Could you tell us about winning the Nobel Prize? It happened not long after Pfizer came out out with Viagra, didn’t it?
Louis Ignarro: Actually, it was the same year. Let me explain. In March — this is hilarious. In March of 1998, that’s when FDA approved the marketing of Viagra, March of ’98. Well, October of ’98 is when I received a phone call about the Nobel Prize in physiology or medicine for nitric oxide. So, after I settled down from all the emotional aspects of being told that you’re going to receive the Nobel Prize, I was thinking, you know, okay, so Viagra was just marketed and now comes the Nobel Prize. So, I decided to look up the Nobel committee. So, I looked up all the members because you could look it up, all the members of the Nobel committee in physiology or medicine, and I found that the great majority of them were men over the age of 65. So, it’s hilarious. But I was assured in Stockholm in December that that was not the main reason. In fact, the cutoff for my Nobel Prize research was actually 1986. So, I received the Nobel Prize really for the discovery that the arteries make nitric oxide to protect us against cardiovascular disease, and that was four years before the neurotransmitter discovery.
Cardiovascular disease still kills many people around the world and certainly here in the U.S. That must be frustrating since you’ve made this major breakthrough in cardiovascular disease research.
Louis Ignarro: Thank you for asking. For the remaining years of my life and career, I’m going to spend to try to convince the American people, and people throughout the world, that we could reduce — markedly reduce — the incidence of cardiovascular disease by just changing our lifestyles. Let me explain this. What the nitric oxide field has shown, not just me but to many others in the area, is that our bodies make the most amount of nitric oxide when we eat a healthy diet, when we’re not obese, when we don’t have diabetes, and when we exercise at least several days a week, getting your heart rate up. There are hundreds and hundreds of publications on this. There’s so many great publications. If you run, or bicycle, or play soccer or basketball, or even walk fast, you can measure it. Your body makes much more nitric oxide. And remember what nitric oxide does. It protects you against heart disease. It also improves blood flow to all your muscles. That’s why you make so much of it, to get blood flow to the muscles while you’re exercising, because you need oxygen and nutrients. I can list a hundred foods that boost nitric oxide production, ranging from fish, fish oils, to antioxidants present in blueberries, pomegranate, to antioxidants present in red wine, spinach, Brussel sprouts. I mean you name it. All those foods are healthy. All those foods need to be eaten. One needs to eat as little beef as possible. One should even reduce the amount of chicken you eat. And I can always get into detail about that.
A healthy diet, plus calorie restriction, plus exercise. If everyone started that when they were a teenager… It’s never too late to start. Don’t get me wrong. But if everyone started that when they were a teenager or in their 20s, I dare say that we could cut deaths due to cardiovascular disease down fivefold. Right now, 70 percent of Americans suffer from some kind of cardiovascular disease. Ninety-five percent of that is due to poor lifestyle. Don’t let anybody tell you it’s genes. Genes may account for five percent. What about the other 95 percent? Genes is just an excuse. It’s unhealthy lifestyle. So I really believe, and so do others working in this area, that we make nitric oxide as an anti-aging molecule to protect us against the development of cardiovascular disease. If we could focus on promoting the production of nitric oxide, I maintain that we will be very healthy. And I’m going to try to get my point across until I’m blue in the face. My desire, my aim — and I don’t know how to do it — is to have my own TV show one hour a week just so I can talk to the people. But most TV shows would rather interview LeBron James or Yogi Berra or somebody. I mean it’s really a world about sports. And when you talk about maintaining your health, it’s very difficult to get that information out.
You mentioned anti-aging benefits of nitric oxide. Are there possible implications for Alzheimer’s disease as well?
Louis Ignarro: Oh my goodness, yes. There are lots of experiments going on showing that in humans with Alzheimer’s disease, certain regions of the brain which develop plaques that are associated with Alzheimer’s Disease have a marked deficiency in nitric oxide. So there are small pharmaceutical companies, small biotech companies trying to develop medications that increase nitric oxide in the brain to try to either reverse or prevent progression of Alzheimer’s disease. So yes, dementia perhaps can be treatable by promoting nitric oxide production.
As a researcher, you must wonder why people adopt and sustain unhealthy lifestyles when the medical research is overwhelmingly clear that this cuts down on their lifespan.
