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==Discovery of cotransport==
==Discovery of cotransport==
In the 1950’s, Crane played a central role in establishing that glucose transport into the cell was the first step in [[Carbohydrate metabolism|glucose metabolism]] and its control. He demonstrated that neither the [[phosphorylation]]-[[dephosphorylation]] nor other covalent reactions accounted for glucose transport in the intestine.
In the 1950s, Crane played a central role in establishing that glucose transport into the cell was the first step in [[Carbohydrate metabolism|glucose metabolism]] and its control. He demonstrated that neither the [[phosphorylation]]-[[dephosphorylation]] nor other covalent reactions accounted for glucose transport in the intestine.
[[Image:Model of cotransport.jpg|right|275px|thumb| Model of cotransport coupling of glucose transport to an Na+ pump by an Na+ circuit. Redrawn from Crane et al.<ref name= The_road_to/><ref name=The_restrictions_on>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. [[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]], Prague, 1961, pp. 439-449. Model of cotransport on page 448.</ref>]]
[[Image:Model of cotransport.jpg|right|275px|thumb| Model of cotransport coupling of glucose transport to an Na+ pump by an Na+ circuit. Redrawn from Crane et al.<ref name= The_road_to/><ref name=The_restrictions_on>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. [[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]], Prague, 1961, pp. 439-449. Model of cotransport on page 448.</ref>]]
In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose [[Co-transport|cotransport]] as the mechanism for intestinal glucose absorption.<ref name=The_restrictions_on/> [[Co-transport|Cotransport]] was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century.<ref>Ernest M. Wright and Eric Turk. [http://www.springerlink.com/content/c7ryue6u68ge924t/fulltext.pdf?page=1 “The sodium glucose [[Co-transport|cotransport]] family SLC5”.] Pflügers Arch 447, 2004, p. 510. "Crane in 1961 was the first to formulate the [[Co-transport|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.”</ref><ref>Boyd, C A R. [http://www3.interscience.wiley.com/cgi-bin/fulltext/119410531/main.html,ftx_abs#b12 “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 [[Co-transport|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 [[Co-transport|cotransport]]er.”</ref>
In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose [[Co-transport|cotransport]] as the mechanism for intestinal glucose absorption.<ref name=The_restrictions_on/> [[Co-transport|Cotransport]] was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century.<ref>Ernest M. Wright and Eric Turk. [http://www.springerlink.com/content/c7ryue6u68ge924t/fulltext.pdf?page=1 “The sodium glucose [[Co-transport|cotransport]] family SLC5”.] Pflügers Arch 447, 2004, p. 510. "Crane in 1961 was the first to formulate the [[Co-transport|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.”</ref><ref>Boyd, C A R. [http://www3.interscience.wiley.com/cgi-bin/fulltext/119410531/main.html,ftx_abs#b12 “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 [[Co-transport|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 [[Co-transport|cotransport]]er.”</ref>
=== Application in oral rehydration therapy===
=== Application in oral rehydration therapy===
Crane’s discovery of [[Co-transport|cotransport]] led directly to the development of [[oral rehydration therapy]].<ref>C. A. Pasternak. [http://www.bioscirep.org/bsr/013/0183/0130183.pdf “A Glance Back Over 30 Years”]. [[Biochemical Society|Bioscience Reports]], Vol. 13, No. 4, 1993, [http://www.bioscirep.org/bsr/013/0183/0130183.pdf 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.”</ref><ref>J.D. Snyder. [http://content.nejm.org/cgi/content/extract/328/23/1705 “Can Bismuth Improve the Simple Solution for Diarrhea?”.] [[New England Journal of Medicine]], Vol. 328, issue 23, 1993, p. 1705. “The discovery in the mid-1960s of the coupled transport of sodium and glucose across the intestinal mucosa led directly to the development of oral rehydration therapy”.</ref> This treatment counter-balances the loss of water and [[Electrolyte|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.<ref> Arthur C Guyton and John E Hall. “Textbook of Medical Physiology”. Elsevier Saunders, Philadelphia, 2006, pp. 814-816.</ref><ref>Canadian Paediatric Society, Nutrition Committee. [http://www.cps.ca/english/statements/N/N06-01.htm “Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis”.] Paediatrics & Child Health, Vol. 11, issue 8, 2006, pp. 527-531.</ref>
Crane’s discovery of [[Co-transport|cotransport]] led directly to the development of [[oral rehydration therapy]].<ref>C. A. Pasternak. [http://www.bioscirep.org/bsr/013/0183/0130183.pdf “A Glance Back Over 30 Years”]. [[Biochemical Society|Bioscience Reports]], Vol. 13, No. 4, 1993, [http://www.bioscirep.org/bsr/013/0183/0130183.pdf 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.”</ref><ref>J.D. Snyder. [http://content.nejm.org/cgi/content/extract/328/23/1705 “Can Bismuth Improve the Simple Solution for Diarrhea?”.] [[New England Journal of Medicine]], Vol. 328, issue 23, 1993, p. 1705. “The discovery in the mid-1960s of the coupled transport of sodium and glucose across the intestinal mucosa led directly to the development of oral rehydration therapy”.</ref> This treatment counter-balances the loss of water and [[electrolyte]]s 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.<ref>Arthur C Guyton and John E Hall. “Textbook of Medical Physiology”. Elsevier Saunders, Philadelphia, 2006, pp. 814-816.</ref><ref>Canadian Paediatric Society, Nutrition Committee. [http://www.cps.ca/english/statements/N/N06-01.htm “Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis”.] Paediatrics & Child Health, Vol. 11, issue 8, 2006, pp. 527-531.</ref>


Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980’s.<ref>W.B. Greenough. [[The Lancet|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.”</ref> 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.”<ref> Editorial. “Water with sugar and salt”. [[The Lancet|Lancet 2]], August 5, 1978, pp. 300–301.</ref>
Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980s.<ref>W.B. Greenough. [[The Lancet|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.”</ref> 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.”<ref>Editorial. “Water with sugar and salt”. [[The Lancet|Lancet 2]], August 5, 1978, pp. 300–301.</ref>


===Applications in pharmaceutical drugs===
===Applications in pharmaceutical drugs===
Crane’s discovery is also used in block buster drugs, such as the [[Selective serotonin reuptake inhibitor|SSRI]] [[Fluoxetine|Prozac]], which treat depression by inhibiting the Na/serotonin cotransporters in the brain.
Crane’s discovery is also used in block buster drugs, such as the [[Selective serotonin reuptake inhibitor|SSRI]] [[Fluoxetine|Prozac]], 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.<ref>[http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/10-09-2007/0004678689&EDATE= “High Rider Reaches Agreement in Principal with French Biopharmaceutical Company”.] [[PR Newswire]], October 9, 2007. “High Rider Capital Inc. (…) [will] develop a chemical process to achieve synthesis of a new class of Sodium Glucose Cotransporters inhibitors (…), for the treatment of Type 2 Diabetes, obesity and other possible metabolic syndrome applications.” </ref>
Furthermore, major pharmaceutical companies are developing inhibitors of the Na/glucose cotransporters to treat diabetes and obesity.<ref>[http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/10-09-2007/0004678689&EDATE= “High Rider Reaches Agreement in Principal with French Biopharmaceutical Company”.] [[PR Newswire]], October 9, 2007. “High Rider Capital Inc. (…) [will] develop a chemical process to achieve synthesis of a new class of Sodium Glucose Cotransporters inhibitors (…), for the treatment of Type 2 Diabetes, obesity and other possible metabolic syndrome applications.”</ref>


