Hear
Coming from Japan, there was something that surprised young Akira Endo when he lived in New York: “the large number of older and overweight people.”.
It was the 60s, he was studying at the Albert Einstein School of Medicine and his house was in the Bronx. There, he noticed that “there were many older couples who lived alone and I often saw ambulances taking an elderly person who had suffered a heart attack to the hospital.” What perhaps he did not imagine is that, years later, he would be key in helping other people not suffer the same thing.
Endo was the pioneer in the development of drugs that saved the lives of millions of people around the world. “The discovery of statins by Dr. Endo in 1973 ranks as the second most important advance of the 20th century, after the discovery of penicillin by Dr. Alexander Fleming in 1928,” he told BBC World Joseph C. Wu, president of the American Heart Association and professor of medicine and radiology at Stanford University.
“It is amazing that the man who began the process of discovering how to deal with the problem of cholesterol and provided a treatment that benefited and saved the lives of many, many millions of people, will never win the (Nobel) prize”said Professor Bryan Williams, scientific and medical director of the British Heart Foundation. “I think it’s a shame,” he told the BBC. This is the story of Dr. Endo, who died on June 5, and his extraordinary contribution to medicine.
The memories of the scientist with whom we began this note were written in an article published in 2008 in Nature Medicine and titled: “A gift from nature: the birth of the statins” (“A gift from nature: the birth of statins”). In it he also said that he had been born in a rural area of Japan and that his family had dedicated themselves to agriculture.
It was his grandfather, who had an inclination for medicine and science, who opened the door to that world for him. “Thanks to his influence, at the age of 8, I dreamed of becoming a scientist.”
Since he was a child he was interested in mushrooms. This is what he said in another text he wrote in 2006, when the Japan Science and Technology Foundation awarded him the prestigious Japan Prize. After reading Fleming’s autobiography in college, the path to follow was very clear: “At that time, I decided that I also wanted to undertake research that used mold”.
When he was studying organic chemistry, he realized that both universities and pharmaceutical companies were doing studies in the area of antibiotics. Endo had already been “deeply” marked by the life-saving power of antibiotics.
After graduating, he worked in a pharmaceutical company and his studies there, on an enzyme, allowed him to obtain a doctorate in 1966. “At that time, I became interested in the biosynthesis of cholesterol.”
That interest took him to New York, where – at the Albert Einstein School of Medicine – he focused on another enzyme, one that was involved in the biosynthesis of lipopolysaccharide, which is one of the components of the membranes that surround a type of bacteria. .
He returned to Japan, where he worked at Sankyo Laboratories. There he focused on creating a drug that reduce the amount of cholesterol produced by the body. His hypothesis was that if a key enzyme in cholesterol formation was inhibited, it would help lower cholesterol levels. To block it, he thought of an antibiotic that was produced by a fungus.
He studied 6,000 strains and, in 1973, found compactin, “a substance that exerts a powerful inhibitory action on enzymes.” Together with his colleagues, he found her in the mushroom Penicillium citrinum, which he saw growing in the rice. “That was the beginning of statins.“, wrote.
Although this substance did not lower cholesterol in rats and its development as a medicine could not begin, Endo was not discouraged. Tests were carried out on other animals, including dogs and monkeys, in whom it did cause a significant reduction in cholesterol.
However, problems related to the toxicity of tests in dogs once again slowed the development of the drug. The truth is The discovery of compactin boosted other pharmaceutical companies to look for statins. Endo said that at the end of 1978, the Merck company, in the United States, had discovered a second statin: lovastatin, “which was very similar to compactin.”
In fact, he explained, he had also found a substance similar to that when he worked at the Tokyo University of Agriculture and Technology. In 1980, Merck began clinical trials and, after receiving approval from the Food and Drug Administration (FDA), In 1987, he introduced the first commercial statin. Sankyo would also develop a drug that turned out to be a “partially modified compactin” and went on sale in 1989.
