 Okay, so I hope you understood that. Now I jump to something a little different because it's another discovery we made this time in 1990. We discovered the nitric oxide as the principal neurotransmitter in mediating erectile function. Now why in the world would we do that experiment? I'm jumping from the heart and blood vessels to erectile tissue. Well, because one day a urologist friend of mine at UCLA came down to ask me what the neurotransmitter was in the nerves that innervate the erectile tissue or corpus cavernosum. I said, what are you asking me? You're the urologist, I don't know. And he said, well, I thought, you know, you might know because you're working with nitric oxide and cycle of GMP. He really didn't have any suggestions. And anyway, I thought about this that afternoon and thought, well, I wonder if it might be nitric oxide because when the nerves are stimulated in the erectile tissue, there's a relaxation not only of the vascular smooth muscle, the arteries, but also the non-vascular smooth muscle. Lots of non-vascular smooth muscle arranged in a cavernous network in the erectile tissue. And I thought, hmm, you know, maybe it could be NO. So anyway, to make a long story short, he helped us set up isolated segments of corpus cavernosum in the laboratory and we electrically stimulated them on and on and on and we discovered that nitric oxide was the neurotransmitter that mediates erectile function or penile erection. And so we published the first study in rabbits in 1990 and then the other paper on human tissue got accepted to the only article I ever had in the New England Journal of Medicine, which as you know is a very prestigious journal. It's even more prestigious when a PhD gets an article in there and this was January 9th, 1992. And the New England Journal of Medicine is linked to the news media. In other words, the news media gets the actual list of the publications and articles one day prior to the appearance of that particular issue of the journal. So on the morning, the next morning, I received all kinds of phone calls from the news media, radio, TV, magazines, journals. And the first phone call I got was from the editor of Hustler Magazine. And I was wondering whether or not I should conduct this interview. I was ready to do so but then I remembered that my mother was still alive and doing well at that time. And I figured all that she would need to hear about was her son conducting an interview with the editor of Hustler Magazine. That would not be a nice thing to do to her. What the hell would she discuss with the neighbors? But I did accept the next interview with the New York Times. And I think it's great when a pharmacologist makes the left-hand column of the front page of the New York Times. This was when President Bush Sr. existed in office. And so it was a nice coverage of our work with an occasional mistake by the editor with a typesetter calling nitric oxide sometimes nitric acid. Anyway, there was a similar article that was published in an Italian newspaper and I'm Italian of course. And I can tell you that Italians often express themselves better in pictures than in words. So in the article was a cartoon. And that cartoon shows a gentleman in bed with his lady. And what I was afraid of is this. He's wearing a nitric oxide gas tank. And the writing on there is in Italian of course and it's aussido tazzotto. That means nitric oxide or oxide of nitrogen. And I can't begin to tell you what my mom thought about that cartoon. And a couple of months after that article appeared in the New England Journal of Medicine the journal Science decides to declare nitric oxide as molecule of the year. Very humorous. But what happened six years later? The article was published in 92. Six years later is 98. That's not that long after that. So what happens? Sildenafil gets marketed by Pfizer pharmaceuticals as Viagra. And so the mechanism of action, I'm not gonna get into that here, but the mechanism of action of Viagra translates to be an increase in the actions of cyclic GMP and nitric oxide. So it was really great to see that. I remember when that report came out while I was watching TV one day. And so let's look at the dates more closely. It was in March of 98 that Viagra was marketed. And just a few months later, in October of the same year, the Nobel Prize for nitric oxide gets announced. I thought, is this a coincidence or what? So I decided to look up the committee members of the Nobel Committee for Physiology or Medicine, and I found that the majority of them were men over the age of 60. It's perfect. So let me tell you something about the Nobel Prizes. They're six categories. Most people who are not scientists always hear about the Nobel Peace Prize. Many times I'm congratulated for winning the Nobel Peace Prize. Those of you who know me know that I could never win a Nobel Peace Prize for sure. But one prize is called Physiology or Medicine. It's not that Alfred Nobel couldn't make up his mind, but what he meant to say is Physiology and or Medicine, I guess. There's one in physics, one in chemistry, one in literature, as you know, one in economic sciences, and one in peace. And this is what the Nobel Prize looks like, and maybe you've seen Linus Pauling's two prizes. I only have one, but you know, let me tell you, one's enough. And so the front of the coin, this is my prize, shows Alfred Nobel born 1833, passed away 1896, and then on the opposite side is the symbol or image for Physiology or Medicine, and you can't see it from there, but my name is here and the date 1998 is there for when I receive the prize. So often when I speak, people ask me, how do you get the Nobel Prize? And I always tell them, I have no idea, but let me just go over some of the criteria. For the medicine prize and also physics and chemistry, there's two major requirements. Established by Alfred Nobel, who put these in his last will and testament just before he passed away in 1896. And one is you have to have made an original discovery. It makes no difference how much you have extended or advanced a field. You have to have discovered the field. That's a big difference. And not only do you have to have discovered something, but you have to show its benefit to humankind. So in terms of what I've done, so what is the original discovery? Well, I've told you about that. Nitric oxide is produced by mammalian cells, number one, and it functions as a unique signaling molecule to regulate and control a multitude of different physiological actions. Now, the benefit to