Nature's Pharmacopeia: A World of Medicinal Plants
Édouard Manet, The Absinthe Drinker (1859). (Ny Carlsberg Glyptotek, Copenhagen; photograph by Ole Haupt)
Absinthe wormwood grows as a perennial herbaceous plant up to 1 meter in height, has highly dissected silver-green compound leaves, and produces many small yellow flower heads on its branches (figure 8.1). It grows wild in Europe, North Africa, and Asia, and it has now been introduced in North and South America.1 Artemisia absinthium is one of many members of the genus Artemisia that grow worldwide, throughout the tropical and temperate zones. These related plant species include African wormwood (A. afra, eastern Africa), sweet sagewort or annual wormwood (A. annua, eastern Europe and Asia), mugwort (A. vulgaris, Europe, Asia, and North Africa), and gray sagewort (A. ludoviciana, North America). There are over 100 species and subspecies under Artemisia, making taxonomy a challenge in this widespread group of plants. The common names for many of these species reflect their long history of use and diverse geographic-cultural environments. A single botanic species can bear a dozen or more vernacular names (in English alone) based on variations of wormwood, mugwort, sagewort, and so on. Interestingly, dozens of wormwood species are associated with traditional medical use in those areas in which they are found.
FIGURE 8.1 Absinthe wormwood.
ANCIENT USE IN MEDICINE
The use of wormwood likely predates the earliest recorded medicine of the Mediterranean, where it is documented as an ingredient in numerous pharmaceutical preparations in the early Egyptian medical work known as the Ebers papyrus (ca. 1550 B.C.E.). According to the text, ancient physicians employed wormwood in remedies for constipation and abdominal obstruction, intestinal worms, and menstrual pain.2 More than fifteen centuries later, Pliny the Elder (23–79) described in detail the known properties of wormwood during his time, recognizing it first as a rather familiar and versatile herb, particularly among his countrymen: “As to its general utility, a plant so commonly found and applied to such numerous uses, people are universally agreed; but with the Romans more particularly it has been always held in the highest esteem.”3 He detailed the many ways that it was prepared, including a wine made by soaking the stems and leaves with grape must, called absinthites; a decoction produced by soaking or boiling the shoots in water; and mixed in vinegar or honey.4 As for remedies, Pliny counted forty-eight, including to strengthen the stomach, treat nausea, eliminate intestinal worms, prevent seasickness, reduce flatulence, improve eyesight, heal bruises, and cure scorpion bites. Pliny also recommended that wormwood be kept with clothes to prevent them from being damaged by pests, as an oil or a fumigant to repel insects, and mixed with ink to prevent manuscripts from being nibbled by mice. In contrast to his scholar brethren of a much earlier time in Egypt, Pliny warned that “it must never be administered in fevers.”5
An herb in widespread use in the Mediterranean, wormwood figures prominently in the works of many influential ancient physician authors, including Hippocrates (ca. 450–370 B.C.E.) and Galen (129–ca. 216).6The pioneering herbalist Pedanius Dioscorides (ca. 40–90) also wrote extensively on wormwood’s properties. Calling it “astringent and warming,” the prolific Greek physician noted apsinthion’s diuretic property and recommended it for earaches, to regulate menstruation, as an antidote to hemlock (Conium maculatum) poisoning, and for sore throat, in addition to many of the therapeutic and prophylactic uses offered by Pliny.7 While recommending for medical use the steeped shoots and the vapor produced by boiling the liquid, both Pliny and Dioscorides warned against using wormwood juice as an internal medicine. “We disapprove of using it in drinks,” Dioscorides wrote, “because it is bad for the stomach and gives headaches.”8
