In reviews of manuscripts and grants, the words “mechanistic” and “descriptive” are often misused as synonyms for “good” and “bad,” respectively (6, 9). The extraordinary power of these words requires us to wield them carefully when critiquing science. In an earlier essay, we considered the epithet “descriptive” as applied to science and argued for an important role of descriptive studies in biology, while also acknowledging a general preference for studies that go further by including experimental work (3). Here we consider the more favored adjective “mechanistic” and explore its usage, meanings, implications, and limitations. Recognizing the centrality of mechanistic research to the history of science (1), we seek to explore what biological scientists mean when they use this term. Definitions. At first glance, one is struck by the fact that the terms “descriptive” and “mechanistic” are often used antagonistically as descriptors of scientific quality, yet they are not antonyms. “Descriptive” is defined as “referring to, constituting, or grounded in matters of observation or experience,” while “mechanism” is defined as “the fundamental processes involved in or responsible for an action, reaction or other natural phenomenon” (http://www.merriam-webster.com/dictionary/). From these definitions, “descriptive” can be seen as analogous to the interrogatives “who,” “what,” “where,” and “when,” whereas “mechanistic” in turn asks “how” and “why.” Hence, these terms collectively encompass the spectrum of inquiry. But if “descriptive” and “mechanistic” are not antonyms, what accounts for the general preference for mechanistic over descriptive work? As “descriptive” and “mechanistic” denote different qualities, at least in the minds of reviewers, we must probe further to ascertain what these terms mean in the scientific vernacular. We suggest that these words mean different things to different people. Since practically all laboratory-based biological science is based on recording evidence from experimentation, an argument can be made that all science is in some form descriptive. However, this is unsatisfactory because every scientist intuitively knows that there are qualitative differences in scientific studies. Hence, the first problem we encounter is in the precision of language, as we try to understand and convey meaning in words. The word “mechanistic” is used to refer to both complex natural phenomena and man-made mechanical devices. The machine as an analogy for the natural world owes much to the writings of Hobbes and Descartes (even though the latter could not bring himself to ascribe the human soul to a mechanical process). Like Hobbes, the modern scientist makes the implicit assumptions that phenomena have rational explanations and that events may be connected as cause and effect. Scientists seeking mechanisms to explain the workings of the natural world are only the latest practitioners in a philosophical continuum extending back to the 17th century (1, 4). The explanation for many biological phenomena requires a basic understanding of causal mechanisms (4). However, “mechanism” can mean different things in different fields. For example, in the late 1950s the problem of protein synthesis was central to biology, and “mechanism” to biochemists meant the formation of covalent bonds in polypeptides, whereas to molecular biologists “mechanism” was the means by which the genetic code is translated into proteins (5). Although these approaches were eventually reconciled during the great synthesis of the mid-1960s (5), it is noteworthy for our discussion that the word “mechanism” can hold different meanings even in closely related fields like biochemistry and molecular biology. Furthermore, the meaning of the term “mechanism” with respect to science has changed over time, from a version of philosophical materialism in opposition to vitalism to a stepwise explanation of how system components interact to produce an outcome (1). Where is the line of demarcation between “descriptive” and “mechanistic?” Starting with the assumption that there is a difference between “descriptive” and “mechanistic” science and seeking a clear line of demarcation that can be expressed in words, one immediately runs into the problem that the description of a process can be considered the mechanism for another process. To further illustrate this point, let us consider a hypothetical situation. A scientist walks into a dark room and encounters impenetrable darkness. A candle is lit and the scientist now perceives the outline of the room. The scientist decides to investigate the phenomenon of light. The mechanism responsible for the light is the candle. However, the scientist notes that only part of the candle emits light and determines that the mechanism for light is the flame. In describing the flame, the investigator establishes that the mechanism for the flame is combustion. Describing combustion, the scientist determines that the mechanism is a series of oxidation-reduction reactions that in turn are explained by electron transfer and, ultimately, quantum mechanics. At each step, the description of a process provides only a partial explanation in search of a deeper mechanism that must in turn be described (Table 1). What is striking in this hypothetical situation is that the difference between description and mechanism is one of proximate causation. Hence, the epithets “descriptive” and “mechanistic” are epistemologically related and differ quantitatively rather than qualitatively. In other words, observations become regarded as progressively less descriptive and more mechanistic as one probes more deeply into a phenomenon. In fact, one might argue that there is no real line of demarcation between descriptive and mechanistic science but that the difference is rather a matter of depth and one’s preferences. The scientist in the dark room also gives us a model with which to explore the difference between descriptive and experimental science, a point that we emphasized in our earlier essay Published ahead of print on 13 July 2009.