humankind, again, as you've heard, there's quite a few. NO controls blood pressure, blood flow, blood clotting. We know now that endothelial cells make NO to prevent stroke, prevent heart attack, and so on. Another benefit to humankind was NO is the mediator of penile erection and sexual arousal. I don't know about you, but I think that discovery alone is worth the Nobel Prize. NO controls bladder function, GI function. I mean, it does so many things. Many of these, of course, I had nothing to do with. Other people who jump on the bandwagon afterwards made these discoveries. And NO is a pretty good universal anti-inflammatory molecule. Depends how you look at it. Mechanisms vary, but it has the chemistry of being an anti-inflammatory molecule. Now, every year when there's a Nobel Prize, the Nobel Foundation has artists who make a poster of that particular Nobel Prize. So this was for 1998, I shared the prize with Bob Furchcott. I told you who discovered EDRF. I identified EDRF as NO and did the other things I told you about. And Fred Mirad started the whole field. He was the one who first showed that nitric oxide could stimulate guanylate cyclase to elevate cyclic GMP. So you can see how the Nobel Committee members put the three of us together. We didn't work together, if anything. We were competitors, especially this character at the end and me. But yet, we were able to solve these problems. So with this poster shows, and it's supposed to be shown to people who are not scientists. That's what the Nobel Foundation does with their posters. So this coronary artery from this heart is very healthy. Lots of space for the blood to flow through. There's no inflammation of the wall. There's no atherosclerosis, no cholesterol plaques. This probably, this artery came from a healthy person eating a healthy diet and having lots of physical activity. On the other hand, this artery, the very sick artery probably came from someone who led a sedentary lifestyle, eating a lot of hamburgers and fries and so on and so forth. Not a healthy diet. And you can see the cholesterol plaques in the lumen. You can see the overgrowth of the smooth muscle cells here compared to here. This all impinges on the space for the flow of blood. So the lumen gets smaller and smaller until finally no blood can flow through. If that happens in the heart, you get a heart attack. If that happens in the brain, you can get a stroke. Also, some of these cholesterol plaques can come loose and circulate all through the body. And wherever they deposit, especially in the brain, that can cause a stroke and other problems. So in ending this presentation, I just have a few more minutes. I wanted to describe to you where I was when I first heard about the Nobel Prize, which was on October 12th, 1998. I was not home. I was in the middle of teaching a pharmacology course. I was course director. And I took a break in October to go to Italy to give a lecture. I didn't know that they were gonna make a decision about the Nobel Prize. And so I was visiting Naples, Italy. And this is so ironic. My mom never lets me forget it. My dad was born many years prior to the announcement of the prize. That is, he passed away many years prior to the prize. But he was born in the foothills of Mount Vesuvius in Napoli or Naples. And I was here when the prize was announced. So needless to say, there was a lot of commotion in Naples. A couple of days, I can't forget. But I stayed to give the lectures that I was invited to give. And then I went home and I was greeted by my medical students who were so happy and proud that their professor came back with a Nobel Prize. And they were hoping that I was not gonna give any more exams for the rest of the course. I made them a little easier, but I still gave them the exams. And then we were invited a month later to go to the White House to meet the president. Here, my wife Sharon, who's an anesthesiologist. She's the real doctor, not like me. But we're waiting in the red room to meet the president. And who was the president in 1998? Bill Clinton. It was really a pleasure to meet him. You know, I'm kind of glad that I didn't get the Nobel Prize last year, if you know what I mean. So here we were taking some very nice photos. And I remember this very well, because while this photo, right after this photo was taken, I could see, or while it was being taken, I could see Hillary Clinton walking in the background. I wanted to see where she was going because I wanted to catch up with her to finish our discussions that we were having early on. Early on. And I must have turned around to look at her for maybe two or three seconds, that's all. Then I turned back around to look at Sharon, and this is what I find. Let me tell you something, most of you know about this guy. I can tell you that from personal experience, he's faster than a speeding bullet. The only thing more disconcerting about this is the expression on my wife's face. But it was all in fun. Then we're off a month later to Stockholm. The Nobel festivities are the first week in December. The actual Nobel Prize ceremony is on the anniversary of Alfred Nobel's passing, December 10th, every year. And it's hard to see this, I have a more close up view, but this is the venue, so the Nobel laureates for this particular year are seated here. Behind us are Nobel laureates from prior years, well-known scientists, distinguished scientists as well. And on the right side are members of the different Nobel committees, in medicine, physics, chemistry, literature, and so on. And up here was the Stockholm Philharmonic Orchestra, which played the most incredibly beautiful Baroque music for the entire ceremony. It was really great. Here's a close up view. We have the three laureates in physics, John Popel in chemistry, then Bob, myself, and Fred. Then we have the literature prize winner, the economic sciences prize winner. You can spot me immediately by just looking for the change in reflected light up here. And in the last slide I wanna share with you is my favorite slide, of course, something I could never forget, and that is when I received the prize from King Karl Gustav of Sweden. It's really an amazing slide. Here's Fred Murad looking on. And what I want you to remember from this slide is not necessarily my getting the prize, but I want you to look at what the king and I are standing on on the carpet. We are standing on NO, nitric oxide. I think I'm gonna stop here and I wanna thank you so much for your attention. You've been a great audience. Thank you.