Henry Kunkel, Stephanie Smith, clinical immunology, and split genes

The York Avenue (New York) 'ecosystem' from the 1940s through the 1980s enabled Henry Kunkel to apply new scientific methodology to understanding human disease. Stephanie Smith, a young woman with lupus, was treated at the Rockefeller University Hospital in the 1960s. Studies of her antinuclear antibodies by Kunkel and Eng Tan led to the discovery of a precipitin line specific for lupus, and the responsible antigen was designated Sm (for 'Smith'). This review outlines the history of Sm antigen from an interesting precipitin line to the identification of small nuclear RNA molecules and small nuclear ribonucleoproteins, and subsequently the discovery of RNA splicing. The story illustrates Henry Kunkel's approach to science, emphasizing how 'accidental' clinical observations, in the hands of skilled investigators, can have unexpected and potentially momentous implications.