Aspirin is unique. A little white pill so versatile that it can relieve your headache, ease your aching limbs, lower your temperature and treat some of the deadliest human diseases. A roundup of evidence suggests that it helps prevent heart attacks, stroke, deep vein thrombosis, cataracts, migraine, infertility, herpes, Alzheimer's disease and even some of the most devastating cancers, such as bowel, lung and breast. It's a list that continues to grow, which may help to explain why more than 25,000 scientific papers have been written on aspirin and why an estimated one trillion tablets have been consumed since the drug was first produced.

These remarkable achievements are the result of decades of clinical studies and scientific hard graft, frequently celebrated in headlines around the world. Indeed, there's been so much good news in recent years it is tempting to believe that the future will be just as bright. But that is unlikely. Just as aspirin really begins to earn its spurs, the researchers investigating the unknown benefits it might provide are facing a mountain of problems that threaten to halt much of the groundbreaking work.

"Unless we think of new ways to work, the discoveries, or at least those that can be proven through clinical trials, are going to dry up," says one researcher.

To truly appreciate aspirin, it helps to know a little of its history. This marvel didn't appear from nowhere. It's the product of thousands of years of ingenuity and endeavour. Its origins lie in prehistory, when humans first began experimenting with plant and mineral remedies to alleviate pain and discomfort. Aspirin's key ingredient is drawn from the salicylates, chemicals found in a range of plants, the most famous being the willow tree. Five thousand years ago, ancient Egyptian physicians were using willow extract to treat aches and pains; centuries later Greek and Roman doctors, from Hippocrates to Galen to Pedanius Dioscorides, learned to value its therapeutic effects.

But it wasn't until its accidental rediscovery by Edward Stone, an 18th-century Oxfordshire vicar - who believed, mistakenly, that willow bark's bitter taste signified its similarity to the malaria remedy quinine - that the salicylates became the subject of serious scientific enquiry. In the century and a half that followed, researchers across Europe became obsessed with identifying this active ingredient and replicating it synthetically to reduce its corrosive effect on the stomach - always the remedy's achilles heel. Finally, at the end of the 19th century, a German tar dye company, Friedrich Bayer & Co, found a way of combining salicylic acid with an acetyl group that made it palatable, relatively safe and extremely effective. Acetylsalicylic acid was renamed aspirin and sold as a treatment for rheumatic fever. Within a few years, its analgesic and anti-inflammatory effects were noted and it was on its way to medical stardom.

For most of the next 70 years, aspirin retained its status as a valuable pharmaceutical commodity, but 33 years ago, as newer analgesics such as paracetamol and ibuprofen threatened to knock it off its perch, someone asked a question that had been largely ignored: how does aspirin work?

The answer came in 1971 from John Vane, a British researcher who discovered that aspirin suppressed certain prostaglandins - substances variously responsible for pain and inflammation in the body. Most intriguingly of all, he found that aspirin interfered with a prostaglandin called thromboxane A2, responsible for a process called platelet aggregation. Platelets are the body's frontline defence against bleeding - the cavalry that race to a damaged or leaking blood vessel and coagulate into a sticky mass to patch up the hole. It didn't take much of an intuitive leap for others to realise that aspirin might help prevent unwanted coagulation - such as when a vein or artery becomes thrombotic, one of the principle causes of heart disease. Vane later won a Nobel prize and a knighthood for his efforts.

That aspirin might help to prevent one of the 20th century's deadliest diseases set off a flurry of research that has continued to this day. Researchers have shown the drug's effectiveness against an astounding range of diseases and conditions from cancers to dementia. In the process, aspirin has shaken off its status as a humdrum headache pill to become a wonder drug.

So what has gone wrong? To deal with the ethical dilemmas first: none of the work carried out in labs in the past would have mattered much had it not been for the epidemiological studies that proved aspirin worked in the way the theories suggested. Rigorous clinical trials are always a necessary component of a drug's development and unless studies prove a medicine is both effective and relatively safe, governments are reluctant to license its use. Aspirin's status as an approved remedy for aches and pains did not give doctors the all-clear to prescribe it for more serious conditions.

