In 1745, London doctor William Heberden wrote a scathing essay debunking what others considered the most marvellous of medicines – a peculiar concoction called mithridatum. For almost two millennia, mithridatum had been considered a cure for every illness imaginable, from indigestion and insomnia to boils and bubonic plague. The most that could be said for it, wrote Heberden, was that it would make the sick sweat, “which is commonly the virtue of a medicine which has none”. Yet such was its reputation – and cost – that apothecaries were required to prepare it in elaborate public ceremonies lest they be tempted to leave out a vital ingredient or skip a step in the laborious manufacturing process. If mithridatum was useless, why was it revered for so long?
IT BEGAN with a king, Mithridates VI, ruthless ruler of the ancient kingdom of Pontus on the southern shores of the Black Sea. In the 1st century BC, Mithridates took on the Roman Empire and won – for a while. The king’s epic struggle with Rome is legendary, and so too is the medicine he is said to have invented.
Like many powerful people of the time, Mithridates was afraid of being poisoned, and with good reason. Poisoning was a popular way to dispatch enemies, remove rivals or hurry along an inheritance. Assassins could choose from any number of deadly plants, with henbanes, hellebores and hemlocks firm favourites, or take their pick of venoms from local snakes, scorpions or spiders. The king’s answer was to create an antidote that would protect him against them all.
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According to some accounts, Mithridates systematically tested every known antidote on condemned prisoners. He soon learned that while one particular remedy worked best against snakebite, another was more effective against scorpion stings. As for plant poisons, it seemed something different was needed to counter each of them. Once he had established those that worked best, he combined them into a single universal antidote. Other accounts suggest the Persian physician Zopyrus sent Mithridates the recipe and a prisoner to test it on. Either way, the ultimate antidote included extracts from around 50 plants, a legless lizard and musk from a beaver’s scent glands, all mixed into a palatable paste with honey. Mithridates, the story continues, took his medicine daily in an attempt to build up immunity to poison.
Apparently it worked, for not only did Mithridates reach old age, when he was finally defeated in 63 BC by the Roman general Pompey and tried to poison himself, he found he couldn’t. “The poison, although deadly, did not prevail over him, since he had inured his constitution to it, taking precautionary antidotes in large doses every day,” wrote Roman historian Cassius Dio.
Whatever the truth of the story, it was good for sales of the stuff in Rome. Rumour had it that Pompey found the recipe among the vanquished king’s possessions and took it home. Soon Rome’s pharmacists were making it, which was good news for the inhabitants of a city that harboured some of the most notorious poisoners of the ancient world. There were other antidotes – known as theriacs – but Mithridates’s theriac, or mithridatum, clearly outclassed all others.
By the time the Emperor Nero came to power in AD 54, Rome’s pharmacists had tinkered with the formula, adding yet more components. Nero himself took a keen interest in the subject: poison was his preferred method of assassination but he feared it too, and exhorted his physician Andromachus to develop a still better theriac.
Andromachus added extra herbs, upped the opium content and dropped the lizard, opting instead for viper flesh – assuming that it must contain something that protected the snake from its own venom. Andromachus’s mithridatum contained 64 ingredients and was much more than an antidote, he claimed. Not only did it “counteract all poisons and bites of venomous animals”, it would also “relieve all pain, weakness of the stomach, asthma, difficulty of breathing, phthisis [tuberculosis], colic, jaundice, dropsy, weakness of sight, inflammation of the bladder and kidneys and the plague”.
A century after Nero, Andromachus’s theriac received the ultimate seal of approval – an endorsement by the most influential man in the history of medicine. Claudius Galenus, physician to Emperor Marcus Aurelius, is credited with inventing the science of pharmacy, and his writings remained the last word on the subject for the next 1500 years. In his book on theriacs, Galenus, or Galen as we know him, declared Andromachus’s formula the best: “Whoever took a proper dose in the morning was ensured against poison throughout that day.”
Word of the amazing remedy spread across Europe. Soon it was regarded not just as proof against poison but as a panacea, an effective remedy for all manner of illnesses, including the most feared disease of all, bubonic plague. Its popularity soared whenever there was an outbreak of poisoning: in France, the installation of the murderous Catherine de Medici as queen in 1547 saw sales rocket; while the rise of the Borgias in 16th-century Italy prompted many to lay in supplies. Business was brisk when the Black Death swept across Europe in the mid-14th century, and again with each new wave of plague. In England, theriac, or “treacle” as the English called it, was the best the plague doctors had to offer, unrivalled as both preventive and treatment, they maintained.
“Soon it was regarded not just as proof against poison but as a panacea”
To begin with, most mithridatum was made in Italy, and Venice soon dominated the trade. “Venice treacle” was reputed to be the finest, because Venetian vipers were best. That prompted the city to establish viper gardens to guarantee the supply of snakes. The authorities also took steps to oversee production, mindful that any drop in quality or allegation of adulteration could see rival producers move in on its markets. Other cities followed suit, introducing regulations and inspections to prevent greedy apothecaries taking short cuts or leaving out the more expensive ingredients.
From Byzantium to Bologna and Padua to Paris, the manufacture of theriac became a public spectacle, with elaborate procedures and ceremonies designed to reassure the public that the carefully selected apothecaries who made it never deviated from the rules or the recipe. First, the ingredients were laid out for public inspection and then, when the apothecaries were allowed at last to grind and mix the materials, they did so under the watchful eyes of official scrutineers and crowds of townspeople. Authenticity was crucial and suspicion rife. In Holland, one doctor accused apothecaries of plying inspectors with wine so their attention wandered while the apothecaries switched ingredients that had already been checked for something cheaper.
In England, doctors grumbled that theriac was always in short supply and that foreign rogues often sold them sub-standard stuff. The answer was for English apothecaries to make English treacle. Business flourished, although local apothecaries sometimes had to substitute local herbs for Mithridates’s Mediterranean species. Foreign suppliers responded by reducing their prices, undercutting English producers and triggering accusations of fraud. “Strangers do daily send into England a false and naughty kind of mithridatum and treacle in great barreles,” grumbled Elizabeth I’s apothecary in 1585. In 1612, there were complaints about the rubbish being passed off as “Tryacle of Genoa”, and the College of Physicians was persuaded to supervise production and so guarantee the quality of English treacle.
So much trouble, and for what? In 1745 William Heberden, a London doctor, wrote An Essay on Mithridatium and Theriaca ridiculing the remedy. It did little more than make a patient sweat, he argued. By the end of the century, theriac had been dropped from the London Pharmacopoeia, although versions remained in some European pharmacopoeias until the late 19th century. But was theriac really so useless, or was Galen right?
The most famous ingredient, the vipers, contain no antidote to snake venom and it’s doubtful any other ingredient protected against poison. The opium, though, would have eased pain, reduced anxiety and encouraged restful sleep. , soothing their cough, reducing fever and drying up diarrhoea, says Christiane Nockels Fabbri, an expert on medieval medicine at Yale University (Early Science and Medicine, vol 12, p 247). also indicates that it had powerful anti-inflammatory action, useful for wounds, bruising and some intestinal disorders. It may have had other benefits too, but until someone makes a fresh batch of mithridatum and puts it to the test, who knows?
