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A Nobel Past, A Colonial Future

The world according to Ferid Murad, M.D., Ph.D., is a place where rules are made to be broken. Research, he reminds us, is a creative process; and belief in your own heretical observations, he proves, is more fruitful than subscription to scientific dogma. He cracks jokes at formal speaking engagements, and — despite an esteemed and decades-long career — the word “retirement” evades his vocabulary.

This is Ferid Murad, the newest — and only — Nobel Laureate at The George Washington University. Set to join the GW faculty in April as University Professor, Murad will teach an undergraduate course, mentor graduate and medical students, and lead a lab program in the Department of Biochemistry and Molecular Biology.

“Dr. Murad is more than brilliant Nobel Laureate; he is a compassionate collaborator and mentor whose infectious intellectual curiosity will also spark a fresh spirit of creativity on our campus,” says Rakesh Kumar, Ph.D., Catharine Birch Williams & McCormick Chair of the Department of Biochemistry and Molecular Biology. “We have been given a wonderful and rare opportunity, and I greatly look forward to watching our students and faculty grows in his presence.”

Murad and two colleagues won the Nobel Prize in Science or Medicine in 1998 for uncovering the first biological effects of Nitric Oxide (NO), a gas previously believed to be present only in the environment. He identified NO as an intracellular cellular messenger, playing a key role in many biological functions including cardiac smooth muscle relaxation. By identifying Nitroglycerin’s ability to release NO in the blood vessels, Murad is also credited with explaining why the drug was successful in treating angina, a painful chest condition caused by a lack of oxygen-rich blood in the heart.

“[NO] is the only molecule that can be an intracellular messenger, a local extracellular messenger, or a distant messenger as a hormone. Nothing else fulfills all of those criteria at the same time,” explains Murad. “It's just remarkable what it can do. If you were asked: Does it do this? Does it do that? Chances are, the answer is yes."

Since Murad’s discovery, the field of NO research has morphed from virtually nonexistent to one of the most popular fields in biology. His work has influenced key discoveries in cardiovascular disease, cancer, and arthritis; and he is credited with providing the basis for Viagra — material Murad considers comedic fair game, much to his wife’s dismay. Today, NO is also known to be active in such processes as inflammation, blood flow regulation, cell growth, smooth muscle relaxation, and memory preservation.

An American Dream

Call it cliché, but Murad’s story is the epitome of the American Dream. Born in rural Indiana, he and his two brothers were raised by an Albanian immigrant (their father) and an Illinois native (their mother), who eloped at ages 39 and 17, respectively. As youth, the boys worked each night and weekend in their parents’ restaurant adjoining their small home. “With this background, I knew that I wanted considerable education so I wouldn’t have to work as hard as my parents,” he writes in his autobiography.

Though not at the expense of hard work, Murad earned a scholarship to DePauw University, where he excelled and also met his future wife. He continued on to graduate school at Western Reserve University, becoming one the first students in the country to earn a dual M.D./Ph.D. degree. Consistently at the top of his classes, Murad “was in [his] element,” he writes. “There was no doubt in my mind about an academic career in medicine, research, and teaching.”

Meanwhile, by the time Murad had completed graduate school, he and his wife had four children — including a set of twin girls. And so the hard work continued. To supplement his modest stipend, Murad moonlighted at a clinic throughout graduate school, assisting OB/GYNs several nights a week, and scrubbing tables and floors after each delivery. The couple had their fifth child (and only boy) as Murad finished his residency.

The Research Road Less Traveled

Throughout his education and career, the direction of Murad’s research took many turns.
He first became interested in intracellular messaging in graduate school under the mentorship of Earl Sutherland, M.D., and Theodore Rall. As Murad predicted at the time, Sutherland later earned a Nobel Prize for identifying cyclic adenosine monophosphate (cyclic AMP) as the first intracellular second messenger.

Murad continued to study cyclic AMP for the next ten years, which included work at Massachusetts General Hospital and the National Institutes of Health. But, he recalls, research on the messenger was “becoming rather straightforward, predictable, [and] crowded.” Wanting to find an area that had more opportunity, Murad pursued a newly emerging second messenger, cyclic guanosine monophosphate (cyclic GMP) — a decision he now calls “intuitively right.”

This work revealed that guanylate cyclase (GC), a family of enzymes, is the receptor for NO — which is, to date, the only enzyme activated by a free radical. “A lot of colleagues thought we were crazy,” recalls Murad. But he plowed forth, connecting cyclic GMP with smooth muscle relaxation, and eventually discovering that NO was activating GC by acting like an intracellular messenger. This “was heresy” to others in the field, he says, because it was thought that “a free radical just can’t be a messenger, a gas messenger.” But again his intuition was correct — and later it became the source of a Nobel Prize.

“You go down many blind alleys in research,” Murad insists. “By definition, it’s high risk, and if you are really lucky, it turns out to be important…There’s no way to determine if what you’re working on is going to result in a Nobel Prize. It comes as a surprise 20 years later, and that’s the way it all happens.”

A Colonial Future

Murad will move to GW from the University of Texas Health Science Center at Houston, where, among other roles, he is currently director emeritus of the Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. The transition to GW will mark the first time in 22 years Murad has worked on a complete campus — the type of stimulating, collaborative environment he craves.

“I think I have something to offer young people that gets them excited about medicine. I love research. I love to answer tough questions. I love to figure out how this information can be beneficial in clinical medicine to treat people,” he says. “GW is changing. I think it is ready to strike out and take off.”

And when Murad arrives on campus, it will not be empty-handed. His research agenda will be packed with heavy goals to develop a treatment for glioblastoma (the aggressive cancer that killed Ted Kennedy), manipulate embryonic stem cells to obviate the need for organ transplants, and continue testing and marketing a cure for diarrhea in third world countries.

What’s more, Murad hopes to leave a lasting impression on rising scientists at GW. Backed by a Nobel lineage (Murad’s mentor, Earl Sutherland, and his mentor’s mentor, Carl Cori, both won Nobel Prizes in Science or Medicine), Murad suspects a future Nobel Laureate may be lurking in the GW student body.

“I’ve trained almost 150 people in my lab over the years… and I tell them that one of them has to get the prize because I don’t want this lineage in genetic communication disrupted,” he said. “It’s not happened yet, but one of my goals is to identify that next generation here at GW.”