During the Middle Ages, wormwood was used for a variety of concerns, from the veterinary to the hygienic. For example, in France during the thirteenth century, it was given as an oil called absince to dogs suffering from flatulence. In another veterinary application, the fifteenth-century Saint Albans Book of Hawking recommended administering wormwood juice to kill mites infesting a hawk.9 Of course, people took the herb as well, as a treatment for assorted stomach and lower digestive issues.10 The twelfth-century German medical writer and mystic Hildegard of Bingen (1098–1179) named it the “principal remedy for all ailments” and considered it useful to warm the stomach, purge the bowels, and improve digestion.11 Its English name derives from an important use in Britain as a treatment for internal parasites. In an herbal published in 1597, the physician-botanist John Gerard (1545–1611?) stated, “Wormewood voideth away the wormes of the guts” while also declaring it useful to strengthen the stomach and stimulate the heart.12
The plant was employed in medieval Europe, as Greek and Roman writers had recorded many centuries earlier, to repel vermin. A sixteenth-century book from England provided the following poetic housekeeping advice: “Where chamber is sweeped, and wormwood is strown, no flea for his life dare abide to be knowne.”13 Stuffed under pillows, hung from the rafters of a home, or burned to fumigate it, people also used the herb to fend off the plague.14 From digestive concerns to epidemic shield, wormwood saw use for so many medical conditions that it is of little surprise that the seventeenth-century courtesan Madame de Coulanges, after taking wormwood for a stomach illness, declared, “My little wormwood is the remedy for all ills.”15
Wormwood drinks during pre-Renaissance times were bitter beverages often made by soaking the leafy parts of the plant in wine for many days. The resulting harsh medicines were typically sold by apothecaries for therapeutic use or made privately, the wormwood plant being widely available in the wild. The bitterness of wormwood probably gave it its Greek name, as apsinthion means “undrinkable.”16 Its flavor alone rendered it useful as an aid to the weaning of children, as captured in a few lines from William Shakespeare’s (1564–1616) Romeo and Juliet, in which Juliet’s nurse recalls applying wormwood to her breast many years earlier to wean the girl of her milk:
When it did taste the wormwood on the nipple
Of my dug and felt it bitter, pretty fool
To see it tetchy and fall out with the dug!17
Although wormwood is bitter, some consumers must have found it agreeable, as both medicine and refreshment, as evidenced by an expansion of the plant into the arena of recreation. The use of wormwood for both mental and physical health inspired a seventeenth-century French aphorism by Martin: “Wormwood calms the nerves, and is also good for worms.”18 One place into which wormwood entered as a beverage of social enjoyment is the tavern. In an era when freshwater was unsafe to drink, mildly alcoholic fermented grain ales, flavored and preserved with plant extracts, served as liquid sustenance. Wormwood ale, known as purl, was widely consumed in seventeenth- and eighteenth-century Britain, eventually giving way by the nineteenth century to bitter ales and beers flavored with plants such as hops (Humulus lupulus).19 In addition to purl, Britons enjoyed purl-royal, a wormwood wine that also fell out of favor in more recent times.20 The advance of wormwood beverages into the social life of Europe during the Renaissance and early modern era presaged the use of absinthe as a recreational drink in the nineteenth century.
In addition to the growing acceptance of wormwood-infused beverages as social drinks beginning before the seventeenth century, the development of distillation technology allowed apothecaries and merchants to offer wormwood in a novel and more potent form.21 Distillation concentrates the alcohol and volatile oils from a water-based solution because their lower boiling point allows them to vaporize before water. The cooled vapor, partitioned into a separate vessel, is richer in alcohol than the original solution, with purified and concentrated flavors and medicinal compounds. According to one of the early proponents of medicinal distillation, Hieronymus Brunschwig (1450?–1512?), distilled wormwood had many therapeutic uses (he enumerated thirty-five), such as to treat malarial fevers, moisten the mouth, and heal sores (figure 8.2).22 During the sixteenth, seventeenth, and eighteenth centuries, distilleries produced concentrated absinthe liqueurs and potent elixirs of wormwood steeped in wine and mixed with spirit alcohol, adding an inebriating punch to the medication.
