How the JCI’s most-cited paper sparked the field of lipoprotein research

A profound medical triumph of the last half of the 20th century was the elucidation of the transport system mediated by plasma lipoproteins. Scientists identified the proteins that carry water-insoluble lipids in the plasma, the enzymes and receptors that remove these lipids, and the separate roles that each lipoprotein plays in physiology and disease. Genetic and environmental abnormalities of lipoprotein metabolism were defined, and powerful treatments were developed and instituted. The JCI played a major role in the lipoprotein transport story. The JCI’s publication of a seminal 1955 paper that outlined a method by which lipoproteins could be separated from other plasma proteins in quantities that permit structural and functional characterization was crucial (1). The paper was entitled, “The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum” (Figure 1A). Its three young authors were Richard Havel, Howard Eder, and Joseph Bragdon, all of whom worked at the National Heart Institute at the NIH in Bethesda, Maryland. The impact of their paper is reflected in the number of times it has been cited — no fewer than 8,913 times. Figure 1B shows the annual citations, which peaked when lipoprotein research was most intense in the late 1990s and declined thereafter when the major questions had been answered. The 8,913 citations are the most for any of the 31,282 […].