“Since then, Professor Endo’s remarkable discoveries have led to the commercialization of six more statins”, highlighted the European Society of Cardiology in 2021, when it gave him an award.
“The road to the discovery of statins was long and challenging, but thanks to Professor Endo’s perseverance, these drugs are now used to prevent cardiovascular events in tens of millions of people around the world every day.”
Professor Wu not only highlighted Endo’s ingenuity and dedication, but also his humility. The scientist obtained many international recognitions, inside and outside the scientific field. One of his favorites was to be known as the one who found “penicillin for cholesterol”says the Washington Post.
He won Lasker Award, commonly called the American Nobel. After learning of his death, at the age of 90, the organization that presented him recalled that his discovery represented “a revolution in the prevention and treatment of coronary heart diseases.”
Williams stated that “there are very few treatments in medicine that have emerged in recent years that have had such an extraordinary impact.” Patricia Guillem, professor of Epidemiology, Public Health and Preventive Medicine at the European University of Valencia, agrees with this. “They remain in the top rankings, they have not been able to be exiled for another medication,” he told BBC World. And he added: “That is good because it means that they work and that the adverse effects are, as far as possible, controllable.”
Statins are among the most prescribed drugs worldwide: Johns Hopkins Medicine estimates that more of 200 million people around the world They take them for heart health.
Our body produces cholesterol, a fatty substance that is transported in the blood and is vital for producing estrogen, testosterone, vitamin D, among other essential compounds. There are two main types of cholesterol: LDL (low-density lipoprotein), known as “bad” cholesterol, and HDL (high-density lipoproteins), known as the “good” one. We all need that to stay healthy.
On the contrary, high levels of “bad” cholesterol are related to diseases such as arteriosclerosis, as it can lead to the formation of plaque that sticks to the walls of the arteries and, when accumulated, obstruct blood flow. That increases the risk of heart attack and stroke.
“The function of the statin is to block an enzyme within the liver that prevents that organ from synthesizing cholesterol and releasing it into the bloodstream,” said Guillem. What the drug does is lower the levels of “bad” cholesterol and helps raise the “good” cholesterol.
Although statins are one of the most common drugs among people over 65 years of age, they are also used in younger patients. “There are people who genetically have familial hypercholesterolemia and they may be young. They also prescribe statins to control cholesterol.”
Familial hypercholesterolemia is a disease that clinically manifests from birth. It is caused by a defect in chromosome 19, which causes the body to be unable to eliminate “bad” cholesterol from the blood at the liver level. The medication is also key when a first cardiovascular event has been suffered, as the expert explained.
“Imagine a patient who suffered a heart attack that was not fulminant, but was an obstruction with an atheroma of a vein of the heart.”
“As happens with earthquakes, in which there are later aftershocks that lead to a second earthquake, heart attacks work the same: sometimes they precede other infarctions that can affect larger veins and, of course, have greater consequences.”
“People forget that when we talk about cardiovascular events it is not only the heart but also the peripheral venous circulation and also the cerebral circulation.” In this way, statins also help reduce strokes.
Guillen explained that apart from their main function, there are many scientific research teams that have tried to use statins in trials to demonstrate that they also have applications in diseases related to cognitive impairment, bacterial sepsis and in certain types of cancer.
“I think it is very important that a medication as common as the statin has other possible therapeutic indications”, he pointed. “Because sometimes we are waiting to find new medications and old drugs that have more applications than we had initially discovered can go unnoticed.”
As with other medicines, the professor indicated, with statins, regular checks must be made to ensure that the medicine does not produce adverse effects or any parallel damage.
According to the World Health Organization, “Cardiovascular diseases are the leading cause of death in the world and, according to estimates, claim 17.9 million lives each year.”. To combat them, it is essential to eat a balanced diet, low in saturated fats, avoid tobacco and harmful alcohol consumption, and exercise regularly.
In fact, there are cases in which improvements in diet and physical activity manage to reduce cholesterol levels. Therefore, it is key to consult with your doctor and not self-medicate.
BBC World
