Research clinician prized for his efforts in scientific discovery

Honours are being showered upon Garret FitzGerald. Nearly four decades after he graduated from UCD medical school, the Dublin-born research clinician and chairman of the department of pharmacology at the University of Pennsylvania has won four major awards this year.

The Grand Prix Lefoulon-Delalande was conferred beneath the dome of the Institut de France, where the Académie Francaise convenes, on June 5th. It carries €500,000 in prize money and is considered the world’s most prestigious award for cardiovascular research.

FitzGerald shared it with his Italian colleague, Carlo Patrono, who chairs the pharmacology department at the Catholic University in Rome.

The two scientists met 30 years ago at a conference in Florida and, in FitzGerald's words, "competed and collaborated" for the following decade in research on the use of low-dose aspirin to prevent cardiovascular disease. Because of illness in the family, FitzGerald's prize was collected by his son John, the eldest of his and his wife Kate's three children.

Clinical pharmacology
FitzGerald attended Belvedere College in Dublin. He met Kate at UCD, trained at St Vincent's and the Mater hospitals and moved to the department of clinical pharmacology at the Royal Postgraduate Medical School in London. "It was the time of the IRA campaigns," he recalls.

“Not a day passed without someone reminding you that you were Irish. I asked if I could ever become a professor of pharmacology in Britain, and after a long pause the department head said, ‘Perhaps’. I thought, ‘We’re out of here’.”

FitzGerald was fascinated by the effect of aspirin on prostaglandins, the lipids or fats that cause blood to clot, but which also cause platelets to aggregate and block arteries. It was 1979.

With their two small children – a third was born in the United States – the FitzGeralds moved to Nashville. He began his post-doctoral degree, and 11 years later became the head of the pharmacology division at Vanderbilt University, in Nashville, Tennessee.

The “economic challenge” is an important reason why so few doctors go into academic medicine, FitzGerald says.

“We lived very frugally. We slept on the floor for three years. I almost waited tables. It’s a huge sacrifice for a medical doctor . . . You see your peers driving large cars, knowing they’ll be successful.

“Doing research is like pursuing your muse in music or the arts. A minority of scientists discover one big thing, the way that only a few musicians or painters leave something that survives the test of time.”

Two-person-effort
FitzGerald says he could not have achieved all he has without Kate. It has been "a two-person-effort, one-person-award scene . . . I had someone who shared the sacrifice and enabled me to do it."

He is infinitely grateful for his wife’s “courage, willingness to sublimate her own career, tenacity and focus on the goals of my work”.

The scientists who discovered that aspirin blocks the enzyme that gives rise to prostaglandins did so in a test tube, and won a Nobel prize. “To translate that into practical use, you need to know how it works in humans,” FitzGerald explains.

It was at that stage he met Patrono. The scientists had so much in common that Patrono spent Thanksgiving with the FitzGeralds. It was pre-internet, so they communicated via fax, telephone and trans-Atlantic journeys.

“We defined how to give aspirin in the most effective way to block heart attacks,” FitzGerald says. “Before our work, 10 years of trials attempting to show that aspirin could decrease heart attacks failed.”

The patient who benefits most, they found, is “someone who has hardening of the arteries and acute coronary syndrome, who is barrelling up to having a heart attack”. “We showed that if you combine aspirin with clot-busting drugs, it doubles the effect. We identified the target population.”

Daily low doses of aspirin are now used this way throughout the world, and are credited with saving tens of millions of lives. But aspirin can cause serious gastro-intestinal bleeding, and should not be used by someone without a history of heart disease, or who has never had a heart attack or stroke.

In those who have experienced heart failure, it reduces the risk of recurrence by up to one-third. Doses of 75mg are as effective as higher dosages, with less stomach bleeding, FitzGerald says.

To address the risk of internal bleeding, pharmaceutical companies marketed enteric-coated aspirin.

Research published by FitzGerald late last year found that the coating delayed and rendered erratic the effect of low-dose aspirin.

“We demolished the concept,” he says. “It’s a myth. But in the same research, we destroyed the myth that there are patients who are aspirin-resistant.”

In the 2000s, FitzGerald conducted research showing that older nonsteroidal anti-inflammatory drugs or NSAIDs, including Naproxen, Aleve and Ibuprofen, undermine the cardiovascular protection of aspirin.

The US Food and Drug administration issued an advisory telling people not to combine them.

FitzGerald also predicted that other NSAIDs, including Vioxx, Celebrex, Bextra and Diclofenac, would increase the risk of thrombosis, high blood pressure, heart failure and irregular heart rhythm.

This evidence was confirmed in a study in the current issue of the medical journal, The Lancet. Vioxx has been withdrawn from the market.

And FitzGerald is currently the principal investigator in an international consortium of 25 laboratories studying molecular clocks – how our body clocks influence physiology and cardiovascular function. “As your clock breaks down, it predisposes you to Alzheimers, hardening of the arteries and diabetes,” he explains.

Other awards
The recent prize is not the first conferred on FitzGerald for his research on aspirin.

In 2005, The Irish Times and the Royal Dublin Society presented him with their Boyle Medal for scientific excellence.

This spring, FitzGerald won the Lucian award for circulatory disease from McGill University in Montreal, for his lifelong contribution to research on aspirin, nonsteroidal anti-inflammatory drugs and molecular clocks.

This autumn, he will receive the Schottenstein prize n cardiovascular science from Ohio State University, and the Scheele prize from the Pharmaceutical Society of Sweden.

The latter prizes are for his work predicting the cardiovascular hazards of nonsteroidal anti-inflammatory drugs.