A timeline of hydrogen sulfide (H 2 S) research: From environmental toxin to biological mediator.

The history of H2 S - as an environmental toxin - dates back to 1700, to the observations of the Italian physician Bernardino Ramazzini, whose book "De Morbis Artificum Diatriba" described the painful eye irritation and inflammation of "sewer gas" in sewer workers. The gas has subsequently been identified as hydrogen sulfide (H2 S), and opened three centuries of research into the biological roles of H2 S. The current article highlights the key discoveries in the field of H2 S research, including (a) the toxicological studies, which characterized H2 S as an environmental toxin, and identified some of its modes of action, including the inhibition of mitochondrial respiration; (b) work in the field of bacteriology, which, starting in the early 1900s, identified H2 S as a bacterial product - with subsequently defined roles in the regulation of periodontal disease (oral bacterial flora), intestinal epithelial cell function (enteral bacterial flora) as well as in the regulation of bacterial resistance to antibiotics; and (c), work in diverse fields of mammalian biology, which, starting in the 1940s, identified H2 S as an endogenous mammalian enzymatic product, the functions of which - among others, in the cardiovascular and nervous system - have become subjects of intensive investigation for the last decade. The current review not only enumerates the key discoveries related to H2 S made over the last three centuries, but also compiles the most frequently cited papers in the field which have been published over the last decade and highlights some of the current 'hot topics' in the field of H2 S biology.