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This Ancient Cure Was Just Revived In A Lab. Does It Work?

For nearly 2,000 years, people living in the Near East and Europe relied on one miracle medicine to protect themselves poison, plague, and a host of other maladies. This magical cure-all was known as theriac—a black, sticky substance crafted from dozens of ingredients, including black pepper, bread, opium, and viper flesh.

Theriac eventually faded into history with the rise of modern medicine, but a team of Polish researchers has now re-created theriac from a 17th-century apothecary recipe to study the miraculous claims that surround the cure.

An ancient remedy

Theriac was a hit in 17th century Poland. But its popularity and reach went far beyond Eastern Europe, and the idea of a "universal antidote" stretches all the way back to antiquity. Ancient sources like Galen and Pliny suggest that versions of theriac existed from at least the second century B.C., and their popularity soon spread in elite circles.  

Among the most famous seekers of cure-all was Mithridates VI Eupator, an Anatolian emperor and noteworthy opponent of ancient Rome who ruled from 120 to 63 B.C. Mithridates was obsessed with poisons and their cures.

"Arsenic was called the powder of succession at the time," says Adrienne Mayor, a research scholar in Stanford University's department of classics who was not involved in the study. In her biography of Mithridates, she tracks how that obsession sparked an expensive hunt for a way to evade poisoning—leading to the creation of a lasting theriac recipe.

Haunted by the possibility of poisoning and in consultation with medical experts from far and wide, Mithridates delved into the human body's ability to become immune to certain poisons by ingesting small amounts of toxins over time, a concept known in modern medicine as mythridatism.

"It's all in the dosage," says Major. And Mithridates' daily dose of poison-laced theriac seemed to work: He died by suicide at 70 after poisoning his daughters. Though the recipe he used is lost, it appears to have been passed to other nobles, whose court doctors brewed and experimented with it. Though their recipes varied—and dabbled in a vast variety of expensive ingredients—the basic makeup of theriac usually included honey, spices like cinnamon and cardamom, and a variety of herbs, barks, oils, and even wood. At some point after Mithridates, poison was removed from its long list of ingredients.

Nevertheless, theriac became a daily must-have for paranoid monarchs from Nero—whose court doctor replaced Mithradates' snake venom in the medicinal mixture with viper flesh—to Elizabeth I. Mayor notes that the opium that later became standard in such mixtures "really ensured patient compliance."

An everyday antidote

Theriac's royal heritage was part of its appeal, and it eventually became a widely available, though expensive, remedy for everyday people. For the cost of a chicken, Jakub Węglorz, an assistant professor of history at the University of Wrocław, explains, a 17th-century Polish plebeian could buy some of the substance from a licensed apothecary who had been trained for that purpose.

For Węglorz, who studies the history of medicine and the early modern era, it wasn't enough to read about theriac in medical textbooks—he wanted to see if it was possible to make the kind of theriac that was sold in Poland centuries ago. With funding from Poland's National Science Center, he teamed up with another historian and two pharmacists to try to reconstruct a 400-year-old theriac. It would be the first time modern researchers with a pharmaceutical background attempted to make theriac—and the first complete reconstruction and analysis of the drug.  

They relied on a 1630 recipe from Paul Guldenius, the city apothecary of what is now Toruń, Poland. Guldenius was one of a small group of apothecaries licensed to produce and sell theriac, and like his colleagues, he prepared the brew in public with what the researchers call "much pomp and ceremony."

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These acts of public theriac production were a way to ensure total transparency about what went into the medicine, and a way to advertise to a curious public. "They displayed all of these precious, costly ingredients" during public preparations, says Mayor.

Written in Latin, Guldenius' recipe lists the names and quantities of 61 ingredients. Węglorz and his team worked to decode the Latin and common names of the compounds used, cross-checking the recipe with contemporary books and other texts like diaries and letters.

