|December 2, 1999
Volume 30 Number 9
|A publication for the faculty, staff, administrators, and friends of California State University, Chico|
Nobel Prize Winner Ferid Murad Speaks
"It's very, very exciting to do something that's never been done before and to get an answer to a question where only you know the answer for the first time. That's a really wonderful experience. And if you're lucky, that turns out to be important," Ferid Murad said. The answers Murad, Robert Furchgott, and Louis Ignarro found were important enough to earn them the 1998 Nobel Prize in Physiology or Medicine for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system.
Murad, research physician, pharmocologist, chair of the Department of Integrated Biology and Pharmacology & Physiology, and director of the Institute of Molecular Medicine at University of Texas-Houston, presented his research on November 11 as part of the CSU, Chico President's Lecture Series, co-sponsored by the City of Chico, the CSU, Chico Office of the President, Butte College, and Chico Performances. Turhon Murad, anthropology, introduced his brother. He told of hearing his brother speculate on what it would take to win the Nobel Prize someday. Ferid Murad confirmed the story, saying he first thought about it at the beginning of his career in the 1960s.
Toward the end of the last century, Alfred Nobel used nitroglycerin in his invention of dynamite. He was later prescribed nitroglycerin for his heart disease, and, although he refused to take it, millions of other people have used it to relieve chest pain. Until Murad's work, however, no one knew precisely how nitroglycerin worked. His discovery came from his interest in intercellular communication and the role of second messenger molecules.
Cells communicate with each other in a variety of ways, through a variety of molecules (such as hormones or neurotransmitters) that are processed and released outside the cell. "They're given lots and lots of names, but basically they're all messenger molecules that come in different flavors, structures, sizes, and shapes," Murad explained. When these molecules attach to a receptor molecule on the outside of a cell, they generate second messenger molecules. Today, there are about twenty known second messenger molecules "that transmit the information from hundreds and hundreds of first messenger molecules," Murad said.
His research focused on cyclic GMP (guanosine monophosphate), a second messenger molecule. He was convinced that cyclic GMP "was important in terms of hormone signaling and the effects of various drugs."
When guanyl cyclase, an enzyme, is activated it transforms GTP (guanosine triphosphate) to cyclic GMP. A variety of substances can be introduced to tissues to activate guanyl cyclase, which then leads to increased levels of cyclic GMP. These increased levels lead to smooth muscle relaxation. In blood vessels, this leads to dilation. Murad found that the way this process works is that the substances are converted to a guanyl cyclase activator, which turned out to be nitric oxide.
"So what's happening is nitroglycerin is being converted to nitric oxide which increases cyclic GMP formation which induces a biochemical cascade that results ultimately in the relaxation of the blood vessel," Murad explained.
Prior to Murad's work, nitric oxide was best known as a pollutant, a toxic substance that fills the air with smog. Murad's discovery that nitric oxide had beneficial effects was a surprise, and one that has vast medical implications. Nitric oxide is "a product of many of the drugs that we use in cardiovascular medicine," Murad explained. These drugs are used for a variety of cardiovascular problems, such as controlling blood pressure and congestive heart failure.
Not only is nitric oxide produced by the body's interaction with a variety of therapeutic agents, but nitric oxide occurs as a "a natural substance in the body to mediate the effects of numerous hormones," Murad said. Nitric oxide is involved in a myriad of biological processes including blood flow and blood pressure, memory, diabetes, platelet aggregation, arthritis and other inflammatory conditions, heart contractions, penile erection, and gene regulation. In larger quantities, nitric oxide kills bacteria.
Understanding the ways nitric oxide works in the body is leading to new medications for a variety of ailments. Murad explained there are now "a lot of tools or reagents to enhance this pathway or block it in various steps along the way. We're carrying those drugs in various clinical protocols as potential therapeutic agents for various disease. For example, some of the inhibitors in this pathway have been induced as anti-inflam-matories....By making more nitric oxide in the presence of a cancer cell, maybe we can kill that cell.... Maybe we can remodel blood vessels."
Murad may have achieved his long-term goal of winning the Nobel Prize, but that doesn't mean he's ready to retire. After all, what's "more exciting for the scientist is the ability to solve a problem and get an answer. I think that motivates most scientists, to do something different," Murad said. "Science is always exciting and I'm still very turned-on." -- BA
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