Road To The Nobel Prize

Ferid Murad, M.D., PhD.'s thoughts on being a scientist and Nobel Laureate. Dr. Murad is currently Professor, Chair of Integrative Biology and Pharmocology, and Director of the Institute of Molecular Medicine at the University of Texas at Houston.

I knew when I was eleven years old that I wanted to become a doctor. However, it wasn't until my senior year in college at DePauw University that I also became interested in research because of a senior elective research project in biology. As a result, I went to Western Reserve University since it was the first and only medical school to develop a novel seven year program for both M.D. and Ph.D. degrees. I graduated Phi Beta Kappa from DePauw, was the top student in the M.D./Ph.D. program and received both the clinical and research prizes at graduation. I was then a resident for two years in medicine at Massachusetts General Hospital followed by a research fellowship for three years at the National Institutes of Health. The sixteen years of training after high school was a long period that required scholarships and multiple jobs to make ends meet.

My wife, Carol A. Leopold, and I met as juniors in college and married shortly after graduation. We had four children when I finished the M.D./Ph.D. program and out fifth was born as I began my fellowship at NIH, identical twin daughters accelerated our proliferation. Carol terminated her high school teaching to care for the family, but periodically worked part-time as a substitute teacher, secretary, or hospital receptionist. She is a wonderful and caring mother who permitted me to work 70 to 110 hours per week with my training and moonlighting activities to provide for the growing family. It was extremely important to both of us that Carol work as little as possible to look after the children particularly with my frequent absence from home.

The long training period paid off in that I joined the faculty at the University of Virginia as an Associate Professor and bypassed the Assistant Professor appointment. Five years later, I was promoted as the youngest full Professor at the University.

It was there that I initiated the work that resulted in the Nobel Prize. I was interested in cellular communication or "cell signaling"; how hormones and drugs altered cellular function and permitted cells "to talk" to each other. I was interested in cyclic guanosine monophosphate (cyclic GMP). Cyclic AMP was discovered by my Ph.D. mentors Earl Sutherland and Theodore Rall in 1957. I worked on cyclic AMP with them as a student and Sutherland received the Nobel Prize in Medicine for this work in 1971. After cyclic GMP was discovered in 1963, I thought it would also be a messenger molecule to mediate the effects of some hormones and drugs.

In 1976-77 we found that drugs such as nitroglycerin release nitric oxide in tissues which then increase cyclic GMP formation to cause smooth muscle relaxation (airway, gastrointestinal, and vascular smooth muscle). Although nitroglycerin had been used for about 100 years for angina pectoris (heart pain) to dilate the coronary vessels, its molecular mechanism of action was unknown until our work in the mid and late 1970's.

Today we know that most tissues produce nitric oxide which is a gas and reactive free radical and a pollutant in our atmosphere from the combustion of fossil fuels. Our work was first to show that nitric oxide, a free radical and gas, can activate an enzyme and function as a messenger molecule.



Today there are more than 55,000 publications on nitric oxide research, more than any other area of biology. Many pharmaceutical and biotechnology companies have developed drug candidates that enhance or inhibit the nitric oxide/cyclic GMP signaling pathway.

Some of these agents are approved for marketing in the U.S. and/or other countries such as the organic and inorganic nitrates for angina, systemic hypertension, pulmonary hypertension in premature babies and some children with certain congenital heart defects, and erectile dysfunction (i.e. Viagra). Many other compounds are in clinical research trials for septic shock, cardiogenic shock, cancer, arthritis, glaucoma, angiogenesis, atherogenesis, wound healing, diabetic ulcers, diarrheal diseases, etc.

Millions of people have already benefited from our pioneering research. I hope that millions more can benefit from our current and future research. It has been extremely rewarding, as a scientist, to see your research have so many application and benefits for so many patients. To have received the Nobel Prize in Medicine in 1998 for our work was also very rewarding as well, as it meant significant recognition by the scientific community and one's peers.

Although it took years of training and many hours of work to attain these goals, it has certainly been well worth the effort. I hope that our current research can also have such an impact on health care in the future.

For additional reading, see Ferid Murad and/or the Nobel Foundation on their websites:

http://nobelprize.org/medicine/laureates/1998/illpres/index.html

http://ibp.med.uth.tmc.edu/faculty/fmurad/fmurad.htm

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