Luckily, Guldenius was a thorough recipe writer, including the exact weights of the theriac components. Cardamom, allspice, wood, sweet wine, and wheat bread were all part of the potion. But his theriac wasn't just a catch-all. It had two vital ingredients that were key to both its effectiveness and its prestige: opium and viper flesh. Opium would have had an analgesic effect, while viper flesh was supposed to confer immunity to snake bites and have a "drying" effect on the body. According to the theory of bodily "humors" widely accepted at the time, spicy and intense flavors had the ability to "dry out" humors that predisposed a person to illness or infirmity.

Recreating theriac

It took four years to collect the ingredients needed to recreate Guldenius' brew. First, the researchers turned to suppliers of pharmaceutical-grade raw materials. But some of the herbs and spices were unavailable or not grown in the European Union, so the researchers either sought out the plant itself or used garden websites to source ingredients.

Theriac based on a 1630 recipe from Paul Guldenius, the city apothecary of what is now Toruń, Poland.

Photograph Courtesy Dr. Danuta Raj

"Even for something simple, like saffron or mint, we would get the plant on our own or buy it from a certified supplier, not from a grocery store," says Węglorz.

Then there was the issue of viper flesh: The team didn't want to kill snakes themselves, and Poland isn't exactly known for its abundance of reptiles. But vipers do live in its mountainous regions, and Węglorz traversed Poland by car, following tips from foresters who alerted him when they found a viper that had died of natural causes or became roadkill. Eventually, the team obtained almost seven ounces of fresh viper flesh, which was dried and then incorporated into the theriac.

Opium has proven even trickier. Poland's drug policies are strict, though individuals can get permission to grow opium poppies. The team is still trying to legally obtain 3.5 ounces of the drug, which was excluded from the brew for now.

After studying the potential effects of the theriac ingredients—many known for their therapeutic properties—the researchers got to work in a lab at the University of Wrocław, boiling, mixing, drying, and adding in the components. It took two days for the pharmaceutical experts to combine the ingredients, cooking them down over low heat. The result, a sticky molasses-like clump, would have been segmented into small pills that patients combined with water or wine, but scholars note that theriac was also sometimes used on the skin or in the eyes. They produced 9 pounds of theriac, which was then set aside to mature for a full year.

"We didn't taste it," says Węglorz. "But if we did, we could say the taste is really warming. It's hot. It's spicy. It has the taste of tar." The inclusion of herbs and spices like cinnamon, valerian, lavender, and black pepper seem to confer a whiskey-like burn to the concoction, which other scholars surmise was part of the medicine's appeal.

Though theriac contains ingredients that do have properties that can help human health, the researchers believe the placebo effect, helped along by royal influencers who relied on the drug, was behind most of theriac's purported ability to counteract poison and keep a person in good health. But that doesn't mean it's not worth recreating—both Mayor and Węglorz note that theriac is important evidence for the extent of scientific inquiry and folk remedies in antiquity and beyond.

Now, Węglorz's team is looking at variations of theriac that incorporated popular substances whose use came and went over time. Like us, people of the past were susceptible to medical fads—even if those fads involved opium, viper flesh, and a spicy black substance rumored to cure kings and peasants alike.

13 Facts About The Black Death

The pandemic of bubonic plague—later dubbed the Black Death—raged through Europe from 1347 to 1351 and wiped out between one-third and two-thirds of the entire population. But it wasn't all bad: the calamity actually led to better literacy and labor conditions. Here are 13 facts about the Black Death.

Recent archaeological research has found evidence of bubonic plague in two Bronze Age skeletons uncovered in Russia, suggesting the disease has been around for thousands of years. The Justinianic Plague, which swept through the Mediterranean and Near East in the 6th century CE, is the first recorded pandemic of bubonic plague. (It coincided with the reign of Byzantine emperor Justinian, hence the name.) Historians consider the multiple waves of plague in the 14th century, later dubbed the Black Death, to be the world's second plague pandemic.

