Tale of two kings.

Abstract

It was a pleasure to read Gretchen Vogel's News Focus article about the liver enzyme CYP3A and its possible role in physiology, and historically as a poison resistance mechanism for legendary rulers such as King Mithridates (“How the body's ‘garbage disposal’ may inactivate drugs,” 5 Jan., p. [35][1]). Accompanying the article was a picture of a stone carving of “King Mithridates” shaking hands with Hercules; however, the Mithridates in the carving is not the King Mithridates of Pontus (Mithridates Eupator/Euergetes VI “the Great,” 120 to 63 B.C.) featured in the article and in A. E. Housman's poem (LXII in “A Shropshire Lad) for having built up his poison resistance by ingesting small amounts throughout his lifetime. The famous stone carving pictured was located in ancient Arsameia in what is now southeastern Turkey. In the first century B.C., the area belonged to the kingdom of Commogene and was referred to by the Romans as Cappadocia. The region of Pontus, on the other hand, was located to the north, bordering the Black Sea. The carving was erected around 50 B.C. by King Antiochus I Theos in the memory of his father, King Mithridates I Callinicus, son of Samus I and King of Independent Commagene, who reigned from 96 to 70 B.C. These two “Mithridati” are separate historical rulers whose lives and names nevertheless overlapped, with King Mithridates of Pontus admittedly gaining more historical clout and the ever-coveted title “the Great” by defeating some of Rome's best generals of the day such as Pompey, Lucullus, and Sulla, and resisting assassination attempts by poison—apparently by priming his CYP3A enzyme—to feature in a Housman poem. Science regrets the error, which John Spitzer of the Peabody Conservatory in Baltimore, Maryland, also brought to our attention. As Spitzer noted, “With friends like Hercules, [Mithridates of Commagene] didn't need any CYP3A enzymes to protect him against his enemies.” [1]: /lookup/doi/10.1126/science.10.1126/SCIENCE.291.5501.35