I am constantly amazed at the role of luck (and an astute observer) in scientific advancement. You will be surprised how researchers discovered nitroglycerin, an important coronary artery disease management drug.

I’ll explore the remarkable nitrate discovery story. Then, I look forward to examining the contributions of Dr. Murad. We’ll end with five top tips for reducing your chances of suffering from cardiovascular disease.

“Diseases desperate grown,
By desperate appliance are relieved,
Or not at all.”

― William Shakespeare, Hamlet

Museums and Medicine

You might wonder why I notice connections such as heart medicines and dynamite.

My dear mother had something to do with my inclinations. When I was young, she took me to a museum every month. New York’s Museum of Modern Art, the Metropolitan Museum of Art, and the Yale Gallery.

When I visited New York last week, my first destination? The Whitney Museum in Manhattan’s Meatpacking District.

Why do I bring this up? My former school, Yale School of Medicine (USA), has an observational skills training workshop for first-year medical students.

The workshop is an exercise in visual training that allows students to look at something foreign to them early in their medical careers ‒for instance, an 18th-century British painting‒and extract the relevant information.

Why Yale Medical Students Go to a Museum

Here’s course creator Irwin M. Braverman, M.D. ’55, professor emeritus of dermatology:

“[Looking at art works] is a far cry from what we had,” said Braverman, recalling his medical education. “We were taught to look for patterns that were already known to exist.”

Shadows on an X-ray are this kind of problem. But what happens when a doctor encounters a situation they were not exposed to in medical school? They have no pattern on which to fall back.

According to Braverman, it takes about ten years to develop the skills to solve medical puzzles, and he wanted to give his students a head start.

“In essence, [examining art] is a physical examination of a patient,” said Braverman. The exhibit hall is the examination room, and the painting becomes the patient.

You Should Consider Going to a Museum

Examining great works of art teaches us observational skills. At Yale, students have 15 minutes to observe an assigned painting individually and gather as much detail as possible.

Based on their observations, the medical students discuss what may occur in each painting as a group.

Braverman explains that 18th- and 19th-century British paintings are perfect for this exercise because many offer stories about a real historical event. However, similar to patients with unexplained symptoms, they often contain ambiguous or contradictory information.

Trekking to your local museum or gallery might improve your observational skills.

Looking at paintings, sculptures, and performance art slows me down. It forces me to stand (or sit, a phenomenon more necessary as I age) and observe.

This year, for the first time, Braverman replaced the standard post-workshop evaluation with a specific question: what have you learned about yourself as an observer?

Nearly every medical student explained that, though they considered themselves adequate observers before the art workshop, they realized they previously looked at things superficially.

The course helped them learn to look at the world and their patients more in-depth.

Finally, I think of my museum times as ones of mindfulness. (And, it’s easier than vinyasa flow yoga for me.)

The Remarkable Discovery of Nitroglycerin

Have you heard of nitroglycerin? Nitroglycerin prevents angina (chest pain) caused by coronary artery disease.

This medicine is also used to relieve an angina attack that is already occurring.

Nitroglycerin belongs to a class of drugs known as nitrates. Angina happens when the heart muscle is not getting enough blood.

The drug works by relaxing and widening blood vessels to allow blood to flow more easily to the heart. Nitroglycerin will not relieve chest pain once it occurs.

It is also not intended to be taken just before physical activities (such as exercise or sexual activity) to prevent chest pain. Other medications may be needed in these situations.

The Nobel Prize

What do you think of when I mention Aldred Nobel? My mind immediately goes to the Nobel Prize.

I’m speechless! — Maria Ressa’s reaction when Olav Njølstad, Secretary of the Norwegian Nobel Committee, awarded her the 2021 Nobel Peace Prize for her “efforts to safeguard freedom of expression, which is a precondition for democracy and lasting peace.”

For over a century, Nobel Prizes have recognized extraordinary human achievements, ranging from literature to science.

The Nobel Prize is gifted “to the person who shall have done the most or the best work for fraternity between nations, the abolition or reduction of standing armies and for the holding and promotion of peace congresses,” according to the last will of founder Alfred Nobel.

The 2023 Nobel Prize announcements will occur from October 2nd through the 9th.

Alfred Nobel, Dynamite, and More

But our tale has a dark side, including death and mayhem. Let me back up a bit to talk about Alfred Nobel’s father.

Immanuel Nobel created the first truly usable sea mines on behalf of the Russian Czar. This development occurred in the mid-19th century during the Crimean War.

Alfred Nobel developed dynamite. He did not plan on its being used in war. Of course, you know the rest of the story.

Dynamite was soon used in the Franco-Prussian War. The Prussians used it first, followed by the French.

Alfred Nobel, Merchant of Death?

While many associate Nobel with pacificism, whether he approved dynamite’s military use is unclear.

In 1888, Alfred Nobel’s brother Ludvig died. A journalist erred and printed Alfred’s obituary. The piece scorned the living brother as a man who made millions through the deaths of others.

A French newspaper wrote, “Le marchand de la mort est mort,” or “The merchant of death is dead.” The obituary described Nobel as a man “who became rich by finding ways to kill more people faster than ever before.”

Stunned by what he read, Nobel was determined to improve his legacy. One year before he died in 1896, Nobel signed his last will, which set aside most of his vast estate to establish the five Nobel Prizes, including one awarded for pursuing peace.

Nitroglycerin Discovery

Let’s return to the strange story of heart and erectile dysfunction medicines. First, did you know that nitrate medications can trigger airport bomb detection scanners?

Nitrate-containing drugs also get the attention of explosive-sniffing dogs, a reminder of the origins of this extremely useful medication.

