Mithridates: the first experimental toxicologist

Humans can become resistant to poisons via the body’s inbuilt adaptability. Eating small amounts of them is sometimes successful; and the technique is called Mithridatism, after a famous figure from classical history called Mithridates who pioneered the technique. Historian Adrienne Mayor described the man to Phil Sansom...

Adrienne - Mithridates was a powerful king of a small kingdom on the black sea. He was born in the second century BC. He was quite a successful rebel against the Roman Republic.

Phil - When did he first start taking poison?

Adrienne - I think he began experimenting even as a young man. When he took over the kingdom, he poisoned his mother and brother, and then he began experimenting himself with poisons and antidotes because he was always in danger of poisoning himself. His mother, even when he was a child, attempted to poison him. Poisoning was pretty rife in that time and place. He experimented on himself and his friends at first, and then when he became a powerful king, on condemned criminals and even allies and enemies. So he goes down in history as the world's first experimental toxicologist.

Phil - Wow. What kind of poisons are we talking about?

Adrienne - Well, there were myriad poisons known in antiquity from toxic plants to snake venoms. There was even poisonous honey in his territory made by bees that fed on toxic plants and then made honey that was a neurotoxin. And there were also many minerals in his kingdom that were highly toxic, such as arsenic.

Phil - Instead of using an antidote, did he actually build up a resistance to them just from taking the poison itself?

Adrienne - Yes. Arsenic was probably the most common poison in those days and it was sometimes called the powder of succession. It's odourless, doesn't have a flavour, but highly toxic. So that would have been the first poison that Mithridates sought to defend himself against because he had used it to poison so many people in his family and other enemies. Now arsenic interferes with metabolism. If you take small doses, however, very tiny doses of it, your liver produces enzymes that will inactivate the arsenic. And if you keep taking these small doses, it allows the liver to produce more of those enzymes that allow you to survive what would normally be a lethal dose. So Mithridates first achieved that. And then in his toxicological experiments with plants and other poisons, he was essentially investigating whether a similar process might work with plant poisons and venoms and other toxic minerals. That's a real scientific method that he was using. And we're talking about the first century BC. So it is quite an incredibly scientific approach to finding an antidote.

Phil - At the same time, it sounds like it's a really dangerous one, right?

Adrienne - Yes. I think it would be dangerous, but he had access to all kinds of resources. It's possible that he even had Hindu treatises on antidotes and poisons. He was able to speak more than a dozen languages. And of course it was risk-taking, but he felt it was worth trying to find a universal antidote. And he finally did come up with a concoction that later became known as the Mithradatium. But Mithridates' invention, you might say, was to not just include beneficial substances, but to also include tiny amounts of poisons or toxins as I said. We do have all of this documented in ancient sources, the problem is we don't know the exact recipe of his concoction that has been lost. On the other hand, physicians of the Roman emperors after the death of Mithridates claimed that they had the recipe of the Mithridatium and every Roman emperor thereafter took a concoction that they believed was the Mithridatium. All royalty throughout Europe took it - I believe up through Elizabeth the first.