Abstract

A science is an intellectual activity defined by its mechanisms that prevent its scientists from always reaching the conclusions that they set out to reach. Such mechanisms are needed because, if scientists are given full control over what hypotheses they select, what data they discard, and what results they publish, they can communicate any conclusion that they desire. Synthesis, by setting a grand challenge, forces scientists across uncharted territory where they encounter and solve unscripted problems. When theory is inadequate, the synthesis fails, and fails in a way that cannot be ignored. Therefore, synthesis drives discovery and paradigm change in ways that simple hypothesis testing cannot. Here, we describe the discoveries that emerged when synthetic biologists were challenged to create an alternative genetic system that has different molecular structures than DNA and RNA. In pursuit of this particular “grand challenge,” synthesis forced the recognition that the community did not know as much about the double helix as it had constructively assumed. In general, a field of science having access to synthesis as a research strategy can create knowledge even if its practitioners do not fit the ideal of a dispassionate, advocacy-free scientist