FIGURE 8.2 Wormwood. (Woodcut from Hieronymus Brunschwig, Vertuose Boke of Distylacion [early sixteenth century]; Peter H. Raven Library, Missouri Botanical Garden, St. Louis)
The birth of modern absinthe was a stroke of advertising rather than invention. By the late eighteenth century, residents of the western Swiss Alpine countryside had for generations made wormwood elixirs of various formulas. One particularly successful manufacturer, a woman by the name of Henriette Henriod, sold a distilled alcoholic extract of wormwood that found its way into the hands of a Frenchman, Major Daniel-Henri Dubied, who used it frequently to treat fevers and prevent indigestion.23 In 1797, Dubied purchased the formula from Henriod, and with his son-in-law Henri-Louis Pernod set about producing his own absinthe in the French border town of Pontarlier in 1805. Dubied and Pernod aggressively marketed their liqueur in France as a tonic of unrivaled virtue and established a brand with enduring appeal.
The wormwood liqueurs of the day were of diverse recipes, always with wormwood and alcohol to a strength of at least 65 proof, but otherwise variable in ingredients.24 The recipe for Henriod’s concoction has been lost to history, but likely included an assortment of traditional herbs such as anise (Pimpinella anisum), hyssop (Hyssopus officinalis), dittany (probably Dictamnus albus), sweet flag (Acorus calamus), melissa (Melissa officinalis, also known as lemon balm and sweet balm), coriander (Coriandrum sativum), veronica (Veronica officinalis, also known as speedwell), chamomile (probably Matricaria chamomilla), parsley (Petroselinum crispum), and spinach (Spinacia oleracea).25 The distilled beverage resulting from this herbal mélange was bitter but richly flavored, strongly alcoholic but with a spicy and intriguing aroma. In addition to its unique taste and smell, absinthe was colored green by the chlorophyll in the leaves used to create it. Furthermore, the high alcohol content gave rise to one of its most captivating features. In a high-alcohol solution, the oils distilled from the herbal ingredients in absinthe easily dissolve, rendering a clear green liqueur. In common practice, drinkers add cold water to the absinthe before drinking, causing the oils to fall out of solution. Minute droplets become suspended in the green liquid, resulting in a milky greenish-white beverage that many find entrancing (figure 8.3). Among its devotees, such distinctive flavor, aroma, and color earned absinthe the nickname la fée verte (the green fairy).26
FIGURE 8.3 Henri Privat-Livemont, advertising poster for Absinthe Robette, 1896.
Pernod and other absinthe makers successfully marketed their product as a health tonic during the early nineteenth century, gaining a strong following particularly in France. During the French conquest of Algeria in the 1840s, absinthe was issued in soldiers’ field rations to fight off fevers, and when mixed with water, it was thought to kill germs.27 Later, the French military employed absinthe against the illnesses encountered throughout their growing colonial domain, from Africa to Indochina.28 Some French doctors of the nineteenth century suggested the drink to treat gout and dropsy and even to stimulate intellectual activities.29 The Pernod factory continued producing absinthe, from 400 liters a day in the early nineteenth century, to 20,000 liters a day around 1850 and 125,000 liters a day by 1896.30 Rising to the challenge of supplying a worldwide demand for absinthe, hundreds of companies in France and Switzerland began producing the beverage using a variety of names and processes.
