The History of Acetylsalicylic acid

It took more than 200 years to explain the mechanism of action of acetylsalicylic acid. Acetylsalicylic acid, also known as Aspirin, is one of the most widely used medications in the world. This drug was derived from the barks of willow trees. A stone tablet of medical text dated ca. 2000 BC, lists willow among plant-based remedies. In ancient times, Sumerians and Egyptians, as well as Hippocrates, Celsus, and Galen used this plant for pain, fever and inflammation.

Willow bark (Salix alba) preparations became a standard part of the Materia Medica of Western medicine; the Greek physician Hippocrates recommended it (in the fifth century BC) to ease the pain of child-bearing and to reduce fever. Celsus in his De Medicina of ca. 30 AD suggested willow leaf extract to treat the four signs of inflammation: redness, heat, swelling and pain. By the time of Galen, willow was commonly used throughout the world as a small part of a large, growing botanical pharmacopoeia.

The major turning point for Acetylsalicylic acid medicines came in 1763, when a letter from English chaplain Edward Stone was read at a meeting of the Royal Society describing the dramatic power of willow bark extract to cure a group of symptoms, including intermittent fever, pain, and fatigue that was primarily called Malaria. Inspired by the doctrine of signatures, Edward Stone had tasted the bark of a willow tree in 1758 and noticed astringency reminiscent of the standard Malaria cure of Peruvian bark. He collected, dried, and powdered a substantial amount of willow bark, and over the next five years tested it on a number of people sick with fever and malaria. In his letter, Stone reported consistent success, describing willow extract’s effects as identical to Peruvian bark, though a little less potent. The difference is that the active constituent of Peruvian bark is quinine, which was believed to attack the infectious cause of malaria. However the active constituent of Willow extract is salicin, which relieved the symptoms of malaria but could not cure it.

In the 19th century, as the young discipline of organic chemistry began to grow in Europe, scientists attempted to isolate and purify the active components of many medicines, including Willow bark. After unsuccessful attempts by Italian chemists Brugnatelli and Fontana in 1826, Joseph Buchner obtained relatively pure salicin crystals in 1828; the following year, Henri Leroux developed a better procedure for extracting modest yields of salicin. By 1838, Italian chemist Raffaele Piria found a method of obtaining a more potent acid form of Willow extract, which he named salicylic acid.The German chemist who had been working to identify the  Spiraea  extract, Karl Jacob Löwig, soon realized that it was in fact the same salicylic acid that Raffaele Piria had found.

Through the middle decades of the 19th century, the use of salicylate medicines including salicin, salicylic acid, and sodium salicylate, grew significantly, and physicians increasingly knew what to expect from prescribing these medicines: reduction of pain, fever, and inflammation. However, the unpleasant side effects, particularly gastric irritation, limited their usefulness.

It is important to note that the mechanism of acetylsalicylic acid (aspirin’s) analgesic, anti-inflammatory and antipyretic properties was unknown through the early- to mid-twentieth century. Initial explanation, widely accepted since the drug was first brought to market, was that aspirin relieved pain by acting on the central nervous system. In 1958 Harry Collier, a biochemist in the London laboratory of a pharmaceutical company, began investigating the effects of aspirin. In tests on guinea pigs, Harry Collier realized that cutting the guinea pigs’ pneumogastric nerve (vagus nerve) did not affect the inhibitory effect of aspirin – thus aspirin worked locally to combat pain and inflammation, rather than on the central nervous system. In 1963, Collier began working with University of London pharmacology graduate student Priscilla Piper to determine the precise mechanism of aspirin’s effects. However, it was difficult to pin down the precise biochemical goings-on in live research animals.

After five years of collaboration, Harry Collier arranged for Priscilla Piper to work with pharmacologist John Vane at the Royal College of Surgeons of England, in order to learn Vane’s new bioassay methods. They found that aspirin inhibited the release of an unidentified chemical generated by guinea pig lungs, a chemical that caused rabbit tissue to contract. In a June 23, 1971 paper in the Nature journal, John Vane and Priscilla Piper suggested that aspirin worked by blocking the production of prostaglandins (the prostaglandins are a group of hormone-like lipid compounds in the body). Later research showed that aspirin worked by inhibiting Cyclooxygenase, the enzyme responsible for converting Arachidonic acid into a prostaglandin.

To conclude – we can be optimistic that one day soon, the medical community worldwide will understand and acknowledge the mechanism of action of homeopathic medicine through the language of science. This is achievable with advancement of nano-technology. It took such a long time in the history of medicine to explain Aspirin’s mechanism of action in the body, and as science is evolving, the current explanation may one day be revised and updated with a newer explanation that would satisfy the human’s limited logic for that time.

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