==Awards and honors==
==Awards and honors==
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* Dr. Harold Lamport Award, [[New York Academy of Sciences]], 1977.
* Dr. Harold Lamport Award, [[New York Academy of Sciences]], 1977.
* [[Doctor of Science]] ([[Honorary degree|honoris causa]]), [[Washington College]], 1982.
* [[Doctor of Science]] ([[Honorary degree|honoris causa]]), [[Washington College]], 1982.
* Honorary Chairman, International Symposium on the 25th Anniversary of the Gradient Hypothesis, Aussois, France, 18, 19 and 20 September, 1985.<ref> Robert K. Crane. “Questions”. In : [http://catalogue.nla.gov.au/Record/534834 the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport], Editors: Francisco Alvarado and others, [[Institut National de la Santé et de la Recherche Médicale|INSERM]] symposium, No. 26, [[Elsevier]]-North Holland, Amsterdam, 1986; pp. 431-438.</ref>
* Honorary Chairman, International Symposium on the 25th Anniversary of the Gradient Hypothesis, Aussois, France, 18, 19 and 20 September 1985.<ref>Robert K. Crane. “Questions”. In : [http://catalogue.nla.gov.au/Record/534834 the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport], Editors: Francisco Alvarado and others, [[Institut National de la Santé et de la Recherche Médicale|INSERM]] symposium, No. 26, [[Elsevier]]-North Holland, Amsterdam, 1986; pp. 431-438.</ref>


