Aspirin is now a century old, but until recently, no one had a clue how it worked. Biochemists Bill Smith, Dave Dewitt, and Mike Garavito found the clue to aspirin's mystery hidden in a cell protein called COX 1, where, among a sequence of some 600 amino acids, they located its precise target.
Smith explains the difficulty of their sleuthing; "It is impossible to unravel the entire amino acid sequence from a protein; they are too big. So we worked backwards through its DNA [ a molecule critical to life that serves as a code to other molecules.] After cracking the DNA, we could translate it into the amino acid structure." Garavito took the process further. He crystallized the protein in the presence of an aspirin-like substance and x-rayed it. The resulting three-dimensional picture not only mapped the entire protein structure but identified the exact point at which the drug knocked out inflammation and pain.
Building on this significant discovery, other scientists found COX 1's near twin, COX 2. Abnormal functioning of this protein shows up in 85 percent of all colon cancer. "Over the past ten years," says Smith, "researchers have found that taking aspirin or NSAIDs also reduces the incidence of colon cancer because these drugs interfere with the ability of COX 2 to function at exactly the same position as the one we identified in COX 1. Ten years ago we would never have dreamed of this spinoff. No one would every have guessed that there would be a second COX and that it would captivate the pharmaceutical industry."
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