Louis Ignarro: Yes, I know. I wish I could answer that question. I often ask people that, but I have to do so very carefully. It’s difficult for me to walk up to a person who is very obese and is eating a hamburger and having potato chips. It’s difficult for me to ask them, “Why are you doing that? Don’t you know that’s very unhealthy?” It’s easier for me to go up to somebody who’s smoking cigarettes and tell them, “You know, you should stop smoking. Don’t you know that smoking kills?” And they’ll go, “Well yes, I understand that smoking is dangerous. It might kill me. It might not. But you know, I have this habit, and I keep smoking.” But if I challenge a person who’s eating a hamburger or French fries or potato chips, often I get the answer back, “Well you know, if eating a hamburger or eating fries and eating potato chips was so dangerous, why are there so many shops, so many stores that sell this?”So that’s what I have to deal with. I don’t know how to get back to them. I try to explain that it is very unhealthy. They say they love the hamburger, they love this, they love that. It’s difficult to cook a healthy meal at home I guess. Years ago, I think, when most women — wives, if I may us that phrase — stayed home to cook healthy for the family, I think there was far, far lower incidence of cardiovascular disease. We didn’t have these fast-food shops. But now that more and more women of course are out working and making a living and so on, there’s no time to cook at home. I think that’s how the fast-food shops probably developed, or what sustained or drove them to develop. And now everybody’s going out. Families are going out quite frequently to eat. And that food is just — it may taste good, but it’s not healthy. It’s not a home-cooked meal.
It’s addictive food too.
Louis Ignarro: It’s very addictive. I have to tell you that, I admit, once a year my wife and I, we look at each other and we say well, let’s not cook our healthy meal. Why don’t we go out? And we whisper. “Why don’t we go out next door and have a hamburger, fries and a shake?” And we do that. Once a year. And I have to tell you it’s delicious.
Have there been setbacks in your career that really gave you pause? It sounds like things went rather smoothly.
Louis Ignarro: There were many, many setbacks. I think 20 percent of all the experiments I ever did worked according to plan and 80 percent didn’t. So that’s very frustrating. However, there’s a caveat there, and that is that many of those experiments that didn’t work, I would ask myself, “Okay, why didn’t it work? Did we do the experiment technically correctly?” We had to be sure that no mistakes were made in the experimentation, so we repeat it, but the results were not what we expected. So we would go back. I would go back and think about that and say, “Okay, this means our original hypothesis could not be correct because this experiment didn’t work as planned. So let’s rethink the hypothesis and change it, modify it, and let’s do a different experiment.” So many times those negative experiments turn out to be positive, and that helps you to think outside the box. But many scientists, they get frustrated when the hypothesis — when the experiments don’t work, and they’re so convinced that their hypothesis is correct that they won’t do experiments to change it. Then they’re stuck with an incorrect hypothesis. So you have to be fearless, as you said. You have to be fearless and just — you’re after the truth. I don’t care what it takes to get there. You’ve just got to get there and find out what the truth is.
It sounds like you also have to stop thinking about your career implications and keep your eye on the ball rather than worrying that people will consider something a failure.
Louis Ignarro: That is so true. When we had our first hypothesis that nitric oxide lowers the blood pressure, and does this and that, and was the active species of nitroglycerin, I wrote a grant, a large research grant to further investigate the pharmacology of this noxious, poisonous gas. And it was the first grant that was turned down. It was totally refused. I didn’t get it. Okay. But I published some of that work anyway. And then a couple of other people reproduced that work and extended it. Then I went back and applied for that grant, and I got it funded. Okay. So that was good. Then, when I had the idea that our bodies may make nitric oxide, that grant was turned down. My first publication was turned down because I was thinking outside the box. No one thought it possible. How could our bodies make this poisonous gas? That’s ridiculous. We would all die if our bodies made it. On and on and on. One thing led to another, the paper got published, and then I raised more funds than I knew what to do with. And Alfred Nobel came through. So there!
You need to have a lot of faith in your own instincts, don’t you?
Louis Ignarro: You do. You have to really believe that what you’re doing is correct and don’t let anything stand in your way to get there. I learned this. It’s a very popular phrase, “Never give up.” I learned that in sports, because I was never a very big person, but I loved baseball and football, and I played that throughout grade school and high school, and and a little bit in college, but not much. Columbia didn’t have much of a baseball or football team. But I did play sports, and track and field of course, when I was much younger. And it was always a struggle for me, because of my smaller size than the others, but I never gave up. I just had to work harder, run harder, cut corners harder, but never, never gave up and was pretty good at it. So I applied the same principles when I was a scientist. As a scientist you have to adapt that thinking. Never give up, because as soon as you give up, it’s over. You can never give up. If you really believe in something, you’ve got to pursue it until you’ve convinced yourself with experimentation, “Okay, you had a great idea, but it’s just not going to work. It’s not true.” And that’s happened to me. Now most have worked. So that’s good. But I’ve had some ideas which I thought were perfect and they were not.
So you have to know when to go in a new direction too.
Louis Ignarro: Yes, you do. Often that’s not so easy, but I manage to sort things out.
It sounds like being a scientist requires having faith in yourself and trusting yourself.