==Selected Bibliography==
==Selected Bibliography==
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* Alberto Sols and Robert K. Crane. [http://www.jbc.org/content/210/2/581.full.pdf “Substrate specificity of brain hexokinase”.] [[Journal of Biological Chemistry]] 210, 1954, [http://www.jbc.org/content/210/2/581.full.pdf pp. 581-595.]
* Alberto Sols and Robert K. Crane. [http://www.jbc.org/content/210/2/581.full.pdf “Substrate specificity of brain hexokinase”.] [[Journal of Biological Chemistry]] 210, 1954, [http://www.jbc.org/content/210/2/581.full.pdf pp. 581-595.]
* Robert K. Crane, Richard A. Field and [[Carl Ferdinand Cori|Carl F. Cori]]. [http://www.jbc.org/content/224/2/649.full.pdf “Studies of tissue permeability I. The penetration of sugars into Ehrlich ascites tumor cells“.] [[Journal of Biological Chemistry]] 224, 1957, [http://www.jbc.org/content/224/2/649.full.pdf pp. 649-662.]
* Robert K. Crane, Richard A. Field and [[Carl Ferdinand Cori|Carl F. Cori]]. [http://www.jbc.org/content/224/2/649.full.pdf “Studies of tissue permeability I. The penetration of sugars into Ehrlich ascites tumor cells“.] [[Journal of Biological Chemistry]] 224, 1957, [http://www.jbc.org/content/224/2/649.full.pdf pp. 649-662.]
* Robert K. Crane and T. Hastings Wilson. [http://jap.physiology.org/cgi/content/citation/12/1/145 “In vitro method for the study of the rate of intestinal absorption of sugars”.] Journal of Applied Physiology, Vol. 12, 1958, pp. 145–146.
* Robert K. Crane and T. Hastings Wilson. [http://jap.physiology.org/cgi/content/citation/12/1/145 “In vitro method for the study of the rate of intestinal absorption of sugars”.] Journal of Applied Physiology, Vol. 12, 1958, pp.&nbsp;145–146.
* Stephen M. Krane and Robert K. Crane. [http://www.jbc.org/content/234/2/211.full.pdf “The accumulation of D-galactose against a concentration gradient by slices of rabbit kidney cortex“.] [[Journal of Biological Chemistry]] 234, 1959, [http://www.jbc.org/content/234/2/211.full.pdf pp. 211-216.]
* Stephen M. Krane and Robert K. Crane. [http://www.jbc.org/content/234/2/211.full.pdf “The accumulation of D-galactose against a concentration gradient by slices of rabbit kidney cortex“.] [[Journal of Biological Chemistry]] 234, 1959, [http://www.jbc.org/content/234/2/211.full.pdf pp. 211-216.]
* Robert K. Crane. [http://physrev.physiology.org/cgi/content/citation/40/4/789 “Intestinal absorption of sugars”.] [[Physiological Reviews]], Vol. 40, 1960, pp. 789–825.
* Robert K. Crane. [http://physrev.physiology.org/cgi/content/citation/40/4/789 “Intestinal absorption of sugars”.] [[Physiological Reviews]], Vol. 40, 1960, pp.&nbsp;789–825.
* 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. [[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]], Prague, 1961, pp. 439–449.
* 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. [[Academy of Sciences of the Czech Republic|Czech Academy of Sciences]], Prague, 1961, pp.&nbsp;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.
* 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.&nbsp;281–293.
* Robert K. Crane. “Hypothesis for mechanism of intestinal active transport of sugars” Federation Proc. 21, 1962, pp. 891–895.
* Robert K. Crane. “Hypothesis for mechanism of intestinal active transport of sugars” Federation Proc. 21, 1962, pp.&nbsp;891–895.
* David Miller and Robert K. Crane. [http://www.ajcn.org/cgi/reprint/12/3/220.pdf “The digestion of carbohydrates in the small intestine“.] [[American Journal of Clinical Nutrition]] 12, 1963, [http://www.ajcn.org/cgi/reprint/12/3/220.pdf pp. 220-227.]
* David Miller and Robert K. Crane. [http://www.ajcn.org/cgi/reprint/12/3/220.pdf “The digestion of carbohydrates in the small intestine“.] [[American Journal of Clinical Nutrition]] 12, 1963, [http://www.ajcn.org/cgi/reprint/12/3/220.pdf pp. 220-227.]
* Alexander Eichholz and Robert K. Crane. [http://jcb.rupress.org/content/26/3/687.full.pdf “Studies on the organization of the brush border in intestinal epithelial cells I. Tris density gradient disruption of isolated hamster brush borders and separation of fractions”] [[Journal of Cell Biology]] 26, 1965, [http://jcb.rupress.org/content/26/3/687.full.pdf pp. 687-691.]
* Alexander Eichholz and Robert K. Crane. [http://jcb.rupress.org/content/26/3/687.full.pdf “Studies on the organization of the brush border in intestinal epithelial cells I. Tris density gradient disruption of isolated hamster brush borders and separation of fractions”] [[Journal of Cell Biology]] 26, 1965, [http://jcb.rupress.org/content/26/3/687.full.pdf pp. 687-691.]
* Jane Overton, Alexander Eichholz and Robert K. Crane. [http://jcb.rupress.org/content/26/3/693.full.pdf ”Studies on the organization of the brush border in intestinal epithelial cells II. Fine structure of fractions of tris-disrupted hamster brush borders“] [[Journal of Cell Biology]] 26, 1965, [http://jcb.rupress.org/content/26/3/693.full.pdf pp. 693-706.]
* Jane Overton, Alexander Eichholz and Robert K. Crane. [http://jcb.rupress.org/content/26/3/693.full.pdf ”Studies on the organization of the brush border in intestinal epithelial cells II. Fine structure of fractions of tris-disrupted hamster brush borders“] [[Journal of Cell Biology]] 26, 1965, [http://jcb.rupress.org/content/26/3/693.full.pdf pp. 693-706.]
* 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.
* 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.&nbsp;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.
* 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.&nbsp;179–192.
* Robert K. Crane. [http://www.ajcn.org/cgi/reprint/22/3/242.pdf “A perspective of digestive-absorptive function“.] [[American Journal of Clinical Nutrition]] 22, 1969, [http://www.ajcn.org/cgi/reprint/22/3/242.pdf pp. 242-249.]
* Robert K. Crane. [http://www.ajcn.org/cgi/reprint/22/3/242.pdf “A perspective of digestive-absorptive function“.] [[American Journal of Clinical Nutrition]] 22, 1969, [http://www.ajcn.org/cgi/reprint/22/3/242.pdf pp. 242-249.]
* Robert K. Crane. “Speculations about mechanism: The ecstasy of transport”. 21st annual meeting of the Gastrointestinal Section, [[American Physiological Society]], 1971, pp. 1–16.
* Robert K. Crane. “Speculations about mechanism: The ecstasy of transport”. 21st annual meeting of the Gastrointestinal Section, [[American Physiological Society]], 1971, pp.&nbsp;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.
* 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.&nbsp;123–134.
* Robert K. Crane. [http://www.springerlink.com/content/w08x70125u3l02u9/ “The gradient hypothesis and other models of carrier-mediated active transport”] Reviews of Physiology, Biochemistry and Pharmacology, Vol. 78, 1977, pp. 99–159.
* Robert K. Crane. [http://www.springerlink.com/content/w08x70125u3l02u9/ “The gradient hypothesis and other models of carrier-mediated active transport”] Reviews of Physiology, Biochemistry and Pharmacology, Vol. 78, 1977, pp.&nbsp;99–159.
* 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. “Digestion and absorption: water-soluble organics”. International review of physiology, Gastrointestinal physiology II, Vol. 12, Robert K. Crane, Ed., University Park Press, 1977, pp.&nbsp;325–365.
* Robert K. Crane. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638101/pdf/envhper00478-0008.pdf “Intestinal structure and function related to toxicity“.] [[Environmental Health Perspectives]] 33, 1979, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638101/pdf/envhper00478-0008.pdf pp. 3-8.]
* Robert K. Crane. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638101/pdf/envhper00478-0008.pdf “Intestinal structure and function related to toxicity“.] [[Environmental Health Perspectives]] 33, 1979, [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1638101/pdf/envhper00478-0008.pdf pp. 3-8.]
* Robert 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.
* Robert 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.&nbsp;43–69.
* Robert K. Crane. “Questions”. In : [http://catalogue.nla.gov.au/Record/534834 the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport], Editors: Francisco Alvarado and others, [[Institut National de la Santé et de la Recherche Médicale|INSERM]] symposium, No. 26, [[Elsevier]]-North Holland, Amsterdam, 1986; pp. 431–438.
* Robert K. Crane. “Questions”. In : [http://catalogue.nla.gov.au/Record/534834 the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport], Editors: Francisco Alvarado and others, [[Institut National de la Santé et de la Recherche Médicale|INSERM]] symposium, No. 26, [[Elsevier]]-North Holland, Amsterdam, 1986; pp.&nbsp;431–438.


