Winning the Nobel Prize with Lou Ignarro

May 20, 2022

Winning the Nobel Prize with Lou Ignarro

May 20, 2022

About This Episode

Let’s listen to the inspiring journey of a Nobel prize laureate in this episode. Tristan interviews Dr. Lou Ignarro, the pharmacologist granted the 1998 Nobel Prize in Physiology or Medicine for his research on nitric oxide and its role in maintaining the cardiovascular system. Lou has received many achievements and titles in his life, both as a researcher and a professor, but his favorite is to be recognized as the “Father of Viagra.” 

Tune in to their fun and inspiring conversation about Dr. Lou’s life passion and the insatiable curiosity that has kept him going in his research.

Lou’s Journey Towards Stockholm

In his recent book titled Dr. NO: The Discovery That Led to a Nobel Prize and Viagra, Lou tells his story on how his childhood interests and passion for explosives paved the way to getting a ticket to Stockholm to receive his Nobel Prize.

Despite Lou's multiple accolades and recognitions over the course of his 60-year career as a pharmacologist, researcher, and professor, Tristan observes the humility that resonated in Lou's book. Lou is proud to say that his parents taught him how to conduct himself, whether in writing or communicating with others.

How it all began

Lou had a lifelong fascination with chemistry and experimentation, which frequently irritated his mother.

It all started with a childhood infatuation with the July 4th fireworks spectacular. He intended to create his own firecrackers and began burying himself in public library books. He made a list of the chemicals he required to make a firecracker and went to the pharmacy to buy them.

His mother, who was concerned for his safety, was not pleased when he began creating his own explosives. But his father noticed his potential and supported his numerous experiments, acting as a go-between between the young Lou and his mother when his experiments became a little too loud and chaotic.

Lou credits his father as one of the early figures who encouraged him to pursue his passions and dreams. "Son, I want you to grow up to be somebody," his father would always tell him. "I do not want you to be a laborer, a carpenter, like me.”

And later in life, he learned that his father confided in his mom, “Please, let our son do [these experiments] because don’t you see? He’s doing things that we don’t even understand. Let him continue to do this.”

As a kid whose parents never had any form of formal education, his handicapped position wasn’t enough to curb the brimming curiosity in him.

“It was [a great childhood],” Lou says. “I am one of the lucky ones. My parents encouraged me to do well in school. And like I said, my father wanted me to become a doctor or a lawyer, or a businessman. He wanted me to be anything but a politician—he didn’t trust politicians.”

The dynamite story

At the age of 14, Lou tried making a bomb after reading Alfred Nobel’s work on dynamites.

He set out to create dynamite, but the active component in dynamite is nitroglycerin, which is a risky and difficult chemical to procure.

“You can’t buy that, you can’t make that. It has to be a special procedure to make or it explodes as soon as you have the chemicals together,” Lou explains.

Instead, he utilized modified gunpowder made of sulfur, charcoal, and potassium nitrate–all of which he could get at a local pharmacy. It was his final and most powerful firework. Although it caused some damage, no one was injured [during the experiment].

“I read about [Nobel], and I realized I couldn’t use nitroglycerin. So, I went back and I was reading what he used before he used nitroglycerin. Before nitroglycerin was invented, he used different kinds of gunpowder. And they were very effective. If you use enough gunpowder, and you put it tightly wrap it in a cylinder, when it explodes, this great force is liberated, as I learned the hard way,” Lou shares, laughing at the memory.

University life

As a kid, Lou was not just interested in chemistry, but also biology. He used to drive his parents crazy by asking so many questions about how the human body functions and his dad would tell him, “I don’t understand, son, but maybe you could learn about it.”

As a result, he had to wait years before learning chemistry and biology in school. Because of his passion in chemistry and biology, he majored in both.

“I wanted to apply chemical principles to the understanding of how drugs affect physiology and our bodies. To do that, you understand both chemistry and biology. You have to understand physiology,” Lou says.

He was absorbed by whatever he was learning, and this continued through graduate school and medical school. Lou refers to his field as chemical pharmacology.

“Pharmacology is the study of the action of drugs and other chemicals on the body. I took a chemical approach rather than a biological approach to study how drugs worked in the body,” he explains.

And that really paid off.

Graduate school

Lou shares his fond memories of his time at Columbia University. One was Nedick's hotdog and orange juice he would always buy from a stand at Penn station on the way home.

The other is his encounter with Nobel Prize-winning chemist, Paul Boyer, who is one of the influential figures that helped him get the Nobel Prize.

