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Since its origin in the 19th century, epidemiology has faced an internal tension between an approach oriented toward biology and the study of mechanisms, and an approach oriented toward populations and their interactions with the environment. Initially, this tension took the form of an opposition between microbiology and statistics. We describe the early roots of the quantitative approach to health and disease and several historical examples of the above tension. The search for the causes of pellagra exemplifies our thesis. In Italy, where pellagra was endemic, contrasting opinions coexisted between the hypothesis of contaminated maize, supported by Cesare Lombroso, and the hypothesis of a prevailing role of poverty and poor nutrition. In the United States, Joseph Goldberger found no evidence for the hypothesis of contaminated maize or for a microbiological agent, but recognized the central role of nutrition. The "cure" Goldberger proposed was land reform, but he continued studying the disease from a mechanistic point of view; shortly after his death, niacin deficiency was identified as the cause of pellagra. The tension between mechanistic and population-based studies is still present within epidemiology and is in fact essential for the success of the discipline.

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Syphilis is the prime example of a “new disease” which triggered a transnational (European) discussion among physicians. It appeared between the end of the Middle Ages and the beginning of the Modern Times (at the beginning of the sixteenth century), a time in which medicine was changing from a dogmatic to an experimental discipline. The main changes were in the field of anatomy: in 1543, the same year of the astronomy-disrupting work by Nicolas Copernicus, the new less dogmatic and more empirical approach to anatomy by Andreas Vesalius was published. Nevertheless, in the Renaissance, medicine remains a tradition-bound discipline, proud of its millennial history and its superiority over the empirical, non-academic healers. When syphilis appeared in Europe, several explanations were elaborated. In the mid-16th century, an Italian doctor Luigi Luigini (born in 1526) published in Venice a collection of all the works on syphilis that appeared until 1566. He wanted to entrust to colleagues, contemporary and future, a compendium of all that was known about the “new” disease (the Latin term Novus means both “new” and “strange”). According to the most authors of the collection, the disease is in fact “new” and “strange”. Some authors of the collection find it impossible that authorities like Hippocrates and Galen overlooked it. Luigini’s work shows the authors’ effort to absorb syphilis in the corpus of academic medicine and affirm the authority of academic physicians against the empirical healers.

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