Ernest Beutler
Encyclopedia
Ernest Beutler was a German-born American hematologist and biomedical scientist. He made important discoveries about the causes of a number of diseases, including anemia
s, Gaucher disease, disorders of iron metabolism and Tay-Sachs disease
. He was also among the first scientists to identify X-inactivation
as the genetic basis of tissue mosaicism in female mammals, and pioneered a number of medical treatments, including bone marrow transplantation techniques. Beutler served as a Professor, then Chairman, of the Department of Molecular and Experimental Medicine at The Scripps Research Institute
in La Jolla, California from 1979 until 2008.
to a Jewish family , his family home was located on Reichskanzlerplatz, renamed “Adolf Hitler Platz” after Hitler’s ascent to power, and then Theodor Heuss Platz after the Second World War. Both of his parents (Alfred and Kaethe, née Italiener) were physicians. His mother, a pediatrician, was in pre-war times the physician to the children of Magda Quandt née Rietschel, later Magda Goebbels
, wife of the German propaganda minister. The second of three children, Beutler was preceded by an older brother, Frederick (b. October 3, 1926, later a professor of mathematics at the University of Michigan), and followed by a younger sister, Ruth (b. November 23, 1932, later a clinical psychologist; d. July 14, 1993). In 1935, when Beutler was seven years of age, the family emigrated to the United States to escape Nazi persecution. Beutler was raised in Milwaukee, Wisconsin.
At 15, Beutler enrolled in a special program at the University of Chicago
, founded by Robert Hutchins
, then President of the University. He completed his undergraduate, medical school and residency training at the University of Chicago, receiving his doctorate in medicine in 1950 at the age of 21. He was the valedictorian of his graduating class.
, was aimed at the development of an assay for a humoral radioprotective factor, and reflected a chance observation. Beutler also developed an early interest in iron metabolism, prompted by his clinical observation of the rapid symptomatic improvement of iron deficient patients treated with iron: an improvement that preceded any major hematologic change, and showed that numerous enzymes were sensitive to iron deficiency.
After completing his residency (1953), Beutler applied for a commission as a Lieutenant in the U.S. Army, and was assigned to the Army Malaria Research Program. During this period, he worked at Joliet Prison
in Illinois (1953–1954), investigating anemia produced by antimalarial drugs. In the course of his work, he identified glucose-6-phosphate dehydrogenase
(G-6-PD) deficiency as a genetic defect that leads to the lysis of red blood cells under conditions of oxidative stress. This work hinged on his demonstration that red blood cell glutathione was unstable to oxidative stress. Later, he was to develop an assay for glutathione that was widely used in studies of red cell oxidative metabolism.
He was later transferred to Camp Detrick
in Frederick, Maryland (1954–1955), where he studied Q fever
. He was honorably discharged from the Army with the rank of Captain.
Beutler then joined the faculty of the Department of Medicine at the University of Chicago
, where he studied iron metabolism and red blood cell metabolism. In 1959, he became chairman of the Department of Medicine of the City of Hope National Medical Center
in Duarte, California, and in 1979 assumed the chairmanship of the Department of Clinical Research at the Scripps Clinic and Research Foundation. Three years later, he was asked to become Chairman of a merged department (the Department of Molecular and Experimental Medicine) at Scripps, which later became The Scripps Research Institute
in La Jolla, CA. He maintained his position as Chairman until his 80th birthday, only a few days before his death.
Not long after moving to California, Beutler made one of his most important contributions. A new colleague at the City of Hope and ultimately a life-long friend, Susumu Ohno
had recently demonstrated that the histologically observable Barr body present in the nuclei of mammalian female cells was a hyperchromatic X chromosome. Beutler immediately recognized that this might account for the variable expression of X-linked genes in females heterozygous for X-linked mutations. He soon determined that random X chromosome inactivation causes tissue mosaicism in female mammals, in that each somatic cell expresses one (but not both) of the alleles of X-linked genes with which it is endowed. This he accomplished by showing that two populations of erythrocytes exist in the blood of African American women who are heterozygous for G6PD deficiency. Mary F. Lyon
independently hypothesized that variegated coat colors in mice might arise from random X chromosome inactivation. This, too, flowed from Ohno’s observations.
