A Virginian by birth, an Ohioan in his youth, and a Methodist by name and inclination, John Wesley Monette moved to the new state of Mississippi in 1821. Excelling in his studies at the south's preeminent educational institution, Transylvania College, Monette received his MD in 1825, and returned to Washington to establish a medical practice. He married Cornelia Jane Newman three years later and settled into a life that brought him increasing renown, both as a physician and writer.
The deadly disease environment of the south -- only four of his ten children survived to maturity -- provided the first avenue for Monette to rise to fame. He earned local notice for a broadside published locally in 1833 on the treatment of cholera, but his epidemiological studies of the occurrence of yellow fever at Washington, Miss., (1825) and particularly in Natchez (1838) provided important insights into the disease. His Observations on the epidemic yellow fever of Natchez, and of the South-west (Louisville, 1842) strongly recommended the use of quarantine to prevent the spread of the disease, and his techniques were credited with enabling Natchez to avoid the worst effects of the great epidemic of 1841.
By the mid-1840s, Monette began increasingly to rely upon his sizeable fortune earned from felicitous investments to indulge an interest in the history of the Mississippi region. Characteristic of many learned mid-Victorians, his "historical" interests extended to the history of mankind, the flora, fauna, geology, and geography. He was a frequent contributor to southern periodicals, including the Western Medical and Physical Journal, the Commercial Review of the South and West, and the redoubtable DeBow's Review, but the fullest fruits of his labors are found in his massive History of the Discovery and Settlement of the Valley of the Mississippi. The first half of Monette's magnum opus appeared in 1846, dealing largely with the prehistory of the Mississippi Valley and the early attempts to explore and colonize the region by the three great European powers, England, France, and Spain. He was preparing to extend the scope of his History to include two additional volumes on physical geography, but in 1851 before his work could be completed, he died at age 48.