Louis Ignarro: Oh yes. You have to have trust in yourself, and you have to be — what I found that in this profession — now, I’m not saying other professions are not. What I’m saying is that in this research profession you have to be incredibly honest to yourself and to others because you’re after the truth. I think that a lot of people who conduct research, if the experiments don’t work and don’t work and don’t work and their jobs become at risk, they maybe tend to stretch the data. I don’t mean falsify. No, no, no, no. I mean they may interpret things a little differently just to get a publication. I never did that to myself. I mean, there are many times where we had volumes of data which I would not even write up for a publication because it didn’t make sense. And as the years went by, I could fill in those missing gaps. I would take out that manuscript. I’d put in the missing data, publish it, and there it was. So you have to be very careful, and you have to be brutally honest to yourself. Absolutely.
Do you stress that with students?
Louis Ignarro: All the time. You have to be very honest, otherwise you’re going to wind up getting in trouble. And luckily, I’ve never had a student or a postdoctoral fellow or a visiting scientist who’s gotten himself or herself into trouble. I said, “If things don’t work, and you’re frustrated, it’s better to lose your job than it is to stretch your data.” Because somewhere down the line, when people cannot reproduce what you did, then you’re in trouble, and that happens a lot. You can’t just make up data, publish a good paper. You might feel good about it the first year, but then, when other people try to reproduce your work and say you’re wrong, you are in a lot of trouble.
What do you think is the next frontier in pharmacology? Where do we need to go next?
Louis Ignarro: I don’t think I’m going to see it, but I hope I do. I think that many younger people are going to see this. I think that what we’ve learned so far about genes, genetics in pharmacology, that’s going to be the wave of the future. What I envision seeing, and I’m sure you’ve heard this — but I read a lot, I talk to a lot of people. What I envision seeing, I think in 25 years, I really do, that as soon as a newborn comes to be, or even maternally, a newborn will be tested with a small sample, maybe cheek cells or something very non-invasive. The entire genome will be analyzed. Every defect that there is in the gene will be noticed, and then it will be very clear as to what needs to be done to prevent that gene from developing. That is, to correct the genetic defect so that person may not develop Alzheimer’s disease. That person may not develop high blood pressure or whatever. I really see that coming. And that is going to be great for treating disease, preventing disease, but it will create other problems, because you’re going to have a lot of 150-year-olds around. What are we going to do with all these people who are over 100 years old once we develop to that stage? But you can’t let that limit your development. I think what you need to do first is try to prevent disease, treat disease so that humans can live a healthy lifestyle. I mean the purpose is not to keep a human alive as long as possible. No, no, no. Why should someone die at the age of 55 for heart disease? Why should someone at 60 develop Alzheimer’s disease? If all those diseases can be avoided, I think everyone would live to 100 or 110 but live a very useful life until then. I see nothing wrong with that.
Average human longevity has expanded remarkably in just the last 40 or 50 years.
Louis Ignarro: Exactly. I see the same thing. It is truly remarkable. A lot of antibiotic drugs, anti-infective drugs have prevented deaths due to a variety of contagious diseases, and that’s allowed people to live longer. I think treating patients who have high blood pressure with drugs to keep the blood pressure manageable, that has extended everyone’s life. So drugs have helped, but the way to go is, in my opinion, preventive medicine. In the United States today, we don’t think about preventive medicine. We talk about you go to the doctor when you’re sick. And then the doctor tries to give you a drug to treat the disease. It’s okay. But that’s very limited in its application. The idea is to prevent getting the disease in the first place, and then you don’t have to worry about treating the disease.
It will cost less.
Louis Ignarro: It will cost much less. But we have a lot of obstacles out there. Schools still don’t teach preventive medicine. Now some may a little bit, but I find that schools hardly teach preventive medicine. I’ll give you 100 bucks for every school you can find that has a nutrition course in the medical school. There’s just very little of that. I find that to be very sad.
Louis Ignarro: It is. It is. It is. Things will change, but I’m getting older, and I want to see things change now. I don’t want to see them change when I’m 90 years old. I may not recognize the changes.
You mentioned visiting students around the world and encouraging them to think outside the box. How do you do that? How do you encourage that?
Louis Ignarro: I ask them about their research and what they’re doing. And of course I talk to their professors first, because I don’t want to embarrass anybody. And then I say, “Okay, you’re doing this. Let me explain to you what I did.” So I would explain to them what I did, and they would always have questions. How did you know about nitroglycerine and nitric oxide? How did you know to look to see if arteries make nitric oxide? How did you know to look in the nerves to see if they release nitric oxide as a neurotransmitter? How did you know? I said, “I didn’t. I just developed this idea, and this was thinking outside the box. And I went and I tested that hypothesis.” So what I try to do, and it’s very difficult, is look at their research, and then suggest to them what they might do in thinking outside the box and go maybe in this direction in addition to this direction. I’ve been doing that for about almost ten years at three different universities. And in several cases it’s worked out very well. The graduates have done better, and they’re very appreciative, they’re very happy and so on. But it’s hard. It’s hard to teach somebody to think outside the box. It’s something that almost comes naturally. It’s very hard to instill in someone.
