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Robert Kellogg Crane (December 20, 1919 – October 31, 2010) was an American
biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...
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. He received a B.S. from Washington College in 1942. After serving in the Navy during World War II, Crane studied in
biochemistry Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, a ...
with Eric Ball at
Harvard Harvard University is a private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher lear ...
from 1946 to 1949, then spent a year with Fritz Lipmann at
Harvard Medical School Harvard Medical School (HMS) is the medical school of Harvard University and is located in the Longwood Medical and Academic Area, Longwood Medical Area in Boston, Massachusetts. Founded in 1782, HMS is the third oldest medical school in the Un ...
, and received a Ph.D. in Medical Sciences in 1950.


Career

He 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.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 Elsevier ( ) is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell (journal), Cell'', the ScienceDirect collection of electronic journals, ...
, Amsterdam, 1983, pp. 43–69. Model of cotransport on page 64.
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 In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writ ...
- dephosphorylation mechanism nor other covalent reactions accounted for glucose transport in the intestine. 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. Cotransport was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century. Crane's discovery of cotransport led directly to the development of oral rehydration therapy. This treatment counterbalances the loss of water and
electrolyte An electrolyte is a substance that conducts electricity through the movement of ions, but not through the movement of electrons. This includes most soluble Salt (chemistry), salts, acids, and Base (chemistry), bases, dissolved in a polar solven ...
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. Oral rehydration therapy saves the lives of millions of cholera patients in underdeveloped countries since the 1980s. In 1978, ''
The Lancet ''The Lancet'' is a weekly peer-reviewed general medical journal, founded in England in 1823. It is one of the world's highest-impact academic journals and also one of the oldest medical journals still in publication. The journal publishes ...
'' 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." Crane's discovery is also used in blockbuster drugs, such as the
SSRI Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that are typically used as antidepressants in the treatment of major depressive disorder, anxiety disorders, and other psychological conditions. SSRIs primarily work by ...
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.


Awards and honors

* Distinguished Achievement Award, American Gastroenterological Association, 1969. * Sir Arthur Hurst Memorial Lectureship, British Society of Gastroenterology, 1969. * Gastrointestinal Section Lectureship, American Physiological Society, 1971. * Dr. Harold Lamport Award, New York Academy of Sciences, 1977. *
Doctor of Science A Doctor of Science (; most commonly abbreviated DSc or ScD) is a science doctorate awarded in a number of countries throughout the world. Africa Algeria and Morocco In Algeria, Morocco, Libya and Tunisia, all universities accredited by the s ...
( 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.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 Elsevier ( ) is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell (journal), Cell'', the ScienceDirect collection of electronic journals, ...
-North Holland, Amsterdam, 1986; pp. 431–438.