The most famous of the new uses, as a preventive treatment for heart disease, took years of laborious clinical testing to demonstrate. The first trials - conducted in Wales in the 1970s by Cardiff-based epidemiologist Peter Elwood - were inconclusive and had to be repeated several times before the authorities in Britain and America acknowledged aspirin's effectiveness.

Ironically though, the success of the studies undermines the ability of future epidemiologists to search for new uses for aspirin. Many epidemiologists believe that nearly everyone over the age of 50 would be better off taking aspirin regularly. The relatively small risk of dangerous side effects - one person in a thousand might suffer serious bleeding - are outweighed by the benefits. It is now generally accepted that a third of all people at risk from a cardiac incident will not have one if they take a small daily dose of the drug. Therefore, it is almost impossible for researchers to give a placebo in an aspirin trial, for fear of a patient succumbing to a preventable heart attack or cancer. Any researcher who tried to justify such a step could run foul of ethical guidelines, enshrined in the Helsinki declaration and endorsed by bodies such as Britain's Medical Research Council. These state that researchers should do nothing knowingly to harm the health of their subjects.

This dilemma is compounded by a more practical problem. Aspirin's benefits are now so widely understood that fewer people are willing to take part in a trial in which they might get a placebo rather than a drug that could save their life. Of those who do, the temptation to nip down to the chemist for a bottle of aspirin - just to be on the safe side - would surely not be far way. The dangers of skewing the evidence in any clinical trial can never be discounted.

The net result is that the use of placebos in many aspirin studies - traditionally the most useful tool for unlocking its new applications - has been widely abandoned, so providing regulators with sufficient proof of fresh benefits has become harder.

One solution is to take advantage of aspirin's known benefits. At a conference of specialists last month, Elwood and fellow specialists discussed the feasibility of getting everyone in Wales at risk of a cardiovascular incident on aspirin (about one million of its three million population). If achievable, this could have a major effect on death rates, but also, because the sample size would be so significant, any protective effect aspirin was having against other serious diseases would show up too.

As problematic as the issues facing aspirin research are, a bigger threat may render them academic. A new EU directive on clinical trials, introduced last month to great protest from the medical research community, seeks to regulate drug research procedures. Its most contentious provision requires anyone conducting research to find a single sponsor to take responsibility - legally and ethically - for the trial. Previously a group of hospitals, universities and researchers may have got together to share the research, the starting costs and any legal liability.

"It's scandalous," says Elwood. "The only people who will benefit are the large pharmaceutical companies because the potential profits they can accrue from new products will justify the financial risk. For someone in a public body conducting ordinary aspirin trials, it will be impossible to get a sponsor who can afford to carry that burden. It's a dead hand on research."

It is because Elwood can see whole swaths of crucial aspirin research drying up that he is now turning his attention to the therapeutic potential of the salicylates in their natural form. "There is increasing evidence that salicylates in organic fruit and vegetables might have very positive effects similar to aspirin," he says. "For the last 30 years I have worked on the drug. For the next 30 I intend to look at the salicylates. If nothing else, it's hard to imagine being taken to court for persuading people to eat fruit and veg."

Strange to think that after 30 years of groundbreaking research, one of Britain's most eminent aspirin researchers must now go right back to the drug's ancient natural origins for answers. But then aspirin has always been full of surprises.

The next generation

· PolyAspirin is an "elastic" aspirin created by Kathryn Uhrich, at Rutgers University in New Jersey. The drug, now being tested, consists of about 100 molecules of aspirin in a chain. The belief is that it won't cause gastric irritation, and its elasticity means that it could be applied to a source of pain or a wound.

· Researchers from the Wolfson Institute of Preventive Medicine in London and the University of Auckland have designed the Polypill, which contains aspirin, a cholesterol-lowering drug, three blood pressure drugs and folic acid. Its creators claim that if taken by everyone in high-risk categories in the Britain it could cut strokes and heart attacks by up to 80%.

· Aspirin: The remarkable story of a wonder drug by Diarmuid Jeffreys is published by Bloomsbury at £18.99. To order a copy for £16.99 plus UK p&p, call the Guardian Book Service on 0870 836 0875