It takes a certain fearlessness, doesn’t it?
Louis Ignarro: Oh yes. Of course. You have to be completely and totally fearless, because if it doesn’t work, it doesn’t work. It’s okay. You’re not going to be penalized for that. Sometimes the way funds are raised to do research throughout the world, especially in this country, make it difficult to think outside the box. For example, you work very hard to write a research application, let’s say, to the National Institutes of Health or any other organization. You write down exactly what you’re going to do, why you’re going to do it, the feasibility of each experiment, blah, blah, blah, and you submit it. And then if you’re lucky, ’cause it’s so hard to get funded these days, you’ll get a few hundred thousand dollars to do your work. Well three years later or four years later, you have to apply for a renewal to continue your research. So you better be able to show that you did those experiments and published them. Otherwise you’re not going to get anymore grants. So when do you think outside the box, and where do you get the money to do the experiments that are not planned here? So what I would do is you borrow from Peter to pay Paul. So I have my grant. Okay. I got to go do this experiment. I use this money to experiment outside the box. It works. That allows me to apply for a brand-new grant, and I get funded, and then I pay this guy back. That’s what you have to do.
We’d like to talk a little about your childhood and youth. You were born in Brooklyn, weren’t you?
Louis Ignarro: Yes. Born in Brooklyn.
At a turbulent time in the world.
Louis Ignarro: Right, exactly. in 1941.
Could you tell us about your parents?
Louis Ignarro: My parents were both Italian immigrants. My dad was born in Naples, Italy, and my mom was born in Sicily. And despite that, they married one another. They actually moved independently to New York, to Brooklyn in the ’20s and ’30s. They met each other in New York. They got married and then I came along in 1941, and then my brother came along in 1944.
What did your father do?
Louis Ignarro: My father was a carpenter and ship builder in Italy. When he moved to the U.S., he was a carpenter at first. Then he became a contractor and helped to build some of the boardwalks on Long Island, but remained essentially as a carpenter working independently by himself.
What kind of education did your folks have?
Louis Ignarro: Neither my mother nor my father ever went to school. That means not even the first grade. They had zero formal education. When my dad moved to the U.S., it took him literally 40 years to learn how to speak and read a little bit of English. My mother was able to adapt more quickly.
Did she work?
Louis Ignarro: My mom took care of her seven brothers and sisters most of the time. And then she met my dad and they got married. My father being a Neapolitan the way he is, he said, “Frances….” That was her name. “Frances, I do the working. I work as the carpenter. I come home and I want dinner every night.” So she stayed home and cooked every night and raised her two sons. Later on she got a job working in a department store when we grew up.
Did you or your parents experience discrimination in those days as immigrants?
Louis Ignarro: No. Everybody seemed to like the Italians. As long as we were turning out some good food and music everybody was happy. But no, I did not personally experience any prejudice or discrimination, but I saw others experience discrimination and prejudice against them in the Brooklyn and the New York area. There were so many different immigrants. Many people made fun of other people, and that was very disturbing to me as a child.
Your parents must have stressed education since you so surpassed their own educational background.
Louis Ignarro: Yes. I still remember, as a very young child my mom and dad speaking Italian — and I learned that even before I learned how to speak English — talking about we have to be sure that our children have the best education possible, and so on and so forth. So even though they couldn’t help me with any homework whatsoever — except maybe addition and subtraction which my mother could do. My dad was still not so good at it. They just made sure that we went to school and we did our homework. My mom never missed a PTA meeting or anything like that. She always checked on us. And my brother and I were good students. She didn’t force anything down us. We would come home and she’d give us a little snack and say, “You got to do your homework first. Then you can go out and play.” I used to love to play ball. And she would always say, “Lou, first homework and then you can go out and play ball.” And that’s what I did. So without pushing us, both of them guided us in the right direction. But it was not easy, because there was no help with homework. Whenever I had a problem, she would go around the neighborhood and find a neighbor who could help. She was very good at that.
When did you first have an inkling that you wanted to pursue science?
