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Dr. Philip Majerus, Aspirin, and Heart Attacks

Aspirin is one of those drugs that’s always been there.

Have a headache? Take a pill, an aspirin, a Bayer aspirin, and “call me in the morning.”

Cotswold British knew that bark of spirea trees helped alleviate painful joints but bark extracts were corrosive to the stomach. So, in the late 19th century, it was discovered that treating the extract of bark—by the time known as salicylic acid—with dehydrated vinegar and a derivative of acetic acid, a product solid that was less difficult on the stomach was produced.  Bayer scientists named acetyl salicylic acid ‘a’ (acetic) ‘spir’ (spirea) + ‘in’ = aspirin (The ‘in’ was added to make the word easier to pronounce in German).

Karl Duisberg, a young chemist at Frederich Bayer und Söhne Farbenfabriken sent samples to a surgeon friend in Berlin where they were tested on patients. When the results were good, a new drug was born.

Bayer marketed heroin, morphine, and aspirin in the United States from 1900 forward. Until World War I, there was a Bayer inviolable trademark so only Bayer aspirin could be legally sold in the US. After the war, the plant manufacturing aspirin located near Albany, NY was sold to Sterling Drug. Aspirin became “the pill”; Bayer aspirin was only sold in Germany, Canada, and a few other countries.  

Aspirin and its story has been detailed in Diarmuid Jeffreys’ Aspirin: The Remarkable Story of a Wonder Drug (New York: Bloomsbury, 2005).

What brings up this post, is the death of an aspirin protagonist – a physician who maintained that an aspirin a day would present strokes. That physician was Philip Majerus.

From The New York Times ("Dr. Philip Majerus, Who Discerned Aspirin's Heart Benefits, Dies at 79," June 14, 2016):  "Even before his findings were confirmed in a study by other researchers a decade later, Dr. Majerus was taking aspirin daily.

"I was already convinced that aspirin prevented heart attacks," he recalled in the journal Advances in Biological Regulation in 2014. "I was unwilling to be randomized into a trial where I might end up with the placebo. I refused to participate."

Dr. Majerus recommended that "all adults should take an aspirin daily unless they are among the few percent of the population that cannot tolerate the drug." The cardiovascular benefit of aspirin was fully achieved by 50 to 75 milligrams daily, he said, and "there is no evidence that branded aspirin, which is much more expensive, is in any way superior to the generic version."

Later studies found that for people in their fifties who are vulnerable to heart disease, taking daily doses of aspirin reduces the risk of heart disease.

In 1998, Dr. Majerus received the Bristol-Myers Squibb Award for Distinguished Achievement in Cardiovascular Metabolic Research for his findings, which were credited with saving countless lives.

When he received the award, Circulation, the journal of the American Heart Association, said it was Dr. Majerus who “first proposed that low-dose aspirin could be used to treat people at risk of heart attack, stroke, and other ailments associated with blood clots.”

He later theorized that aspirin could also be effective in preventing some forms of cancer, pointing the way to recent studies indicating that daily doses of aspirin also reduces the risk of colon cancer. 

Philip Warren Majerus was born in Chicago on July 10, 1936, the son of Clarence Majerus, a manufacturer who owned a five-and-dime store in Quincy, Ill., and the former Helen Mathis.

He received a Bachelor of Science degree from the University of Notre Dame in 1958, graduated from Washington University School of Medicine and did postdoctoral training at the National Institutes of Health. He joined the Washington University faculty in 1966 and retired in 2014 as a professor of medicine and biochemistry and molecular biophysics.

“I got my start in biochemistry because of the Vietnam War,” he recalled in The Journal of Biological Chemistry. “As I was finishing my medical residency at Massachusetts General Hospital in 1963, I had two choices going forward: Either I could go to Vietnam as a physician, or I could become a research associate in the United States Public Health Service at the National Institutes of Health. The choice was easy.”

As early as the 1950s, studies had demonstrated that aspirin reduced clotting; one California doctor, Lawrence Craven, reported that he had prescribed daily doses to thousands of patients without “a single case of detectable coronary or cerebral thrombosis.”

In the 1970s, Dr. Majerus and his postdoctoral research fellow, Gerald Roth, focused on the impact of aspirin on platelets, small cells that precipitate clotting when a blood vessel is injured. They clump together and a clot forms and seals the wound.

“Late one afternoon, I looked in the St. Louis phone directory for aspirin and found a company in town, Rexall, that made aspirin tablets,” Dr. Majerus recalled in 1978. “I called after hours, and a man answered the phone. I explained what I wanted: 100 bottles of 100 tablets containing 160 MG aspirin and the same number of bottles of a matched placebo. The man said he could make them without any problem, and he delivered them to my lab the next morning at no charge.”

He studied patients who were being treated for kidney failure and, to facilitate dialysis, had shunts, which can cause clotting, inserted in their arms. After six months, 18 of the 25 patients who were taking a placebo developed a blood clot, compared with six of the 19 who were given aspirin.

Investigating how aspirin inhibited clotting, Dr. Majerus concluded that the medicine modified an enzyme that leads to the formation of a platelet-made molecule that constricts blood vessels and aggregates platelets. The pills’ effect lasts for the platelets’ life span, typically about two weeks.

“Phil Majerus, more than any other individual, has produced the most original body of work on biochemistry of platelets as it relates to thrombosis,” Prof. Joseph L. Goldstein, a Nobel laureate at the University of Texas Southwestern Medical Center in Dallas, said when the Bristol-Myers Squibb Award was announced.

Harvey Weiss and John Vane were among the other scientists who pioneered research into the efficacy of aspirin in preventing heart attacks. Dr. David Sackett, who died last year, conducted clinical trials that confirmed their findings as he developed what became known as evidence-based medicine.