Tobacco has been a part of human culture for thousands of years, serving as a staple in rituals, social custom, and folk medicine. For centuries, people consumed the plant through smoking, chewing, or snuffing, recognizing its profound physiological effects. Despite this widespread use, the specific compound responsible for the plant’s unique properties remained a mystery until the early 19th century.
The Context of Tobacco Use Before Isolation
Indigenous peoples in the Americas first cultivated the tobacco plant as early as 6,000 BCE, valuing it for ceremonial and therapeutic applications. Following the voyages of Christopher Columbus in the late 15th century, the plant was introduced to Europe as part of the Columbian Exchange, spreading rapidly across the continent. European physicians embraced tobacco, prescribing it for a vast array of ailments, often viewing it as a “sacred herb.”
Its use became cemented in European society, not just as a medicine but as a popular social commodity, particularly as snuff and pipe tobacco. This cultural significance continued to grow for over three hundred years, illustrating that the plant’s perceptible effects were well-known long before the scientific community could investigate its chemical composition.
Isolation and Identification of Nicotine
The identity of this active ingredient was finally revealed in 1828 by two German scientists at the University of Heidelberg: Wilhelm Posselt and Karl Ludwig Reimann. These chemists successfully extracted and purified the compound from tobacco leaves, an achievement that marked the birth of modern alkaloid chemistry. They used distillation of tobacco extracts to isolate the volatile, oily liquid in its pure, concentrated form.
Posselt and Reimann recognized the substance as the plant’s true active agent, immediately noting its potent, poisonous nature. They determined this concentrated liquid was the source of the plant’s characteristic effects, transitioning the understanding of tobacco from a botanical curiosity to a defined chemical entity.
Naming and Initial Chemical Classification
The new chemical substance was named nicotine, a tribute to Jean Nicot de Villemain, the French ambassador to Portugal in the 16th century. Nicot had popularized tobacco at the French court around 1560, believing it possessed medicinal qualities, and the botanical genus for tobacco, Nicotiana, had already been named in his honor.
Further chemical work followed the 1828 isolation, including the determination that nicotine was an alkaloid, a class of naturally occurring organic compounds containing nitrogen. In 1843, the Belgian chemist Louis-Henri-Frédéric Melsens established the empirical formula for the compound as $\text{C}_{10}\text{H}_{14}\text{N}_2$. The complete chemical structure was later determined in 1893 by German chemist Adolf Pinner.
Early Scientific Investigations
With the pure compound available, 19th-century scientists began rigorous investigations into the substance’s pharmacological effects. Posselt and Reimann’s initial assessment of the substance as a poison quickly led to toxicological studies, primarily conducted on animals. These experiments confirmed the extreme potency of pure nicotine, finding it to be a neurotoxin capable of causing convulsions, paralysis, and death.
The realization of nicotine’s toxicity also spurred practical applications. Tobacco extracts and, later, pure nicotine sulfate were adopted for use as early insecticides due to their effective neurotoxic action on pests. Despite the growing understanding of its toxic nature, some 19th-century medical practitioners still explored the use of tobacco extracts as therapeutic agents, a carryover from centuries of folk medicine.

