The principle was soon demonstrated for other genes on the X chromosome as well. Independently, the English geneticist Mary F. Lyon demonstrated the same phenomenon in mice.
The concept ultimately had a more widely applied application in explaining the origin of tumor cells.
Beutler also studied genetic diseases, especially those that manifested in blood cells. One such disorder is galactosemia, a rare hereditary enzyme deficiency in which individuals are unable to metabolize galactose, a sugar found in milk.
He developed a test for the disease in carriers and newborns and identified a variant of the disease gene that was harmless but could be confused with the genuine item. He named it the Duarte variant.
He also purified the enzyme that is dysfunctional in Tay-Sachs disease, a fatal lipid storage disorder.
In 1970, he recognized the potential importance of bone marrow transplants and recruited Dr. Karl Blume to head the program at City of Hope. He and Blume published the first paper supporting the use of marrow transplants from a relative or volunteer donor to treat acute leukemia.
In 1978, Beutler moved to what was then called the Scripps Clinic and Research Foundation, where he established another bone marrow transplant program and continued his work on genetic disorders.
He isolated the gene that is defective in Gaucher disease -- a severe disorder marked by the accumulation of a fatty substance called glucocerebroside in the bone marrow, spleen and liver -- devised a diagnostic test and developed treatments for it.
He also attempted to isolate the gene for hereditary hemochromatosis, in which iron accumulates at high levels throughout the body, but was beaten to it by other researchers.
Hemochromatosis was once thought to be the most common genetic disorder among Europeans because about five out of every 1,000 carry the mutant gene that causes it. But in his studies on 43,000 subjects, Beutler found that only about 2% of those with the gene actually develop symptoms. He argued forcefully that proposed screening programs for the disorder should be abandoned because they would produce a very high number of false positives.
Throughout his career, Beutler had accumulated a very large number of scientific references that he had originally kept on index cards. While he was at City of Hope, he had a programmer develop a program that would allow him to recover references by keyword or author on a primitive PDP-1140 computer.