The highly infectious disease is caused by a bacterium, Yersinia pestis, that infects rats and other small mammals as well as humans. It is spread by fleas that feed on the infected animals and carry the bacteria in its intestines. When their host rodents die from the disease, fleas look for a new source of food and move on to humans and livestock, transferring the deadly bacteria through their bites.

One of the first symptoms of plague to appear are painful, swollen lymph nodes at the neck, groin, and armpit known as "buboes," which give their name to the disease. As the illness progresses, sufferers experience headache, vomiting, and high fever, and their buboes secrete blood and pus. There was no viable treatment in the medieval period and most people with plague would be dead within seven days. Today, plague can be cured with antibiotics.

The episodes of disease that triggered the Black Death originated in central Eurasia. During the 1340s, the plague moved through India, Syria, Persia, and Egypt and decimated communities in its path before reaching Europe in 1347.

In 1347, the Mongol khan Janibeg was in the midst of a siege of Kaffa, a Genoese trading port in modern-day Crimea. He hoped to oust the Genoese merchants from the territory, but his own troops were greatly depleted by the Black Death and victory looked impossible. In a final act of vengeance, Janibeg's army used a trebuchet (a sort of medieval catapult) to fling the plague-ridden bodies of his own soldiers into the walled city. The residents of Kaffa, already weakened by the siege, were soon overcome by disease.

Rats live in proximity to humans and were usually present on the merchant ships that sailed from country to country, often spreading disease with them. Medieval folklore warned that if there were a lot of dead rats around, then disease and pestilence would follow.

Genoese ships carried trade goods—and unintentional cargoes of plague-infected rats—from Central Asia to the port city of Messina, Sicily, in 1347. The plague quickly spread through Europe, first engulfing the Italian peninsula and then moving on through France, Spain, and Germany. The epidemic reach England by 1349 and Scandinavia by 1350. Historians have traced how merchant ships drove the spread of plague: busy shipping ports, such as Kaffa, offered perfect opportunities for the pathogen to find new hosts and catch rides along the world's major trade routes. As a result, the highest death tolls are estimated to have occurred in ports and large cities such as Venice and London.

Because it infects humans via fleas and rats, the Black Death has been mischaracterized as a "peasant's disease" affecting only those who lived in less-than-hygienic environments. Yet the Black Death touched all sectors of society, from the very poor to the very rich. The number of high profile deaths from the plague included Joan, the favorite daughter of England's King Edward III; Eleanor of Portugal, Queen of Aragon; King Alfonso XI of Castile; two archbishops of Canterbury, John de Stratford and Thomas Bradwardine; and the philosopher William of Ockham.

Imagine how terrifying the Black Death must have seemed before anyone understood the germ theory of disease. Some people became convinced that the plague was a punishment sent by God and sought to halt its spread by taking part in public displays of penance.

Many joined the flagellant movement, which had existed in northern and central Europe since the mid-13th century but gained more followers amid the chaos of the Black Death. Groups of monks and religious devotees led processions through cities, towns, and villages while whipping themselves and each other and calling on observers to repent. The flagellation caused such gruesome injury (which, ironically, may have made the flagellants more susceptible to infections) that Pope Clement VI denounced the movement.

While there was no understanding of germ theory in the Middle Ages, people did sense that the Black Death could be transferred from person to person. Officials imposed health regulations aimed at containing the disease. Plague doctors visited communities and told symptomatic families to stay in their homes or go to plague hospitals. Ships were prohibited from disembarking sailors for 30 days after arrival in ports, a method first used in Venice in 1347. The practice proved effective, and the wait was eventually extended to 40 days for each newly arrived ship. Quarantine derives from the Italian quaranta and Latin quadraginta, both meaning "forty."

The initial phase of the Black Death hit Europe in 1347 and rippled through the region until 1351—but this was not the end of the pandemic. The disease recurred in Europe several times over the next 50 years, in 1361–63, 1369–71, 1374–75, 1399, and 1400. These fresh attacks of plague were again carried into Europe by ships from Asia, spreading the disease along trade routes. More epidemics occurred in the 17th century, notably in London in 1665–66, when around a quarter of the city's population died.

