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Four NIH grantees became Nobel laureates during the first week of October. Dr. Richard Axel of the Howard Hughes Medical Institute at Columbia University, who was once an intramural research fellow under Dr. Gary Felsenfeld of NIDDK, shared the Nobel Prize for Physiology or Medicine with Dr. Linda Buck, a researcher at the Fred Hutchinson Cancer Research Center, Seattle. Two of the three scientists who shared the Nobel Prize in Chemistry are also grantees Dr. Irwin Rose of the University of California, Irvine, and Dr. Avram Hershko of the Israel Institute of Technology (Technion) in Haifa; the third chemistry laureate, Dr. Aaron Ciechanover of the Technion, did not receive NIH support.
Axel had been a postdoc in the Laboratory of Molecular Biology, part of what was thenthe National Institute of Arthritis and Metabolic Diseases, for 2 years, 1970-1972. "It was clear almost from the moment he walked in the door that Richard would not be an ordinary postdoctoral fellow," said Felsenfeld, who helped to establish the lab in 1961 and has been there ever since. "He knew exactly what he wanted to do, and he also told me what he thought I should be doing. He was a stimulating presence in the laboratory, and helped us enormously in the early stages of the laboratory's work on chromatin."
Axel had come to NIH, Felsenfeld said, because "[the institute] had a program of training fellowships for M.D.s and was one of the few places where you could get training as an M.D. in laboratory research at the time."
Axel had studied chromatin in Felsenfeld's lab, then continued to be interested in chromatin when he moved to Columbia. He was involved at that time in problems of regulation of gene expression, and "he and his colleagues devised a method of introducing DNA into eukaryotic cells," recalls Felsenfeld. "This was a major contribution to molecular biology, a technique used in virtually every laboratory." Axel turned his attention next to the identification of cell surface receptors, and during the following years began to address problems in neurobiology as a member of the Center for Neurobiology and Behavior at Columbia, an important center for neurobiological research. That led to the work that ultimately resulted in the 2004 Nobel prize.
Axel and Buck were honored for discoveries concerning "odorant receptors and the organization of the olfactory system." In 1991, they reported in the journal Cell the discovery of a large family of receptors selectively expressed in olfactory neurons, which are the cells that detect specific odors. These receptors were later shown to be the cell surface molecules that bind specific odorants, which is the first step in detection and identification.
Dr. James Battey, director of the National Institute on Deafness and Other Communication Disorders, said, "This discovery fueled a revolution in understanding the molecular and cellular interactions responsible for the remarkably sensitive and specific detection of different odors and tastes." NIDCD has funded Buck's work on olfaction since 1992.
Besides NIDCD, other NIH components involved in their work include NIDDK, the National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.
Rose and Hershko, both long-time NIH grantees, won the Nobel Prize in Chemistry "for the discovery of ubiquitin-mediated protein degradation." Said NIH director Dr. Elias Zerhouni of the work: "This is a classic example of how basic research on the chemical mechanism underlying a biological process reveals a pathway essential to life. Understanding how cells maintain internal balance by regulating protein degradation is crucial for knowing how this balance is disrupted in disease. This fundamental research points the way to developing drugs that target the pathway such as Velcade, which is used to treat the blood cancer multiple myeloma."
The chemistry laureates have been supported by the National Institute of General Medical Sciences; the former National Institute of Arthritis and Metabolic Diseases; NIDDK and NCI. Rose first received support from NIH in 1956 and Hershko has been a grantee since 1980. Over the years, NIH has provided $7.5 million to support the two scientists' research.
Since 1954, NIH has supported the work of 34 Nobel laureates in chemistry. And of the 83 American Nobel laureates in physiology or medicine since 1945, 64 either worked at or were funded by NIH before winning his or her prize. Since 1939, a total of 115 Nobel laureates have been supported by NIH.
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