==Further reading==
==Further reading==
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* [http://www.the-aps.org/video/livinghistory/robertcrane.htm Video interview of Robert K. Crane] by Martin Frank, Ph.D., on November 17, 2009, for the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project]. In this interview Crane describes his training, career and professional interactions.
* [http://www.the-aps.org/video/livinghistory/robertcrane.htm Video interview of Robert K. Crane] by Martin Frank, Ph.D., on November 17, 2009, for the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project]. In this interview Crane describes his training, career and professional interactions.
* [http://www.the-aps.org/livinghistory/cvs/cranecv.pdf "For Living History"] by Robert K. Crane : article for the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project].
* [http://www.the-aps.org/livinghistory/cvs/cranecv.pdf "For Living History"] by Robert K. Crane : article for the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project].
* [http://www.the-aps.org/livinghistory/pubs/crane.pdf List of published works of Robert K. Crane] for the the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project].
* [http://www.the-aps.org/livinghistory/pubs/crane.pdf List of published works of Robert K. Crane] for the [[American Physiological Society|American Physiological Society's]] [http://www.the-aps.org/livinghistory/index.htm Living History of Physiology Project].


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Revision as of 20:43, 14 June 2010

Robert K. Crane
Robert K. Crane circa 1960.
Born (1919-12-20) 20 December 1919 (age 104)
Palmyra, New Jersey, United States
NationalityU.S.
Alma materWashington College
Known forCotransport
AwardsAmerican Gastroenterological Association Distinguished Achievement Award (1969)
Dr. Harold Lamport Award, New York Academy of Sciences (1977)
Scientific career
FieldsBiochemistry
InstitutionsWashington University in St. Louis
Chicago Medical School
Rutgers Medical School of the University of Medicine and Dentistry of New Jersey

Robert Kellogg Crane (born December 20, 1919) is an American biochemist best known for his discovery of sodium-glucose cotransport.

