Dr. Ernest Beutler, a Scripps Research Institute physician and researcher who was one of the country's leading experts on diseases of the blood and iron metabolism, died Sunday of lymphoma at Scripps Green Hospital in La Jolla. He was 80.
Beutler was a pioneer in bone marrow transplantation for fighting cancer; made key discoveries about the role of the X-chromosome in women; helped discover G6PD deficiency, the most common clinically significant enzyme deficiency of humans; improved the diagnosis and treatment of Gaucher disease; and developed cladribine, a treatment for both leukemia and multiple sclerosis.
In his spare time, he also wrote the original programming for the widely used software Reference Manager.
"Ernie always had a sparkle in his eye, the energy of a man half his age and a bottomless treasury of new ideas," said Dr. Richard A. Lerner, president of Scripps. He "was a truly extraordinary man who led an exceptional life, full of kindness, wisdom, strength and knowledge."
Beutler developed his interest in blood as a newly commissioned lieutenant in the U.S. Army after he finished his residency in 1953. The Korean War had illustrated the military's need for improved treatments for malaria, and Beutler was sent to Joliet Prison in Illinois to study the severe anemia produced in some people by the malaria drug primaquine.
With his colleagues Ray Dern and Alf Alving, Beutler determined that patients who developed anemia suffered a genetic deficiency of the enzyme glucose-6-phosphate dehydrogenase or G6PD. When stressed by the drug, their red cells were destroyed, producing anemia.
An estimated 400 million people worldwide are now thought to carry this genetic defect. Beutler later developed tests for the condition.
After becoming chairman of the department of medicine at the City of Hope National Medical Center in Duarte in 1959, Beutler built on a chance observation by his lifelong friend Susumu Ohno by exploring the workings of the X chromosome in females.
While males carry both X and Y sex chromosomes, females carry two X chromosomes, one from each parent. Because the two chromosomes carry different genetic information, Beutler deduced that one chromosome must be inactivated in each cell of the body.
He demonstrated that some African American women who inherited the defective gene for G6PD deficiency from only one parent had some blood cells that did not display the deficiency and others that did, indicating that different X chromosomes were being randomly inactivated in the two groups of cells.
