While researching therapeutics for relieving arthritis pain, Felix Hoffman reformulated earlier work with acetylsalicylic acid and developed a method to efficiently synthesize a less irritating, more stable form of the drug, which was named aspirin. Aspirin soon became the first drug to be artificially synthesized in large quantities.

The earliest medical text known to exist dates from the Sumerian city-states period around 3000 b.c.e. Among the extant “prescriptions” discovered from this period is a transcribed stone, known as the Ur III tablet, which lists plants such as myrtle or willow for the treatment of illness. The Ebers Papyrus (c. 1550 b.c.e.), discovered in the 1860’s by German Egyptologist George Ebers Ebers, George , has a reference to the use of willow in the treatment of ear infections and its use in a salve that helps make muscles more supple. While the precise meaning of the writings on the tablet and papyrus is unclear, the general interpretation is that each describes the use of willow for treating pain. Hoffman, Felix
Aspirin
Medicine;aspirin
Chemistry;and aspirin[Aspirin]
[kw]”Aspirin” Is Registered as a Trade Name (Jan. 23, 1897)
[kw]Is Registered as a Trade Name, “Aspirin” (Jan. 23, 1897)
[kw]Registered as a Trade Name, “Aspirin” Is (Jan. 23, 1897)
[kw]Trade Name, “Aspirin” Is Registered as a (Jan. 23, 1897)
Hoffman, Felix
Aspirin
Medicine;aspirin
Chemistry;and aspirin[Aspirin]
[g]Germany;Jan. 23, 1897: “Aspirin” Is Registered as a Trade Name[6230]
[c]Inventions;Jan. 23, 1897: “Aspirin” Is Registered as a Trade Name[6230]
[c]Chemistry;Jan. 23, 1897: “Aspirin” Is Registered as a Trade Name[6230]
[c]Health and medicine;Jan. 23, 1897: “Aspirin” Is Registered as a Trade Name[6230]
Gerhardt, Charles
Hoffman, Felix
Stone, Edward
Kolbe, Hermann

Because willow is among the plants that contain salicylates, the active ingredient of aspirin, the assumption is that these prescriptions represent the earliest descriptions of the chemical for treating inflammation. Hippocrates Hippocrates (c. 450 b.c.e.), in his cornucopia of medical treatments, also included willow tree bark to relieve headaches and the pain of childbirth. Willow bark was used also by the Romans during the period around the turn of the common era (100 b.c.e.-100 c.e.) for treating various types of pain, including muscle and joint aches and ear infections. Most of these remedies included diverse mixtures of various agents, but there existed a strong and persistent belief in the analgesic properties of plant extracts.

Much of the knowledge associated with plant or herbal medicine remained anecdotal until the mid-seventeenth and eighteenth centuries. In 1633, a Spanish monk in Central America described a “fever tree,” Central America;fever trees a cinchona, the bark of which, when made into a powder, would relieve the symptoms of malaria. Malaria;and quinine[Quinine]
Malaria;in Central America[Central America] The extract, named quina or quinine after the Peruvian name kina, represented the first remedy that could be studied.

In the 1750’s, Edward Stone Stone, Edward , a British clergyman as well as an amateur naturalist, observed that the bitter taste of the willow bark was similar to that of the cinchona. Furthermore, he noticed that by chewing ground powder from the willow, the pain associated with ague, a fever (as in malaria) often marked by headache, muscle pain, and sweating, could be relieved. Stone reported his findings to the British Royal Society. His work was acknowledged, but the true significance of his discovery was overlooked.

The active ingredient from willow, salicylic acid, was not isolated until the 1820’s. In 1826, Italian scientist Luigi Brugnatelli partially purified what he called “salicin,” a highly impure form of salicylic acid. A few years later, French pharmacist Henri Leroux Leroux, Henri prepared several grams of a crystalline form of the chemical. In 1838, Italian chemist Raffaele Piria named the crystal salicylic acid (SA) The purified form was found to have pain-relieving benefits, and it joined the list of treatments available in some European apothecary shops.

Because it is an acid, SA has a number of unpleasant side effects, mainly stomach irritation. Aware that SA was both a possible therapeutic agent and an organic one, French chemist Charles Gerhardt Gerhardt, Charles began to study its molecular structure. Techniques in chemistry during the mid-nineteenth century were crude, and Gerhardt’s initial interest was first to classify the molecule. He observed that the basis for SA’s irritating properties was in the hydroxyl (-OH) group. He modified the structure by replacing the hydrogen with an acetyl group, thereby creating acetylsalicyclic acid (ASA), tantalizingly close to the structure found in today’s aspirin. Gerhardt’s primary challenge was to accomplish the process in a timely manner and to make it a relatively simple procedure, something he never was able to carry out. After several unsuccessful attempts, he moved on to other endeavors.