Boyer was Lou’s professor in enzymology during his graduate school at the University of Minnesota, and one of the people Lou looked up to. 

“He was so bright and so intelligent, I was awed by him,” Lou shares. “The way he did things, the way he taught–he didn’t even have any notes in front of him, he just went to the board and wrote on the board.”

“I thought, someday when I grow up and start teaching, I’m gonna be like him,” he admits. “The way he approached his research influenced me dramatically.”

Decades later, when Lou started teaching in UCLA School of Medicine, he was reunited with Paul Boyer, and a year later Boyer won a Nobel prize in Chemistry.

Dealing with Failures

As a scientific researcher, Lou also dealt with a lot of failures.

He lives by two quotes from his book, which he frequently shares with graduate students he counsels when they are frustrated about their research or chosen profession.

The first was a modified version of Winston Churchill’s quote, “The definition of a successful scientist is the ability to move from failure to failure without any loss of enthusiasm.” 

The other was something Nelson Mandela said not too long ago: “The greatest glory in living lies not in “never falling,” but in rising every time you fall.”

Despite the many failures and setbacks he encountered, Lou’s passion is the one that kept him going. Even if he wasn’t sure where that passion came from, or why that specific passion, it was an incredible motivation for him to keep answering questions in medicine that had not been answered previously.

One such question, that would later bring him to Stockholm, was why some people live so long while others die young from cardiovascular diseases. And throughout the years of observation, he noticed that people with healthy diets (not overweight) and who lived an active lifestyle, tended to live longer.

“You’ve got to be motivated, and you have to have that passion for what you are doing. If you don’t have that passion, to do a specific thing where you are not motivated then it’s much more difficult to be successful. It may be worthwhile looking into something else,” Lou says. “But if you believe in what you are doing, and you believe that there is an answer out there, then what I say is, you just have to go after it, and you must never give up.”

For anybody who likes baseball, another good quote Lou shared is “Never let the fear of striking out keep you from playing the game.” 

The Discovery

Another thing that kept Lou motivated was Elton John’s music, specifically the song “I’m Still Standing”. He shares an anecdote about listening to that song while running marathons in his 60s and meeting Elton John backstage before a live concert.

He also shares that he encouraged his students to play some music (at a low level enough for everybody to hear inside the lab, but not blasting it at full volume) while they do experiments in the laboratory.

“When you are doing research, and you do experiment after experiment, and many of them fail, what do you do? You could just leave and go home and go to bed, or go on a long vacation and forget about your work. Or you can continue to work. You could continue to stand there and do the work. That is what I felt when I was playing “I’m Still Standing” by Elton John in the lab. It motivated me. And it also motivated my students to do the same thing.”

And it paid off. Finally, his research showed the results he spent years looking for.

In his book, he put it like this, “The story was now complete. Nitroglycerin relaxes arteries and veins by being converted in smooth muscle cells to nitric oxide (NO) which then stimulates the production of cyclic GMP, which, in turn, causes smooth muscle relaxation.”

Nitroglycerin is used in dynamites, but it is also a drug that has been used for 150 years. During Alfred Nobel’s work on dynamites, they noticed that fumes from making nitroglycerin caused tremendous headaches for the workers who inhaled it. Because the blood vessels would dilate and cause a throbbing headache.

However, the workers who had heart disease and suffered from angina felt no chest and arm pain on the days they worked in the factory. Instead, on the weekend when they were at home and away from the dynamite factory, their chest pains came back.

The local doctors discovered that nitroglycerin is a vasodilator. It dilates the blood vessels and boosts blood flow to the heart, preventing them from experiencing cardiac pain.

The thing is this, the mechanism of action of nitroglycerin as a vasodilator remained unknown for over 100 years until Lou’s laboratory figured it out.

They discovered that nitroglycerin is metabolized and converted in our bodies and in our arteries into a chemical called nitric oxide (NO). And it was NO that was responsible for vasodilation (the widening of the blood vessels) which happens when the smooth muscles of the arteries relax.

We discovered that nitric oxide is the vasodilator.

And from that data, Lou pursued the question of whether nitric oxide is naturally produced in our bodies. Finally, in 1986, their laboratory proved that human arteries actually produce NO.

“It was that discovery–that humans can produce NO and produce it for the purpose of protecting the cardiovascular system–that’s the reason I was invited to Stockholm to accept a Nobel Prize,” Lou shares.

