The Poison King: The Life and Legend of Mithradates, Rome's Deadliest Enemy

by Adrienne Mayor

  With grand gestures and banter, Mithradates awes the guests by swallowing a drop of snake venom. For the climax of the evening, the Poison King invites the guests to salt his own plate of roast lamb or his winecup with arsenic or belladonna. Mithradates was not only a toxicologist; he was a Magus, a magician. Both skills came into play in creating his image of invincibility. With a debonair smile, the Poison King raises his goblet in a toast.4

  The reactions of the courtiers and foreign dignitaries to Mithradates’ sensational demonstrations of immunity fascinated the poet and classical scholar A. E. Housman. This verse from his 1896 poem about Mithradates became famous:

  There was a king reigned in the East:

  . . . . . . . . . . . . . . . . . . . . .

  With poisoned meat and poisoned drink

  He gathered all the springs to birth

  From the many-venomed earth;

  First a little, thence to more,

  He sampled all her killing store;

  And easy, smiling, seasoned sound,

  Sate the king when healths went round.

  They put arsenic in his meat

  And stared aghast to watch him eat;

  They poured strychnine in his cup

  And shook to see him drink it up:

  They shook, they stared as white’s their shirt:

  Them it was their poison hurt.

  —I tell the tale that I heard told.

  Mithridates, he died old.

  It was his mastery of poisons and his long life that made Mithradates a household word in Western literature and popular culture. His name is memorialized in the term mithridatism, the practice of systematically ingesting small doses of deadly substances to make oneself immune to them. With some toxins, the process is effective. It is possible to acquire tolerance for levels of arsenic that would kill others, for example, and it was observed in antiquity that some people in Libya, Armenia, or Egypt were unaffected by local venomous insects, scorpions, and vipers. Mithradates also grasped the little-known fact that snake venom can be safely digested if swallowed—it is deadly only if it enters the bloodstream.5

  The rising popularity of poisoning in the Roman Empire inspired the Roman satirist Juvenal to joke that murder weapons of “cold steel might make a comeback if people would take a hint from old Mithradates and sample the pharmacopia till they are invulnerable to every drug.” Nearly two millennia later, in “Mithridates,” the poet-philosopher Ralph Waldo Emerson (1803–82) visualized the Poison King calling for more and more poisons to test on himself, from blister beetles (cantharids) to cyanide (prussic acid):

  Give me agates for my meat,

  Give me cantharids to eat,

  . . . bring me foods,

  From all zones and altitudes.

  From all natures, sharp and slimy,

  . . . wild and tame,

  Tree, and lichen, . . .

  Bird and reptile be my game.

  . . .. . .. . .. . .. . .. . .. . .. . .. . .. . ..

  Hemlock for my sherbet cull me,

  And the prussic juice to lull me.6

  MITHRADATES’ SECRET ANTIDOTE

  In antiquity, every natural poison—animal, plant, or mineral—was believed to have a natural antidote. Mithradates combined both toxic and beneficial pharmaka into his personal theriac (later called Mithridatium). Traditionally, theriacs combined substances thought to counter poisons. Some common ingredients were cinnamon, myrrh, cassia, honey, castor musk from beaver testicles, frankincense, rue, tannin, garlic, Lemnian earth, Chian wine, charcoal, curdled milk, centaury, aristolochia (birth-wort), ginger, iris (orris root), rue, Eupatorium, rhubarb from the Volga, Hypericum (Saint-John’s-wort), saffron, walnuts, figs, parsley, acacia, carrot, cardamom, anise, opium, and other ingredients from the Mediterranean and Black Sea, Arabia, North Africa, Eurasia, and India. Modern science reveals that some of these substances can counteract illness and toxins. For example, the sulfur in garlic neutralizes arsenic in the bloodstream. Charcoal absorbs and filters many different toxins. The chemical composition of Lemnian earth was recently analyzed and shown to contain toxin-absorbing and antibacterial minerals. Garlic, myrrh, cinnamon, and Saint-John’s-wort are antibacterial. Recent scientific studies of many common Mithridatium ingredients reveal alexipharmic bio-activities in the immune system. Certain plants traditionally used by folk healers in Africa and India can actually neutralize cobra, adder, and viper venoms.7