In general, the fashionable nineteenth-century recipe included wormwood (both la grande absinthe [A. absinthium] and la petite absinthe [probably A. pontica, also called Roman wormwood]); anise, star anise (Illicium verum) or fennel (Foeniculum vulgare) for a prominent aniseed flavor; and hyssop for color, among other possible herbal additives. These flavorings were macerated with wine alcohol and then distilled, or occasionally added after distillation to add particular colors and aromas to the absinthe.31 Among the less reputable firms, grain or beet alcohol—or worse, wood alcohol—might have served as the spirit basis of the drink.32 The beet alcohol (principally ethanol) was seen as a cheaper and less elegant form of alcohol than that from wine (also ethanol); wood alcohol (methanol) was not only cheap but also utterly dangerous, as it is highly toxic and can cause blindness and respiratory failure. Chemical analyses on vintage bottles of unopened absinthe to determine the original formulations of the nineteenth century found that the best-known brands, which probably also sold the more expensive bottles and produced in the largest volume, contained ethanol of high quality and methanol in a range similar to today’s standard.33There is some evidence that smaller producers may have added toxins such as copper salts (to intensify the green color) and antimony trichlorate or zinc sulfate (to augment the desired cloudiness of the prepared beverage).34 Whether absinthe—low grade or high—posed significant health problems because of its inherent ingredients or its adulterants was a contentious issue during the late nineteenth century and has attracted much scholarship in recent years, to no unambiguous conclusion.35 During the twentieth century, many absinthe manufacturers reformulated their drinks without wormwood to comply with new anti-wormwood laws. The beverages maintain much of the herbal flavor and character. For example, Pernod’s pastis, a twentieth-century wormwood-free anise liqueur, is flavored with star anise, coriander, and mint (Mentha spp.).36
The “Green Muse”
The second half of the nineteenth century in France gave rise to a revolutionary movement in art and literature, nucleated in Paris and reverberating throughout bohemian social circles in Europe and the United States. While European public art took on neoclassical proportions and glorified the modern empires that its nations were building, the Paris counterculture rejected its techniques. Rather than represent idealized subjects of ancient and patriotic virtue, a generation of writers, painters, and thinkers preferred to explore the gritty reality of nineteenth-century life, cutting across lines of gender, class, and convention. Among the earliest such artists was the poet and essayist Charles Baudelaire (1821–1867), who defied the standards of his day by passing time with his black girlfriend and publishing works of erotic poetry, critiques of religion, and depictions of drug use, an oeuvre that ultimately resulted in censorship and fines for offenses against public morality.37 Indeed, the artistic countermovement that Baudelaire represented came to be known as la Décadence for its decadent, self-indulgent culture. The French poets Paul Verlaine (1844–1896) and Arthur Rimbaud (1854–1891) and short-story writer Guy de Maupassant (1850–1893) are among its major contributors, along with Oscar Wilde (1854–1900) working in Britain and France, as well as others. Some impressionist and postimpressionist painters, such as Édouard Manet (1832–1883) and Vincent van Gogh (1853–1890), also contributed to the movement.
FIGURE 8.4 Edgar Degas, Dans un café (1876). (© RMN-Grand Palais/Art Resource, N.Y.)
A common element in the work of these artists is a sense that barriers should be crossed in art—barriers between the corporeal and the spiritual and between propriety and indecency. Drawing inspiration from nature as well as nightclubs, communities of artists centered on literary salons, gatherings where ideas and absinthe flowed freely. Of course, many of those engaged in professional decadence lived the part, taking opium, hashish, and alcohol of all sorts to frequent excess. It is not surprising that so few of the most influential men of the era survived past their forties. Baudelaire’s own work attests to his experiences with alcohol and other drugs; in 1860 he published a book of poetry on themes of altered reality under the title Les paradis artificiels (Artificial Paradises).
Absinthe figures strongly in the artwork of the era, as it was a prominent part of these artists’ milieu—at times subject, verb, and object in the creative process (figure 8.4). Painters documented their grisly world of hazy cafés and corner bars, where the working classes mingled with merchants and intellectuals, women exerted their independence from traditional roles by entering the social scene without men, and the milky emerald of the wormwood liqueur inspired all: the “green muse.”38 Painters and poets alike devoted much attention to the ritual of absinthe preparation. In the nineteenth-century tradition, the bitter, green spirit was often served in a particular type of glass that allowed the drinker to measure precisely the desired ratio of absinthe to cold water. The absintheur slowly poured the water into the glass through a sugar cube placed on a flat, perforated spoon spanning the glass’s rim, and into the absinthe below, an action that both sweetened the drink and caused it to cloud into a characteristic creamy jade. Much of the imagery of the era includes such artifacts of absinthe preparation, which evoke a process that transforms the physical nature of the drink from clear to opaque and perhaps transforms as well the creative essence of those who performed the ritual.