Louis Ignarro: At a very young age. I was about ten years old. And for some reason, at ten years old I was interested in chemicals. I’m not exactly sure why. I think one of the neighbors talked about everything having its basis in chemistry, everything was made of a chemical. So I convinced my parents to buy me a chemistry set at the age of ten years old. I still remember it was a Gilbert chemistry set. I don’t think they make them anymore. So again, no one could help me do the experiments. I would read the things as best I could. I think the chemistry set was for 14-year-olds and older. I was ten. But I was able to do the experiments, mix the chemicals. When you’re ten years old and you mix one clear solution into another clear solution and it turns red, it’s very exciting. And then if you add a different chemical to it, it turns blue. Well, that really got my attention! Or you might mix two clear solutions together and it forms a precipitate. In other words, a solid material just comes out of the solution. That was of interest to me, and I kept pursuing that further and further. Then, when I got into my young teenage years, I took it a step further because I wanted to make firecrackers and rocket fuel. But to do that I needed chemicals that were not in a chemistry set. So I would walk into the local pharmacies. Pharmacies back then were very different. Medicines were not in bottles that they just poured into your own bottle. They had to make everything. So I walked in there and I could see what ingredients they had. So then I would have one of my neighbors, older brothers or even his father, go in and get me some of the chemicals. They didn’t really know the dangers in some of these chemicals. They would buy them; I would pay them for it. And then I would have what I needed to make little firecrackers, rocket fuel, and so on and so forth. I got in trouble for that eventually.
Louis Ignarro: Yes. My father was a carpenter, so he would help me build a lightweight rocket out of wood. Then I would line it with “tin foil,” we used to call it then. It’s aluminum foil. I would reinforce it and I would actually make the powder, the rocket fuel. I’d have a fuse, go out in the back yard, light it, and send it up. Believe me, they went up pretty high!
How did you get into trouble with this stuff?
Louis Ignarro: Well, in a couple of different ways. In the initial testing of my firecrackers, I added — so, what I made was gunpowder. Okay. You can buy those ingredients in the pharmacy. I won’t go through the ingredients, but very simple. So the first one I made was just a little too large. To test it out I just put it on the floor under one of our dressers in the basement. We used to rent the upper level and then we lived in the basement. So we had clothes in this dresser. And I lit that, and it actually blew apart the dresser. So of course, my mother was ecstatic. I mean she went crazy. Really gave it to me. I remember her saying, “Wait ’til your father comes home. Wait ’til your father comes home.” So I waited in trepidation. And then when he came home, he wanted to know how I did this in detail. So I explained to him what I did. And he looked at me and he said, “Son, don’t do it again.” And then he left. I remember my mom chasing him saying — his name was Jack — “Jack, you’re not going to scold your son? Look what he did.” He said, “But don’t you understand? He did something that we don’t know how to do. He’s very creative. Leave him alone. He won’t do it again.” That’s a true story.
So, your father recognized the creativity in science right there.
Louis Ignarro: Yes, he did. When I did the rocket fuel, he was very impressed with the way the rockets were going up, and he really helped me with that. And anything else I wanted to do that was related to science he would allow me to do. That’s the chemistry side. I was interested in biology. So I would go out and I would look for small animals that had just died and I would dissect them to see what was on the inside. That drove my mother absolutely crazy. My dad had no problem with that whatsoever. I recognized early on that if you look at the inside, for example, of a squirrel, you just open the abdomen, and if you look at the inside, it looks exactly like that of a human. How did I know that? Because I went to the library and got out a book on Gray’s Anatomy, human anatomy, and I would open that up, and I would say, “Look, Mom, here’s the esophagus. Here’s the stomach. Here’s the small intestine. It’s the same.” Eventually she knew I wasn’t going to stop doing this and she paid more attention.
It’s not the most pleasant thing to have dead squirrels in the house.
Louis Ignarro: No. But you know, she realized what I was doing, and she would always remind me, “Hurry up and finish. Then get rid of it before it starts to smell.” “Yes, Mom.”
You mentioned Gray’s Anatomy. Were there other books that were influential when you were growing up, even if you read them just for fun?
Louis Ignarro: I didn’t read that many books for fun. Still today I don’t do that. I’m not a big book reader, which is rare for someone with an education. I was always interested in science and technology. As a young child, even before taking these courses in high school, I would go to the library and just read up as much as I could on chemistry and biology. I couldn’t wait to eventually take those courses. Then of course I would drive the teachers crazy. “When are you going to talk about this? When are you going to talk about that?” I read other things too. In school you’re assigned certain reading. But to go out and read books other than science and technology on my own, I didn’t do much of that.
You’ve mentioned in previous interviews that there was a tough neighborhood near you and you could have gone a different way in life.
Louis Ignarro: Sure. Because I had all kinds of friends. I’ve always been an extravert. So, I like to make friends with a lot of different people. My high school was good, Long Beach High School and Grade School. I think the better people in the community, or the people who didn’t get themselves in trouble, so to speak, attended that school, but there were a lot of other schools around, especially five or six or eight miles away. When you’re friendly with someone, they have other friends and you meet these people. They led a different kind of a life. They were walking around in the evening and doing this and that. I remember one time, I was pretty young. I don’t think I was a teenager yet. Two of the fellows had this idea of walking into a candy store and just stealing or sneaking some candy bars out, and they asked me to come along. I recognized that that isn’t the right thing to do, and I said “Oh, no thanks. I think I’ll just wait here.” And sure enough they went in and they came out with candy bars, running, and I did not run with them. That’s what I mean by the opportunity existed for me to hang around these fellows. But I knew better so I didn’t do it.