Beutler’s seminal work on G6PD deficiency led him to further explore hemolytic anemias caused by various enzyme deficiencies. The systematic methodology that he developed became the standard approach to study of patients with these disorders.
Beutler made major contributions to the understanding of Tay-Sachs disease. He purified the enzyme that is aberrant in this disease and demonstrated its multimeric structure. His group cloned the gene responsible for Gaucher disease and developed treatments for this disease, as well as diagnostic tests. Beutler also developed a screening test for galactosemia
, which is used to this day to detect the disease in neonates, and prevent its severe consequences.
Beutler was the first to attempt pharmacologic intervention in sickle cell disease by increasing methemoglobin levels, carboxyhemoglobin levels, and fetal hemoglobin levels. The latter approach depended on administration of estrogen, progesterone and human chorionic gonadotropin. These attempts were unsuccessful, but set the stage for presaged the use of hydroxyurea as a treatment modality.
In addition, Beutler designed the first artificial storage media for red blood cells, introduced the use of mannitol (still a mainstay in red cell preservation), and devised a variety of approaches to maintaining red cell ATP and 2,3-DPG levels and determined the viability of the cells in human volunteers.
He also played a major role in pioneering new therapies for leukemia: bone marrow transplantation in acute leukemia, and 2-chorodeoxyadenosine in chonic leukemias and lymphomas.
Beginning in the mid 1990s, Beutler attempted to positionally clone the mutation responsible for the common adult-onset form of hereditary hemochromatosis. He failed to identify the mutation before it was found by others to affect HFE, a member of the major histocompatibility complex family of proteins. However, in contrast to the reports of others, he found that only about 2% of males and no females homozygous for the mutation showed severe clinical manifestations of the disease. This study depended upon genotypic and phenotypic analysis of more than 43,000 subjects .
Beutler served as an editor of Williams Hematology, a widely used text in this medical specialty, for more than 20 years: from its inception until the last year of his life. In keeping with his editorial interests and his requirements as a publishing scientist, Beutler also wrote the software for the first comprehensive bibliographic retrieval system used by publishing scientists. Later commercialized as Reference Manager
, it is still in wide use today.
He authored more than 800 publications, 19 books, and over 300 book chapters over a 55 year scientific career.
Beutler was a president of both the American Society of Hematology
and the Western Association of Physicians. He also received a Doctor Philosophiae Honoris Causa, Tel Aviv University
.He was also elected to the United States National Academy of Sciences
and was presented with the inaugural Award for Lifetime Achievement from The American Society of Hematology
.
, also a biomedical scientist, occasionally collaborated with Ernest Beutler scientifically,,, over a period spanning more than 30 years.
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
s, Gaucher disease, disorders of iron metabolism and Tay-Sachs disease
Tay-Sachs disease
Tay–Sachs disease is an autosomal recessive genetic disorder...
. He was also among the first scientists to identify X-inactivation
X-inactivation
X-inactivation is a process by which one of the two copies of the X chromosome present in female mammals is inactivated. The inactive X chromosome is silenced by packaging into transcriptionally inactive heterochromatin...
as the genetic basis of tissue mosaicism in female mammals, and pioneered a number of medical treatments, including bone marrow transplantation techniques. Beutler served as a Professor, then Chairman, of the Department of Molecular and Experimental Medicine at The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...
in La Jolla, California from 1979 until 2008.
