As an introduction to this article, we call to mind that at the beginning of the 20th century, an atheromatous plaque was known to be responsible for clogging the coronary arteries.

We recall as well that in the late 1900s a significant discovery had been made, identifying the rupture of the atheromatous plaque as one of the causes of heart attacks. 

The medical community was also aware that cholesterol was at the origin of this plaque and that, despite the 2 treatments available at the time, no one knew what the future might bring. The first procedure meant taking a vein from another body part and bridging it over the obstructed area; the alternative was crushing the plaque with a tiny balloon. 

 

Akira   

This is when Akira Endō comes into play. Born in Japan in November 1933, his story begins with a real-life event that happened in his youth as his grandfather was introducing him to the elements of nature. A plant, or rather a mushroom, fascinated them. That particular mushroom could kill flies but was harmless to humans. What he learned that day was to play a decisive role in his future.

In Japan, Akira Endō worked for a pharmaceutical product company, Sankyo, located in Tokyo. While there, his first works impressed and made it possible for him to go to New York and work at the Albert Einstein Medical College; his sojourn lasted 2 years.

 

Lipids are his main field of interest

Akira Endō’s research studies bear on lipid or fat metabolism.

At the time, the left internal mammary artery, located under the thorax, was used in coronary bypass surgery rather than taking a vein from the leg or another body part. This artery is little affected by atherogenesis, a lumpy fat deposit on its inner wall.

Because of his finding, he develops a particular interest in atheromatous plaque. He wants to search for a way of blocking cholesterol buildup inside arteries.

 

Cholesterol sources

Part of the cholesterol found in our blood comes from the food we eat, however, two-thirds of it is fabricated in the liver. Cholesterol becomes the focal point of Akira Endō’s efforts.        

 

A return to nature                

He remembers that mushroom of yore and hypothesizes that some substances are potentially able to kill while inhibiting cholesterol buildup.

Akira Endō uses multiple mushroom varieties in his research, each one with the same frustrating results. However, disappointments fuel his hopes.

When looking for a needle in a haystack, one may find the farmer's daughter. This is exactly what happened! He discovers a member of the statin family, that exceptional coronary disease medication.

 

Penicillium

Strangely enough, this statin comes from a mushroom called Penicillium. Penicillin, discovered way before the start of the Second World War and manufactured right after it ended, had demoted various infections from being the leading causes of death.    

Because the number of deaths had decreased due to the use of antibiotics, coronary heart disease was now at the top of the grim death list.

Statins are the penicillin of the heart and, after a while, they succeeded in removing coronary disease from its unenviable standing as the worldwide leading cause of mortality.

 

A new therapy that raises very little interest

In the 70s, Endo calls his first product Mevastatin. This medication lowers bad cholesterol or LDL from 20 to 35%.

In 1974, Sankyo obtains copyrights on Mevastatin and Endo publishes the data of his research in 1976. During that same year, he talks about his findings at the International Symposium on Drugs Affecting Lipid Metabolism, in Philadelphia. Very few participants show interest.

His conviction is what keeps him going   

Sankyo fires Endo, but he carries on with his research just the same.

In Sankyo's close vicinity, Akira Yamamoto, a doctor, treats a group of patients whose cholesterol levels are abnormally high due to a rare hereditary condition called family hypercholesterolemia. Dr. Yamamoto asked Endo to give him some of his medication. After proper dosage adjustments, the results were astonishing.

 

A shot in the dark 

Endō asks his former employer, Sankyo, to set up and head a clinical study to document this decrease in cholesterol levels, which had never happened before.   Sankyo agrees to do so, however, it excludes Endō entirely from the study and fires him once more, this time permanently.

Sankyo was to never produce or market this discovery.

 

Merck Pharmaceutical shows interest

However, all is not lost. Scientist and physician, Roy Vagelos, the brilliant son of a Greek immigrant from a modest background, had just been promoted as Merck's president. He was looking for a revolutionary new medical product. 

Mr. Vagelos is well aware that cholesterol is manufactured in the liver, and that coronary disease heads the list of fatal diseases. He sees much potential in Akira Endō's research works. 

Sometime later, Merck obtains Endō's working papers and all rights to his subsequent research endeavors. On the other hand, Sankyo still owned Mevastatin’s production rights.

History would reveal later on that Endō developed Lovastatin, a product very similar to Mevastatin.

 

On the way to a primordial therapy

Merck did not stop after its first success and went on with its research in the world of statins.

In April 1994, some 18 years after Endo's presentation in Philadelphia, an important Scandinavian study is published: “The Scandinavian Simvastatin Survival Study (45)”, which is based on the use of Simvastatin, a close relative of Lovastatin, by patients with coronary artery disease and high cholesterol levels. 

According to the above study, after 5 years on this medication, those patients’ cholesterol levels are 35% lower than what they used to be. Hence, a 42% decrease in heart attacks, compared to a placebo effect, eventually.

 

Mr. Endō

Anecdote: in 1994, Endo sees his doctor because his cholesterol level is high. The doctor tells him not to worry because an excellent therapy exists for his problem!

Today, Akira Endō holds several awards for his work. In 2008, he received the prestigious Lasker-DeBakey Clinical Medical Research Award for his overall research work. Several such laureates have gone on to receive the Nobel Prize for work in their own domains. To be continued…