Aspirin: The Tiny Tablet With an Enormous Medical History

Aspirin is the sort of medicine that has become almost invisible through familiarity. It sits in bathroom cupboards, handbags and first-aid boxes looking about as technologically impressive as a mint. Yet this modest white tablet has travelled through ancient herbal medicine, Victorian chemistry, German industrial ambition, two world wars, Nobel Prize-winning science and several spectacular reversals in medical opinion. Few drugs have enjoyed such a long career, and even fewer have managed to reinvent themselves halfway through it.

Its family history begins long before anybody knew what a molecule was. Ancient civilisations used preparations made from willow and other plants containing salicylate-related compounds to treat pain and fever. The familiar claim that Hippocrates prescribed willow bark is harder to document as neatly as popular retellings suggest, but willow certainly belonged to the old medicinal toolkit. Centuries later, in 1763, the English clergyman Edward Stone reported to the Royal Society that willow bark appeared useful for treating feverish illnesses. Medicine was still some distance from a packet of tablets and an instruction leaflet, but the trail had become interesting.

Chemistry eventually took over from herbalism. Scientists isolated salicin and learned how to make salicylic acid, which worked against pain, inflammation and fever but could prove unpleasant to the stomach. French chemist Charles Frédéric Gerhardt produced acetylsalicylic acid in 1853, decades before Bayer entered the story. His version never became a practical medicine, however. The achievement was scientifically important but commercially unhelpful, rather like inventing the motor car and forgetting to make one that starts.

Then came Bayer. In 1897, chemist Felix Hoffmann produced a pure, stable form of acetylsalicylic acid at the German company, and Bayer launched Aspirin in 1899. The traditional story says Hoffmann wanted a gentler treatment for his father, who suffered from rheumatism. It is an appealing tale: devoted son enters laboratory, devoted son invents wonder drug, grateful humanity reaches for the medicine cabinet.

Unfortunately, pharmaceutical history rarely behaves quite so politely. Arthur Eichengrün, a Jewish chemist who worked at Bayer and directed pharmaceutical research, later claimed that he had instructed Hoffmann to synthesise the compound and had personally pushed its development after Bayer’s pharmacology department initially rejected it. Modern historical research gives his claim considerable weight. Eichengrün even described his role in a letter written while imprisoned in the Theresienstadt concentration camp. The controversy remains, although historians increasingly regard aspirin as the product of a team rather than one heroic chemist.

Even its name carries a little botanical archaeology. The “A” referred to acetyl, while the middle of “Aspirin” came from Spiraea, the old botanical name associated with meadowsweet, another source of salicylates. The final “-in” simply gave the product the fashionable pharmaceutical ending of the period. Bayer had created something unusually valuable: not merely a drug, but a brand name that eventually became almost synonymous with the chemical itself.

Aspirin soon conquered the world as a treatment for pain, fever and inflammation. Then something much stranger happened. Scientists discovered that the drug could interfere with the blood’s ability to form clots. In 1971, British pharmacologist John Vane showed that aspirin blocks the production of prostaglandins, signalling molecules involved in pain, inflammation and other processes. That work helped earn Vane a share of the 1982 Nobel Prize in Physiology or Medicine. Suddenly the humble headache tablet had acquired an entirely different professional identity.

Aspirin inhibits an enzyme called cyclooxygenase, reducing production of compounds including thromboxane A2. Platelets use thromboxane to help them clump together. Aspirin therefore makes platelets less sticky, and because platelets cannot manufacture fresh cyclooxygenase, the effect lasts for their remaining lifespan. This explains why a tiny daily dose can matter even though the drug itself disappears from the bloodstream relatively quickly.

That property transformed aspirin into one of the pillars of cardiovascular medicine. Someone who has already suffered a heart attack may receive aspirin because preventing another dangerous arterial clot can outweigh the bleeding risk. NICE recommends aspirin after myocardial infarction in appropriate patients and, in many cases, continuation indefinitely. Aspirin also has an important role in the immediate treatment of some acute coronary syndromes.

From there came one of aspirin’s biggest myths: if it helps people who already have cardiovascular disease, surely everybody over a certain age should take a tablet each morning “just in case”. For years, the idea sounded almost irresistibly sensible. Aspirin was cheap, familiar and apparently capable of preventing heart attacks. What could possibly go wrong?

Bleeding, unfortunately. Aspirin does not selectively stop the clot you dislike while politely preserving every clot you need. The same mechanism that can prevent an artery from becoming blocked can also increase gastrointestinal bleeding and haemorrhagic bleeding elsewhere. Modern preventive medicine has therefore become considerably less enthusiastic about handing daily aspirin to healthy older adults merely because birthdays have happened to them. US preventive guidance, for example, recommends against starting low-dose aspirin routinely for primary cardiovascular prevention in adults aged 60 or over.

That does not mean aspirin has somehow been “disproved”. It means medicine has become better at distinguishing primary prevention from secondary prevention. A person who has already had a heart attack occupies a very different risk category from a healthy person hoping never to have one. The drug has not changed. Our calculation of benefit versus harm has.

Aspirin also turns up in places that surprise people who still think of it mainly as something taken for a headache. In Britain, pregnant women at increased risk of pre-eclampsia may be prescribed 75 to 150 mg daily from 12 weeks of pregnancy until birth. That sounds almost contradictory because people often hear broad warnings about medicines during pregnancy. Yet carefully selected low-dose aspirin has a specific preventive role here and forms part of NICE guidance.

Cancer prevention provides another intriguing chapter. Researchers have studied aspirin for years because observational evidence and clinical trials suggested possible effects on colorectal cancer. The strongest established UK recommendation concerns people with Lynch syndrome, an inherited condition that substantially raises the risk of bowel and several other cancers. NICE advises considering daily aspirin for more than two years to reduce colorectal cancer risk in this group. That is very different from advising the entire population to swallow aspirin in the hope of warding off cancer.

Then there are the restrictions. Aspirin should generally not be given to children under 16 because of the rare but serious association with Reye’s syndrome. People with certain stomach ulcers, bleeding disorders, aspirin-sensitive asthma and some other medical conditions may also need to avoid it. Interactions with anticoagulants and other medicines matter too. Familiarity makes aspirin look harmless, but familiarity is not a pharmacological property.

One popular misconception deserves burial beside the idea that carrots let pilots see in the dark. Modern aspirin tablets are not essentially compressed willow bark. Willow helped lead scientists towards salicylates, but today’s acetylsalicylic acid comes from industrial chemical synthesis. The story runs from plants to chemistry, not from tree directly to tablet.

Another misconception is that aspirin “thins the blood”. The phrase works reasonably well in everyday conversation, but the blood does not literally become thinner like paint diluted with water. Aspirin changes platelet behaviour. That distinction matters because aspirin works differently from anticoagulant drugs such as warfarin or apixaban, even though both types of treatment can reduce dangerous clot formation.

Perhaps that is why aspirin remains such a fascinating medicine. It repeatedly punishes simple stories. It was not invented in one glorious moment. Its famous inventor may not deserve all the credit. It does not merely relieve pain. Daily aspirin is not automatically wise for healthy older people. A drug associated with bleeding can nevertheless prevent heart attacks, help selected pregnant women avoid pre-eclampsia and reduce bowel cancer risk in certain genetically vulnerable people.

More than a century after Bayer put Aspirin on the market, medicine still has not finished with it. The little tablet has simply lost its halo. That may actually be progress. Wonder drugs usually become more interesting when we stop calling them wonders and start asking the less glamorous question that good medicine always asks: for this particular person, at this particular moment, does the benefit outweigh the risk?