Ascanio Sobrero in Turin discovered nitroglycerin in 1847, following work with Theophile-Jules Pelouze.

Alfred Nobel joined Pelouze in 1851 and recognized the potential of nitroglycerin. Nobel began manufacturing the substance in Sweden, overcoming handling problems with his patent detonator.

Interestingly, Nobel suffered acutely from angina (chest pain) and refused nitroglycerin as a treatment.

Nitroglycerin in Medicine: Innovation from Tragedy

Today, nitroglycerin is a drug that dilates blood vessels.

The potent medicine is typically administered under the tongue to relieve and prevent angina (chest pain caused by reduced blood flow to the heart) attacks.

Dr. Ferid (“Fred”) Murad (1936–2023), a pharmacologist who shared a Nobel Prize in 1998 for discovering nitric oxide — an air pollutant and byproduct of nitroglycerin— played a key role in relaxing blood vessels.

Dr. Murad’s discovery dates to the 1970s, when he began studying nitroglycerin, the substance that Alfred Nobel, the namesake of the annual awards given in medicine and other disciplines, used to invent dynamite in 1867.

Our story of nitroglycerin as a medicine goes back to the 1900s. Alfred Nobel’s factory workers noticed a curious side effect of the explosive substance.

The workers’ labor-induced chest pains disappeared when they inhaled nitroglycerin fumes inside the factory. Soon, doctors began trying it to remedy angina, high blood pressure, and other cardiovascular disorders.

Nitroglycerin became a common treatment for heart problems, but until Dr. Murad began studying it at the University of Virginia (USA), nobody understood how it worked.

Through elegant experiments, Dr. Murad discovered that nitroglycerin releases nitric oxide, which relaxes smooth muscle cells.

Nitric Oxide and Male Erectile Dysfunction

Dr. Murad’s discovery contributed to the development of Viagra, which helps produce erections by dilating blood vessels.

Viagra facilitates erections by increasing penile blood flow. Murad’s finding of the role of nitric oxide has also helped numerous premature babies (whose underdeveloped lungs need stimulation).

Dr. Murad died September 4th at his Menlo Park, California (USA) home. He was 86.

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The Urology department pilot study sought to analyze penile tissue of men who recovered from symptomatic COVID-19 infection and developed erectile dysfunction (ED) after the infection.

The small study evaluated penile tissue collected from four men scheduled for penile prosthesis surgery due to erectile dysfunction. Two men had a history of Covid-19 infection, and the other two men had no history of illness.

Covid-19 is known to cause widespread damage to blood vessels throughout the body. SARS-CoV-2 causes damage to the cell layer lining blood vessels called endothelial cells. Endothelial cells contain two components that SARS-CoV-2 needs to infect cells. The SARS-CoV-2 spike protein binds to specialized receptors called ACE-2 and enters cells containing an enzyme called TMPRSS-2. Blood vessels have a high number of both ACE-2 receptors and TMPRSS-2.

The Miami research team hypothesized that endothelial damage in penile tissue could be the cause of post-Covid-19 erectile dysfunction.

The researchers evaluated penile tissue collected from four men scheduled for penile prosthesis surgery to test the theory due to erectile dysfunction. Two of the men had a history of Covid-19 infection. One had a severe disease requiring hospitalization. One had a mild case. These two cases were compared to a control group of two men who had no history of infection.

The paper is titled, “COVID-19 Endothelial Dysfunction Can Cause Erectile Dysfunction: Histopathological, Immunohistochemical, and Ultrastructural Study of the Human Penis.“

Urologists took biopsies from an area of the penis called the corpus cavernosum. A variety of tests were performed to evaluate cellular changes in the tissue. Damage to the penile vascular from Covid-19 could explain new onset erectile dysfunction after infection.

The scientists used three techniques to test for the effects of Covid-19. Transmission electron microscopy (TEM), Immunohistochemistry staining (eNOS), and viral PCR testing.

Transmission electron microscopy (TEM) revealed the presence of viral particles in men with a history of Covid-19 infection.

Immunohistochemical staining showed dramatic changes in the penile tissue of men with a history of Covid-19.

The scientists were unable to detect SARS-CoV-2 through PCR testing. The study authors propose the lack of detection is due to a low viral load in the penis.

The sample size of this pilot study is quite small. The results are not meant to provide a definitive scientific answer regarding the effects of Covid-19 on male sexual function. This small pilot study is the first paper to demonstrate penile damage on a cellular level. Further research will be needed.

This paper may also help some men overcome vaccine hesitancy. A study in the American Journal of Men’s Health showed men are less likely to seek help for any medical condition. Data analysis by Kaiser Health showed a gender gap with Covid-19 vaccination. More women are getting vaccinated than men. A CNN poll found 57 percent of Republican men did not plan to get vaccinated against Covid-19.

This paper from The University Of Miami helps men understand the importance of preventing getting infected from Covid-19.

There are three FDA-approved vaccines for Covid-19. The two messenger RNA vaccines from Moderna and Pfizer offer 95% protection against Covid-19. The Covid-19 vaccines from Pfizer and Moderna use messenger RNA (mRNA). A single strand of mRNA delivers instructions to human cells to produce an antibody against the SARS-CoV-2 spike protein.

The Johnson and Johnson’s Janssen vaccine offers 72% protection against infection and 86% against severe disease. The Janssen vaccine uses Adenovirus 26 (AD26) as the vector to deliver DNA material into our cells to provoke an immune response.

The Moderna and Janssen vaccines are approved for those 18 years old and up. The Pfizer vaccine is approved starting at age 16.

All three vaccines are highly effective in preventing death.

This paper shows the Covid-19 vaccine may also protect men from erectile dysfunction.

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