Focus: Aspirin - The secret history of a wonder drug

It cures headaches, prevents strokes and cuts down heart disease. Hardly a week goes by without yet more claims being made for the powers of this tiny pill derived from the willow tree, but can they really all be true? And what have Napoleon, Kafka and Rasputin got to do with it? David Randall tells the extraordinary tale of the world's best-known painkiller

For a pill that is scarcely a centimetre wide, aspirin certainly makes a big impact. Last week, a British study urged everyone over the age of 50 to take one each day to protect against strokes and heart disease. Hardly a week goes by without some new claim that the tablet cures, relieves or helps prevent anything from migraines to miscarriages and even the most serious, life-threatening diseases. At times, this little button of compressed powder seems the closest we have to a kind of elixir of life.

For a pill that is scarcely a centimetre wide, aspirin certainly makes a big impact. Last week, a British study urged everyone over the age of 50 to take one each day to protect against strokes and heart disease. Hardly a week goes by without some new claim that the tablet cures, relieves or helps prevent anything from migraines to miscarriages and even the most serious, life-threatening diseases. At times, this little button of compressed powder seems the closest we have to a kind of elixir of life.

But anyone who finds the claims made for the 106-year-old pill hard to swallow should try the story of its development, involving as it does an eccentric vicar, Napoleon, an old businessman with rheumatism, Rasputin, Franz Kafka, anti-semitism, a far-sighted Californian GP and a rival drug that became not the blessing that it was intended, but a world-wide scourge.

It all began with a willow tree. The ancients on several continents had discovered that the willow's bark reduced pain and fevers when chewed or infused in a drink. Hippocrates, he of the oath, recorded its effect, and the bark continued to be used without greatly exciting the apothecaries, until the vicar of Chipping Norton, Oxfordshire, rediscovered it in texts in 1763. His parishioners were much troubled with ague (fevers), so he prepared a concoction, fed it to his trusting flock, and was able to present the happy results to the Royal Society. No one, however, knew why willow bark worked; and nor would they until forced to by Napoleon. The great fever reducer of his time (opium being the preferred painkiller) was quinine, derived and imported from the cinchona tree of Peru. Until, that is, the Napoleonic War, when naval blockades cut off the continent from its supply. Pioneer chemists got to work on a replacement: in 1828, a professor of pharmacy in Munich isolated the active ingredient in willow bark and called it salicin - but while his crude crystals were gradually refined into salicylic acid by chemists in Italy, France and Switzerland over the next few decades, its applications were not appreciated.

The scene now switches to Wuppertal, in northern Germany, home of Bayer & Co, where worked three men: Felix Hoffman, Heinrich Dreser, and Arthur Eichengrün. Hoffman's father was a martyr to rheumatism, but couldn't take salicylic acid because of the irritant effect on his stomach. His son set out to try to ease his father's pain. His answer gave us aspirin as we are still getting to know it.

What Hoffman did was synthesise acetylsalicylic acid in a pure and stable form for the first time. His boss, Dreser, was not impressed. "Not good for the stomach," he said, and put his faith instead in another drug the company was developing. This was diacetylmorphine, and after the workers upon whom it had been tested declared it made them feel "heroic", he registered it under the trademark Heroin - and you would need a fix of the stuff to believe what came next.

Heroin was marketed by Bayer as a cough soother, especially for babies, and it was only between 1904 and 1907 that serious doubts about it were raised. By then, many morphine devotees had switched their allegiance, the less well off among them funding their habit by selling scrap metal, hence "junkies". It was not until two decades later that the substance was made illegal.

Lucky for Bayer, then, that Hoffman and Eichengrün had pressed on with their work. They patented their drug (No 36433 at the Berlin office), sent it out for trials, and this time persuaded Dreser to take it to market. In 1899, Bayer announced the arrival of aspirin by sending letters and literature to 30,000 doctors in Europe in the drug industry's first mass mail-out.

That, and the drug's qualities, made it a success from the start. Initially sold to pharmacists and doctors as bottles of powder, which had to be dispensed into paper packets, it was soon in tablets (the first mass drug to be so), and became the proprietary pain-reliever of choice. Enrico Caruso swore by it, and so too did Franz Kafka (he called it the only remedy against the misery of being).

Aspirin was even partly responsible for the rise of Rasputin. Tsar Nicholas II's son Alexis was taking it, and Rasputin, appalled at a Western branded medicine being used at the court of St Petersburg, ordered this stopped. He wanted more mystical remedies applied. The effect was instant. The boy was a haemophiliac, and aspirin's then-unknown blood-thinning properties were doing him no good at all. Rasputin's reputation soared as the tsarevich's bleeding quietened down.