The Science Community

Tristan mentions to Lou something he noticed while reading his book. During the time Lou found something from his research that he was unsure of, he called Dr. John Vane to run the finding by him. Tristan says he found it surprising in a good way.

Tristan explained that he primarily interviews business owners and entrepreneurs, and that in the business environment, it is typical to feel pressured to handle a problem you are unsure about on your own. It is rare to run to a fellow professional to consult about your doubts, Tristan shared.

Lou recounts his consultation with Dr. Vane.

Dr. John Vane was a brilliant pharmacologist. He was extremely knowledgeable about the action of substances in the body. He also found other molecules created in human bodies, namely prostaglandins.

Dr. Vane's experiments demonstrated that the production of prostaglandins by the human body causes headaches, fever, and pain. He also mentioned that aspirin is a medicine that alleviates those three symptoms, and he hypothesized that aspirin's function in the body might be suppressing the creation of prostaglandins, which alleviates headaches, fever, and pain.

He found the mechanism and action of aspirin as a medication after a month or two of conducting the crucial experiments to prove his hypothesis. And for that finding, he was awarded the Nobel Prize in medicine in 1983.

So, when Lou came across something similar in his own research, he visited Dr. Vane, who had previously demonstrated his expertise in a comparable study. Dr. Vane provided him with advice on how to approach Lou's research question.

“You have to have some certain facts in the back of your head, but you also have to think ahead, think outside of the box, and go where other people have not gone before. Don’t follow in the footsteps of others. Create your own footsteps, which of course, is more difficult to do,” Lou says. “But that’s what he [Dr. John Vane] did. He made a great discovery and got the Nobel Prize. So, I worshiped him for the great scientist he is.”

And when Lou went to Stockholm to receive his Nobel prize, Dr. Vane was there on the stage with him.

Unlike in the business world, where competition is fierce, and professionals tend to guard their secrets and strategies more closely, the science community is more collaborative.

“Science is something that is shared by everyone. That is why it is important, when people do science, that they publish it in journals, so other scientists can read,” Lou says.

Lou shares that from personal experience, not one scientist who was ever recognized or awarded in any prestigious awarding ceremonies or grants, ever made it there because they did the work alone.

Not even Watson and Crick, famous for discovering the double helix structure of the human DNA, managed to get to their discoveries without the help of other people.

“I actually had the great opportunity of working with six or seven other prominent investigators who had not yet won their Nobel Prize, but I went to them because I needed to know more from their expertise in order to help me answer questions in my field. And I did not hesitate,” Lou shares.

“I mean, I’m not going to be ashamed to go to someone and ask them how to do something. I can’t know everything. The things I didn’t know, I went to the experts and asked them how to do it,” he admits. “And you know what I found? Not a single scientist turned me down. Everyone wanted to help me answer my question.”

“Because of all of their help I was fortunate enough to be invited to go to Stockholm,” said Lou. “I did not do it by myself.”

How important is the crowd that you continually surround yourself with to your success?

Lou laughs as he tells the anecdote about how he collaborated with six or seven science investigators for the research that won him a Nobel. During the time of working together, these scientists still didn’t have a Nobel prize.

“You go and see someone, you know they have a good laboratory and did some great research, you ask them if they could help my people do these certain experiments. Then we do the experiments and they work. It worked because that individual helped us,” Lou laughs.

“But you know what the thing is though? A few years later, you read in the newspaper or hear on the news on TV or radio, that the person that helped you was just awarded the Nobel prize. That happened to me seven times,” he says.

And when he discovered that the human bodies produce NO as a signaling chemical of the cardiovascular system, he felt pressured to win a Nobel because his peers teased him about it.

“And the day came, and I was so happy I got the prize for one important reason: no more pressure,” Lou said, laughing.

How did it feel when you got the news?

“It was a great feeling,” Lou admits.

He admits that, like any other scientist, conducting research experiments was difficult and exhausting. They enjoy what they do, and the discovery itself is rewarding enough, but everyone wants to be recognized for their accomplishments.

“I mean, there’s no individual out there who doesn’t want to be rewarded,” Lou says.

He admits that he wants to be rewarded as a teacher, and the reward for him is when his students rate his course as the number one course in medical school.

But for research, he finds recognition from his colleagues rewarding, which is what the Nobel prize is for.

From Explosives to Erections: The Story of Viagra

What began as a passion with fireworks and a desire to make dynamite led to the discovery of nitric oxide as a [naturally occurring] vasodilator. This discovery not only earned Dr. Lou Ignarro a Nobel Prize, but it also allowed him to make another significant contribution to the world of medicine and pharmacology.

