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Blobel and Sabatini’s “Beautiful Idea”: Visual Representations of the Conception and Refinement of the Signal Hypothesis

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Abstract

In 1971, Günter Blobel and David Sabatini proposed a novel and quite speculative schematic model to describe how proteins might reach the proper cellular location. According to their proposal, proteins destined to be secreted from the cell contain a “signal” to direct their release. Despite the fact that Blobel and Sabatini presented their signal hypothesis as a “beautiful idea” not grounded in experimental evidence, they received criticism from other scientists who opposed such speculation. Following the publication of the 1971 model, Blobel persisted in conducting experiments and revising the model to incorporate new data. In fact, over the period of 1975–1984, Blobel and colleagues published five subsequent schematic models of the signal hypothesis, each revised based on new laboratory evidence. I propose that the original 1971 model can be viewed as an epistemic creation. Additionally, analysis of the subsequent schematic diagrams over the period of 1975–1984 allows one to track Blobel’s changing conception of an epistemic object over time. Furthermore, the entire series of schematic diagrams presented by Blobel from 1971 to 1984 allow one to visualize the initial conception and subsequent reworking of a scientific theory. In 1999, Blobel was awarded the Nobel Prize in Physiology or Medicine for his work on the signal hypothesis, which was ultimately supported by experimental evidence gathered after the speculative model was published.

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Acknowledgements

I would especially like to thank Dr. Sophia Roosth for incredibly helpful discussions, thoughtful comments on numerous versions of the manuscript, and recommendation of relevant source material. I thank Jessica Murphy at the Center for the History of Medicine at Harvard Medical School for providing me access to the Bernard Davis papers and granting me permission to quote from the papers. I also thank Beth Semel, Richard Fadok, Dr. Stefan Helmreich, Dr. Allan Brandt and Dr. David Jones for directing me to additional sources on visual representation. I am very grateful for the thoughtful and detailed comments offered by two anonymous reviewers as well as the Editor-in-Chief, Dr. Michael Dietrich. Finally, I thank Dr. Jason LaBonte for valuable discussions, comments on an earlier draft of the manuscript, and continuous encouragement.

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    Michelle Lynne LaBonte

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LaBonte, M.L. Blobel and Sabatini’s “Beautiful Idea”: Visual Representations of the Conception and Refinement of the Signal Hypothesis. J Hist Biol 50, 797–833 (2017). https://doi.org/10.1007/s10739-016-9462-7

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