Aspirin and heroin: one man invents two pain relievers in two weeks

These two drugs represent the efforts of late-19th-century chemists to create new substances that could be used as medicines.

Within a two-week period in August of 1897, Felix Hoffmann synthesized aspirin — one of the most widely beneficial drugs ever — and heroin, one of the most harmful of illegal substances.

These two drugs represent the efforts of late-19th-century chemists to create new substances that could be used as medicines, not just to isolate active ingredients from natural products or to imitate them. One approach toward this end was to modify known physiologically active substances; another was to perform chemical operations on one or more of the myriad organic compounds created as products or byproducts of the synthetic dye industry that had developed in the 19th century and was particularly strong in Germany.

The son of a manufacturer in the town of Ludwigsburg in Swabia, Germany, Hoffmann first found employment in pharmacies in various cities and towns around Germany. He later studied chemistry and pharmacy at the University of Munich, graduating in 1893. Recommended by one of his professors, Adolf von Baeyer, Hoffmann joined the newly established pharmaceutical research department at the Bayer Co. in Elbersfeld.

That summer of 1897, Hoffmann was acetylating (adding the acetyl group CH3CO) all sorts of molecules, in hopes of improving the strength or decreasing the toxicity of physiologically active substances. This strategy had worked with Bayer’s first medicines: the fever-reducing Phenacetin (1888), acetylated p-nitrophenol, itself a useless byproduct of manufacturing blue dyestuffs; and the antidiarrheal Tannig (1894), which was acetylated tannic acid, a component of substances used in tanning leather. As Hoffmann recalled 20 years later, the Bayer chemists worked by instinct and talked about having “a good nose” for discovery.

Legend has it that Hoffmann was searching for a medicine to ease his father’s rheumatism pains when he acetylated salicylic acid, the active ingredient in salves and teas made from willow bark and certain other plant materials. Since antiquity, the pain-relieving and fever-reducing properties of willow bark were well known, and in the early 19th century, salicylic acid was isolated from it by several chemists. In 1859, Herman Kolbe determined its chemical structure and synthesized it. In 1874, the Heyden Co. near Dresden began manufacturing and selling synthetic salicylic acid, a cheaper product than the extract from willow bark itself. However, salicylic acid had unpleasant side effects — it irritated the stomach, and some patients were simply unable to tolerate it.

As soon as Hoffmann succeeded in the acetylation of salicylic acid to produce acetylsalicylic acid, Heinrich Dreser, the head of Bayer’s pharmaceutical laboratory, tested the substance for toxicity on himself, and then set up a series of animal experiments. Tests on people, patients in a hospital in Hall an der Saale, began soon afterwards. Acetylsalicylic acid was trademarked with the name “Aspirin,” from the A for “acetyl” and the spirin from Spirea, the genus name for shrubs that are an alternative source of salicylic acid. An application for a German patent was rejected because in fact acetylsalicylic acid was not a new substance, having been first synthesized in 1853 by French chemist Charles Gerhardt, in impure form, and later in crystalline form by German chemist Carl J. Kraut.

Recognizing that it had a potential blockbuster in aspirin, the Bayer Co. aggressively marketed the drug worldwide. In the U.S., Bayer was able to obtain a patent, giving the company the monopoly on manufacturing the drug from 1900 to 1917. When Bayer’s U.S. plants were sold in 1919 as part of the reparations exacted from Germany after World War I, Sterling Products of Wheeling, WV, was willing to invest the unheard of sum of $3 million for Bayer’s drug properties in the U.S. But Sterling was unable to protect the trademark status of “aspirin.” Aspirin became a staple of the over-the-counter market in the U.S. and elsewhere. More than 100 years after its invention, it continues to be a popular drug, with uses extending beyond those envisaged by its original creators.

Heroin is another story. Dreser, while still a professor in Göttingen, had worked on the effect of breathing in codeine, a weaker derivative of opium than morphine. He instructed Hoffmann to acetylate morphine with the objective of producing codeine; the result, instead, was a substance that was named “heroin.” Like aspirin, heroin had already been discovered in 1874 by English chemist C.R.A. Wright, and so was unpatentable. Before the extreme addictiveness of heroin was recognized, it was widely sold to suppress heavy coughs, to relieve the pain of childbirth and serious war injuries, and as a preliminary to anesthesia. Since the 1930s, it has been banned as an illegal substance in most countries.

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Excerpted from Bowden, M. E., et al., “Pharmaceutical Achievers,” Chemical Heritage Foundation, Philadelphia (2003). This article was originally published under the title "We're History" in the April 2004 edition of Chemical Engineering Progress magazine. This article was prepared by Neil Gussman, communications manager for the Chemical Heritage Foundation.