Our first BucketListPaper is from 1899 and introduced the idea that the activity of anesthetics might correlate with  lipophilicity (as measured by partition into oil from water).  This first hint that lipophilicity might be a key property, as found by Overton and Meyer, kick-started the field of QSAR. The papers formed the basis of a theory of anesthesia, which still intrigues and stimulates new scientific studies.

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Picture1 BLP 1 100

  1. Overton E. Studien über die Narkose Zugleich ein Beitrag zur Allgemeinen Pharmakologie. Jena, Germany: Verlag von Gustav Fisher, 1901. Meyer H. Zur Theorie der Alkoholnarkose. Arch Exp Pathol Pharmakol 1899;42: 109-18
  2. Graph abstracted by Campagna et al.: https://www.nejm.org/doi/full/10.1056/NEJMra021261)