Early life and education
Born in BerlinBerlin
Berlin is the capital city of Germany and is one of the 16 states of Germany. With a population of 3.45 million people, Berlin is Germany's largest city. It is the second most populous city proper and the seventh most populous urban area in the European Union...
to a Jewish family , his family home was located on Reichskanzlerplatz, renamed “Adolf Hitler Platz” after Hitler’s ascent to power, and then Theodor Heuss Platz after the Second World War. Both of his parents (Alfred and Kaethe, née Italiener) were physicians. His mother, a pediatrician, was in pre-war times the physician to the children of Magda Quandt née Rietschel, later Magda Goebbels
Magda Goebbels
Johanna Maria Magdalena "Magda" Goebbels was the wife of Nazi Germany's Propaganda Minister Joseph Goebbels...
, wife of the German propaganda minister. The second of three children, Beutler was preceded by an older brother, Frederick (b. October 3, 1926, later a professor of mathematics at the University of Michigan), and followed by a younger sister, Ruth (b. November 23, 1932, later a clinical psychologist; d. July 14, 1993). In 1935, when Beutler was seven years of age, the family emigrated to the United States to escape Nazi persecution. Beutler was raised in Milwaukee, Wisconsin.
At 15, Beutler enrolled in a special program at the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...
, founded by Robert Hutchins
Robert Hutchins
Robert Maynard Hutchins , was an educational philosopher, dean of Yale Law School , and president and chancellor of the University of Chicago. He was the husband of novelist Maude Hutchins...
, then President of the University. He completed his undergraduate, medical school and residency training at the University of Chicago, receiving his doctorate in medicine in 1950 at the age of 21. He was the valedictorian of his graduating class.
Academic Career and Principal Scientific Contributions
Beutler pursued a remarkably eclectic research career, and made fundamental contributions in many different areas of science over 56 years of active publication. His first scientific paper was published in 1952, and concerned the effect of X-irradiation on susceptibility to influenza virus in mice. This was an attempt to determine whether irradiated mice might offer a better experimental model in which to detect human viral infections. Not long afterward, he published a paper on the lag phase of E. coli, which is also influenced by X-irradiation. This work, carried out during his residency in the laboratory of Leon O. JacobsonLeon O. Jacobson
Dr. Leon Orris Jacobson , worked at the University of Chicago as a researcher and educator who made tremendous contributions to radiology and hematology, with major impacts on chemotherapy and radiotherapy. He was a recipient of the Roughrider award in 1976...
, was aimed at the development of an assay for a humoral radioprotective factor, and reflected a chance observation. Beutler also developed an early interest in iron metabolism, prompted by his clinical observation of the rapid symptomatic improvement of iron deficient patients treated with iron: an improvement that preceded any major hematologic change, and showed that numerous enzymes were sensitive to iron deficiency.
After completing his residency (1953), Beutler applied for a commission as a Lieutenant in the U.S. Army, and was assigned to the Army Malaria Research Program. During this period, he worked at Joliet Prison
Joliet Prison
Joliet Correctional Center was a prison in Joliet, Illinois, United States from 1858 to 2002. It is featured in the motion picture The Blues Brothers as the prison from which Jake Blues is released at the beginning of the movie...
in Illinois (1953–1954), investigating anemia produced by antimalarial drugs. In the course of his work, he identified glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase
Glucose-6-phosphate dehydrogenase is a cytosolic enzyme in the pentose phosphate pathway , a metabolic pathway that supplies reducing energy to cells by maintaining the level of the co-enzyme nicotinamide adenine dinucleotide phosphate...
(G-6-PD) deficiency as a genetic defect that leads to the lysis of red blood cells under conditions of oxidative stress. This work hinged on his demonstration that red blood cell glutathione was unstable to oxidative stress. Later, he was to develop an assay for glutathione that was widely used in studies of red cell oxidative metabolism.
He was later transferred to Camp Detrick
Fort Detrick
Fort Detrick is a U.S. Army Medical Command installation located in Frederick, Maryland, USA. Historically, Fort Detrick was the center for the United States' biological weapons program ....
in Frederick, Maryland (1954–1955), where he studied Q fever
Q fever
Q fever is a disease caused by infection with Coxiella burnetii, a bacterium that affects humans and other animals. This organism is uncommon but may be found in cattle, sheep, goats and other domestic mammals, including cats and dogs...
