Drawing on rare books, correspondence, inoculation ledgers, and vaccination pamphlets held at Harvard, Yale, and the New York Academy of Medicine, this project investigates how early physicians learned, adapted, and shared the practical knowledge of vaccination between 1796 and 1870. During this period—before the advent of mass production—successful vaccination required not only viable “matter” (lymph or scabs) but also the correct method of inoculation and propagation. Physicians thus formed information networks to sustain both biological material and procedural know-how. By analyzing these textual and material traces alongside genomic data from the A Pox in All Our Houses collaboration (Dhody Research Institute + McMaster University Ancient DNA Centre), the project reconstructs how vaccine knowledge, technique, and trust circulated between Britain, its colonies, and the early United States. This work bridges archival, curatorial, and biological evidence to illuminate the intertwined evolution of vaccination and communication.