  Building on the work begun by Attalus III, Nicander of Colophon, and others, Mithradates recorded the properties of hundreds of poisons and antidotes in experiments on prisoners, associates, and himself. “Through tireless research and every possible experiment,” says Pliny, he sought ways to “compel poisons to be helpful remedies.” We can imagine Mithradates and his team (Krateuas, Papias, the Magi and Agari healers, and Timotheus, a specialist in war wounds) wearing protective masks made from pig bladders (used by ancient alchemists) and testing, say, the colorless “fiery poison” of Egypt, created by fusing natron (sodium carbonate, common in Egypt) with realgar or orpiment (arsenic). Health-giving essences were compounded with minute amounts of poisons into an electuary, a paste held together with honey. The paste was molded into a pill the size of an almond. The king began each day by chewing his secret theriac tablet with cold spring water. Apparently the concoction caused no serious physical problems and promoted his immune system, since ancient sources agree that Mithradates enjoyed excellent health and sexual vigor throughout his long life.8

  After his death, Mithradates’ personal library and papers were taken to Rome, and translated into Latin by Pompey’s secretary Lenaeus (95–25 BC). Pliny, who studied Mithradates’ own handwritten notes, praised his erudition. “We know from direct evidence and by report,” wrote Pliny, that Mithradates “was a more accomplished researcher into biology than any man before him. In order to become immune to poison by making his body accustomed to it, he alone devised the plan to drink poison every day, after first taking remedies.” At the height of his reign, Mithradates “amassed detailed knowledge from all his subjects, who covered a substantial part of the world.” His international library of ethnobotanical and toxicological treatises may have described drugs used by the Druids of Gaul, Mesopotamian doctors, and the works of Hindu ayurvedic (“long-life”) practitioners. The theriac of Sushruta (ca. 550 BC) boasted eighty-five ingredients, and the Mahagandhahasti of Charaka (300 BC) had sixty.9

  Mithradates could have studied the alchemical writings of Democritus of Egypt, drawing on King Menes who cultivated poisonous and medicinal plants in 3000 BC, and we know Mithradates corresponded with Zopyrus in Egypt, who shared his “universal remedy” of twenty ingredients. Another scientific colleague was Asclepiades of Bithynia, who founded an influential medical school in Rome. He declined Mithradates’ invitation to work in Sinope but dedicated treatises to the king and sent him antidote formulas.

  Perhaps Mithradates sought out the last living members of the Ophiogenes (“Snake people”) near Troy, to learn the secrets of venoms. The Marsi of Italy, whose envoys met with Mithradates in 88 BC, were also known for venom-based pharmaka. We know that the king’s Agari doctors milked the venom of steppe (Caucasian) vipers to make antidotes and medicines. Recently, scientists studying traditional healing practices using Caucasian vipers in Azerbaijan (ancient Baku) discovered that tiny doses can stop life-threatening hemorrhage (as we shall see, this fact, known to the Agari more than two thousand years ago, would save Mithradates’ life). Crystallized Caucasian viper venom is now a valuable medical export.10

  The key principle of Mithradates’ theriac was the combination of beneficial drugs and antitoxins with tiny amounts of poisons, the approach followed by Attalus and Hindu doctors. Myriad poisons were known in antiquity, from vipers, scorpions, and jellyfish venoms to the deadly sap of yew trees and crimson crystals of cinnabar. Pliny described about seven thousand venific substances in his encyclopedia of natural history and listed scores of plants (some toxic themselves)
said to counter them, such as scordion, agaric mushrooms, artemesia, centaury, polemonia, and aristolochia.11

  Arsenic—the notorious “powder of succession”—would have been the first poison Mithradates sought to defend against. Arsenic interferes with essential proteins for metabolism. In small doses, however, enzymes produced by the liver bind to and inactivate arsenic. Taking minuscule amounts over time causes the liver to produce more enzymes, allowing one to survive a normally lethal dose. Might a similar process work with plant poisons? Mithradates had observed tolerances to poison plants in rats, insects, birds, and other creatures. Pliny and Aulus Gellius stated that the poison blood of Pontic ducks was included in his Mithridatium. It is now known that some species of ducks, larks, and quails eat poison hemlock without harm. Because they do not excrete the toxic alkaloids, their blood and flesh are poisonous.12

