Answer: Mercury

In modern culture the closest anyone comes to a “mad hatter” is the endearingly eccentric character in Lewis Carroll’s Alice’s Adventures in Wonderland and the various derivative works. The origin of the phrase “mad as a hatter” was based on the unfortunate fate of early hat makers, however, and for both the hatters and their families “mad hatter” syndrome was all too real.

The majority of hats in the 19th century were made out of felt, and the majority of felt was (from the 17th century well into the mid-20th century) treated and processed using mercuric nitrate. As a result, hatters were exposed to extremely high doses of mercury vapor over the course of their career and nearly all hatters developed some symptoms of mercury poisoning as a result of their chronic occupational exposure.

The most common symptom was tremors and shaking of the hands. It was so common, in fact, that it was called “hatter’s shakes” or “Danbury shakes” (named such after the hat-making industry in Danbury, Connecticut).

When the term “mad as a hatter” came into play, however, was when the exposure was more acute and prolonged and the hatter not only had the shakes, but was experiencing other neurotoxic side effects like extreme shyness, nervousness, irritability, and insomnia. The medical name for this neurological disorder, almost always but not exclusively caused by mercury poisoning, is “Erethism”.

Increased understanding of mercury toxicity as well as reform of labor laws and working conditions in the 20th century led to a radical reduction in global levels of mercury exposure as both the hat making industry and other industries that used mercury either moved away from use of the highly toxic chemical or adopted strict handling and safety standards.