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Do academic publication standards reflect or determine research results? The article proposes minimal criteria for distinguishing useful 'unpublishable' results from low-quality research, and argues that the virtues of negative results have been overlooked. We consider the fate these results have suffered thus far, review arguments for and against their publication and introduce a new initiative -a journal to disseminate negative results and advance debate on their recognition and use.

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In general, research results are perceived to be good and positive things. A carefully

Abstract.A literature less traveled -peaking between 1900-1920 -draws on pre-classical concepts of crystal growth and a trove of field biology, to understand ectopic shell production, the natural source of pearls. By 1907, grafts from the calcifying mantle epithelium on gonads induced nacre mineralization consistently in Pinctada margaritifera, suggesting that anomalously displaced, readily specialized cells are at least a sufficient cause of natural pearl formation. Otherwise, the epithelial sacks wrapping natural nacreous pearls must specialize for nacre production independently from the shell producing mantle -an idea supported by experiments with shell regeneration, but not amenable to a method of inducing pearl formation. At the time, chasing epithelial cell migration was technically unfeasible, signaling was news, stemness was fiction. Boldly, Jameson & Rubbel [1902-1912 marshaled natural pearl nuclei and shell repairs as mineral records of cells specializing de novo into the shell's secretory regimes. Much of this paper reenacts the historic debate on the origin of pearls: thence bold ideas connect smoothly with new work both on bone or shell. I replicate Jameson's choice of samples and revisit his proposal to search for an "agency [other than the] shell-secreting mechanism" acting on "replacement cells" as the origin of pearls. Much has changed: specialized epithelial cells reportedly migrate; non-differentiated cells remain available throughout and near the calcifying mantle epithelium -both, open possibilities for natural pearl nucleation. Interest in understanding the latter now connects with results sketching the signaling cascade in cell specialization toward bone morphogenesis. Replicating Jameson's choice of samples, I describe the more spectacular structural changes in the mineralization of pearls associated with two instances of cell specialization: toward producing one shell material -in the event of natural pearl nucleation, or switching between two in later pearl growth. Clusters of cells producing distinctly novel mineralization -nacre over fibrous-prismatic aragonite -could be singled out next to natural pearls by Jameson. The possibility has not been probed in roughly a hundred years. Natural pearl nucleation as a cellular event has never been explored.Much of the literature debating the origin of natural pearls has been written more than a century ago. Its foundation is a trove of field biology that still contains the most detailed descriptions of the circumstances, anatomic placement, surrounding cells -the natural pearl 'sacs' -associated with a variety of mineralization in natural pearls. The dialogue between two authors -Henry Lister Jameson [1,2,3] and W. A. Herdman [4] -sums the state of the art shortly before the study of natural pearls ebbs into the historical lull in pearling between the invention of grafting -the technical foundation of pearl culture, and the current revival of interest in natural pearls. This is still the state of the art.1 Herdman [4], page 8.