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If you like Louis Ignarro's story, you might also like:
Elizabeth Blackburn,
Linda Buck,
Gertrude Elion,
Judah Folkman,
Robert Langer,
Robert Lefkowitz,
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and Andrew Weil

Louis Ignarro's
recommended reading: Gray's Anatomy

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UCLA
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Louis Ignarro
 
Louis Ignarro
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Louis Ignarro Interview

Nobel Prize in Medicine

September 13, 2014
San Francisco, California

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  Louis Ignarro

You were at Tulane University when you began to seriously study nitric oxide. Can you talk about how that came about?

Louis Ignarro: We had an idea.


Others were doing work on nitric oxide -- had just started to do work on nitric oxide -- which is a very unstable poisonous gas in the earth's atmosphere. So I was wondering, "Why are these people..." there were only two of them -- "Why are they studying nitric oxide?" So I was following what they were doing, talking to them. And then I realize, "Oh, you know, maybe certain drugs that we take to treat disease may work through a nitric oxide mechanism." And I was thinking of that. And then one day, while teaching the pharmacology of blood pressure-lowering drugs in class at Tulane Medical School, one of the medical students after my lecture asked me -- I had just talked about nitroglycerine. Nitroglycerine is a drug. It comes as a little tablet which you put under your tongue if you feel that you're having a heart attack, and it can actually save your life by preventing that heart attack, relieving chest pain. So this medical student asked me what was the mechanism of action of nitroglycerine. I had talked about what it does, but I did not talk about how it worked.



So the student asked me -- she said, "You didn't explain to us the mechanism of action of nitroglycerine. I understand nitroglycerine is also an explosive." And she said, "Well, certainly it couldn't work by causing explosions." I remember the class laughing. And I said, "No, of course not." I said, "But you know, I'm not certain about the mechanism of action. It may not be known. That's why I haven't told you why. Let me look it up." So, I spent the rest of the afternoon reading up on nitroglycerine. The mechanism was completely unknown. Being a chemist, I looked at the chemistry of nitroglycerine. It's nitro. So it has actually three nitro groups -- NO2 groups they're called -- on this little molecule, and I'm thinking, "Hmm, I just wonder whether one or more of those NO2 groups in the body maybe is converted to NO, which is nitric oxide." So a couple of days later, we began to do those experiments in a laboratory. And after about two months of work, sure enough we found that our arteries metabolize or convert nitroglycerine to nitric oxide. So then we purchased some authentic nitric oxide gas, and we tested that pharmacologically, and we found that it produces all the identical effects of nitroglycerine. So we concluded that nitric oxide is the active species in the drug nitroglycerine. We published that, and then many people repeated that work and now we know how nitroglycerine works.


How did you relate that discovery to the cardiovascular system, which led to your Nobel Prize?

Louis Ignarro: Very easily.


Once we ordered the authentic nitric oxide and we found that it was a vasodilator -- it dilated the arteries just like nitroglycerine -- we then tested this nitric oxide further. And we found that it could lower the blood pressure. We found that it could prevent stroke. It could actually prevent -- we have certain cells or elements in the blood called platelets, and when they aggregate or clump together they could block arterial blood flow. And if that occurs in the brain, that's a stroke. If it occurs in the heart, it's a heart attack. So we found that nitric oxide was very, very powerful in preventing that. Okay. Then we synthesized some chemical molecules that make it a lot easier to test nitric oxide. Nitric oxide is a gas. Very hard to add gases to your testing systems. So we had a solid material that had the nitric oxide built into it. So when you put it in solution, it releases the NO or the nitric oxide. So we could do a lot of experiments with that. So we had published many papers showing how powerful nitric oxide was to prevent all the cardiovascular diseases that we knew about: heart attack, stroke, it drops the blood pressure. We also found that it could prevent or slow down the development of atherosclerosis or cholesterol plaques in arteries.



So then, if I remember, it was a Friday afternoon, 1985. We were thinking and discussing in the laboratory. I brought up to my group, I said, "Why do our bodies react so sensitively to an outside chemical like nitric oxide?" I mean, we don't have nitric oxide in the body, we didn't think. So why do our bodies have all this ability to react to this noxious outside chemical that could protect us against cardiovascular disease? That was the first time I thought, "Well, maybe our arteries -- our bodies -- produce nitric oxide." It's just that we don't know that yet. Nobody's tested that. So we set aside a series of experiments, very difficult experiments. It took a year, and we finally showed that our arteries can produce nitric oxide. So then it became clear that yes, we have nitric oxide, and that we make it in order to protect ourselves against cardiovascular disease. That is the principal reason I was awarded the Nobel Prize. So it started with nitroglycerine and then wound up with that discovery.


Then there were other things after that, but you asked me specifically.

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