Bayer's Aspirin Story

Aspirin, a drug that evolved from the 3,500-year-old idea that willow bark could relieve pain, is one of the three classic drugs in the history of medicine, along with penicillin and Valium. Almost every time a major new disease emerges in mankind, a new role for aspirin is discovered, and it is quickly and massively popularized. For the discovery of the mechanism of action of aspirin and won the 1982 Nobel Prize in Medicine John? "Although aspirin is an old drug, we may discover something new in it every day," said Sir Varnay.

Eric Metcalf, author of "The Wonderful Use of Aspirin," claims, "An aspirin a day keeps you away from the doctor." In his book, he discusses the latest medical advances in aspirin's use in the prevention and treatment of breast cancer, colon cancer, prostate cancer, Parkinson's, osteoporosis, and other conditions. By 2007, the use of aspirin to prevent heart disease had joined childhood immunization and smoking cessation as the top medical preventive measures recommended by the U.S. Preventive Service Task Force in 2007. It's no wonder that Buckhorse, the former chairman of Bayer, said proudly that taking two aspirin a day has almost become an American tradition.

110 years of history makes it clear that there are at least two reasons why aspirin as a commodity is selling well: its low price and Bayer's strong push. New uses for aspirin are always being discovered, but proving those extra benefits is complicated, and turning them into a commercial product is even more so. For 110 years, all Bayer has had to do is maximize the drug's potential one marketing campaign at a time, and then hold on to the benefits of the product through patents and trademarks.

On March 6, 1899, the patent application for the invention of aspirin was approved, with the trade patent number 36433. Aspirin began to be manufactured at the Elberfurt plant in Wuppertal, Germany. Its inventor, 29-year-old German chemist Felix Hoffmann, was notified by his mentor. Hoffmann received a note from his mentor telling him to stop the coal tar research at hand and start specializing in one drug-improved salicylic acid-to make a stable antipyretic and analgesic with fewer side effects.

Hoffman was no stranger to this drug, and the stuff wasn't a new invention. But he needed to revamp the time-honored antipyretic and analgesic to take it from an earthy remedy to a commercially available drug. Early on, Hoffman's rheumatism-ridden father had taken salicylic acid for pain relief, except that it caused intolerable vomiting and stomach upset. His father had long been asking him if he could find a way for salicylic acid to achieve its medicinal effects without so many side effects.

Hoffman combed through a series of papers and finally found a way to produce acetylsalicylic acid (ASA, the main ingredient in aspirin) that was stable and had fewer side effects. Luckier than other product developers, he had a powerful company behind him.

Bayer did two things that other pharmaceutical companies don't do: it trademarked the chemical acetylsalicylic acid, "aspirin," and it patented its production process in many countries.

Doctors were not too demanding in those days, either, as long as the drugs were stable and had few side effects: health was a luxury in the early 1900s, when sanitation was so poor. The average American born in 1900 lived to be about 49 years old. Diseases with the highest mortality rates included pneumonia, tuberculosis, enteritis and typhoid fever, most of which were caused by contaminated water and food. So as in Europe, aspirin soon became the drug of choice to relieve fever and pain. Aspirin was available in pharmacies from Siberia to San Francisco.

Aspirin soon had a legion of physician fans. The United States became one of Bayer's most important overseas markets, and aspirin became Bayer's most important product in the United States. By 1907, aspirin accounted for 21 percent of total U.S. sales of Bayer products, reaching 31 percent by 1909.

Originally aspirin was supplied in the form of 250g bottles of powder, which was distributed to patients in paper bags for every 1g of powder. Aspirin later met the world in 500mg tablets, followed by a tube reagent in 1904.In 1915 aspirin was in tablet form and no longer required a doctor's prescription.

Bayer's influence on academia and medicine remained strong, however, and this set the stage for aspirin to see a second peak in commercial demand.

The development process for aspirin's most promising application - heart disease prevention - was not led by Bayer. Bayer's ability to do this was demonstrated by the fact that once aspirin's prevention of heart disease had been academically proven and expensive clinical trials had been completed by government agencies, Bayer quickly began to step in and use its best marketing and patenting leverage to maximize the drug's impact as much as possible.

In the 1940s, Lawrence Craven, a California otolaryngologist, noticed a strange thing when he gave relatively high doses of aspirin to patients whose tonsils were inflamed, causing them to bleed profusely. This reminded him that aspirin might be able to increase the blood supply, and that increasing the blood supply was one way to protect the heart. So he began in 1948 to use aspirin to treat his aging male patients to help reduce their chances of heart disease. By the mid-1950s, he had published several papers claiming that none of his more than 8,000 patients had suffered a heart attack, and that aspirin also helped them prevent strokes.