Selected publications

* Robert K. Crane and Anna K. Keltch
"Dinitrocresol and phosphate stimulation of the oxygen consumption of a cell-free oxidative system obtained from sea urchin eggs".
'' The Journal of General Physiology'' 32, 1949
pp. 503–509.
* Robert K. Crane and Eric G. Ball
"Factors affecting the fixation of C1402 by animal tissues".
'' Journal of Biological Chemistry'' 188, 1951
pp. 819-832.
* Robert K. Crane and Eric G. Ball
"Relationship of C1402 fixation to carbohydrate metabolism in retina".
'' Journal of Biological Chemistry'' 189, 1951
pp. 269–276.
* Robert K. Crane and Fritz Lipmann
"The relationship of mitochondrial phosphate to aerobic phosphate bond generation".
'' Journal of Biological Chemistry'' 201, 1953
pp. 245–246.
* Robert K. Crane and Fritz Lipmann
"The effect of arsenate on aerobic phosphorylation".
'' Journal of Biological Chemistry'' 201, 1953
pp. 235–243.
* Robert K. Crane and Alberto Sols
"The association of hexokinase with particulate fractions of brain and other tissue homogenates".
'' Journal of Biological Chemistry'' 203, 1953
pp. 273–292.
* Alberto Sols and Robert K. Crane
"The inhibition of brain hexokinase by adenosinediphosphate and sulfhydryl reagents".
'' Journal of Biological Chemistry'' 206, 1954
pp. 925–936.
* Robert K. Crane and Alberto Sols
"The non-competitive inhibition of brain hexokinase by glucose 6-phosphate and related compounds".
'' Journal of Biological Chemistry'' 210, 1954
pp. 597–606.
* Alberto Sols and Robert K. Crane
"Substrate specificity of brain hexokinase".
'' Journal of Biological Chemistry'' 210, 1954
pp. 581–595.
* Robert K. Crane, Richard A. Field and Carl F. Cori
"Studies of tissue permeability I. The penetration of sugars into Ehrlich ascites tumor cells".
'' Journal of Biological Chemistry'' 224, 1957
pp. 649–662.
* Robert K. Crane and T. Hastings Wilson
"In vitro method for the study of the rate of intestinal absorption of sugars".
''Journal of Applied Physiology'', Vol. 12, 1958, pp. 145–146. * Stephen M. Krane and Robert K. Crane
"The accumulation of D-galactose against a concentration gradient by slices of rabbit kidney cortex".
'' Journal of Biological Chemistry'' 234, 1959
pp. 211–216.
* Robert K. Crane
"Intestinal absorption of sugars".
'' Physiological Reviews'', Vol. 40, 1960, pp. 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. 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 ''Biochimica et Biophysica Acta'' (''BBA'') is a peer review, peer-reviewed scientific journal in the field of biochemistry and biophysics that was established in 1947. The journal is published by Elsevier with a total of 100 annual issues in ten ...
'' 52, 1961, pp. 281–293. * Robert K. Crane. "Hypothesis for mechanism of intestinal active transport of sugars". Federation Proc. 21, 1962, pp. 891–895. * David Miller and Robert K. Crane
"The digestion of carbohydrates in the small intestine".
'' American Journal of Clinical Nutrition'' 12, 1963
pp. 220–227.
* Alexander Eichholz and Robert K. Crane
"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 The ''Journal of Cell Biology'' is a peer-reviewed scientific journal published by Rockefeller University Press. History In the early 1950s, a small group of biologists began to explore intracellular anatomy using the emerging technology of e ...
'' 26, 1965
pp. 687–691.
* Jane Overton, Alexander Eichholz and Robert K. Crane
"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 The ''Journal of Cell Biology'' is a peer-reviewed scientific journal published by Rockefeller University Press. History In the early 1950s, a small group of biologists began to explore intracellular anatomy using the emerging technology of e ...
'' 26, 1965
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. * 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 ''Biochimica et Biophysica Acta'' (''BBA'') is a peer review, peer-reviewed scientific journal in the field of biochemistry and biophysics that was established in 1947. The journal is published by Elsevier with a total of 100 annual issues in ten ...
'' 193, 1969, pp. 179–192. * Robert K. Crane
"A perspective of digestive-absorptive function".
'' American Journal of Clinical Nutrition'' 22, 1969
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. * 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
"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. "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
"Intestinal structure and function related to toxicity".
'' Environmental Health Perspectives'' 33, 1979
pp. 3–8.
* 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 Elsevier ( ) is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell (journal), Cell'', the ScienceDirect collection of electronic journals, ...
, Amsterdam, 1983, pp. 43–69. * 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 Elsevier ( ) is a Dutch academic publishing company specializing in scientific, technical, and medical content. Its products include journals such as ''The Lancet'', ''Cell (journal), Cell'', the ScienceDirect collection of electronic journals, ...
-North Holland, Amsterdam, 1986, pp. 431–438. * Robert K. Crane
"Robert Kellogg Crane: A Scientist Remembers".
IUBMB Life, Volume 62, Issue 8, August 2010, pp. 642–645.


Further reading

* C. A. Pasternak
"A Glance Back Over 30 Years"
'' Bioscience Reports'', Vol. 13, No. 4, 1993
pp. 183–190.
* Robert Joseph Paton Williams
"The History of Proton-Driven ATP Formation".
'' Bioscience Reports'', Vol. 13, No. 4, 1993
pp. 193, 200–201, 203, 207.
* Daphne A Christie, E M. Tansey (eds)
"Intestinal absorption".
''Wellcome Witnesses to Twentieth Century Medicine'', Vol. 8, The
Wellcome Trust The Wellcome Trust is a charitable foundation focused on health research based in London, United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome (founder of Burroughs Wellcome, one of the predec ...
, London, 2000
pp. 17–35.
* Stephen M. Kavica, Eric J. Frehmb and Alan S. Segalc
"Case Studies in Cholera: Lessons in Medical History and Science".
''Yale Journal of Biology and Medicine'', Vol. 72, Issue 6, 1999
p. 404.


See also

* Cotransport * Cotransporter * Sodium-glucose transport proteins * Glucose transporter * Oral rehydration therapy


References


External links


Video interview of Robert K. Crane
by Martin Frank, Ph.D., on November 17, 2009, for the American Physiological Society'sbr>Living History of Physiology Project
In this interview Crane describes his training, career and professional interactions.
"For Living History"
by Robert K. Crane: article for the American Physiological Society'
Living History of Physiology Project

List of published works of Robert K. Crane
for the American Physiological Society'sbr>Living History of Physiology Project
{{DEFAULTSORT:Crane, Robert K. 1919 births 2010 deaths 20th-century American biochemists Washington College alumni Harvard Medical School alumni Rosalind Franklin University of Medicine and Science faculty University of Medicine and Dentistry of New Jersey faculty Washington University in St. Louis faculty People from Palmyra, New Jersey United States Navy personnel of World War II