily embraced. In spite of superstitions surrounding some of the remedies like the mandrake, many of the treatments were virtually identical to those in the Greco-Roman era and were effective with their use in some cases continuing well into the twentieth century.
During the Renaissance, there were dissenters from the restoration of Galenic writings and the humoral doctrine in the developing medical schools and from the definition of drug actions in those terms. Those dissenters may well have been influenced by knowledge of the long therapeutic tradition of the Middle Ages. Paracelsus (1493 1541) was an outspoken proponent of the concept that each medical condition had its specific remedy and his distain for Galen’s writings was notable [see (5, 31)]. In all his wanderings, Paracelsus could have become familiar with those who knew and used the Pseudo-Apuleius treatise, copies of which from the sixteenth century are still extant (32).
Historical evidence from the Pseudo-Apuleius treatise suggests that the Middle Ages had a background of therapeutics compatible with the new science of alchemy developing in the Renaissance and the subsequent development of chemistry that was eventually to take over drug development in the form of modern science. Although the millennium spanning the fifth to the fifteenth centuries may represent the Dark Ages for many of the arts and sciences, the Pseudo-Apuleius treatise offers clear evidence that this was not the case for the medical traditions established by earlier generations.
- © American Society for Pharmacology and Experimental Theraputics 2009
References
Stata Norton, PhD, is an Emeritus Professor in the Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS. She has published over 120 research articles, reviews, and book chapters on neuropharmacology and neurotoxicology, especially on the effects of drugs and radiation on the developing central nervous system. Email snorton{at}kumc.edu; fax (913) 588 7501.
