[Ed. Note: Dr. KSS writes about medical topics and biotech stocks for the Irregulars. He has agreed to our trading restrictions, and his thoughts and words are his own. Enjoy!]
Any discussion of cholesterol immediately turns Brobdingnagian, such are the extremes in question.
Statins, which lower LDL cholesterol, are bombastically the best-selling drugs of all time. They’ve left a Paul Bunyan-size footprint in medicine. But they are hardly ancient and hoary. The prototype statin was discovered by Akira Endo, PhD, in 1970 while he worked for Japanese chemical giant Sankyo. Despite the Saganesque billions and billions of dollars, euros and yen his discoveries fetch every year, Endo has never seen even a nickel of the profits. Endo has been mildly honored, while those acting on principles he first introduced to the world, such as Brown and Goldstein, have gone on to Nobel notoriety.
Endo began with a hunch: cholesterol is an elemental life-cycle molecule for many organisms, and so maybe other organisms had stumbled onto ways to knock the cholesterol underpinnings out from potential invading pathogens as a safety measure. The fungi, for example, are famous sources of antibiotics that snuff bacteria. Maybe fungi had also devised a way to attack cholesterol production as a defense? Fungi have ergosterol rather than cholesterol in their cell membranes, and so could poison cholesterol-making machinery at no harm to themselves.
I’ve lived in Asia, and so have often searched for analogies to help Westerners understand how sharply Asian cultures differ from each other. One archetype is a thought exercise in which a representative of an Asian nation is given an uncut loaf of bread and asked to slice it in a way that reflects his/her culture. A Thai person, for example, would slice it ornately, lovingly, and so beautifully you’d be reluctant to eat it. A Vietnamese person would have it all sliced for you by the time you are finished explaining what you want. A Japanese person would devise a way to make bread slices that are but a few molecules thick. No culture has the fixity of purpose and ruthless attention to microscopic painstaking detail that the Japanese have. Endo went after this issue like a good Japanese scientist, and personally screened 6,000 individual compounds that had been purified from various fungi for one that could inhibit cholesterol synthesis. He didn’t have a high-throughput nanosensor-based microchip array to do it for him. He rolled up sleeves, told his wife not to wait up, and did it the old fashioned way.
Endo’s work led to identification of monacolin K, later dubbed lovastatin, the first such agent used as a drug, in certain oyster mushrooms and other species of fungi. To this day, many statins used as drugs are purified from fermenting yeast rather than synthesized. Although the fungus-derived statins are natural products, somehow patent protection on them was finagled (now lapsed). Meanwhile, in its most legendary abuse of power, the FDA in 1998 tried to ban red yeast rice because it naturally contains lovastatin, made by the yeast. All statins are inhibitors of a liver enzyme called hydroxymethylglutaryl CoA reductase. 85-90 per cent of the body’s total cholesterol burden is made in liver, which is why the weak anti-cholesterol agent ezetimibe, which only blocks absorption of dietary cholesterol, has little effect and really does not warrant clinical use as it is not cost-effective.
The Brobdingnagian thing, again: no topic incites more vigorous discussion, more one-off hyperbole, than statins. Character X emerges from stage left to say he knows someone who lived to be 100, ate bacon and fried eggs for breakfast every morning, and never took any pills. Mrs. Y flies out of stage right to say that one dose was all it took…..a statin near