Less than two months before his death in December 1896, Alfred Nobel wrote a note to a colleague: "Isn't it the irony of fate that I have been prescribed nitro-glycerin, to be taken internally! They call it Trinitrin, so as not to scare the chemist and the public." Nobel suffered recurring attacks of the intense chest pain known as angina pectoris, and physicians of his day knew that nitroglycerin--the active ingredient in dynamite--provided effective relief. The irony, of course, was that the Swedish inventor and industrialist had made much of his considerable fortune from developing and manufacturing dynamite. Moreover, from his own laboratory experiments, Nobel had learned that exposure to the chemical caused severe headaches. He declined to take it for his angina.

Although nineteenth-century scientists understood why nitroglycerin was a potent explosive, they had no idea what made it an effective treatment for angina. Somehow it relaxed the smooth muscles that surround blood vessels, allowing the vessels to dilate so that more blood could flow to the starved heart muscle. The secret of nitroglycerin emerged at last in the 1970s, when researchers realized that it works by reacting in the body to form a messenger molecule called nitric oxide, or NO.

Outside the body, NO is an unstable, potentially toxic gas that forms in lightning strikes and car exhaust. But as a messenger molecule inside the body it plays a crucial regulatory role. Every cell type and tissue sends and receives messages--telling muscle cells when to contract, for instance, or fat cells when to release their stores. Several message systems regulate our web of blood vessels so that they deliver oxygen-carrying blood to the tissues and organs that need it most while also keeping our blood pressure at an appropriate level. The various messengers selectively dilate or constrict blood vessels, diverting blood flow as the body requires--to the gastrointestinal tract after a meal, for example, or to the muscles of movement in an emergency.

Nitric oxide is at the center of the most important relaxation system, thus explaining why nitroglycerin helps angina patients. But NO's importance does not stop with angina. Inhaled NO can help premature babies when the blood vessels in their lungs are not absorbing oxygen adequately. Local application of NO-related drugs may prevent cells from growing and blocking repaired arteries. Drugs that release NO at the site of an infection also may help immune cells kill invading pathogens and tumor cells.

As often occurs in science, the path to using NO in such diverse medical treatments was guided by chance observations and was filled with odd turns. Just over a century after Alfred Nobel's death, the prizes that he founded with his fortune would be awarded to three researchers who had set out to investigate the mechanisms of the body's signaling systems--work that ultimately led to an understanding of how an explosive chemical can also relieve the pain caused by cardiovascular disease.