  What other poisons were included in the original Mithridatium? Perhaps toxic honey from Pontus—bees were immune to the poison nectar, and in tiny amounts it was considered a tonic. Reptiles—toxic skink, salamander, or viper—were said to be part of Mithradates’ recipe, based on the ancient belief that all poisonous creatures produce antidotes to their own toxins in their bodies. Recent scientific experiments show that nonfatal doses of snake venom can stimulate the immune response and allow humans to withstand up to ten times the amount of venom that would be fatal without inoculation. A similar process works with some insect stings and a variety of toxins. Surprising new studies of a “counterintuitive” process called hormesis show that very low doses of certain toxins activate a protective mechanism, so that when a larger dose is encountered, it is not as damaging. As the scientists describe this new concept—remarkably akin to Mithradates’ own hypothesis—minute doses of poison substances can be beneficial, analogous to a vaccine.13

  Saint-John’s-wort, Hypericum, listed in many Mithridatium recipes, might help solve the ancient riddle of Mithradates’ immunity to poisons. Molecular scientists have recently discovered Hypericum’s astounding antidote effect. This herb activates the liver to produce a potent enzyme that can neutralize literally thousands of potentially dangerous chemicals. The scientists suggest that if Saint-John’s-wort was included in Mithradates’ antidote, it would have stimulated a powerful “chemical surveillance system” on “high alert,” able to sense and break down “otherwise deadly doses” of many different toxins.14

  After Mithradates’ death, imperial doctors in Rome claimed to possess the top-secret Mithridatium formula. Poisonings and fears of poisoning had become rife in Rome—as dictator, Sulla had enacted strict laws against poison sellers. “If you want to survive to gather rosebuds for another day,” commented Juvenal, “find a doctor to prescribe some of the drug that Mithradates invented. Before every meal take a dose of the stuff that saves kings.”15

  How might Mithradates’ recipe have come into the hands of the Roman emperors? One possibility is that Mithradates entrusted the secret to his friend Asclepiades, the most famous doctor in Rome. A doctor named Aelius prescribed Mithridatium for Julius Caesar, who was in Pontus only sixteen years after Mithradates’ death. Aelius was a colleague of Asclepiades and perhaps knew Mithradates himself.16

  An intriguing inscription from the time of Augustus, Rome’s first emperor (b. 63 BC), was discovered near the Appian Way. It describes one L. Lutatius Paccius (a non-Roman name) as an “incense-seller, from the family of King Mithradates.” Reinach assumed that L. Paccius was a liberated slave or relative of Mithradates who was the king’s “chief perfumer.” But there is little doubt that Paccius, like other ancient apothecaries, sold more than aromatics; why else might an “incense” purveyor advertise his relationship to the legendary Poison King? (Poisons had been strictly regulated since Sulla’s legislation, which explains why an apothecary might advertise only aromatics for sale.) Many of Mithradates’ family and friends ended up in Italy. The inscription suggests that Paccius might have known (or claimed to know) the original Mithridatium recipe and produced this famous “trademark” antidote in Rome. In fact, another Paccius, probably this man’s son, later made a fortune selling a very special medicine in Rome. This Paccius family formula was a profound secret, and Paccius the Younger bequeathed it to the Emperor Tiberius, Augustus’s successor in AD 14.17

  Was the Paccius family formula the basis for the later imperial Roman recipe, said to improve on Mithradates’ original, compounded by the imperial doctor Andromachus for Nero? Andromachus’s Mithridatium had 64 ingredients; he replaced minced lizards with venomous snakes and added opium poppy seeds. Italian archaeologists made an exciting discovery at a villa near Pompeii (AD 79) in 2000. Analysis of the residue inside a large vat consisted of reptile remains and several medicinal plants, including opium poppy seeds. The archaeologists concluded that the vat might have been used to prepare Andromachus’s Mithridatium.18

  After Nero (d. AD 68), every Roman emperor religiously ingested what his doctor claimed was a version of the Poison King’s own personal antidote. Recipes multiplied—more and more costly and rare ingredients were added along the way. A century after Mithradates’ death, Celsus in Gaul listed 36 ingredients mixed into a concoction weighing nearly three pounds, good for about six months’ worth of pills, to be taken with wine. In AD 170, Galen of Pergamon, who prescribed a liquid Mithridatium for the emperor Marcus Aurelius, added more opium and fine vintage wine, improving the flavor and ensuring that his patient drank his medicine every day. Later medieval recipes contained as many as 184 ingredients.19