Critics of the era and commentators since have speculated that absinthe’s unique psychoactive properties contributed to the inspired hedonism of la Décadence and gave rise to a whole host of societal ills.39As the use of absinthe and other distilled liquors permeated the bourgeois and toiling classes, absinthe became associated with poverty and ill health (figure 8.5). Whether absinthe’s chemical attributes or the social environment that accompanied its use gave rise to an artistic revolution in nineteenth-century Europe—and, indeed, whether it may have prevented an even greater achievement of literary and visual talent—remains a topic of debate in scholarly circles. As for Baudelaire, the forerunner of a movement that broke through entrenched norms and created an environment ripe for a flourishing of expression in the nineteenth and twentieth centuries, he left his comrades some advice in the title of one of his last poems, published posthumously in 1869: “Get Drunk.”40
FIGURE 8.5 Louis Emile Benassit, L’absinthe! (1862). In this lithograph, absinthe issues from a fountain of death. (National Gallery of Art, Washington, D.C., 2010.75.2)
The End of Absinthe
The psychoactive and toxic effects of absinthe and its associated lifestyle alarmed many Europeans, who sought to limit its dangers. In time, these activists joined forces with a preexisting temperance movement, in effect taking aim at an entire genre of alcoholic beverages by maligning one of its most hazardous examples. Unlike the temperance movements in the United States and Britain, which targeted all drinks containing alcohol, the French temperance movement vilified only the distilled spirits, such as absinthe, whiskey, and cognac, while considering beverages such as beer and wine to be quite wholesome.41The French physician Valentin Magnan (1835–1916) was one of absinthe’s most lettered detractors. After performing a series of experiments, he concluded that the essence of the wormwood plant produced muscular shocks, vertigo, hallucinations, and epileptic attacks in animals, effects that he asserted were fundamentally different from, and faster acting than, those of alcohol alone.42 He examined a few case studies of hospitalized alcoholics and extended his findings to the human animal, warning of absinthe consumption’s dire consequences.
The essential oil of wormwood, first studied chemically during the 1840s after careful distillation of the wormwood plant’s leaves, is principally composed of thujone, a terpene compound also found in arborvitae (Thuja spp.), sage (Salvia spp.), and a number of other plants.43 Magnan and others concluded that thujone, one of many constituents of absinthe, was responsible for delirium and hallucination among its drinkers. They did not consider the possibility that habitual absinthe drinkers—or alcoholics in general—might have an underlying psychiatric disorder, nor did they consider that commercial absinthe was formulated with several herbal extracts in addition to wormwood. In cheap varieties, bootleggers and counterfeiters doctored their drinks with copper compounds to make them greener and used industrial alcohols of dubious quality. (Despite Magnan’s apparent shortcuts of logic, he was an accomplished and influential psychiatrist and one of the first to detail the effects of—and possible connections between—drug use and epilepsy.)
Some of the other traditional ingredients in absinthe may have medicinal effects of their own. For instance, a study conducted in 1889 by two French chemists labeled hyssop oil a “dangerous … convulsant” along with anise and fennel, and the essential oils of melissa and mint were considered sedative and “stupefying” substances.44 These claims, based on self-experimentation using high doses of isolated oils, nevertheless recognized the complexity of absinthe and the challenge to identifying any single active principle in the wormwood drink. Furthermore, it is difficult to gauge the toxicity of black-market additives and alcohol, although they likely did much more damage than did absinthe’s herbal extracts.45 These inconsistencies notwithstanding, European and American leaders saw wormwood-containing absinthe as a dangerous poison and engaged themselves to ban it (figure 8.6).