Biography

Crane was born on December 20, 1919 in Palmyra, New Jersey, to Wilbur Fiske Crane, architect and engineer, and Mary Elisabeth Crane. He is the grandson of Stephen Crane's brother Wilbur.[1]

He received a B.S. from Washington College in 1942. After serving in the Navy during World War II, Crane studied in biochemistry with Eric Ball at Harvard from 1946 to 1949, then spent a year with Fritz Lipmann at Harvard Medical School, and received a Ph.D. in Medical Sciences in 1950. He then joined Carl Cori’s Department of Biological Chemistry at Washington University School of Medicine in St. Louis, where he began his long interest in glucose metabolism and worked until 1962. After that, he was professor and chairman of the department of Biochemistry at the Chicago Medical School until 1966 and then became professor and chairman of the department of Physiology and Biophysics at Rutgers Medical School (now known as Robert Wood Johnson Medical School) of the University of Medicine and Dentistry of New Jersey until 1986. He received a Sc.D. from Washington College in 1982.[2]

Discovery of cotransport

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 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]

Application in oral rehydration therapy

Crane’s discovery of cotransport led directly to the development of oral rehydration therapy.[6][7] This treatment counter-balances 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]

Applications in pharmaceutical drugs

Crane’s discovery is also used in block buster drugs, such as the SSRI Prozac, 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]

Awards and honors

Selected Bibliography

Further reading

See also

References

  1. ^ Robert K. Crane. "Stephen Crane's Family Heritage". Stephen Crane Studies 4.1, 1995.
  2. ^ a b Robert 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.
  3. ^ a b 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. Model of cotransport on page 448.
  4. ^ Ernest M. Wright and Eric Turk. “The sodium glucose cotransport family SLC5”. 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.”
  5. ^ 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.”
  6. ^ 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.”
  7. ^ J.D. Snyder. “Can Bismuth Improve the Simple Solution for Diarrhea?”. New England Journal of Medicine, Vol. 328, issue 23, 1993, p. 1705. “The discovery in the mid-1960s of the coupled transport of sodium and glucose across the intestinal mucosa led directly to the development of oral rehydration therapy”.
  8. ^ Arthur C Guyton and John E Hall. “Textbook of Medical Physiology”. Elsevier Saunders, Philadelphia, 2006, pp. 814-816.
  9. ^ Canadian Paediatric Society, Nutrition Committee. “Oral rehydration therapy and early refeeding in the management of childhood gastroenteritis”. Paediatrics & Child Health, Vol. 11, issue 8, 2006, pp. 527-531.
  10. ^ 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.”
  11. ^ Editorial. “Water with sugar and salt”. Lancet 2, August 5, 1978, pp. 300–301.
  12. ^ “High Rider Reaches Agreement in Principal with French Biopharmaceutical Company”. PR Newswire, October 9, 2007. “High Rider Capital Inc. (…) [will] develop a chemical process to achieve synthesis of a new class of Sodium Glucose Cotransporters inhibitors (…), for the treatment of Type 2 Diabetes, obesity and other possible metabolic syndrome applications.”
  13. ^ Distinguished Achievement Award. American Gastroenterological Association, 2008, p. 2.
  14. ^ “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).”
  15. ^ “American physiological society”. 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 o[ the Federation of American Societies for Experimental Biology in Chicago, Ill. The title of his lecture is Speculations About Mechanism: The Ecstasy of Transport.”
  16. ^ Robert K. Crane. “Speculations about mechanism: The ecstasy of transport”. 21st annual meeting of the Gastrointestinal Section, American Physiological Society, 1971, pp. 1-16.
  17. ^ Robert K. Crane. “Questions”. In : the proceedings of an International symposium on 25 years of Research on the Brush Border Membrane and Na+ gradient-coupled transport, Editors: Francisco Alvarado and others, INSERM symposium, No. 26, Elsevier-North Holland, Amsterdam, 1986; pp. 431-438.
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