  Arabic (tiryaq-i-faruq, mithruditus) and Persian (daryaq) theriac recipes in ancient and medieval Islamic toxicology manuscripts followed Mithradates’ concept of combining poisons with antidotes. In his treatise on tiryaq, Averroes, the learned Spanish-Arabic philosopher-physician (b. 1126), cautioned against the prolonged use of theriac by a healthy person, warning that it “could actually transform human nature into a kind of poison,” an allusion to paranoid despots of his day who were obsessed with poisoning. In AD 667, Islamic ambassadors from Rum (or Rumieh, the Byzantine Roman Empire) presented the Tang emperor of China with a gift of the Mithridatium theriac (Chinese tayeqie, diyejia). It was described as a dark red lump the size and shape of a pig’s gall bladder. Chinese manuscript illustrations show foreigners wearing Persian-style clothing offering these Mithridatium pills as tribute to the emperor.20

  In Europe, from the Middle Ages on, Mithridatium was eagerly ingested. European laws required apothecaries to openly display all the precious, expensive ingredients and to concoct Mithridatium in the public squares. For more than two millennia after the death of Mithradates, aristocrats and royalty, from Charlemagne and Alfred the Great to Henry VIII and Queen Elizabeth I, swallowed some version of the Mithridatium faithfully every day of their lives. The royal mixture was kept in ornate apothecary jars illustrating scenes from the life of Mithradates (see fig. 15.3, plate 4). There were also cheaper versions of Mithridatium for the poor. The Poison King’s universal antidote became the most popular and longest-lived prescription in history, available in Rome as recently as 1984.21

  Most of the surviving recipes for theriacs in Latin, Greek, Hebrew, Indian, Arabic, and early Islamic medical writings include an array of plant, animal, and mineral pharmaka to counteract toxins and disease. Aside from Andromachus’s addition of chopped vipers for Nero’s antidote, however, most of these theriac recipes did not deliberately include poisons. Yet the ancient writers agreed with Pliny that Mithradates achieved immunity to poisons by ingesting deadly substances along with a cocktail of specific or general antidotes. In Pliny’s words, he “thought out the plan of drinking poisons daily, after taking remedies, in order that sheer habit might render the poisons harmless.”22

  FIG. 11.1. Mithridatium jars, sixteenth–seventeenth century. Wellcome History of Medicine Museum collections, London, photo courtesy of Christopher Duffin.

  Although we can guess some of the counteracting drugs that Mithradates is likely to have put in his formula, his m
ethod of calibrating minuscule doses of poisons and exactly what they were remain a mystery. Mithradates worked in secrecy. The original lost recipe was believed to contain more than fifty ingredients, many of them expensive substances from faraway lands. Oddly, however, the notes translated after his death revealed only a few commonplace ingredients, with the exception of the blood of Pontic ducks. Even the learned naturalist Pliny expressed surprise at the lack of arcane or toxic substances in the Mithradatic notes he studied. He ridiculed a scrap of paper in the king’s handwriting: “Pound together two dried walnuts, two figs, and twenty leaves of rue with a pinch of salt: he who takes this while fasting will be immune to all poison for that day.” As Pliny remarked, this mundane recipe cannot be taken seriously; some modern scholars suggest it was a forgery or hoax.23

  So what happened to Mithradates’ formula? Several possible explanations come to mind. The archives taken to Rome may have recorded only Mithradates’ earliest experiments, superseded by successful tests whose records we do not have. The genuine records could have been lost or hidden during the chaos of the Mithradatic Wars. The documents may have been encrypted. Ancient alchemists wrote in codes or obscure languages; Mithradates possessed the linguistic skills to facilitate this. Perhaps the real formula was kept secret by the imperial Roman doctors who inherited Mithradates’ papers or Paccius’s recipe, but was later forgotten or lost. Maybe written versions of the perfected formula were destroyed on Mithradates’ orders, or entrusted only to closest friends and allies, such as Tigranes, who, like Mithradates, enjoyed robust health and an extremely long life. Perhaps it was destroyed when Callistratus, Mithradates’ personal secretary, was murdered by Roman soldiers. Pompey might have burned some of Mithradates’ archives, as he did with Sertorius’s papers. Or—as suggested by historian Alain Touwaide—maybe Pompey obtained the recipe but kept it secret within his circle.24 Finally, the instructions for the Mithridatium may never have been written down; perhaps they were recorded only in Mithradates’ prodigious memory.