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 In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

Biography

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. A Bachelor of Science (BS, BSc, SB, or ScB; from the Latin ') is a bachelor's degree awarded for programs that generally last three to five years. The first university to admit a student to the degree of Bachelor of Science was the University of ...

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 and ...

with Eric Ball at

Harvard Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of higher le ...

from 1946 to 1949, then spent a year with

Fritz Lipmann Fritz Albert Lipmann (; June 12, 1899 – July 24, 1986) was a German-American biochemist and a co-discoverer in 1945 of coenzyme A. For this, together with other research on coenzyme A, he was awarded the Nobel Prize in Physiology or Medicine in ...

Harvard Medical School Harvard Medical School (HMS) is the graduate medical school of Harvard University and is located in the Longwood Medical Area of Boston, Massachusetts. Founded in 1782, HMS is one of the oldest medical schools in the United States and is consi ...

, and received a

Ph.D. A Doctor of Philosophy (PhD, Ph.D., or DPhil; Latin: or ') is the most common degree at the highest academic level awarded following a course of study. PhDs are awarded for programs across the whole breadth of academic fields. Because it is a ...

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 Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms. Carbohydrates are central to many essential metabolic pathways. Plants ...

and worked until 1962. After that, he was professor and chairman of the department of Biochemistry at the

Chicago Medical School The Chicago Medical School (CMS) is a medical school located in North Chicago, Illinois, United States. It is one of the graduate schools of Rosalind Franklin University of Medicine and Science (RFUMS). It was founded in 1912 and obtained app ...

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 The University of Medicine and Dentistry of New Jersey (UMDNJ) was a state-run health sciences institution of New Jersey, United States. It was founded as the Seton Hall College of Medicine and Dentistry in 1954, and by the 1980s was both a major ...

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'', the ScienceDirect collection of electronic journals, '' Trends'', th ...

, Amsterdam, 1983, pp. 43–69. Model of cotransport on page 64.

Discovery of cotransport

In the 1950s, Crane played a central role in establishing that glucose transport into the cell was the first step in

and its control. He demonstrated that neither the

phosphorylation In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

- dephosphorylation mechanism nor other covalent reactions accounted for glucose transport in the intestine. Model of cotransport

In August 1960, in Prague, Crane presented for the first time his discovery of the sodium-glucose

as the mechanism for intestinal glucose absorption.

Cotransport In cellular biology, ''active transport'' is the movement of molecules or ions across a cell membrane from a region of lower concentration to a region of higher concentration—against the concentration gradient. Active transport requires cellul ...

was the first ever proposal of flux coupling in biology and was the most important event concerning carbohydrate absorption in the 20th century.

Application in oral rehydration therapy

Crane's discovery of

led directly to the development of oral rehydration therapy. This treatment counterbalances the loss of water and

electrolyte An electrolyte is a medium containing ions that is electrically conducting through the movement of those ions, but not conducting electrons. This includes most soluble salts, acids, and bases dissolved in a polar solvent, such as water. Upon dis ...

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 and one of the oldest of its kind. It is also the world's highest-impact academic journal. It was founded in England in 1823. The journal publishes original research articles, ...

'' 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."

Applications in pharmaceutical drugs

Crane's discovery is also used in blockbuster drugs, such as the SSRI

Prozac Fluoxetine, sold under the brand names Prozac and Sarafem, among others, is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is used for the treatment of major depressive disorder, obsessive–compulsive disorde ...

, 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

* First Place, Southeast Regional Scholarship Competition, Lehigh University, 1938. * Kent County Scholar, Washington College, 1941–42. * Atomic Energy Commission Predoctoral Fellow, 1948–49. * Fellow,

American Association for the Advancement of Science The American Association for the Advancement of Science (AAAS) is an American international non-profit organization with the stated goals of promoting cooperation among scientists, defending scientific freedom, encouraging scientific respons ...

, 1957. * Headmaster's Alumni Medal, St. Andrew's School, 1963. * Alumni Award, Washington College, 1963. * Fellow
American Institute of Chemists
1968. * Distinguished Achievement Award, American Gastroenterological Association, 1969. * Sir Arthur Hurst Memorial Lectureship,

British Society of Gastroenterology The British Society of Gastroenterology (BSG) is a British professional organisation of gastroenterologists, surgeons, pathologists, radiologists, scientists, nurses, dietitians and others amongst its members, which number over 3,000. It was founde ...

, 1969. * Gastrointestinal Section Lectureship, American Physiological Society, 1971. * Fellow, New York Academy of Sciences, 1976. * Dr. Harold Lamport Award, New York Academy of Sciences, 1977. *

Doctor of Science Doctor of Science ( la, links=no, Scientiae Doctor), usually abbreviated Sc.D., D.Sc., S.D., or D.S., is an academic research degree awarded in a number of countries throughout the world. In some countries, "Doctor of Science" is the degree used f ...

(

honoris causa An honorary degree is an academic degree for which a university (or other degree-awarding institution) has waived all of the usual requirements. It is also known by the Latin phrases ''honoris causa'' ("for the sake of the honour") or ''ad hono ...

), 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,

-North Holland, Amsterdam, 1986; pp. 431–438.

Selected bibliography

* 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 The ''Journal of Biological Chemistry'' (''JBC'') is a weekly peer-reviewed scientific journal that was established in 1905., jbc.org Since 1925, it is published by the American Society for Biochemistry and Molecular Biology. It covers research in ...

'' 188, 1951
pp. 819-832.
* Robert K. Crane and Eric G. Ball
"Relationship of C1402 fixation to carbohydrate metabolism in retina".
''

'' 189, 1951
pp. 269–276.
* Robert K. Crane and

"The relationship of mitochondrial phosphate to aerobic phosphate bond generation".
''

'' 201, 1953
pp. 245–246.
* Robert K. Crane and

"The effect of arsenate on aerobic phosphorylation".
''

'' 201, 1953
pp. 235–243.
* Robert K. Crane and Alberto Sols
"The association of hexokinase with particulate fractions of brain and other tissue homogenates".
''

'' 203, 1953
pp. 273–292.
* Alberto Sols and Robert K. Crane
"The inhibition of brain hexokinase by adenosinediphosphate and sulfhydryl reagents".
''

'' 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".
''

'' 210, 1954
pp. 597–606.
* Alberto Sols and Robert K. Crane
"Substrate specificity of brain hexokinase".
''

'' 210, 1954
pp. 581–595.
* Robert K. Crane, Richard A. Field and

Carl F. Cori Carl Ferdinand Cori, ForMemRS (December 5, 1896 – October 20, 1984) was an Austrian-American biochemist and pharmacologist born in Prague (then in Austria-Hungary, now Czech Republic) who, together with his wife Gerty Cori and Argentine physio ...

"Studies of tissue permeability I. The penetration of sugars into Ehrlich ascites tumor cells".
''

'' 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".
''

'' 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-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 specialised ...

'' 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'' 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'' 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". ''

'' 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.),

, 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,

-North Holland, Amsterdam, 1986, pp. 431–438. * Robert K. Crane
"Robert Kellogg Crane: A Scientist Remembers".

IUBMB Life ''IUBMB Life'' is a peer-reviewed scientific journal of developmental biology that was established in 1999. It is one of four official journals of the IUBMB. The journal is published monthly by John Wiley & Sons. According to the ''Journal Ci ...

, Volume 62, Issue 8, August 2010, pp. 642–645.

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 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