Did you have a sense of wanting to kind of give back to your parents by achieving?
Louis Ignarro: Absolutely, because they always talked about my education. I didn’t recognize that until I got into college. In grade school you’re a child. So I studied. I did okay. I was not a straight-A student. In science and math I was a straight-A student. In English and history I was a C student. So in high school I grew up and in those subjects where I had gotten Cs, I would get Bs, but then all the science and math courses I would get As. And I began to realize how hard they worked to get me to that point. I realized that in the last year of high school. That’s when I got all As and scored very high on what is called the New York State Regents Examinations. Every high school in New York State, on the same day the students have to take a test. Then they look at the results, and that’s how they rank the students. So Bronx High School of Science was number one and so on. The school I went to was number four. I did very well. They were very pleased. Then I went on to college. I didn’t think I was going to get accepted to Columbia College, but I did. When I got in there, my goal and intention, besides getting an education, was to please my mom and dad. And then the first year I was afraid I might not be able to do that, because I found it to be so difficult. What a school that was! But I did. I did very well. That made them happy and made me very happy.
Were there teachers who inspired you when you were growing up? It sounds like you were very independent.
Louis Ignarro: I can’t remember any particular person in grade school, but in high school there were two or three very inspiring professors. Now, I haven’t thought about this in a long time and I’m going to try to think of their names. There was the English professor for my third and fourth years of high school, his name was Shanker, Dr. Shanker. I don’t remember his first name. But I was not very good in English. I mean the language yes, but taking the course, no. I was much more interested in chemistry and physics and math. So he pointed out to me how important it was to be able to communicate in English, because I had told him I want to go into science. So he’s the one who really turned me around, and by the end of the third year I was getting an A in English. And in the fourth year, on these special exams that I told you about, the New York State Regents Exam, I scored one of the highest in the state. So he was so happy about that, and he made that clear to my parents. So, that was one person. And Dr. Hirsch was my mathematics teacher for at least three courses, maybe four, in high school. He was very good, and he really stimulated me to think, and to go on and taught me how to use numbers, how to use math.
We understand at one point you were interested in possibly becoming a pharmacist.
Louis Ignarro: When I was in high school, as I said before, I loved chemistry. So I was going to go and just get a degree in chemistry. And my dad, even though he had no education, says to me, he says, “Lou, when you become a chemist, what are you going to do with that?” I said, “Well, Dad, I’m not sure. Maybe I’ll go work in a drug company. Maybe I’ll teach chemistry in a university.” He said okay. He said, “Doesn’t a pharmacist know chemistry?” I said yeah. He said, “Well, if you go to pharmacy school, that’s also chemistry. When you graduate, you could have a job right away, and then you can decide what you want to do after that.” So my dad, completely uneducated. Of course, as a carpenter he did a lot of work for pharmacists in the pharmacies, in the stores, in their homes, and so on. So the net result was I went to pharmacy school, but I took three or four additional courses I didn’t have to take in pure chemistry. So I graduated with a degree in pharmacy and chemistry, and I used that to move forward.
I worked in a pharmacy the summer after my third year in pharmacy school, which was what everyone did if you were in pharmacy school. So my job was to really stock the shelves and watch what they were doing in terms of filling prescriptions. I was not old enough or advanced enough to actually fill the prescriptions, but they gave me some opportunity to do a little bit of that. But to make a long story short, after three months I recognized that after all the education I had received in college, that it was just inadequate for me to simply fill prescriptions. It just wasn’t for me. Also, I was not a businessman, and in those days if you owned your own pharmacy, you made good money. But I wasn’t thinking that. I was really thinking more research in chemistry and biology. So I knew right away after my third year that once I finished pharmacy school, I was going to go on to get a Ph.D. in either chemistry or pharmacology. So in my senior year, again, I worked in the pharmacy. This time they allowed me to fill some prescriptions, but it wasn’t for me. So right after that summer was over, I started at Columbia University in New York City. I had already applied to graduate school to the University of Minnesota for the Department of Pharmacology. So, that’s what I decided to pursue, and I’m very happy that I did that. I found that to be very rewarding.
At Minnesota you studied under a future Nobel laureate, Dr. Paul Boyer.