FIGURE 8.6 “Another Imported Fashion”: an engraving depicting the evils of absinthe and alcoholism. (From Harper’s Weekly, September 15, 1883; National Library of Medicine, 139741)
One by one, nations of the West enacted legislation to restrict absinthe production or sales (figure 8.7). Belgium outlawed absinthe in 1905, followed by Holland and Switzerland in 1910 and the United States in 1912.46 France, the nation consuming the largest quantity of absinthe (33.9 million liters annually at its peak at the outset of World War I), was among the last to criminalize it in 1915.47 Absinthe remained legal in Spain and a number of other countries, but the absinthe culture faded, and with production in Switzerland and France so limited, the economics of the business changed. Producers in Europe reformulated to produce the anise liqueur pastis and vermouth (an ancient fortified wine traditionally made bitter with wormwood) without the absinthe wormwood plant. (The restrictions were imposed on the absinthe drink but never the wormwood plant: the plant and its seeds are widely available in horticulture.)
FIGURE 8.7 “La fin de la ‘fée verte’”: a satirical poster marking the end of the absinthe era in French Switzerland (the text reads: “Gentlemen, it’s time!”). (Lithograph after A.-H. Gantner ; Wellcome Library, London, L0030543)
According to U.S. law, food and drink must be thujone free, interpreted by the government as under 10 parts per million (ppm).48 Until recently, suppliers ventured to sell only wormwood-free products such as pastis. Since 2001, some companies have developed absinthe drinks using varieties of wormwood naturally low in thujone, and in small amounts, and thus have re-created much of the flavor and aroma of the nineteenth-century beverage while remaining under the government thujone threshold.49 By the end of the first decade of the twenty-first century, several wormwood liqueurs were approved for sale in the United States, including those of both domestic and foreign manufacture, provided that the name and label do not imply any mind-altering property.50 While thujone levels remain low in today’s products, it is interesting to note that recent tests of vintage absinthe bottled in the late nineteenth and early twentieth centuries yielded thujone concentrations in the 20 to 50 ppm range.51 While certainly this figure is above the 10 ppm threshold of U.S. regulators, the notion that fin-de-siècle absinthe contained extremely high levels of thujone cannot be supported.52 Nor has thujone unequivocally been demonstrated as the main psychoactive chemical in absinthe.
SWEET WORMWOOD (ARTEMISIA ANNUA)
Sweet wormwood, also known in English as Chinese wormwood, annual wormwood, and sweet sagewort, and in Chinese as qinghao, is an annual herbaceous plant native to temperate Asia. It grows to about 2 meters and produces highly dissected yellow-green leaves and numerous small yellow flowers (figure B.1).1 The use of Chinese wormwood is documented over 2000 years ago, when it was listed in a medical manuscript of the second century B.C.E. as part of a treatment for hemorrhoids.2 In later texts, the plant is recommended to heal wounds, stop pain, dab on bee stings, control joint pain, reduce fevers, grow hair on the head, and eat as a vegetable.3 The herb was deemed cold in nature, according to the framework of Chinese medicine, and the fresh shoots and seeds were employed to treat heat-related illnesses, “pernicious qi and demonic poison.”4 By the time of the influential Chinese physician Li Shizhen (1518–1593), the role of qinghao had been thoroughly established in the prevailing medical system.
FIGURE B.1 A field of sweet wormwood. (Photograph by Jorge Ferreira/Wikimedia)
In Li’s Grand Materia Medica of 1596, the author summarizes the uses of the plant by previous generations of herbalists and then enumerates eighteen medicinal formulas using sweet wormwood to treat a wide range of symptoms, from diarrhea to bruises to the effects of “depletion and overexertion.”5 Among the descriptions of illnesses are some that resemble what biomedicine would call malaria. Briefly, malaria is caused by a mosquito-borne parasitic protozoan (single-celled microorganism) that enters the bloodstream after a bite, then multiplies first in the human liver and later in the red blood cells, ultimately rupturing them after a few days. The cycle of red blood cell infection and bursting produces alternating periods of fevers and chills in the patient. Li recommended qinghao to treat “intermittent heat and coldness due to the intermittent fever illness.”6 Importantly, Li and some previous authorities instructed physicians to prepare the herb by squeezing the fresh leaves and stems to extract the juice rather than making an herbal tea in boiling water. This observation indicates that the medically active component is not water soluble, a notion that corresponds well with the biochemistry of sweet wormwood’s active principle.7
In the mid-twentieth century, China faced a growing population and a resurgence of malarial infections after the rise of parasites resistant to existing antimalarial treatments, a situation that threatened the nation’s military effectiveness in subtropical Asia and the interests of its allies. In a stroke of remarkable authority, China’s leader, Mao Zedong (1893–1976), ordered more than 500 scientists in about sixty locations to search secretly for new antimalarials both from synthetic chemicals and among China’s traditional medicines, an endeavor code-named Project 523.8 One of the most promising chemicals to emerge from the search was artemisinin, a compound of the terpenoid family that is highly concentrated in the glandular trichomes (leaf hairs) of sweet wormwood and extractable in organic solvents but not water (figure B.2).