. He was honorably discharged from the Army with the rank of Captain.
Beutler then joined the faculty of the Department of Medicine at the University of Chicago
University of Chicago
The University of Chicago is a private research university in Chicago, Illinois, USA. It was founded by the American Baptist Education Society with a donation from oil magnate and philanthropist John D. Rockefeller and incorporated in 1890...
, where he studied iron metabolism and red blood cell metabolism. In 1959, he became chairman of the Department of Medicine of the City of Hope National Medical Center
City of Hope National Medical Center
City of Hope National Medical Center, is a private, not-for-profit clinical research center, hospital and graduate medical school located in Duarte, California, United States...
in Duarte, California, and in 1979 assumed the chairmanship of the Department of Clinical Research at the Scripps Clinic and Research Foundation. Three years later, he was asked to become Chairman of a merged department (the Department of Molecular and Experimental Medicine) at Scripps, which later became The Scripps Research Institute
The Scripps Research Institute
The Scripps Research Institute is an American medical research facility that focuses on research in the basic biomedical sciences. Headquartered in La Jolla, California, with a sister facility in Jupiter, Florida, the institute is home to 3,000 scientists, technicians, graduate students, and...
in La Jolla, CA. He maintained his position as Chairman until his 80th birthday, only a few days before his death.
Not long after moving to California, Beutler made one of his most important contributions. A new colleague at the City of Hope and ultimately a life-long friend, Susumu Ohno
Susumu Ohno
was an Asian American geneticist and evolutionary biologist, and seminal researcher in the field of molecular evolution.- Biography :Susumu Ohno was born of Japanese parents in Seoul, Korea, on February 1, 1928. The second of five children, he was the son of the minister of education of the...
had recently demonstrated that the histologically observable Barr body present in the nuclei of mammalian female cells was a hyperchromatic X chromosome. Beutler immediately recognized that this might account for the variable expression of X-linked genes in females heterozygous for X-linked mutations. He soon determined that random X chromosome inactivation causes tissue mosaicism in female mammals, in that each somatic cell expresses one (but not both) of the alleles of X-linked genes with which it is endowed. This he accomplished by showing that two populations of erythrocytes exist in the blood of African American women who are heterozygous for G6PD deficiency. Mary F. Lyon
Mary F. Lyon
Mary Frances Lyon, FRS is an English geneticist, who is best known for her discovery of X-chromosome inactivation, an important cytogenetic phenomenon.-Childhood and education:...
independently hypothesized that variegated coat colors in mice might arise from random X chromosome inactivation. This, too, flowed from Ohno’s observations.
Beutler’s seminal work on G6PD deficiency led him to further explore hemolytic anemias caused by various enzyme deficiencies. The systematic methodology that he developed became the standard approach to study of patients with these disorders.
Beutler made major contributions to the understanding of Tay-Sachs disease. He purified the enzyme that is aberrant in this disease and demonstrated its multimeric structure. His group cloned the gene responsible for Gaucher disease and developed treatments for this disease, as well as diagnostic tests. Beutler also developed a screening test for galactosemia
Galactosemia
Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...
, which is used to this day to detect the disease in neonates, and prevent its severe consequences.
Beutler was the first to attempt pharmacologic intervention in sickle cell disease by increasing methemoglobin levels, carboxyhemoglobin levels, and fetal hemoglobin levels. The latter approach depended on administration of estrogen, progesterone and human chorionic gonadotropin. These attempts were unsuccessful, but set the stage for presaged the use of hydroxyurea as a treatment modality.
In addition, Beutler designed the first artificial storage media for red blood cells, introduced the use of mannitol (still a mainstay in red cell preservation), and devised a variety of approaches to maintaining red cell ATP and 2,3-DPG levels and determined the viability of the cells in human volunteers.
