Ernest Beutler

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).

Ernest Beutler (September 30, 1928 – October 5, 2008) was a German-born American hematologist and biomedical scientist.

He made important discoveries about the causes of a number of diseases, including anemias, 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.

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 a member of Pi Lambda Phi and the valedictorian of his graduating class.

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. Jacobson, 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.

Beutler was the Chairman of Medicine at the City of Hope Medical Center in Duarte, CA from 1959 until 1979 and 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.

Born in Berlin, 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 Harald Quandt, son of Magda Quandt née Rietschel, later Magda Goebbels, wife of the German propaganda minister.

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 lifelong 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.