Others attempted to continue Gerhardt’s Gerhardt, Charles work in developing more efficient means of synthesizing modified forms of SA. In part, the impetus for the work was the belief that the compound could serve as a food preservative, despite its taste. Among the more successful chemists was Hermann Kolbe Kolbe, Hermann . Best known for his research on structural theory related to inorganic and organic molecules, Kolbe found he could efficiently synthesize various forms of SA from relatively simple molecules. The ability to synthesize large quantities of ASA was applied by one of Kolbe’s students, Friedrich von Heyden, whose chemical factory, Heyden Chemical, was founded in 1874, mostly to produce the molecule. SA became the first artificially produced pharmaceutical substance; ironically, its application was in part based upon assumed antiseptic Antisepsis;and aspirin[Aspirin] properties, properties it did not possess.

In 1894, Felix Hoffman Hoffman, Felix was hired by Friedrich Bayer and Company. Hoffman showed an early interest in science and was trained as a pharmaceutical chemist. Anecdotal evidence suggests he began looking into the development of pain relievers as a means to relieve the arthritis suffered by his father. While his father in all likelihood did suffer from arthritis, the reality of Hoffman’s work suggests other reasons for his research. By the 1890’s, it was clear that SA provided benefits as an analgesic. What was needed was a more efficient method of production as well as a means to chemically modify the structure to increase its stability and eliminate side effects, all in keeping with the role of Bayer Bayer Aspirin as a pharmaceutical company; Hoffman was assigned the task. While researching the background of the chemical, Hoffman found Gerhardt’s Gerhardt, Charles original paper.

By treating SA with various chemicals, Hoffman found a method to neutralize its acidic properties without inhibiting its analgesic properties. Ironically, using the same modification procedure on a different chemical, Hoffman also discovered morphine.

Hoffman’s Hoffman, Felix reformulated ASA quickly underwent simple field trials. The analgesic was given to dentists, who found that it relieved toothaches. On January 23, 1899, ASA was given the trade name aspirin because it could also be obtained from the meadowsweet plant, genus Spiraea (aspirin = “a” for acetylation; “spir” from the plant name; “in,” commonly used at the time as a drug name ending). First sold as a powder, Bayer aspirin was marketed in tablet form in 1915, the first such drug to be sold in such a manner.

Aspirin can be considered one of the earliest wonder drugs. Initially manufactured by Bayer as an analgesic, or pain reliever, acetylsalicylic acid is more commonly known by its registered trade name, Bayer aspirin. It has been utilized as an anti-inflammatory, as a means to treat and even prevent heart attacks or certain forms of stroke because of its anticlotting ability, and as a possible preventive for certain forms of colon cancer.

A variety of companies market generic forms of the drug under several trade names, but Bayer Bayer Aspirin AG remains the most prominent drug manufacturer of aspirin. It produces approximately 50,000 tons of ASA each year. Estimates are that 137 million tablets are consumed each day worldwide.

The pharmacological basis for the function of ASA was determined only during the 1970’s. Pharmacologist John R. Vane at the University of London observed that the active ingredients in aspirin could prevent the action of prostaglandins, molecules released in the body during inflammatory activity. With the determination of the role played by prostaglandins in inflammation and blood clotting, for example, it finally became possible to understand how aspirin plays an inhibitory role in a variety of functions in the human body.

• Banks, Grace. “John R. Vane.” In The Nobel Prize Winners: Physiology or Medicine. Vol. 3. Pasadena, Calif.: Salem Press, 1991. Examines how Vane determined how aspirin treats inflammation and headaches.
• Feldman, David. How Does Aspirin Find a Headache? New York: HarperCollins, 2005. This book’s title refers to one of the numerous questions addressed that are both trivial and more scholarly in nature, making an enjoyable read.
• Jeffreys, Diarmuid. Aspirin: The Remarkable Story of a Wonder Drug. London: Bloomsbury, 2004. Historical account of the history and discovery of aspirin as well as the fortuitous events that led to its widespread application.
• Mann, Charles, and Mark Plummer. The Aspirin Wars: Money, Medicine, and One Hundred Years of Rampant Competition. New York: Alfred A. Knopf, 1991. The history of the marketing competition behind one of the most successful pharmaceuticals in modern medical history.
• Van Dulken, Stephen. Inventing the Nineteenth Century: One Hundred Inventions That Shaped the Victorian Age. New York: New York University Press, 2001. Among the inventions examined is the development of aspirin.

Wakley Introduces The Lancet

Safe Surgical Anesthesia Is Demonstrated

Behring Discovers the Diphtheria Antitoxin

Ross Establishes Malaria’s Transmission Vector

Beijerinck Discovers Viruses

Suppression of Yellow Fever

William Thomas Green Morton. Hoffman, Felix
Aspirin
Medicine;aspirin
Chemistry;and aspirin[Aspirin]