Nobel for chemistry rewards decades of molecular work

The Washington Post

Two Americans and a Japanese won the Nobel Prize in Chemistry on Wednesday for devising innovative ways to build molecules without creating a mirror-image opposite, a principle used today in making hundreds of drugs to treat conditions ranging from high cholesterol to Parkinson’s disease.

The Royal Swedish Academy of Sciences said William Knowles, 84, a retired chemist from the Monsanto Co. of St. Louis, will share half the $943,000 prize with Ryoji Noyori, 63, of Japan’s Nagoya University. The other half will go to K. Barry Sharpless, 60, of the Scripps Research Institute in La Jolla, Calif.

The three were honored for their research on chirality, or "handedness," which describes how organic molecules often appear in two forms, one a mirror image of the other, much as a person’s two hands mirror each other.

In nature, one form often dominates, so human cells naturally bind to one form of a molecule over the other, while the other form is ignored or may even be harmful. Handedness is what caused the thalidomide catastrophe in the late 1950s: One molecular form prevented nausea in pregnant women, while the other could cause serious defects in the fetus.

Working independently between the 1960s and 1980s, the three Nobelists developed catalysts for chemical reactions designed to create high concentrations of one form of the molecule while producing only minuscule quantities of the undesirable mirror image.

"People had been trying to do this for a long time, but they had attained only very minor efficiencies," said University of Pennsylvania chemist Amos Smith, editor of the journal Organic Letters. "What these guys were able to do is raise the ratios very high — to 90 or 95 percent (of one form), even above 99 percent."

The principles used in the Nobelists’ research have become so entrenched in today’s pharmaceutical production that the Food and Drug Administration requires that companies make only one molecular form.

Chiral drugs today include everything from L-DOPA, a treatment for Parkinson’s disease, to the so-called statin drugs for cholesterol, beta-blockers for heart function and the protease inhibitors for AIDs. In all, drug companies in 2000 sold $133 billion in chiral drugs.