It has been over 35 years since Ferid Murad, Nobel laureate, accidentally stumbled on the miracle molecule Nitric Oxide (NO) and began studying its biological properties.

Since 1977, when he first published his paper on nitroglycerine and its related compounds, which released nitric oxide to widen blood vessels and relaxed muscles, there has been a whole body of work on the various properties of NO. Over 1,30,000 research papers have been published on the various properties of NO.

The clinical benefits and therapeutic properties of NO continue to be discovered and applied even today, 79-year-old Dr. Murad, currently a Professor at the Department of Biochemistry and Molecular Biology, George Washington University, said.

He was delivering the first G. Parthasarathy oration at the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Thiruvananthapuram on Thursday.

Dr. Murad, along with two other scientists, won the Nobel Prize in 1998 for his discovery that NO is a molecule naturally produced by the human body and that it acts as a signalling molecule in the cardiovascular system, making blood vessels dilate.

Surprise

The discovery took the scientific community by storm, because it was unbelievable that a toxic gas, found in automobile exhausts and was responsible for ozone depletion, could be an endogenous substance, leave alone being a neurotransmitter.

The audience, consisting of students and academics, were in rapt attention as Dr. Murad took them through his journey to Stockholm, which began in the 1960s, when as an MD student he joined the laboratories of Earl Sutherland and Ted Rail for research.

His interest in the role of cell signalling and enzymes like cyclic GMP (cGMP), which act as intra cellular messengers in the human body, helped him uncover the effect of cGMP in helping the relaxation of smooth muscles. He later made the astounding discovery that cGMP was activated by an endogenous substance, which turned out to be NO.

Dr. Murad later associated with Robert Furchgott who had made the discovery that it was a signal molecule produced from the inner layer of the artery called endothelium that relaxed the blood vessels. He called this the endothelium-derived relaxing factor or EDRF. Louis Ignarro, another researcher, provided the next link that EDRF was in fact Nitric Oxide and that only a healthy endothelium could produce NO.

“Endothelial dysfunction in those with hypertension, diabetes, atherosclerosis or those who smoke, leads to reduced production of NO, restricting blood flow and, in turn, resulting in poor cardiovascular health. NO is thus crucial for cardiovascular function. So we later developed supplements of L-arginine, the amino acid which triggers the production of NO,” Dr. Murad said.

“There has been no other molecule in the body with as much capabilities or roles in biological processes as NO. Today we know that NO plays a key role in the functioning of the immune system, neurotransmission, wound healing, gene regulation, stem cell proliferation and differentiation, and blood pressure regulation. In fact, it was clinical trials on NO, involving patients who were being treated for hypertension and angina, which led to the accidental but dramatic discovery of sildenafil or Viagra, for treating erectile dysfunction,” he said.

One of the most satisfying clinical applications of the property of NO was the finding that delivering low concentrations of this gas to the lungs of premature, very-low-birth-weight babies in incubators prevented the development of chronic pulmonary disease in them, he said.

“Infusing NO in the bypass pump during an open heart surgery can prevent the possibility of air embolism in patients, because NO inhibits platelets aggregation. However, this method is yet to take off in a big way,” Dr Murad pointed out.Stem cell research is one of many areas where Nitric Oxide has been found to play a significant role.

It is known to impact stem cell differentiation and proliferation.

Founder-director of SCTIMST M.S.Valiathan, and Director, Jaganmohan Tharakan, were present.