Histories

IT BEGAN with a king, Mithridates VI, ruthless ruler of the ancient kingdom of Pontus on thesouthern 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 isthe medicine he is said to have invented.

Like many powerful people of the time,Mithridates was afraid of being poisoned, andwith good reason. Poisoning was a popular way to dispatch enemies, remove rivals orhurry along an inheritance. Assassins couldchoose from any number of deadly plants,with henbanes, hellebores and hemlocks firmfavourites, or take their pick of venoms fromlocal snakes, scorpions or spiders. The king’s answer was to create an antidote that would protect him against them all.

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 tocounter each of them. Once he had establishedthose that worked best, he combined them into a single universal antidote. Other accounts suggest the Persian physicianZopyrus sent Mithridates the recipe and aprisoner to test it on. Either way, the ultimate antidote included extracts from around50 plants, a legless lizard and musk from a beaver’s scent glands, all mixed into apalatable paste with honey. Mithridates, thestory continues, took his medicine daily inan 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 generalPompey 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 goodfor 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 makingit, which was good news for the inhabitantsof a city that harboured some of the mostnotorious poisoners of the ancient world. There were other antidotes – known as

In 1745, London doctor William Heberden wrote a scathing essay debunking whatothers considered the most marvellous of medicines –a peculiar concoction called mithridatum. For almost two millennia, mithridatum hadbeen considered a cure for every illness imaginable, from indigestion and insomnia to boils and bubonic plague.The most that could be said forit, wrote Heberden, was that it would make the sick sweat,“which is commonly the virtueof a medicine which has none”. Yet such was its reputation – and cost – that apothecarieswere required to prepare it in elaborate public ceremonies lestthey be tempted to leave out a vital ingredient or skip a stepin the laborious manufacturing process. If mithridatum was useless, why was it reveredfor so long?

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theriacs – but Mithridates’s theriac, or mithridatum, clearly outclassed all others.

By the time the Emperor Nero came topower in AD 54, Rome’s pharmacists hadtinkered with the formula, adding yet more components. Nero himself took a keen interest in the subject: poison was hispreferred method of assassination but hefeared it too, and exhorted his physicianAndromachus to develop a still better theriac.

Andromachus added extra herbs, uppedthe opium content and dropped the lizard, opting instead for viper flesh – assuming that it must contain something that protected thesnake 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 mostinfluential man in the history of medicine. Claudius Galenus, physician to EmperorMarcus Aurelius, is credited with inventingthe science of pharmacy, and his writingsremained the last word on the subject for thenext 1500 years. In his book on theriacs, Galenus, or Galen as we know him, declaredAndromachus’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 deMedici as queen in 1547 saw sales rocket; while the rise of the Borgias in 16th-centuryItaly prompted many to lay in supplies.

“Soon it was regarded not just as proof against poison but as a panacea”

Marvellous mithridatum

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Business was brisk when the Black Deathswept across Europe in the mid-14th century,and again with each new wave of plague. InEngland, theriac, or “treacle” as the Englishcalled it, was the best the plague doctors had to offer, unrivalled as both preventive and treatment, they maintained.

To begin with, most mithridatum wasmade in Italy, and Venice soon dominatedthe trade. “Venice treacle” was reputed tobe 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 tooversee production, mindful that any dropin quality or allegation of adulteration couldsee rival producers move in on its markets. Other cities followed suit, introducing regulations and inspections to prevent greedy apothecaries taking short cuts orleaving out the more expensive ingredients.

From Byzantium to Bologna and Padua to Paris, the manufacture of theriac becamea public spectacle, with elaborate procedures and ceremonies designed to reassure thepublic that the carefully selected apothecarieswho made it never deviated from the rules or the recipe. First, the ingredients were laidout for public inspection and then, whenthe apothecaries were allowed at last to grind

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and mix the materials, they did so underthe watchful eyes of official scrutineers and crowds of townspeople. Authenticity was crucial and suspicion rife. In Holland, one doctor accused apothecaries of plyinginspectors with wine so their attention wandered while the apothecaries switchedingredients that had already been checkedfor 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 Englishapothecaries to make English treacle. Business flourished, although local apothecaries sometimes had to substitutelocal herbs for Mithridates’s Mediterranean species. Foreign suppliers responded by reducing their prices, undercutting Englishproducers 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 1745William Heberden, a London doctor, wrote AnEssay on Mithridatium and Theriaca ridiculing the remedy. It did little more than make apatient sweat, he argued. By the end of thecentury, theriac had been dropped from theLondon Pharmacopoeia, although versions remained in some European pharmacopoeiasuntil the late 19th century. But was theriacreally 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 protectedagainst poison. The opium, though, would have eased pain, reduced anxiety and encouraged restful sleep. It would have helped those withplague too , soothing their cough, reducing fever and drying up diarrhoea, says ChristianeNockels Fabbri, an expert on medievalmedicine at Yale University (Early Science andMedicine, vol 12, p 247). Modern analysis of some of the herbs that went into mithridatum also indicates that it had powerful anti-inflammatory action, useful for wounds, bruising and some intestinal disorders. It mayhave had other benefits too, but until someone makes a fresh batch of mithridatum and puts it to the test, who knows? Stephanie Pain ●

In late-18th-century Bologna, the manufacture of mithridatum was a colourful public spectacle

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