Robert Kellogg Crane (December 20, 1919 – October 31, 2010) was an American biochemist best known for his discovery of sodium–glucose cotransport.
Early life
Crane was born on December 20, 1919, in Palmyra, New Jersey, to Wilbur Fiske Crane, Jr. architect and engineer, and Mary Elizabeth McHale Crane. He is the grandson of Stephen Crane's brother Wilbur.[1]
In the 1950s, Crane played a central role in establishing that glucose transport into the cell was the first step in glucose metabolism and its control. He demonstrated that neither the phosphorylation-dephosphorylation mechanism nor other covalent reactions accounted for glucose transport in the intestine.
Model of cotransport coupling of glucose transport to an Na+ pump by an Na+ circuit. Redrawn from Crane et al.[2][3]
In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose cotransport as the mechanism for intestinal glucose absorption.[3]Cotransport was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century.[4][5]
Crane's discovery of cotransport led directly to the development of oral rehydration therapy.[6][7] This treatment counterbalances the loss of water and electrolytes caused by cholera via a glucose containing salt solution that accelerates water and electrolyte absorption. This is possible because cholera does not interfere with sodium-glucose cotransport.[8][9]
Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980s.[10] In 1978, The Lancet wrote: "the discovery that sodium transport and glucose transport are coupled in the small intestine, so that glucose accelerates absorption of solute and water, was potentially the most important medical advance this century."[11]
Crane's discovery is also used in blockbuster drugs, such as the SSRIProzac, which treat depression by inhibiting the Na/serotonin cotransporters in the brain. Furthermore, major pharmaceutical companies are developing inhibitors of the Na/glucose cotransporters to treat diabetes and obesity.[12]
Robert K. Crane, D. Miller and I. Bihler. "The restrictions on possible mechanisms of intestinal transport of sugars”. In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439–449.
D. Miller and Robert K. Crane. "The digestive function of epithelium of the small intestine. 1. An intracellular locus of disaccharide and sugar phosphate ester hydrolysis". Biochimica et Biophysica Acta 52, 1961, pp. 281–293.
Robert K. Crane. "Hypothesis for mechanism of intestinal active transport of sugars". Federation Proc. 21, 1962, pp. 891–895.
Robert K. Crane. "Structural and functional organization of an epithelial cell brush border". Intracellular Transport, Symp. Intnl. Soc. Cell BioI. Vol. 5, B. Warren, Ed., Academic Press, 1966, pp. 71–102.
Alexander Eichholz, K. E. Howell and Robert K. Crane. "Studies on the organization of the brush border in intestinal epithelial cells VI. Glucose binding to isolated intestinal brush borders and their subfractions". Biochimica et Biophysica Acta 193, 1969, pp. 179–192.
Robert K. Crane. "Speculations about mechanism: The ecstasy of transport". 21st annual meeting of the Gastrointestinal Section, American Physiological Society, 1971, pp. 1–16.
Alexander Eichholz and Robert K. Crane. "Isolation of plasma membranes from intestinal brush borders in Methods in Enzymology". Vol. 31, part A, Biomembranes, S. Fleischer and L. Packer, Eds., Academic Press, 1974, pp. 123–134.
Robert K. Crane. "Digestion and absorption: water-soluble organics". International review of physiology, Gastrointestinal physiology II, Vol. 12, Robert K. Crane, Ed., University Park Press, 1977, pp. 325–365.
Robert K. Crane. "The road to ion-coupled membrane processes". Comprehensive Biochemistry. Vol 35: Selected Topics in the History of Biochemistry, Personal Recollections l. (Neuberger, A., van Deenen, L. L. M. and Semenga, G., Eds.), Elsevier, Amsterdam, 1983, pp. 43–69.
^Robert K. Crane. "Stephen Crane's Family Heritage". Stephen Crane Studies 4.1, 1995.
^ abRobert K. Crane. "The road to ion-coupled membrane processes". In: Comprehensive Biochemistry. Vol 35: Selected Topics in the History of Biochemistry, Personal Recollections l. (Neuberger, A., van Deenen, L. L. M. and Semenga, G., Eds.), Elsevier, Amsterdam, 1983, pp. 43–69. Model of cotransport on page 64.
^ abRobert K. Crane, D. Miller and I. Bihler. "The restrictions on possible mechanisms of intestinal transport of sugars". In: Membrane Transport and Metabolism. Proceedings of a Symposium held in Prague, August 22–27, 1960. Edited by A. Kleinzeller and A. Kotyk. Czech Academy of Sciences, Prague, 1961, pp. 439–449. Model of cotransport on page 448.
^Ernest M. Wright and Eric Turk. "The sodium glucose cotransport family SLC5".[dead link]Pflügers Arch 447, 2004, p. 510. "Crane in 1961 was the first to formulate the cotransport concept to explain active transport [7]. Specifically, he proposed that the accumulation of glucose in the intestinal epithelium across the brush border membrane was coupled to downhill Na+ transport cross the brush border. This hypothesis was rapidly tested, refined and extended [to] encompass the active transport of a diverse range of molecules and ions into virtually every cell type.”
^Boyd, C A R. "Facts, fantasies and fun in epithelial physiology".Experimental Physiology, Vol. 93, Issue 3, 2008, p. 304. "The insight from this time that remains in all current text books is the notion of Robert Crane published originally as an appendix to a symposium paper published in 1960 (Crane et al. 1960). The key point here was 'flux coupling', the cotransport of sodium and glucose in the apical membrane of the small intestinal epithelial cell. Half a century later this idea has turned into one of the most studied of all transporter proteins (SGLT1), the sodium–glucose cotransporter."
^C. A. Pasternak. "A Glance Back Over 30 Years". Bioscience Reports, Vol. 13, No. 4, 1993, p. 187. Crane: "I have recently been reassured that this formulation of sodium ion-coupled glucose transport in the intestine was the basis for the development by others of the simple glucose-sodium chloride solution taken by mouth that is used world-wide to treat victims of life-threatening diarrhea as in cholera. A practical development based on my little piece of basic research has saved thousands upon thousands of lives."
^W.B. Greenough. Lancet 345, June 1995, p. 1568. "The life saving power of oral rehydration therapy was first demonstrated in cholera patients. By 1971 there was sufficient knowledge to reduce death from 40% to less than 3%, even under chaotic field conditions — 'Now used for all diarrheal diseases it saves the lives of over one million children a year and if fully used could save 3–4 million lives every year."
^Editorial. "Water with sugar and salt". Lancet 2, August 5, 1978, pp. 300–301.
^"The British Society of Gastroenterology". Gut, Vol. 10, 1969, p. 1044. "The Sir Arthur Hurst Memorial Lecture 'Digestion and Absorption at the Brush Border Membrane: A Lesson in Functional Organisation' was given by Dr Robert K. Crane (Rutger's Medical School, New Jersey, USA)".
^"American physiological society".[dead link]Digestive Diseases and Sciences, Vol. 16, No. 4, 1971, p. 332. "Dr. Robert K. Crane, Department of Physiology, Rutgers Medical School, will give the Twenty-First Annual Lecture for the Gastrointestinal Section of the American Physiological Society on Thursday, April 15, 1971, at 8:00 PM fit the Conrad Hilton Hotel during the Spring Meeting of the Federation of American Societies for Experimental Biology in Chicago, Ill. The title of his lecture is Speculations About Mechanism: The Ecstasy of Transport."
^Robert K. Crane. "Speculations about mechanism: The ecstasy of transport". 21st annual meeting of the Gastrointestinal Section, American Physiological Society, 1971, pp. 1–16.