The world's third plague epidemic emerged in Yunnan, China, in the mid-19th century, spreading quickly to Taiwan, Hong Kong, Japan, India, and farther afield. It killed 12 million people in India alone.

By the 1890s, medical knowledge had advanced sufficiently to identify the bacteria responsible for the bubonic plague. Researchers from multiple countries headed to Asia in the late 19th century to study the disease as it spread. In 1894, Japanese bacteriologist Kitasato Shibasaburō traveled to India and succeeded in identifying the bacterium; mere days later, French-Swiss bacteriologist Alexandre Yersin also isolated it. A controversy erupted over who would receive credit for the discovery. Many historians now consider the two researchers to be co-discoverers, but the microbe's scientific name is still Yersinia pestis. (The genus Yersinia was established in 1944 in Yersin's honor.)

The breakthrough allowed Yersin's successor, Paul-Louis Simond, to test a hypothesis based on reports that thousands of dead rats in the streets seemed to accompany an outbreak of plague in people. "On the rats captured alive, and on the rats which had just died, the fleas were thicker than I have ever seen them," he wrote. "We have to assume there must be an intermediary between a dead rat and a human. This intermediary might be the flea." 

A simple experiment demonstrating that fleas transmitted plague from an infected rat to a healthy one proved Simond's theory.

In England, the Black Death was popularly known as "the pestilence," and in much of the rest of Europe as "the plague" or "the great dying." Elizabeth Penrose, in her 1823 book A History of England, dubbed the plague of 1347–51 the "Black Death"—a suitably terrifying name that stuck.

But even before then, 16th-century Danish and Swedish chronicles described a deadly plague in Iceland in 1402–03 as the "Black Death," though no one is sure why. The chronicles were later translated into German and English and the description they used was retrospectively applied to the 14th-century plague in Europe.

Despite the terrible death toll, in which an estimated 60 percent of Europe's population died, the Black Death did lead to some positive social changes. The labor shortage following the pandemic had far-reaching effects, ultimately sparking a rise in wages and better conditions for the peasants who worked the land. These shortages also created an impetus to develop new labor-saving technologies, such as smaller, faster boats that needed fewer crew members, making exploration (and exploitation) of Asia and the Americas possible.

And, after many of the monks responsible for copying manuscripts perished in the plague, societies needed new ways to copy and distribute books—precipitating the invention of the printing press and encouraging the spread of ideas.

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Causes And Effects Of The Black Death

There are various estimates of how many people died during the 1348-49 outbreak. Most historians believe between a third and half of the population were killed by the Black Death. The population of England at the time of the Black Death is estimated to have been around 6 million, so that means approximately 2 to 3 million people died.

Despite the scale of the fatalities, there is evidence that there was some sort of organised response from local government. Mass graves of victims have been found from the Middle Ages. The way the bodies are carefully laid in side by side suggests bodies were treated respectfully and in a dignified way.

A result of the high mortality rateclosemortality rateThe percentage of people who would normally die from a disease. So a disease with a mortality rate of 50% would mean an average of 50 people would die out of every 100 infected. Was a shortage of workers. This led to rapid wage rises as landowners had to compete for workers by paying more. In 1351 a law was introduced to force wages to go back to the levels they had been at before the Black Death. This was one of the causes of the Peasants' Revolt in 1381.

As no one knew exactly what caused the Black Death, they could do little to stop future outbreaks. There were further Black Death cases throughout the Middle Ages and beyond. There was another significant outbreak in 1665, particularly affecting London. This outbreak shows there had been no real increase in understanding about what was really causing the disease or how to prevent it.

It wasn't until the work of Louis Pasteur and Robert Koch in the 1800s that it was discovered germs are the cause of disease. The plague bacteria was finally discovered by Alexandre Yersin in 1894. The bacteria was named after him; 'Yersinia pestis.'

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