Dr. Garret FitzGerald's career in medicine almost fell through because of a cockroach.
His big zoology exam at University College, Dublin, involved dissecting the mouth of a cockroach under a microscope. To his horror, one of the major components jumped out of his field of vision. "It's over," he thought.
But it wasn't. The exam proctor, whom he remembers looking like Helen of Troy, got down on her hands and knees to help. After about five minutes of searching, she emerged with the mouth part on her thumb.
"If she hadn't found it, I would not be a physician," he said. "It's these quirks of nature that lead you to what you do."
FitzGerald went on to show that low-dose aspirin could prevent cardiovascular disease. He recently shared the Grand Prix Scientifique from the Lefoulon-Delalande Foundation of the Institute of France, a €500,000 ($668,000) award. Last year he won Canada's top cardiovascular research prize, the Louis and Artur Lucian Award.
"Dr FitzGerald for the past 30 years has been one of the leaders in cardiovascular disease research," said Dr. Jacques Genest, Lucian Award chairman and cardiovascular researcher at McGill University Health Center. "He has (been) just like a surfer, perpetually riding the crest of the wave, and he hasn't come down yet."
Now a professor of medicine and pharmacology at the University of Pennsylvania School of Medicine, FitzGerald's work on the cardiovascular implications of pain medicines has resulted in therapies that save lives and improve the quality of life for millions of patients, said Dr. Sanjay Kaul, cardiologist at Cedars-Sinai Medical Center and professor at the University of California, Los Angeles, School of Medicine.
"He's fearless, he's passionate, he's curious, visionary, very, very, collaborative, and most important, he's very nurturing. In my opinion he's the real deal," Kaul said.
FitzGerald's spacious office has a full view of the Philadelphia skyline, but his accent betrays his Irish origins. He grew up in Dublin during a time of austerity in the 1950s and '60s.
He trained clinically in Dublin, but the institutions there didn't have a lot of money for science. FitzGerald was interested in mechanisms, and wanted to work in laboratories, so he headed to London. He worked at what was then called the Royal Postgraduate Medical School, a pre-eminent spot for physician researchers in Europe. He also completed a master's degree in statistics at the London School of Hygiene.
The late 1970s were a difficult time to be Irish in Britain, because of violent attacks by the Irish Republican Army. FitzGerald commonly heard Irish jokes as well as hostile comments.
"It taught me a little bit about being a despised minority, and gave me a certain empathy with people who have to fill that role in this country," he said.
How aspirin works
FitzGerald fell into cardiovascular disease research without any personal connection to the subject. Much later, he found out his father had some cardiovascular problems, and his mother had hypertension, but most people do as they age, he said.
"If any of us discover one thing that matters, we're lucky, because most of us don't," he said. "I think what people often don't understand is that it takes decades for stories to unfold, particularly to know if something stands the test of time. Persistence, focus and hard work are really important."
FitzGerald and his wife headed to the United States to Vanderbilt University in Tennessee in 1980. This is where FitzGerald began to focus on aspirin.
Specifically, he studied fats called prostaglandins, which are instrumental in blood clotting. They also play a role in metabolism, sleep-wakefulness cycles, fertility and cardiovascular disease.
The first step in forming a clot that can lead to heart attacks is the aggregation of blood cells called platelets. In a test tube, it was shown that aspirin can block the platelets sticking together. Specifically, it blocks thromboxane, a type of prostaglandin (fat) that platelets form.
"So, it seemed like a short leap from those observations to showing that aspirin had clinical usefulness," FitzGerald said. "But it turned out it wasn't a short leap."
The 1982 Nobel Prize in Medicine was awarded to Sune Bergstrom, Bengt I. Samuelsson and John R. Vane for the discovery of how anti-inflammatory drugs including aspirin prevent prostaglandins from forming by blocking an enzyme called COX.
Over a decade, researchers conducted trials looking for evidence that aspirin had cardioprotective effects. The Nobel Prize-winning research showed aspirin could potentially prevent heart attack and stroke, but researchers could not find an association in clinical trials.
What was missing, FitzGerald said, was understanding the mechanism by which the drug actually worked in humans, so that populations in which it would be useful could be identified.
FitzGerald and Dr. Carlo Patrono, chairman of pharmacology at the Catholic University, Rome, with whom he recently shared the big French prize, investigated this. They established that lower doses of aspirin than were used for pain relief in arthritis were just as effective in blocking platelets.
"Low-dose aspirin protected the heart and minimized the risk of harm to the stomach, a common complication of the higher doses in arthritis," FitzGerald said.