His knowledge of aspirin's effect on the heart was contrary to that of the entire world at the time, but he was proven correct. Unfortunately his data was very sketchy, and the journal in which he published his paper was not well known enough to reach a very limited audience, and his results did not attract much attention as a result. His findings didn't even help himself, and he died of a heart attack in 1957.

In those days, the idea that aspirin could protect the heart was considered an absurd claim. That's because when people took salicylic acid for antipyretic and analgesic purposes, many of them would become short of breath and have rapid heartbeats. When aspirin was first synthesized in Bayer's labs, it stayed there for a long time, precisely because Bayer's medical director at the time couldn't figure out what it would do for the heart. To solve this problem, a Bayer scientist scrutinized the historical dosages of salicylic acid taken and found that when smaller doses of aspirin were used, it had fewer heart side effects. Bayer then commissioned several German doctors to quietly conduct clinical trials, and only dared to formally develop the drug after it proved safe enough for the heart.

Bayer remained vigilant about aspirin's effects on the heart until the 1950s. Charles Hennekens, a Harvard professor and aspirin expert, holds a 1950s aspirin advertisement in the Journal of the American Medical Association with a series of words specifically assuring that aspirin would not affect the heart.

It wasn't until 1971 that scientists discovered that aspirin protected the heart by ensuring that platelets in the blood clumped together, thus maintaining the blood supply to the heart. Throughout the 1970s, however, clinical studies of aspirin for heart disease prevention were too small to convince the public.

That's when Bayer's decades of academic marketing came into play. The drug's impact, combined with its unusually cheap price, led more academics to commit to clinical studies of the drug. Soon academic proof of aspirin's ability to prevent cardiovascular disease continued to emerge, and after a 1977 study published in the U.S. journal Stroke first proved that aspirin could prevent strokes, more and more studies confirming aspirin's role in preventing cardiovascular events were published in the world's leading medical journals.

Not all the credit for aspirin's transformation from a drug to a commodity can be given to Bayer. The exact conditions for which aspirin can be used still need to be proven in large-scale, FDA-approved clinical studies. Such studies cost enormous amounts of money and resources, but it's not Bayer but the National Institutes of Health (NIH) that pays for them.

The internist study was a key point in aspirin's qualification for primary prevention of myocardial infarction. The study was organized by the NIH beginning in 1983 and involved 22,071 healthy male U.S. physicians. The purpose of this large-scale clinical study was to evaluate whether low-dose aspirin could prevent first-time myocardial infarction in healthy individuals. Participating physicians carried and took the study medication with them in every corner of the world, with an average follow-up period of five years.

The study, which was supposed to take eight years, was terminated early by the ethics committee in its fifth year. The reason was that aspirin was simply too effective. The interim results of the study were sufficient to show that aspirin reduced the risk of myocardial infarction by 44 percent, the incidence of first fatal myocardial infarction by 66 percent, and the incidence of first myocardial infarction in people with diabetes by 61 percent. The Ethics Committee felt that physicians in the control group had a right to take low-dose aspirin for the prevention of coronary heart disease in order to benefit from it.The results of the study were published in 1988 in Newsweek in the United States and caused a huge sensation.

Similarly, the Women's Health Study of Aspirin included nearly 40,000 American female health care workers over a ten-year period, and the Nurses' Health Study included 120,000 American female nurses over a 24-year period. These studies, in which healthcare workers participated personally, gave a major boost to cardiovascular disease prevention and signaled that aspirin had passed the most rigorous test of the research and development phase.

In 1971, Bayer aspirin with vitamin C effervescent tablets were introduced; in 1993, Bayer aspirin enteric-coated tablets were launched. The enteric-coated tablets add a coating to the outside of the aspirin, and this tablet does not dissolve in the stomach until the intestines take effect, thus almost completely solving the problem of side effects of stomach upset. 2003 saw the introduction of Bayer aspirin in granular form (without drinking water). 2007 saw research published in The Lancet that showed that daily use of 300 milligrams or a high dose of aspirin over a period of five years resulted in a reduction in the number of people treated with the medication. 74% reduction in the incidence of colon cancer 10 to 15 years after treatment. This corroborates a 1988 study by Australian Prof. G. Kune, and is seen by Bayer as aspirin's third leap forward after antipyretic and heart disease prevention.

There have always been both commercial and scientific drivers in the development of aspirin. The question of who should be half a step ahead, business or science, is one that Bayer has been considering for 110 years, and I'm afraid it will continue to do so.