In the early part of the twentieth century, many physicians considered tuberculosis (TB) to be responsible for a host of chronic diseases, including RA. Since heavy metal therapy was considered to be useful in treating TB, it made sense to use gold to treat the deforming arthritis thought to be “related” to TB. In 1914, Dr. Holger Møllgaard introduced the concept of intravenous gold to treat TB, and in 1926, Drs. Frederic Lewy and Rudolf Freund observed the benefits of a new gold compound, solganal, in treating streptococcoal infections. That same year, Dr. Ingemar Hedenius reported favorable results using gold to treat septic polyarthritis.
By most accounts, the French rheumatologist Jacques Forestier is credited with being the first to publish a favorable clinical study of gold in RA in 1932. Working in a hospital in Aix-Les-Bains, the site of the ancient Roman baths in France, he completed a reasonably well-designed study of 48 patients. His conclusion that, “it [gold] may be regarded as the best chemical for the treatment of rheumatoid arthritis,” held sway for the next several decades.
The popularity of gold salt therapy was aided by the relatively slow progress of rheumatology research over the next several years. Then Philip Hench and his colleagues at the Mayo Clinic in Rochester, Minn., made a remarkable set of observations. The story begins on April Fools Day of 1929, when a 65-year-old patient of his with RA told him a remarkable story. After four years of relentless disease, he abruptly went into remission after developing the sudden onset of jaundice. The jaundice lasted five weeks, but the RA did not relapse until several weeks after the jaundice disappeared.
Over the next fifteen years, Dr. Hench observed this similar phenomenon in sixteen other patients. He began to suspect that the “ameliorating effect of pregnancy,” which many clinicians had previously observed, “was analogous to, if not identical with, that which may occur during jaundice and that the same agent might be responsible for both, although the mechanism for developing the chemical agent might be different.” The Mayo group noted this phenomenon in other diseases as well, including psoriatic arthritis, asthma, hay fever, and myasthenia gravis. They concluded that there must be a substance X that provided group-specific rather than disease-specific benefits. Working with his Mayo colleagues Dr. Charles Slocumb and the biochemist Edward Kendall, they concluded that this mystery compound could be derived from the adrenal cortex.
