Makio Murayama

Biochemist and scientist

• Pronunciation: mah-KEY-yoh mur-ah-YAH-mah
• Born: August 10, 1912
• Birthplace: San Francisco, California

Makio Murayama’s biochemical research on sickle-cell anemia led to his uncovering the molecular mechanism of the disease. This discovery subsequently allowed for the creation of a new diagnostic test. Murayama was among the first medical researchers to propose using urea in the treatment of sickle-cell anemia.

Areas of achievement: Medicine, science and technology

Early Life

Makio Murayama was one of seven children born in California to Hakuyo and Namiye Murayama. When Murayama was four years old, his father died, which led to his mother sending Murayama to live with a great aunt in Japan. Murayama remained in Japan for ten years and returned to San Francisco at the age of fourteen. He attended San Francisco’s Lowell High School, where he became interested in chemistry. Upon graduation in 1933, Murayama enrolled at the University of California, Berkeley, and received a bachelor’s degree in 1938. He worked throughout college as a janitor in order to fund his education. Murayama remained at the university and earned a master’s in biochemistry and physics in 1940.

Because of the attack on Pearl Harbor during World War II, Murayama’s family was forced to leave California and move to south central Idaho, where they were interned at the Minidoka Relocation Center. Murayama, however, was separated from the family and sent to Chicago, Illinois, to work as a physicist with the Manhattan Project, aimed at creating an atomic bomb. Only after the supervisors realized he was Japanese was Murayama barred from working on the project. He instead accepted a position as a chemist with the Children’s Hospital of Michigan, but he still reported being observed by the government due to his Japanese ancestry.

Life’s Work

It was at the Children’s Hospital of Michigan that Murayama first learned about sickle-cell anemia, an inherited blood disorder in which abnormal hemoglobin in red blood cells causes the cells to “sickle,” becoming narrow and curved; this results in episodes of pain in the bones and joints, as well as other life-threatening complications. Murayama would later move around the country with his colleague James L. Wilson in order to study the disease. The duo first relocated to Bellevue Hospital in New York City, where Murayama assumed the role of the pediatric laboratory director in 1943. They both returned to the University of Michigan in 1945.

In 1953, Murayama received his doctorate in immunochemistry. He completed two years of postdoctoral research on sickle-cell anemia with Linus Pauling, a prominent leader in the field, at the California Institute of Technology in Pasadena. There, Murayama began hypothesizing that the abnormal bonding of hemoglobin causes cells to sickle, but the theory was not initially accepted by colleagues. Murayama moved to the University of Pennsylvania in Philadelphia for two more years of related research, from 1956 to 1958.

After completing his postgraduate work, Murayama accepted a position as a biochemist with the National Institutes of Health (NIH) in Bethesda, Maryland, where he was the only researcher studying sickle-cell disease. Murayama also worked with the National Institute of Arthritis and Metabolic Diseases. During his time in these positions, Murayama built a large hemoglobin molecule model, which he credits with helping him come to understand the sickling process of the disease (1966). By using the model, Murayama discovered that the abnormal amino acids present in the disease disrupt normal hemoglobin bonding and instead cause an abnormal hydrophobic bond. This discovery of the molecular mechanism of cell sickling allowed Murayama to develop a new laboratory test for the disease, termed the Murayama Test. In 1970, Murayama proposed a new and controversial treatment for the disease involving urea, a substance found in urine that breaks the abnormal hemoglobin bonds of sickle-cell disease and reduces the sickling of red blood cells. Murayama published his work on the disease and possible treatments in his 1973 book Sickle Cell Hemoglobin: Molecule to Man.

Murayama’s awards and honors include the Association for Sickle Cell Anemia Award (1969) and the Martin Luther King Jr. Medical Achievement Award (1972). He was acknowledged as a key figure in Asian history by the United States Congress in 1998 as a part of Asian Pacific Heritage Month. He is a supporter of the American Red Cross and the American Association for the Advancement of Science.

Murayama married his wife Sonoko (Soga) Murayama in 1945. He resides in Bethesda, Maryland.

Significance

Murayama overcame the ethnic prejudices of his time to become one of the leading US biochemists researching sickle-cell disease. His discovery of the molecular mechanism of hemoglobin sickling led to the implementation of a new, accurate, and easily performed test for detecting sickle-cell disease. Although Murayama’s is no longer the standard-of-care test for diagnosing the disorder, the fundamental principles of the test allowed for significant advancement in sickle-cell knowledge and research. Originally the subject of much criticism, his proposal to use urea—or more specifically hydroxyurea—for the treatment of sickle-cell anemia remains in clinical practice over forty years later.

Bibliography

Murayama, Makio. “Structure of Sickle Cell Hemoglobin and Molecular Mechanism of the Sickling Phenomenon.” Clinical Chemistry 14.7 (July 1967): 578–88. Print. Murayama’s original article describing his model of hemoglobin that led to the discovery of the molecular pathology of sickle-cell disease.

Nalbandia, Robert M., et al. “Molecular Basis for a Simple, Specific Test for S Hemoglobin: The Murayama Test.” Clinical Chemistry 16.11 (Nov. 1970): 945–50. Print. Journal article detailing the methods of performing the Murayama Test, which diagnoses classical sickle-cell disease and a common hemoglobin C variant.

Tripathi, Avnish, et al. “Clinical Complications in Severe Pediatric Sickle Cell Disease and the Impact of Hydroxyurea.” Pediatric Blood Cancer 56.1 (2011): 90–94. Print. Study detailing the treatment originally proposed by Murayama and colleagues and its current use in modern medicine.