  Some critics of the somatic mutation theory and its associated search for mechanisms of cancer at the cell and molecular level are far more radical in their ambitions. In the late 1990s, and early 2000s, two researchers proposed what they took to be an alternative theory or “paradigm” to the “somatic mutation theory” (SMT), namely, the Tissue Organization Field Theory (or, TOFT) (Soto &amp; Sonnenschein 2000). Soto and Sonnenschein object not only to reductionist methodology, but reductionist assumptions about the causes of cancer. That is, their concern is not only with experimental approaches that focus on dysregulated growth of cancer cells in cell culture, but also with the claims regarding the role of mutations in cancer. In their view, cancers are not the result of mutations, but instead “alterations in the communication among cells and tissues that affect tissue architecture” (2013, p. 90). On this view, mutations do not lead the way—or, directly affect these signaling pathways—but follow upon disruptions to tissue organization. It is these alterations of patterns of interaction between cells that leads to “downward causation effects” on cells and cellular components, inducing aneuploidy and mutations (Soto &amp; Sonnenschein 2006; Sonnenschein &amp; Soto 2008). Arguments such as this one raise several interesting philosophical questions. First, Soto and Sonnenschein are skeptical of the scientific methodology supporting SMT. They bring attention to some interesting broader questions as to when are we warranted in inferring from cell culture or model organism work to general claims about cancer etiology.