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The Great Connection

Cholesterol was first discovered in gallstones in 1784.  Obviously the guy didn’t make it.  It wasn’t until the early 20th century that a connection to cholesterol and heart disease was seen.  In fact it was a Russian pathologist who fed pure cholesterol to rabbits and found it led to their aortas filling with cholesterol plaque in 1913 (Granted the cholesterol in the rabbits diet was 1000’s of times higher than what a human would eat – wonder if my kids aortas are full of sugar?).  Two decades later,  a Norwegian doctor observed that several families with genetic cholesterol problems had heart attacks at very young ages.  Maybe, he thought, there was a connection between heart disease and cholesterol levels in the blood?

The Great Association

It was a scientist at the University of California at Berkeley who discovered how to measure the different types of cholesterol in the blood and showed that the higher the LDL cholesterol the more likely one was to have a heart attack.  He also showed something good.  The higher the blood HDL level the lower the chances of a heart attack.  But scientists wondered “how was cholesterol made?”  

The Great Science

In 1964 the Nobel prize in medicine was given to two biochemists who determined the steps the body takes to make cholesterol. The question then became – if we stop the body from making cholesterol will that prevent heart attacks?  Here’s the chemical pathway for one of the most important cholesterol making steps (all you had to do was write that out before 1964 and you too could have won the Nobel prize):

The Great Biochemist

Akiro Endo was born in Akita, Japan – a small rural, farming community in 1933.  His hero was his grandfather who had an interest in medicine.  At age 10 Akiro became fascinated with molds and mushrooms and dreamt of studying them as a scientist.  His heroes became Hideyo Noguchi who had studied syphylis and yellow fever in America as well as the Scottish scientist-physician Alexander Fleming who discovered penicillin (That’s a great story).  Akiro became a brilliant biochemist and began working in Tokyo for Sankyo Research Laboratories where he was told he could work on a project of his choosing.  He began looking for a mold or mushroom that made something to stop bacteria from making cholesterol in hopes of finding a new antibiotic like Alexander Fleming.

The Great Search    

After searching through 3,800 strains of fungus, Akiro found a substance that stopped cholesterol from being made.  Unfortunately it gave rats kidney failure.  He stopped pursuing this substance because, let’s face it, who would want to be sued by a bunch of rats?  In the end it gave him motivation to continue his search.

The Great Search Continues

In 1972, Akiro bought some rice from a grain shop in Kyoto Japan – the rice contained a mold called Penicillium cirtinum.  The compound they discovered from the mold completely stopped the production of cholesterol and didn’t cause kidney failure in rats.  Better yet – now no rat lawyers to worry about!  As Akiro said  it “seemed to be a wonderful gift from nature.”

The Great Outcome

In February of 1978, an 18 year old girl with a genetic cholesterol problem in Osaka, Japan was the first to receive this newly discovered substance called “Compactin.”  It dropped her cholesterol significantly.  Soon five others were tried on the medication in Japan with a drop in cholesterol of 30%.

The Great Race

Though effective, Compactin experiments were stopped when it was noted to cause lymphoma in dogs (the dogs received 200 x’s the normal human dose).  Scientists throughout the world began the hunt for similar compounds and in September 1987 the drug company Merck won the race for the safe and effective drug to lower cholesterol.  This medicine was called Lovastatin (Note that all statin drugs end in “statin.”).  Now there are 7 different statins approved for use in the US.

Statins Are Commonly Taken and Safe

Statins are now taken by 36 million people in the United States.  That’s about 1 in every 10 Americans.  The most common side effect is muscle aching or cramping.  Changing the statin medication usually stops this side effect.  They do not cause dementia, cancer, or cataracts.