Photo by Rick Geary

How does aspirin know it should go to my head and not to my foot?

When I take aspirin for a headache, how does the pill know that it’s my head that hurts and that it should go there and not to my foot? — Melissa, El Cajon

Dear Matthew Alice: I'm fascinated to learn of the origin of the “miracle drug” aspirin. How was the source known to be pain-relieving? How was it tested to determine this, and on whom? Does this date back to some ancient primitive remedy such as the bark or root of some shrub or tree? If so, what, when, where, and who? — Curious in Clairemont

The “what” is willow bark. When? Oh, hard to say. But if Confucius stubbed his toe, odds are his doctor said, “Chew two twigs and call me in the morning.” Hippocrates prescribed it too. Written records trace it back to at least 500 B.C. Where? Everywhere the willow grows, apparently. It was a North American Indian remedy as well. Who? Who knows? Some nameless caveperson, after a tough day clubbing dinner into submission, maybe.

The painkiller salicin in the bark of the willow tree is only a few molecules away from our present-day aspirin (acetylsalicylic acid or ASA). But until 1971, how salicin worked was as much a mystery as a miracle. The guy who figured it out bagged himself a Nobel Prize in 1982. (For Curious in Clairemont, I’ll add that it was British pharmacologist )ohn Vane who did it, and he used a bioassay technique that employed rabbit aortas, chicken rectums, and ground-up guinea pig guts. No people.) What Vane discovered explains why aspirin knows right where to go when you’re hurt.

The inner wall of each of our cells is lined with a greasy substance (arachidonic acid) that keeps the cell wall flexible. Without it, we’d be as stiff as Ken and Barbie. Injured or irritated cells release tiny bits of this acid, which our bodies use to create dozens of powerful hormone-like fatty acids called prostaglandins. It’s the action of various prostaglandins that results in fever, swelling, pain, and other symptoms of injury. Aspirin interferes with the catalyst needed to create the prostaglandins. (In detail, molecules of the catalyst plug into “keyholes” in the arachidonic acid, then the catalyst is converted to prostaglandins and released again. Aspirin sneaks into the keyholes and plugs them permanently, so the catalyst can’t get in.) So aspirin is looking for only these injured, leaky cells. That also explains other quirks, like why aspirin will bring down an abnormally high body temperature but won’t lower a normal body temp. Unfortunately, ASA also interferes with the prostaglandin that helps generate the mucus protecting our stomach lining. Stomach acids then get at the tissue itself and create one of aspirin’s common side effects — stomach irritation. In fact, aspirin has enough negative side effects that some pharmacologists have opined that if it were submitted today for FDA approval, it might fail. Ibuprofen (Motrin) and acetaminophen (Tylenol) are synthetic, aspirin-like drugs that have slightly different effects on prostaglandin production, which account for their different patterns of symptom relief.

Mark your calendar: October 10, 1997, aspirin’s 100th birthday. When this little white pill replaced willow bark powder, it set off a vicious global conflict still fought nightly on our TV screens — the undignified battle of the drug companies for the biggest piece of the enormous painkiller pie. The history of the invention and marketing of aspirin makes gruesomely amusing reading in The Aspirin Wars (Charles Mann and Mark Plummer, Knopf, 1991). One particularly funny section, titled “Pounding Hammers,” details the golden age of the aspirin commercial, the 1970s and ’80s, when drug companies alternately whined and backstabbed, romancing government agencies and the courts while trying to snuff the competition. To quote the authors, “The annals of aspirin give a glimpse of the incredible lengths to which people will go to put something in a box and sell it.”