Louis Ignarro: Yes. Very good. He was in biochemistry. My major was pharmacology with a minor in physiology. I was always interested in the chemical aspects of biology. So pharmacology is the perfect discipline. But because of my interest in chemistry as a child and chemistry all through high school and college, I decided to take some extra courses in chemistry and biochemistry during my graduate studies. So I took an advanced enzymology course, and it was taught by Paul Boyer. And I remember that being the most difficult course I ever took in my life. I remember that when I was done, I received — after the final exam I had a 77 average out of 100 — and he gave me an A. And I realized that he gave me an A because it was the second-highest grade in the class. What’s funny about Paul Boyer is… He was great. He made a lot of discoveries. In 1997, one year before I received the Nobel Prize, Paul Boyer received the Nobel Prize. And Paul Boyer, by the way, had moved from Minnesota to UCLA way before I got there. He moved there in the ’60s or ’70s. I got there in 1985. And you know, we used to talk to each other all the time. And then in ’97, when he was awarded the Nobel Prize, I was one of the first to go over there and congratulate him and so on and so forth. Then the next year I got the Nobel Prize. So he comes over to my office congratulating me. And I remember telling him — I said, “Paul, I’m so glad you got the prize before I did,” because he had taught me everything I knew, many, many years before that.
So the enzyme study was very important as it turns out.
Louis Ignarro: Very important, because I studied enzymes for my entire research career, from graduate school, after Dr. Boyer taught me, up until my last experiments. Enzymes are proteins in the body that facilitate a lot of different reactions. Your body is loaded with different biochemical reactions, all mediated by enzymes. So I became an expert in enzymology, and almost every important study that I conducted and published involved enzymes of one type or another. Paul and I often discussed this. He’s about 94 or 95 years old, but he’s still doing very well, and we meet once in a while to talk about the good old days.
What does the American Dream mean to you?
Louis Ignarro: The American Dream to me means — it signifies how successful a citizen of the United States can be if you really take advantage of all the things that America has to offer. We have great freedoms here. We have the ability — capacity — to go to whatever schools we want to go to, provided we do well and educate ourselves in order to get into those schools. But I guess what I’m trying to say is there’s still, even today, so many different opportunities in the U.S. I think the majority of the universities and higher schools of learning in the U.S. surpass those in other parts of the world. There are great opportunities here to take on any kind of profession. And then, once you finish schooling, there’s so many opportunities for great jobs here. The United States is, I think, synonymous with science and technology. Now there are great advances, don’t get me wrong, in Europe and especially in Asia, but still I think the center of attraction for science and technology — which I can speak to — is right here in America. So for those who are interested, they could take the opportunity, or they can use this to their advantage, and really learn something and excel in science and technology.
It seems like in a way you’re almost the embodiment of the American Dream, given your heritage as the son of immigrants.
Louis Ignarro: Yes, absolutely. I really took this a long way. My parents were completely uneducated, and yet despite that, I was able to climb to the top of my profession, if I may say that.
Do you think that there’s a creative aspect to having that flair for research? It seems you were always pushing yourself to think outside the box.
Louis Ignarro: Yes. That’s what I’ve done for my research career. Research, biomedical research, if you’re not highly motivated but you do it because it’s a job, those individuals don’t think outside the box. They just read up in the literature, and they see what has developed so they’ll know what direction to go to, to extend our knowledge in a particular area. I did a lot of that, but that never made me happy. I didn’t want to extend what we knew about an area. I wanted to discover something new. That’s the way I always was. And not because I wanted to be number one or be first. No, no, no. That’s competition. I compete only against myself. I never compete against anyone else. So that wasn’t the intent. The intent was there’s so much information to be learned out there. There’s so much to be learned. Okay? So if I just follow in the footsteps of others, I’m not going to be able to make those discoveries and learn all the new things out there. So I took every opportunity I had to think outside the box and go somewhere where no one else has been, if I may plagiarize that show. So that’s what I’ve always done in my career.
Where do you think that creative spark comes from? Are there ways to foster it?
Louis Ignarro: It took me about 60 years to figure out where that came from, and I finally figured out, my brother and I, that it came from my father. Let me explain. My father never went to school, okay, but he was a carpenter. And in the summers before going to college, he took me to work with him so I could help him on his job and I could see what he could do, being completely uneducated. And also, by the way, in those days, no such thing as a power tool. You didn’t plug anything in. You used a saw, hammer, chisel, nails, a screwdriver, a drill. I mean nothing. There were no power tools. And I watched what he did, and I was always impressed, but I never thought about it ’til many, many, many years later. I remember that he could draw a perfect circle without a compass. He could draw a straight line, a perfectly straight line, using his thumb and placing the pencil in a certain way. I mean all these things. He had his own designs he added to windows and other things. I think that’s creative. So I’m creative. That creativity had to come from somewhere. And my brother and I concluded, although we loved our mother dearly, the creativity had to come from our father.
