The link between protein chemical shifts and protein secondary structure (specifically alpha helices) was first described by John Markley and colleagues in 1967.  With the development of modern 2-dimensional NMR techniques, it became possible to measure more protein chemical shifts. With more peptides and proteins were being assigned in the early 1980s it soon became obvious that amino acid chemical shifts were sensitive not only to helical conformations, but also to β-strand conformations. Specifically, the secondary Hα chemical shifts of all amino acids exhibit a clear upfield trend on helix formation and an obvious downfield trend on β-sheet formation. By the early 1990s, a sufficient body of  C and N chemical shift assignments for peptides and proteins had been collected to determine that similar upfield/downfield trends were evident for essentially all backbone Cα, Cβ, C', HN and N (weakly) chemical shifts. It was these rather striking chemical shift trends that were exploited in the development of the chemical shift index.