I would like to add a historical footnote to Barquet and Domingo's concise history of smallpox [1]. In 1803, Thomas Jefferson outlined his plans for Meriwether Lewis's exploration of the Louisiana Purchase and western continent. Well-versed in the value of the kine-pox (cow pox) vaccination, Jefferson advised, "Carry with you some matter of the kine-pox; inform those of them with whom you may be, of its efficacy as a preservative from smallpox; & instruct & encourage them in the use of it. This may be especially done wherever you winter" [2].

Lewis intended to follow this prescription, but in a communication to the president in October 1803 he asked for a reorder of cowpox vaccine: "I would thank you forward[ing] me some of the Vaxine matter, as I have reason to believe from several experiments made with what I have, that it has lost its virtue" [2]. Additional vaccine material was never received.

During the winter of 1804-1805, Lewis and Clark camped near several Mandan and Hidatsa villages on the banks of the Missouri River. They learned that these Indian tribes, like many others, had been devastated by previous smallpox epidemics. Thirty-two years later, another smallpox epidemic with a 90% mortality rate would befall the same tribes who had been deprived of the benefit of Jefferson's kine-pox vaccine.

History is replete with "ifs." If Lewis's "kine-pox matter" had maintained its virtue, if Lewis could have propagated it and vaccinated the people where he wintered, if these native people would have accepted Lewis's "medicine" and adopted the vaccination methods, then Jefferson's vision of safeguarding the nonimmune native population from the ravages of smallpox would have been realized for the Mandan and Hidasta people and perhaps other Indian nations.