How do you maximize your creativity in your work? By taking care of yourself, or surrounding yourself with certain hobbies or certain habits?
Louis Ignarro: I’m retiring now from my original research. But I’ve started a company in which I deal with other companies, trying to help them develop nutritional supplements rich in antioxidants and other things. So I’m trying to take my ideas to a different level. But I stay motivated. I try to stay motivated in a variety of other areas. I am a visiting professor in several universities. I visit several countries often, and I work with those students to try to teach them how to be original and think outside the box. I have gone back to revisit two hobbies I had when I was a young child and a teenager. So now I’m back into owning racing cars. I used to race cars when I was a teenager. So now I have one of the fastest production cars ever made, although I don’t race it at the track. I also don’t race it in the street, by the way. I just like to have it. But the key thing I have done to stay motivated is — when I was a young child even before getting my first chemistry set, I convinced my dad to buy me a model railroad made by Lionel, and I had model trains, a small set we put around the Christmas tree, and then eventually I built it in the basement. So today I have a huge garage. It’s not for parking cars, but I have a very large model railroad layout that I built and maintain, and I’ve been working on it for about seven years. It’s been in all kinds of magazines and videos and so on. I love to do that. By the way, the Nobel Foundation has told me that I am the only Nobel laureate they’re aware of who has a model railroad.
What was it about research that attracted or excited you?
Louis Ignarro: The one thing about research being very exciting is the fact that you really don’t know what to expect. So you have to be very creative. You have to be able to ask the right questions and then answer them in a timely manner. And then, once you get answers back, you need to know what direction you’re going to go next. It sounds very exciting, but it can be very frustrating because, for example, in the laboratory when you’re conducting experiments, not all experiments work, or they don’t work the way you thought they were going to work. So now what do you do? Research carries with it a great deal of frustration. There’s no instant gratification in research. You do an experiment, okay, fine. Now you’re taking it this direction, you’re taking it in that direction. You may not know if your project has been successful, or if you’ve made an important finding, for a year or two or three years. So that’s what I mean by “no instant gratification” in most aspects. Sometimes there have been experiments where there was that instant gratification. But at the beginning, it’s very frustrating. It takes many, many hours. Doing original research in a laboratory does not mean that you go in at 8:00 in the morning and you go home at 5:00 in the afternoon and you take weekends off. Sorry. That’s not the way it works. You may be going at 6:00 in the morning. You may be staying until midnight. I’ve always worked on weekends, at least the first 20 years of my career. And depending on the experiment, sometimes you have to stay awake for 24 to 48 hours, depending upon what you’re doing to monitor the experiments.
I think it’s the most difficult profession of all to do biological research, biomedical research, if you will. I’m sure other successful scientists will tell you the same thing.
It sounds like you have to live in the time frame of your experiments.
Louis Ignarro: Yes. Absolutely. You have to be on the time frame of your experiments. Also, to do experiments you need money. Just because you have a position in a university does not mean that you have money to do research. Universities will accept you so that you can be an instructor, an assistant professor, associate professor, professor. What do they provide? They give you an office, and they give you laboratory space, and that’s it. It’s up to you to stock the laboratory with equipment. It’s up to you to raise money, to hire technicians, nurses, other people you may need. It’s up to you to get the money to hire a secretary. The school provides none of that. They give you the opportunity and the space to be successful and then you’re on your own. So you spend a great deal of time raising funds to conduct the research. It’s not easy.
And it’s up to you to recruit students to help you in what you’re doing.
Louis Ignarro: Oh yes. The principal investigator, which is me let’s say, we have to do it all. I had to do everything. And you have other obligations. You’re not in a university just to do research. You’re in a university to teach students. So I was teaching undergraduate students, I was teaching graduate students, and I was teaching medical students. I loved to teach medical students. I did that for many, many years.
Finally, how would you describe, to someone who doesn’t really have experience in science, what makes it so exciting for you?
Louis Ignarro: I think the best thing that makes science exciting is that you have the opportunity to think about important questions in science. Whether it’s science, technology, medicine, chemistry, whatever it is, you have the opportunity to think about important and exciting questions. You have the opportunity to then try to answer those questions. And it’s up to you. In other words, everything was up to me. So everything is up to you. You can design the experiments. You test the hypothesis. You look at the data. You draw the conclusions. And then you go from there. And the greatest thing about all of this is when you’re able to answer a question satisfactorily, then you’ve made an important contribution to humankind. I said, “Even if it’s not an important contribution to humankind, even if you’ve answered your own question satisfactorily and you could publish it somewhere,” I said, “that’s very gratifying and that’s a great reward in life,” because it’s one profession where you could have a lot of those rewards, but you do have to work hard.
That’s a good place for us to end. Thank you so much.
Louis Ignarro: Oh, it’s been a pleasure. Thank you very much.