FIGURE B.2 Artemisinin.
While originally commissioned to aid China’s military, Project 523 ultimately yielded a product that was of great utility among civilians in malaria-prone areas, in Asia and elsewhere. Purified artemisinin was found effective to treat malarial infections in laboratory mice and rats, acting in the infected red blood cells to increase the level of oxidation and damage the parasite.9 (Because artemisinin targets the parasite in the red blood cell, it can treat but not prevent malarial infection.)
In high-yielding cultivated varieties, artemisinin accumulates to approximately 1 percent in leaves. Artemisinin cannot yet be synthesized from basic chemical building blocks and must instead be prepared from biological material.10 Therefore, vast amounts of sweet wormwood are grown in China and Southeast Asia to meet the demand, particularly in Asia and sub-Saharan Africa. As effective antimalarial drugs are in short supply, the World Health Organization recommends the use of artemisinin as part of a combination therapy, paired with another antimalarial drug. This strategy, it is hoped, will delay the spread of artemisinin-resistant parasites and extend the drug’s useful lifetime.11 Because such parasites were already detected in Southeast Asia late in the first decade of the twenty-first century, artemisinin resistance is being met by renewed efforts to semisynthetically modify the artemisinin molecule and evade the parasite’s defenses. Furthermore, there is concern that counterfeit or diluted-strength artemisinin or artemisinin combination-therapy pills in the developing world may risk further resistance and increased malaria deaths.12
The story of sweet wormwood demonstrates how ancient practices can provide clues for the biochemical study of active principles from medicinal plants. The classical authorities, by explaining the preparation of qinghao’s juice, rather than as a boiled herbal tea, had deduced some of the features that led twentieth-century technicians to purify artemisinin from the oil-rich hairs of the shoots. By transforming ancient knowledge into biomedical therapeutics, the Chinese reshaped a centuries-old relationship with a medicinal plant to address a long-standing problem of public health, saving countless lives.
1. A detailed study of qinghao in ancient Chinese medical literature is Elisabeth Hsu, “Qing hao 青蒿 (Herba Artemisiae annuae) in the Chinese Materia Medica,” in Plants, Health, and Healing: On the Interface of Ethnobotany and Medical Anthropology, ed. Elisabeth Hsu and Stephen Harris (New York: Berghahn, 2010), 83–130. The name qinghao 青蒿 means “blue-green hao herb.” Hsu outlines a lexicographic curiosity in that the botanical description of qinghao in an influential sixteenth-century medical text corresponds more closely to the species Artemisia apiacea than A. annua, yet the latter is widely accepted today as qinghao. A. annua, whose leaves tend toward yellow-green, is more strongly medicinal than A. apiacea, whose leaves are blue-green.
2. Hsu, “Qing hao,” 88.
3. Hsu, “Qing hao,” 90–109.
4. These last two conditions are quoted from the Tang-era scholar Da Ming’s Rihuaizu Bencao (Materia Medica of Master Sun Rays), in Hsu, “Qing hao,” 96.
5. Hsu, “Qing hao,” 107.
6. Hsu, “Qing hao,” 107.
7. Hsu, “Qing hao,” 116; C. W. Wright et al., “Ancient Chinese Methods Are Remarkably Effective for the Preparation of Artemisinin-Rich Extracts of Qing Hao with Potent Antimalarial Activity,” Molecules 15 (2010): 804–812.