It began with a question from Jake Rajfer: “Lou, do you know what causes a penile erection?”

“It’s really funny. When I wrote that line, the editor from my publisher said, ‘I don’t know if you should say that in the book, that’s too crude.’ And I said, ‘That stays or I look for a new publisher.’”

But what Jake Rajfer meant when he asked that question was “What is the mechanism of a penile erection?”

They discovered the answer in 1990, but before that, the physiology of what causes an erection was not known.

Every organ in the body has nerves and the nerves attach to an organ, and every nerve releases a chemical called a neurotransmitter. Neurotransmitters in the brain and periphery were well known. But the neurotransmitter released from the nerves attached to the erectile tissue in the penis was unknown.

And because it was not known, the medical community had no idea what causes impotence or erectile dysfunction. How can they know what causes impotence if they don’t know what causes an erection in the first place?

He entertained the idea that NO might be the answer, but since NO is a gas, Lou thought initially that it probably was not the case.

After visiting the library to look up the nerves attached to the erectile tissue, he remembered his friend in England studying similar nerves found in the brain. According to this researcher’s findings, the nerves in certain regions of the brain release NO.

It got Lou thinking that if the nerves in the brain can release NO, perhaps nerves in the body's periphery, such as those leading to the penis, can as well.

Erection occurs when there is increased blood flow in the arteries of the penis. And what does NO do? It is a vasodilator that widens the arteries so that the blood vessels become engorged with blood. The erectile tissue is filled up with blood because the arteries are dilated properly.

After he and Jake Rajfer did the necessary experiments, they discovered that the neurotransmitter responsible for penile erection was indeed nitric oxide.

Lou published the findings in a very prestigious journal called the New England Journal of Medicine, and the paper caught the attention of the world, including Pfizer, which is one of the world’s largest biopharmaceutical companies. Pfizer followed their research and discovered sildenafil citrate, a drug that works by increasing the action of NO in the penis.

That drug is called Viagra.

Does nitric oxide have a big play in adrenaline?

It is important to remember that NO is not the only vasodilator in the body.

Adrenaline (also known as epinephrine), is also a vasodilator. It is released from the adrenal glands and plays an important role when you are excited, running, or during fight-or-flight situations. It is a fast-acting vasodilator necessary for emergency situations.

“NO is a more slow-acting vasodilator. And that’s what makes sense in penile erection. You don’t have to break a record in getting an erection in the score of seconds. Just slow development,” Lou laughs.

“If adrenaline were the neurotransmitter [responsible for penile erection] it could kill you,” he says.

What’s going on now for Lou Ignarro?

Lou has been enjoying retirement for six to seven years now, but his curiosity is far from waning. Although he is not actively researching anymore, he is still giving lectures regarding his field.

When asked what he would be researching right now if he wasn’t retired, Lou admits that he is interested in studying the possibilities of NO to help patients suffering from dementia or Alzheimer’s disease. Studies showed that people with dementia have reduced levels of NO in certain regions of the brain that are involved in memory.

He is interested in studies made by companies trying to develop drugs that would stimulate NO formation or increase its action in those regions of the brain to help people with dementia.

At the same time, he also wants to discover the reason behind NO production in other areas of the brain, and why our body finds it necessary to produce nitric oxide in those neurological regions.

“The NO is in the brain for a reason, it is not just sitting there doing nothing. I believe it’s got to be doing so many different things that are important for our health and we just don’t know yet,” Lou says.

What can we do to enhance NO production in the body?

According to Lou, it boils down to two things: good nutrition and physical activity. Especially when they go together.

What are you reading right now?

Lou reads scientific journals, although he doesn’t follow them as much as before he retired. He also enjoys reading novels by James Patterson, especially the stories with Alex Cross.

Since retiring, he makes it a point to relax, read stuff that isn’t necessarily scientific literature, and watch more TV. He enjoys watching Netflix with a glass of good wine these days.

Final thoughts from Lou Ignarro

“Google the advantages of NO to your body. And although you might not want to change your diet or do physical activities, keep looking for evidence of what specific foods and exercise can do to your NO levels, and you’ll see some incredibly tasty food that can boost NO, instead of junk food,” he advises.

“I think you will really benefit from it,” Lou says.

DISCLAIMER: The people interviewed are well-trained experts and highly skilled in their areas of practice. They take many safety precautions prior to attempting the activities described. The activities or research discussed in these podcasts should not be attempted without qualified supervision and training with professionals.

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