Nobel Prize Winner: Dr NO

Lou Ignarro, Nobel Prize winner in Physiology or Medicine in 1998, for discoveries concerning the crucial role played by the chemical nitric oxide in our blood vessels...

Lou - There's a drug called nitroglycerine, which is used to lower the blood pressure to treat pain. When you have an impending heart attack and patients take nitroglycerine, it dilates the blood vessels. That action had been known from the Alfred Nobel dynamite factories back in the 1800's, but the mechanism of action was not known for over 100 years. Being a chemist and a biologist, I looked at the chemical structure of nitroglycerine and thought, "Well, maybe our bodies metabolise nitroglycerine to something like nitric oxide, nitrogen dioxide - or something like that. Maybe that would be the act of principle that causes the vasodilation." So, we did those experiments, and that's exactly what we found - that the active vasodilator ingredient that lowers the blood pressure and increases blood flow in nitroglycerin is a tiny molecule: NO - one atom of nitrogen, one atom of oxygen. After looking at all of these actions, I thought to myself, "My goodness, if this molecule were made in our bodies, it could serve as a tremendous protective molecule against high blood pressure, stroke, heart attack, etc." In a number of different experiments, we were able to show for the first time that mammalian cells, including in human tissue, are able to produce this relatively simple gas called nitric oxide. That was the reason I was awarded the Nobel prize.

Chris - And how does Viagra come into it?

Lou - Every nerve releases a chemical signalling agent, called a neurotransmitter, that then interacts with the tissue that it innervates to cause an effect. Once we discovered that this neurotransmitter was nitric oxide, then it all made sense; because NO is a vasodilator - it causes vasodilation, and engorgement of the erectile tissue to fill up with blood. That's what the erectile response is all about. The FDA fast tracked the development of this drug and, in 1998, sildenafil, with the trade name of Viagra, was marketed.

Chris - Going back to how all this began, you mentioned that the bomb industry were playing around with nitroglycerin. Did people who were working in the bomb industry really notice that their heart problems got better?

Lou - Yes, absolutely right. In Alfred Nobel's factory, what was noticed when the people came into work on Monday were two things: first, many of them got a tremendous headache, because vasodilation of the arteries in the head can give you a migraine-like headache. More importantly, however, as working in Sweden was very difficult and there were a lot of diseases (the air was not pure, and many people had angina and impending heart problems), the workers noted that when they went into the factories on Monday morning, the heart and arm pain disappeared, but came back on the weekend when they were home. The physicians in the community recognised this effect and traced it down to nitroglycerin. Within a few years, they were able to get tiny, tiny amounts of nitroglycerin, mix it with sugar - because otherwise it was too explosive by itself - put it in tiny tablets they would then put under their tongue, and relieve the angina. That drug, which is marketed today as Nitrostat, and others were available in the 1870s. But, as I said, the mechanism by which it works was not found until we did it in about 1980.

Chris - You really are the proper paid up Dr No, aren't you?

Lou - My wife even suggested I should be called 'Dr. No' because she liked the James Bond movie and she was always in love with Sean Connery! Even my license plate on my car in California says DRNO.