Ernest Beutler (September 30, 1928 - October 5, 2008) is a German-born hematologist and biomedicalist. He made important discoveries about the causes of a number of diseases, including anemia, Gaucher's disease, metabolic iron disorders and Tay-Sachs disease. He was also among the first scientists to identify inactivation of X as the genetic basis of tissue mosaics in female mammals, and pioneered a number of medical treatments, including bone marrow transplantation techniques. Beutler served as Professor, then Chairman, Department of Molecular and Experimental Medicine at The Scripps Research Institute in La Jolla, California from 1979 to 2008.
Video Ernest Beutler
Early life and education
Born in Berlin, the Jewish family, his family home is located in the Reichskanzlerplatz, renamed "Adolf Hitler Platz" after Hitler's ascent to power, and then Theodor Heuss Platz after the Second World War. Both his parents (Alfred and Kaethe, nÃÆ'  © e Italiener) are doctors. His mother, a pediatrician, was in the pre-war doctor for Harald Quandt, son of Magda Quandtnà © é e Rietschel, then Magda Goebbels, wife of German propaganda minister. The second of three children, Beutler was preceded by his older brother Frederick (October 3, 1926, then a professor of mathematics at the University of Michigan), and followed by a younger sister, Ruth (November 23, 1932), then a clinical psychologist , d 14 July 1993). In 1935, when Beutler was seven years old, the family emigrated to the United States to escape the Nazi persecution. Beutler grew up 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 education, medical school and residency training at the University of Chicago, receiving his doctorate in medicine in 1950 at the age of 21 years. He is the heir of his graduation speech.
Maps Ernest Beutler
Academic career and scientific contribution
Beutler pursued a very eclectic research career, and made fundamental contributions in various disciplines during the 56 years of active publication. His first scientific paper was published in 1952, and concerns the effects of X-irradiation on susceptibility to influenza viruses in mice. This is an attempt to determine whether the irradiated mice might offer a better experimental model for detecting human viral infections. Not long after that, he published a paper about the lag phase of E. coli , which is also influenced by X-irradiation. This work, undertaken during his residency at Leon O. Jacobson's laboratory, is devoted to the development of tests for radiopa- phective humoral factors, and reflects the observation of opportunities. Beutler also developed an early interest in iron metabolism, driven by his clinical observation of the rapid increase of symptoms of iron-deficient patients treated with iron: improvements that precede major hematologic changes, and show that many enzymes are sensitive to iron deficiency.
After completing his residency (1953), Beutler applied for a commission as Lieutenant in the US Army, and was assigned to the Army's Malaria Research Program. During this period, he worked at Joliet Jail in Illinois (1953-1954), investigating anemia produced by antimalarial drugs. In his work, he identifies the deficiency of glucose-6-phosphate dehydrogenase (G-6-PD) as a genetic defect that leads to lysis of red blood cells under oxidative stress conditions. This work relies on his demonstration that red cell glutathione is unstable against oxidative stress. Later, he developed a test for glutathione that is widely used in the study of oxidative metabolism of red blood cells.
He was then transferred to Camp Detrick in Frederick, Maryland (1954-1955), where he studied Q fever. He was dismissed with respect 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 National Hope City Medical Center in Duarte, California, and in 1979 took over the Department of Clinical Research at the Scripps Clinic and Research Foundation. Three years later, he was asked to become Chair of the combined department (Department of Molecular and Experimental Medicine) at Scripps, which later became The Scripps Research Institute in La Jolla, CA. He retained his position as Chairman until his 80th birthday, just days before his death.
Not long after moving to California, Beutler made one of his most important contributions. A new colleague at City of Hope and finally a lifelong friend, Susumu Ohno recently pointed out that Barr's histologically observed body present in the female cell nucleus of a mammal is a hyperchromatic X chromosome. Beutler soon realized that this might explain the expression of X-linked gene variables in heterozygous women for an X-linked mutation. He immediately decided that the inactivation of random X chromosomes caused tissue mosaics in female mammals, where each somatic cell expresses one (but not both) of the blessed X-linked gene alleles. This he accomplished by showing that two erythrocyte populations exist in the blood of African American women who are heterozygous for G6PD deficiency. Mary F. Lyon independently hypothesized that multicolored fur color in rats may arise from the inactivation of chromosomes X randomly. This, too, flows from Ohno's observation.
Beutler's seminal work on G6PD deficiency leads him to further explore hemolytic anemia caused by various enzyme deficiencies. The systematic methodology he developed into a standard approach to studying patients with this disorder.
Beutler made a major contribution to understanding Tay-Sachs disease. He purified the deviant enzyme in this disease and showed its multimeric structure. His group cloned the gene responsible for Gaucher's disease and developed treatments for the disease, as well as diagnostic tests. Beutler also developed a screening test for galactosemia, which is used today to detect disease in neonates, and prevent severe consequences.
Beutler was the first to attempt pharmacological interventions in sickle cell disease by increasing levels of methemoglobin, carboxyhemoglobin levels, and fetal hemoglobin levels. The final approach depends on the administration of estrogen, progesterone and human chorionic gonadotropin. These attempts are unsuccessful, but set the stage for presaged hydroxyurea use as a treatment modality.
In addition, Beutler designed the first artificial storage media for red blood cells, introducing the use of mannitol (still a mainstay in the preservation of red blood cells), and designing various approaches to maintaining red blood cell ATP and 2.3-DPG levels and determined. the survival of cells in human volunteers.
She also plays a major role in pioneering new therapies for leukemia: bone marrow transplantation in acute leukemia, and 2-chorodeoxyadenosine in chonic leukemia and lymphoma.
Beginning in the mid-1990s, Beutler attempted to clone mutations responsible for the adult onset form of hereditary hemochromatosis. He failed to identify mutations before they were discovered by others to influence HFE, a member of the major histocompatibility protein family. However, in contrast to other people's reports, he found that only about 2% of men and no homozygous women for mutations exhibit severe clinical manifestations of the disease. This study relies on genotypic and phenotypic analysis of over 43,000 subjects.
Beutler served as editor of Williams Hematology, a text widely used in medical specialties, for more than 20 years: from the beginning to the last year of his life. In keeping with its editorial interests and requirements as a publishing scientist, Beutler also wrote software for the first comprehensive bibliography collection system used by publishing scientists. Later commercialized as Reference Manager, is still widely used today.
He wrote over 800 publications, 19 books, and over 300 book chapters during his 55 years of scientific career.
Awards and honors
- Member of the National Academy of Sciences (1976)
- Fellow of the American Academy of Art and Science (1975)
- Gairdner Foundation International Award (1975)
- Member of the Institute of Medicine (2004)
Beutler is president of the American Society of Hematology and the Western Association of Physicians. He also received Doctor Philosophiae Honoris Causa, Tel Aviv University. He was also elected to the United States National Academy of Sciences and was given the Inaugural Award for Lifetime Achievement of The American Society of Hematology.
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. Beutler, also a biomedical scientist and 2011 Nobel Laureate in Physiology or Medicine, occasionally collaborated with Ernest Beutler scientifically, over a period spanning over 30 years.
References
External links
Ernest Beutler (1928 - 2008) - Profile, including oral history, from The American Society of Hematology.Source of the article : Wikipedia
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