Aspirin: The evolution of a 'wonder drug' that changed medicine

• Aspirin was first synthetized in 1897 by a chemist who worked for Bayer.
• A similar natural substance, acetylsalicylic acid, comes from plants that contain salicin.
• It relieves pain, fever, and inflammation by inhibiting the production of prostaglandins.

Aspirin is one of the most widely used and well-known medications around the world. It is an effective pain reliever, fever reducer, anti-inflammatory, and antiplatelet drug that has been used for over a century to treat a wide range of health issues and symptoms —from mild headaches to blood clots. 

Given that it is a mostly safe over-the-counter, low-cost medicine with a long shelf life, it can be taken even in resource-limited settings. 

For all these reasons, aspirin is included on the World Health Organization’s list of most essential medicines, which is a selection of the most effective and cost-effective medications that address the most important health needs in the world. 

What is aspirin?

Commercial aspirin, also known as acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug (NSAID). This means that it inhibits the production of certain enzymes in the body, specifically cyclooxygenases (COX) enzymes, which are responsible for the production of prostaglandins, hormone-like chemical messengers that contribute to pain, inflammation, and fever. 

Prostaglandins also play a role in blood clotting. When blood vessels are harmed, prostaglandins regulate the formation of blood clots to stop the bleeding.

To do this, they promote the aggregation of platelets, small blood cells produced in the bone marrow that stick together to form “plugs” at the site of an injury.

Given that aspirin reduces the production of prostaglandins, it prevents the aggregation of platelets. This is why some people who take aspirin regularly can also experience more bruising and longer blood clotting times (their wounds take more time to stop bleeding).

Also, taking high doses of aspirin over a prolonged period of time can put people at a higher risk of bleeding, mainly internal bleeding.

But in the right doses, aspirin can help prevent clot blood formation, such as the ones that lead to heart attacks and clot-related strokes.

What is aspirin used for?

Aspirin has traditionally been used to relieve mild to moderate pain, such as headaches (especially tension-type headaches), period pain, and toothaches. Because of its antipyretic properties, it has also been used to reduce fevers from colds or other conditions since it was FDA-approved at the beginning of the 20th century.

As an anti-inflammatory drug, it is sometimes applied as a treatment for injury-related inflammation, such as strains or sprains. It is also prescribed to combat inflammation in rheumatoid arthritis and similar conditions.

Although aspirin was first synthesized in 1897, its antithrombotic effect wasn’t demonstrated until several studies that took place between the 1960s and the 1980s confirmed it. 

Now, it is often prescribed in low doses on a case-by-case basis to individuals who are at risk of getting life-threatening blood clots,  such as people who have already had a heart attack or a clot-related stroke, or people who have gone through coronary artery bypass surgery or stent placement.

Although aspirin is approved for use in children older than the age of three, it is primarily recommended for use in adults because of the link of aspirin intake with Reye syndrome in children under 18 years old.  

Children and teenagers recovering from chickenpox or flu-like symptoms should not take aspirin.

Reye syndrome is a rare condition that causes brain and liver damage in children recovering from viral infections such as chickenpox and the flu. 

After a large number of cases in children were associated with aspirin use in the early 1980s, the Centers for Disease Control and Prevention (CDC), the American Academy of Pediatrics (AAP), and the Food and Drug Administration (FDA) advised against the use of aspirin-containing medications in children, which greatly reduced the incidence of the disease.

When was aspirin discovered?

Aspirin is a synthetic medication derived from natural-occurring salicylates found in plants, such as myrtle, meadowsweet, and willow.

According to clay tablets from the Sumerian period, the Assyrians used willow leaves to treat rheumatic disease. Ancient Egyptians resorted to willow leaves to treat pain and inflammation, and the Greek physician Hippocrates (460-377 BCE) wrote about willow bark’s pain-relieving and fever-reducing properties.

In traditional Chinese medicine, willow bark was used to treat pain and other ailments. The Druid Celts used meadowsweet as a source of acetylsalicylic acid. In 1763, an English clergyman, Reverend Edward Stone, carried out the first scientific study of the benefits of willow bark in the treatment of fever.

The active ingredient in willow bark, salicin, was first isolated by  Johann Andreas Buchner, a German Professor of Pharmacology at the University of Munich, in 1828.

The chemical structure of salicylic acid was worked out in 1859 by Professor Hermann Kolbe at Marburg University. Although successful clinical trials of the compound were later made, it had an unpleasant taste and irritated the stomach, so was rarely used.

Salicylic acid is a benzene ring with a phenol (HO) group and a carboxylic acid (COOH) group. It still needed acetylation —the addition of an acetyl group, which was necessary for the creation of acetylsalicylic acid, the active ingredient of aspirin. 

Who was the first to make aspirin?

German chemist Felix Hoffmann managed to synthesize pure acetylsalicylic acid for the first time in 1897 while he was working for the pharmaceutical company Bayer.  

Bayer conducted clinical trials and verified that the compound was safe and effective as an antipyretic analgesic.

It registered the name “aspirin” (the ‘A’ stands for acetyl and ‘spir’ is from Spirea ulmaria, the Latin name for Meadowsweet) on February 1, 1899, and began mass-producing it and marketing it as a pain reliever, fever reducer, and anti-inflammatory medication. 

Scientists didn’t really understand how aspirin worked, though. It was thought that it acted on the central nervous system, a hypothesis formulated by Heinrich Dreser, another chemist from Bayer.

It wasn’t until 1971 that British pharmacologists John Vane and Priscilla Piper discovered that aspirin blocked the production of prostaglandins. In 1982, Vane was awarded the Nobel Prize for Medicine in recognition of this work.

On the other hand, studies of aspirin's effects on platelets started in the 1950s, after practitioner Lawrence Craven noticed that some of his tonsillectomy patients, who were using aspirin-laced chewing gum to treat their pain, had been hospitalized due to severe bleeding.

Several subsequent studies demonstrated that aspirin could be used as an antiplatelet agent, except in patients over 70 years old with increased bleeding risk (2019).

Why is aspirin called the wonder drug?

Bayer called aspirin “the wonder drug” in its marketing campaigns from the 1950s and 1960s. The nickname referred to aspirin’s vast range of therapeutic uses. 

Aspirin has been confirmed as an analgesic, antipyretic, anti-inflammatory, and antiplatelet agent. But more recently, it has been studied for its alleged cancer-prevention properties. 

In 1988, Australia-based physician and medical researcher Gabriel Kune concluded that people who took aspirin had a 40% lower risk of developing colon cancer.

In 2011,  British physician and geneticist Sir John Burn conducted a study that suggested aspirin could be beneficial in preventing cancer in carriers of hereditary colorectal cancer.

According to the study, taking a daily dose of aspirin for at least two years could reduce the incidence of colorectal cancer by over 60%. 

Aspirin could also have a protective effect against other types of cancer, such as endometrial cancer, breast cancer, and prostate cancer. Additionally,  it could potentially reduce the risk of cancer metastasis as prostaglandins —which are inhibited by aspirin— may play a role in tumor growth and metastatic processes.