By the Great War, despite a glut of fakes, aspirin was a worldwide money-spinner for Bayer. But not for much longer. As part of Germany's post-war reparations, it was ordered to dispose of the trademark in the US and elsewhere. Efforts to produce a wartime substitute bore fruit in 1915 when Australian George Nicholas devised, after several explosions at his laboratory, a product called Aspro. (Its early sales force found that the very concept of pills needed explaining, especially after they spotted a headache sufferer with an Aspro strapped to his head.)

In Britain, the search for a soluble painkiller was not making much headway until bombing forced experiments into a laundry where starch was stored. This proved the elusive ingredient, and disprin was born (ibuprofen was not developed by Boots until the 1960s).

The Second World War produced another twist in the aspirin saga. Of the original three Germans at Bayer, Dreser retired rich but died a suspected heroin addict, Hoffmann devoted himself to the history of art, but Eichengruün, a Jew, had worked on until he found his work blighted by anti-semitism. His reward for developing the wonder drug of the 20th century was to have his chemical works confiscated and to be sent to a concentration camp.

He survived, and emerged in 1945 to claim that the major part of aspirin's refinement was his work, and that he had been robbed of the credit. Academic study has since supported his case.

For its first 50 years, the drug had been thought of purely as a painkiller, but in 1953 a Californian GP noticed a strange thing: none of the 400 patients for whom he had prescribed aspirin had suffered a heart attack. In the 1970s, Sir John Vane discovered the science behind how aspirin works, and it began to dawn on scientists and clinicians that the world's little helper might be quite a big thing after all.

In the past 10 years, this cheapest of medicines (which sells today for 1p a tablet) has been proved to cut heart attacks (ironically, a 1920s advertisement for aspirin assured consumers "Does not affect the heart"), to cut the risk of strokes by 25 per cent, the risk of breast cancer by 20 per cent, and to profoundly help women with a history of multiple miscarriages to give birth. It also may assist in fighting Alzheimer's, certain forms of blood poisoning, and protect against ovarian, lung, oesophageal, breast, colon and bowel cancers.

There have been notes of caution, too. About three people in every 1,000 can experience stomach bleeding with aspirin, stroke survivors who stop their daily aspirin treble their risk, some asthmatics react to the drug with an increased risk of attacks, long-term use may increase the risk of pancreatic cancer in women, and so on.

So just how valuable is aspirin? Professor Peter Elwood, of the University of Wales, who produced last week's study on the drug's benefits for over-50s, says: "Low-dose aspirin is useful in reducing the risk of heart attacks and strokes and more than 140 large-scale trials have confirmed this."

He says the risk of side effects, mainly bleeding, were "very low" (about one or two per thousand), and that people have to balance this against the devastating, often fatal, effects of a stroke or heart attack. "It is often said you should see a doctor before taking it. But healthy people know if they have had stomach trouble or asthma. Doctors are not prophets. It is for the individual to decide." (The maximum effect, he says, is at a dose of 70mg-80mg.)

As far as aspirin's other benefits go, Professor Elwood says: "There is growing evidence the risk of dementia is reduced, and suggestive evidence that aspirin may protect against certain cancers." Having worked with aspirin for decades, his verdict on this once hum-drum little pill is simple: "An American once called it 'the first miracle drug'. I would go along with that - and its full potential has yet to be proved."

Jeremy Laurance: So what can it really do?

Why is it called a wonder drug? The first universally available painkiller is still more widely used than any other over-the-counter analgesic. Nearly 50,000 tons of acetylsalicylic acid, its active ingredient, are produced a year, more than 100 billion tablets.

What else does it do? One low- dose aspirin a day can cut the risk of heart attacks and strokes. It prevents blood clots by stopping platelets from clumping together.

Is that all? No. It also reduces the incidence of colon cancer, prostate cancer and breast cancer. It may protect against other cancers too. All diabetics are recommended to take a low-dose aspirin daily to reduce the effects of the condition on the blood vessels. The drug also reduces mental decline in people with some types of dementia.

Does it have side effects? Yes. About six in every 100 people suffer stomach upsets, nausea and vomiting. In some, it irritates the stomach lining causing bleeding, which can lead to ulcers. About one in 500 people develops an intense itch or asthma attack.

Is it safe for children? It is not recommended for children under the age of 12 because of the risk of Reye's syndrome, a rare, life-threatening illness, which causes inflammation of the brain.

Jeremy Laurance is the Health Editor of the IoS