Beginning in the 1790s, the American Philosophical Society began to accumulate vocabularies and texts written in Native American languages, guided by Thomas Jefferson's idea of using comparative linguistics to reconstruct the histories of Indian peoples and discern their origins. The American Indian Vocabularies Collection was initially assembled by the Historical and Literary Committee of the APS for publication in 1816. They include information on seventeen North American languages and one each from the Caribbean and Central America, collected between 1784 and 1828. A number of individuals were invovled in recording the vocabularies, including Benjamin Hawkins, William Thornton, David Campbell, Daniel Smith, Constantine Volney, Constantine Rafinesque, William Vans Murray, John Heckewelder, Martin Duralde, Campanius Holm, and Jefferson himself. Most followed the standardized word set established by Jefferson.

A physician, natural historian, and professor at the University of Pennsylvania, Benjamin Smith Barton (1766-1815) was one of the central figures in Philadelphia's early national scientific establishment. Having received his medical training in European universities, Barton was appointed Professor at the University of Pennsylvania in 1789, lecturing on botany, materia medica, natural history. A prolific author, he established his reputation as one of the nation's preeminent botanists through his botanical text book The Elements of Botany (1803), but his contribtions to zoology, ethnology, and medicine were equally noteworthy. Barton's monograph on the "fascinating faculty" of the rattlesnake and his efforts in historical linguistics (New Views of the Origin of the Tribes and Nations of America, 1798) were widely read, and his Philadelphia Medical and Physical Journal (1804-1809) was one of the nation's first medical journals and an important outlet for natural historical research. The Barton Papers offer a comprehensive view of the professional work of Benjamin Smith Barton from the time of his return to the United States in 1789 until his death. The collection is divided into five series: Correspondence, Subject Files, Bound Volumes, Graphic Materials, and Printing Plates. The collection includes a particularly valuable series of botanical, medical, and natural historical drawings collected by Barton for research, reference, and publication. Among the many artists represented are William Bartram, Frederick Pursh, Pierre Turpin, and Benjamin Henry Latrobe.