He also played a major role in pioneering new therapies for leukemia: bone marrow transplantation in acute leukemia, and 2-chorodeoxyadenosine in chonic leukemias and lymphomas.
Beginning in the mid 1990s, Beutler attempted to positionally clone the mutation responsible for the common adult-onset form of hereditary hemochromatosis. He failed to identify the mutation before it was found by others to affect HFE, a member of the major histocompatibility complex family of proteins. However, in contrast to the reports of others, he found that only about 2% of males and no females homozygous for the mutation showed severe clinical manifestations of the disease. This study depended upon genotypic and phenotypic analysis of more than 43,000 subjects .
Beutler served as an editor of Williams Hematology, a widely used text in this medical specialty, for more than 20 years: from its inception until the last year of his life. In keeping with his editorial interests and his requirements as a publishing scientist, Beutler also wrote the software for the first comprehensive bibliographic retrieval system used by publishing scientists. Later commercialized as Reference Manager
Reference Manager
Reference Manager is a commercial reference management software package sold by Thomson Reuters. It was the first commercial software of its kind, originally developed by Ernest Beutler and his son, Earl Beutler, in 1982 through their company Research Information Systems...
, it is still in wide use today.
He authored more than 800 publications, 19 books, and over 300 book chapters over a 55 year scientific career.
Awards and honors
- Member of the National Academy of SciencesUnited States National Academy of SciencesThe National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
(1976) - Fellow of the American Academy of Arts and SciencesAmerican Academy of Arts and SciencesThe American Academy of Arts and Sciences is an independent policy research center that conducts multidisciplinary studies of complex and emerging problems. The Academy’s elected members are leaders in the academic disciplines, the arts, business, and public affairs.James Bowdoin, John Adams, and...
(1975) - Gairdner Foundation International AwardGairdner Foundation International AwardThe Gairdner Foundation International Award is given annually at a special dinner to three to six people for outstanding discoveries or contributions to medical science. Receipt of the Gairdner is traditionally considered a precursor to winning the Nobel Prize in Medicine; as of 2007, 69 Nobel...
(1975) - Member of the Institute of MedicineInstitute of MedicineThe Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
(2004)
Beutler was a president of both the American Society of Hematology
American Society of Hematology
The American Society of Hematology is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted nearly 20,000 attendees. The society publishes the medical journal Blood, one of the most cited peer-review...
and the Western Association of Physicians. He also received a Doctor Philosophiae Honoris Causa, Tel Aviv University
Tel Aviv University
Tel Aviv University is a public university located in Ramat Aviv, Tel Aviv, Israel. With nearly 30,000 students, TAU is Israel's largest university.-History:...
.He was also elected to the United States National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...
and was presented with the inaugural Award for Lifetime Achievement from The American Society of Hematology
American Society of Hematology
The American Society of Hematology is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted nearly 20,000 attendees. The society publishes the medical journal Blood, one of the most cited peer-review...
.
Family
Married to Brondelle May Fleisher in 1950, Beutler had four children (Steven Merrill Beutler, Earl Bryan Beutler, Bruce Alan Beutler, and Deborah Ann Beutler). Bruce A. BeutlerBruce A. Beutler
Bruce Alan Beutler is an American immunologist and geneticist. Together with Jules A. Hoffmann, they received one-half of the 2011 Nobel Prize in Physiology or Medicine, for "their discoveries concerning the activation of innate immunity" Bruce Alan Beutler (born December 29, 1957) is an American...
, also a biomedical scientist, occasionally collaborated with Ernest Beutler scientifically,,, over a period spanning more than 30 years.
External links
- Ernest Beutler (1928 - 2008) - Profile, including an oral history, from The American Society of HematologyAmerican Society of HematologyThe American Society of Hematology is a professional organization representing hematologists. It was founded in 1958. Its annual meeting is held in December of every year and has attracted nearly 20,000 attendees. The society publishes the medical journal Blood, one of the most cited peer-review...
. - Scientific Publications – All publications of articles by Ernest Beutler listed in PubMed.