8. Louis Miller and Xinzhuan Su, “Artemisinin: Discovery from the Chinese Herbal Garden,” Cell 146 (2011): 855–858.
9. Joseph M. Vinetz et al., “Chemotherapy of Malaria,” in Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 12th ed., ed. Laurence L. Brunton, Bruce A. Chabner, and Björn C. Knollmann (New York: McGraw-Hill, 2011), 1395; Miller and Su, “Artemisinin.” The precise mechanism of artemisinin toxicity has not yet been established. See Paul M. O’Neill, Victoria E. Barton, and Stephen A. Ward, “The Molecular Mechanism of Action of Artemisinin—The Debate Continues,” Molecules 15 (2010): 1705–1721.
10. Geoffrey D. Brown, “The Biosynthesis of Artemisinin (Qinghaosu) and the Phytochemistry of Artemisia annua L. (Qinghao),” Molecules 15 (2010): 7603–7698.
11. Despite the World Health Organization’s recommendation of combination therapy, many malaria patients take only artemisinin, which acts so quickly (within hours) that, feeling better, they discontinue malaria treatment, leaving a small number of artemisinin-resistant parasites in their blood, which multiply and infect other victims—a situation lamented by Miller and Su, “Artemisinin”; and R. M. Fairhurst et al., “Artemisinin-Resistant Malaria: Research Challenges, Opportunities, and Public Health Implications,” American Journal of Tropical Medicine and Hygiene 87 (2012): 231–241.
12. Gaurvika M. L. Nayyar et al., “Poor-Quality Antimalarial Drugs in Southeast Asia and Sub-Saharan Africa,” Lancet Infectious Disease 12 (2012): 488–496.
MECHANISM OF ACTION
Thujone exists in α and β forms (figure 8.8), differing in their stereochemistry (the three-dimensional arrangement of their atoms). The psychoactive α-thujone is a GABA receptor antagonist, binding to and preventing signaling by this neurotransmitter.53 GABA normally is responsible for reducing the level of signaling through a number of different neurotransmitter systems, thereby lowering the level of stimulation. By blocking the GABA receptor, thujone acts as a stimulant and can be a strong convulsant in animals, lethal at an injected dose around 45 milligrams per kilogram of body weight.54 Since absinthe drinkers take thujone at a very low oral dose, they would not reach this level, even among the most ardent of habitués.55 However, subtle, biologically relevant effects are detectable in laboratory assays within the range that might occur by drinking absinthe. As for the role of β-thujone, if any, in the absinthe experience, it has yet to be elucidated.
FIGURE 8.8 α-thujone (left) and β-thujone (right) differ in their stereochemistry.
Interestingly, tests of the wormwood compound produce a range of effects similar to those of picrotoxinin from the fish-berry plant (Anamirta cocculus). Picrotoxinin is probably responsible for some of the fish-berry plant’s medicinal properties: it is used in traditional South Asian medicine as a stimulant and to reduce the nausea of travel sickness.56
The GABAergic system is also implicated in mood and anxiety, which might help explain some of the changes in feelings experienced by absinthe drinkers, in concert with the role of alcohol.57 However, animal studies have not yet explained how or whether absinthe alters sensory perception in such a profound way that it might inspire the work of artists and draw so many others to its peculiar effects.
Since ancient times, people have valued wormwood as a digestive aid and vermifuge, among other uses. During the nineteenth century, Swiss and French manufacturers produced ample quantities of the wormwood-based alcoholic drink absinthe, a libation that helped fuel a generation of avant-garde artists. The vivid imagery they created by pen and by brush is steeped in their absinthe experience. Although many Western governments restricted the wormwood content in absinthe and similar beverages during the twentieth century under suspicion of the chemical thujone’s toxicity, modern days have seen a resurgence in the popularity of the absinthe drink, now produced (relatively) thujone free. La fée verte—the green fairy—has returned to inspire another generation.