Guest editorial – Lawrence J. Marnett, Ph.D.

Exploring inflammation: A modern-day “Corps of Discovery”

Lawrence J. Marnett, Ph.D.
Director, Vanderbilt Institute of Chemical Biology
Published: December, 2004

Photo by Dean Dixon
Inflammation is a series of biochemical and cellular events that constitute our body’s response to infection. Inflammatory cells surround invading pathogens and generate highly reactive and toxic chemicals including Clorox (sodium hypochlorite) and chlorine gas. They also synthesize antibodies to help clear bacteria, viruses, and other noxious stimuli, and they produce a range of signaling molecules such as prostaglandins and cytokines to amplify the inflammatory response.

This vigorous attack causes some collateral damage to surrounding tissue but normally it is local and transient. However, prolonged exposure to inflammatory stimuli or incorrect regulation of the inflammatory response leads to chronic and occasionally systemic tissue damage. As outlined elsewhere in this issue, this contributes to many important human diseases.

There is a rich history of research on the cause and treatment of inflammation, which illustrates the role that trained observation, serendipity, initiative, and hard work play in science and medicine. Some very interesting personalities have devoted their lives to inflammation research and their discoveries have had enormous impact on human health.

Drugs that treat inflammation are among the most prescribed therapeutic agents, and pharmaceutical companies spend billions of dollars trying to improve them. The complexity of the inflammatory response offers many potential strategies and targets for new drug development. So this is a very exciting and rewarding area for research.

The hallmarks of inflammation—pain, swelling, redness, and heat—and methods for its treatment were documented over 3,000 years ago. The Ebers Papyrus (1534 B.C.) describes the use of an infusion of dried myrtle for rheumatic and back pain. Hippocrates of Kos (400 B.C.) recommended a tea extract from the bark of the willow tree for pain and fever.

In 1763, an English clergyman, the Rev. Edward Stone, reported in a letter to the Royal Society, Britain’s national academy of science, that powdered willow bark administered in water is effective in reducing fever in a clinical study of 50 of his parishioners. A major component of these plant extracts, called salicin, was isolated in 1828 by the German chemist, Johannes Buchner. Salicin is converted to salicylic acid, which is the actual anti-inflammatory agent.

A small German dye company founded by Friedrich Bayer developed an industrial scale synthesis of salicylic acid in the late 1800s, but it was too harsh on the mouth and stomach to be very useful as a drug. A chemist at Bayer, Felix Hoffman, added an acetyl group to form acetylsalicylic acid (i.e., aspirin) and with a pharmacologist, Heinrich Dresser, found that it had promising anti-inflammatory activity. Bayer began marketing aspirin as a drug in 1899 and it became available over the counter in 1915. The synthesis and marketing of aspirin is viewed by many as the birth of the modern pharmaceutical industry.

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