1815

Cholesterol

François Poulletier de la Salle (1719–1788), Michel-Eugène Chevreul (1786–1889), Otto Paul Hermann Diels (1876–1954), Adolf Otto Reinhold Windaus (1876–1959), Heinrich Otto Wieland (1877–1957)

Cholesterol goes back a long way because it’s relatively easy to isolate in a pure form. French chemist François Poulletier de la Salle studied a human gallstone in 1769 and found that it seemed to be a single waxy substance. In 1815, fellow Frenchman Michel-Eugène Chevreul realized that the same material was found in many other sources of animal fat and named it cholesterine, pairing the Greek word chole (bile) with stereos (solid). Gallstones are still the purest natural source of cholesterol—if not exactly a convenient one—but it gradually became clear that it was found throughout the body. It’s a starting material for the steroid hormones and the main ingredient of bile from the gallbladder (which allows for the absorption of lipids and fat-soluble vitamins from food), but its most important role is as a key ingredient in every animal cell. It increases the flexibility of the lipid layers that make up the cell membrane, in sliding arrangements like liquid crystals. This allows cell-surface proteins to fit into the membrane with one face on the outside of the cell and one face on the inside, which lets them respond to signaling molecules from other parts of the body. Cholesterol has had bad press for its role in heart disease, but it is absolutely essential for human life.

Unraveling its structure took many years and strained the structure-determination methods of the time. It was not until 1932 that German chemist Adolf Windaus proposed the correct arrangement, common to all steroids: three six-membered rings and a five-membered one. He and Heinrich Wieland, among others, laid the foundations of steroid chemistry, took on much painstaking work in the pre-spectroscopy days. This meant observing what reactions an unknown compound could undergo, speculating on the product structures, and then trying to re-create those products through other routes to confirm (or complicate!) their hypotheses. Logic combined with knowledge and intuition was key. To a modern chemist, determining chemical structure by this method looks like an attempt to solve jigsaw puzzles in the dark, but instruments like NMR and mass spectrometry have turned the lights on for us.

Polarized light shines through a thin layer of pure cholesterol crystals.