In 1956, the JCI published a paper by Richard Havel, Howard Eder, and Joseph Bragdon on a method using an ultracentrifuge to physically separate plasma lipoproteins and chemical methods to analyze their lipid constituents. This paper has been much cited (7081 times as of this writing) in part because it represents a solid method that, with various modifications, has been applicable for the study of lipoproteins for almost half a century.
Scott M. Grundy
Endothelial cells derived from human umbilical veins were first successfully cultured in vitro in 1973. Weibel-Palade bodies and the von Willebrand factor antigen were used as morphological, immunohistochemical, and functional markers to unequivocally identify the cells. These landmark studies helped initiate the growth of modern vascular biology.
Ralph L. Nachman, Eric A. Jaffe
In 1956, the JCI published an article by Vincent Dole on a method for titrating plasma fatty acids that uncovered the importance of fatty acids as a substrate for glucose metabolism. When asked to prepare a historical perspective on this very popular paper, I paid Dole a visit and we reminisced. His answer to my question of how he came to do this work on plasma fatty acids was: “Well, one thing leads to another.” Let me remind the reader of what “things” were like in 1956 and how they might have related to Dole’s important contribution.
Nearly fifty years ago, Arthur B. DuBois, Julius H. Comroe Jr., and their colleagues published two papers on the use of body plethysmography to measure lung volume and airway resistance. These two articles in the JCI are almost the most-cited doublet in the Journal’s entire archive. Remarkably, the methods described then are still in use today in clinical pulmonary function laboratories. Though body plethysmography had been used before, there were serious technical problems; it was extraordinary that DuBois managed to solve most of these in one week. Times have changed and molecular medicine now dominates the JCI, but these articles remind us that biomedical research goes beyond the molecular.
John B. West
In 1948, Seymour S. Kety and Carl F. Schmidt published back-to-back papers in the JCI that are widely acknowledged as landmarks. Upon publication, the studies resolved a century-old debate, irrefutably demonstrating that cerebral blood flow is regionally regulated. The reported findings turned out to be so powerful in their implications that they provided the inspirational spark that illuminated a brand-new field: functional brain imaging. Thus these papers are landmarks of the rarest kind, not only ending a controversy, but also giving birth to one of the most exciting fields within modern day neuroscience.
Scott A. Small
In 1945, Homer W. Smith published an article in the JCI that clearly demonstrated that para-aminohippuric acid is the most suitable agent for the evaluation of renal plasma flow in both humans and dogs; in addition, the paper provided detailed methodology that is still in use today. This paper is but one of many outstanding works performed by Smith and his colleagues that clearly established the clearance technique as a powerful noninvasive approach to gain mechanistic insights into intrarenal function.
L. Gabriel Navar
The isolation of insulin in 1921 by Banting, Best, Collip, and Macleod stands as one of the most dramatic stories in modern medical investigation. Only two years passed between the initial experiments in dogs to widespread human application to the awarding of the Nobel Prize in 1923. Insulin-related research has also served as a focus, at least in part, for the work of three other Nobel Prize recipients: determination of the chemical structure of insulin by Frederick Sanger in 1958; determination of the three-dimensional structures of insulin and vitamin B12 by Dorothy Hodgkin in 1964; and finally, the development of immunoassay by Solomon Berson and Rosalyn Yalow in 1959–1960, which led to a Nobel Prize for Yalow in 1977 (five years after the untimely death of Berson). The history of Yalow and Berson’s discovery and its impact on the field is an illustration of the adage that every story has two sides.
C. Ronald Kahn, Jesse Roth
It was 32 years ago that Bernard Babior, Ruby Kipnes, and I submitted a paper to the JCI reporting that polymorphonuclear leukocytes produce superoxide (O2–) during phagocytosis and that this highly reactive oxygen radical might function as a microbicidal agent. The story of how our lab came to this discovery is one of a special relationship between a student and his brilliant mentor.
John T. Curnutte
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