Issue: July 10, 2009
July 10, 2009
4 min read

Aspirin: a natural remedy turned pharmaceutical milestone

The pain reliever was made available over the counter in 1911.

Issue: July 10, 2009
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No single drug may be more historically associated with its manufacturer than Bayer’s Aspirin. The drug was a commercial pharmaceutical “hit” that put Bayer, originally a dyestuff manufacturer, on the map. Today, over 110 years later, aspirin is still one of the most widely consumed medications in the world.

The history of acetylsalicylic acid begins with its use as a natural remedy as far back as the ancient Egyptians. In ancient times, the Egyptians and other cultures were believed to have used willow tree leaves or bark for their analgesic effects. Hippocrates himself is said to have recommended the use of the willow tree’s bark to relieve fever and back pain.

The transition from natural remedy to pharmaceutical took several hundred years, however. The first scientific description of willow bark is frequently credited to Edward Stone. In 1763, Stone is said to have “prescribed” the bark to patients to relieve fever. The dosage was about 1 g of powered bark in water taken every four hours, according to a report submitted to The Royal Society.

Discoveries involving willow bark’s medicinal uses increased throughout the 1800s. In 1828, Johann Andreas Buchner purified the extract of willow bark into a yellow material called salicin. In 1838, Raffaelle Piria split salicin to create salicylic acid. Word of this discovery spread and additional experimentation led to the discovery of the chemical structure of the acid. The compound could then be produced on an industrial scale, bringing the drug to a mass market.

Widespread use of salicylic acid began as a pain reliever; however, the adverse effects of the drug were inescapable. It was associated with stomach irritation and an unpleasant taste.

Bayer steps in

It was the unpleasant effects of the drug that supposedly prompted a Bayer chemist to experiment with salicylic acid to make it more tolerable. Felix Hoffman — who undertook the experiments to help his often rheumatic father — is frequently credited with discovering acetylsalicylic acid in a pure and stable form on Aug. 10, 1897.

Bayer’s fledgling pharmaceutical arm was working concurrently on another pain-relieving drug. Heroin — named such for making patients feel ‘heroic’ — was made by diluting morphine with acetyls. Heroin was supposed to be a nonaddictive alternative to morphine and was marketed by Bayer as a cough suppressant. Later research proved that heroin was essentially a faster acting form of morphine, an embarrassing discovery for Bayer.

Bayer Aspirin
Aspirin, manufactured by Bayer, was originally sold in powder form.

Source: Bayer AG: Corporate History & Archives

It was a preoccupation with marketing heroin that is suspected to have delayed efforts related to aspirin. Eventually, Heinrich Dreser, head of pharmacology at Bayer, tested aspirin on himself and conducted a series of animal experiments as well. In 1899, Dreser published his findings in a German journal.

The new drug was named Aspirin on Feb. 1, 1899 — Bayer would later lose the trademark on the name aspirin as part of the 1919 Treaty of Versailles. According to one historian, Bayer is said to have circulated information on the drug to more than 30,000 doctors.

Originally manufactured in powder form, Bayer later developed a tablet, providing patients with an exact dosage. In 1911, the drug became available as an over-the-counter remedy.

Murky history

The traditional story of aspirin’s discovery may not be entirely clear cut. In 1949, Arthur Eichengrün, a colleague of Hoffman’s at Bayer, published a different account of the discovery of aspirin in Pharmazie. This account echoed a letter that Eichengrün wrote about the topic while imprisoned in Theresienstadt concentration camp during World War II.

The basis of the alternative theory — backed by materials found in Bayer’s archives — is that the scientists at Bayer, under Eichengrün’s instructions, were testing several derivatives of salicylic acid including acetyl ester, butyryl and benzoyl salicylic acids. The goal was to find a compound that would reduce many of the adverse effects related to salicylic acid. Dreser concluded that acetylsalicylic acid was better than the alternatives but decided not to initiate clinical studies.

Later, around 1898, Carl Duisberg, a chemist and research manager at Bayer asked about the progress being made on acetylsalicylic acid. At this time Dreser reinitiated testing of the compound, which “might explain why Hoffman synthesized stable, pure acetylsalicylic acid on Aug. 10, 1897.”

It is believed that before 1949, Eichengrün was unable to dispute the accepted story of aspirin’s discovery because he was Jewish and living and working in Nazi Germany.

More than meets the eye

Despite who gets credit for its discovery, aspirin was a hugely influential pharmaceutical discovery. Even after aspirin was widely accepted as a pain reliever, its role as an antithrombotic medication was not discovered for decades. The Physician’s Health Study, which began in 1989, was the first properly conducted clinical trial to prove that aspirin prevented myocardial infarction and stroke. These data breathed new life into an old drug whose share of the over-the-counter pain relief market had decreased drastically with the birth of Tylenol in the 1950s and Advil in the 1980s.

However, a physician named Lawrence Craven suspected aspirin’s antithrombotic effect as early as the 1950s. Little credence was given to Craven’s observations because they were not confirmed in clinical trials. Initially, Craven based his suspicions about aspirin on the increased bleeding he observed in patients who had chewed aspirin to relieve the pain of dental procedures.

In 1948, Craven prescribed 400 patients aspirin; two years later none had had a myocardial infarction. In fact, Craven published four major medical papers on the topic, even recommending in one that all men aged 45 to 65 — believed at the time to suffer many more heart attacks than women — who were sedentary or overweight should take daily doses of the drug.

Craven made this recommendation at a time when the most pivotal study of cardiovascular diseases, the Framingham Heart Study, was only just beginning.

For more information:

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  • Sneader W. BMJ. 2000;321:1591-1594.