Irwin Rose, 1926 – 2015

Nobelist Irwin Rose, an assiduous enzymologist who helped to explain how cells destroy unwanted proteins, died in June. He was 88.

Rose did his prize-winning work in the 1970s and ’80s at the Fox Chase Cancer Center in Philadelphia and shared his 2004 Nobel Prize in chemistry with Israeli scientists Avram Hershko and Aaron Ciechanover of Haifa’s Technion-Israel Institute of Technology.

At a time when other researchers were occupied with how proteins were created, the three found that cells label damaged or old proteins with the protein ubiquitin, which acts, among other things, as a kiss-of-death molecule, keying the proteins to be chopped to bits in proteasomes. This discovery of protein disposal led to the development of a class of cancer drugs and other medicines that can either halt protein breakdown or kill off diseased proteins.

Rose had a reputation for tireless research that was on dramatic display the day he won his Nobel. According to colleagues at the University of California, Irvine, rather than taking time to celebrate the news, Rose fielded some calls and then tucked a couple of test tubes into his shirt pocket and slipped off to analyze their contents at the school’s mass-spectrometry facility.

Irwin Allen Rose, whom everyone called “Ernie,” was born in 1926 in Brooklyn, N.Y. His younger brother caught rheumatic fever, and when a doctor advised the family to move the boy to a high, dry climate, Rose’s mother chose Spokane, Wash., where she had a sister who could take them in. The boys’ father stayed in Brooklyn to tend his flooring business, and Rose, who was 13 at the time of the move, recalled seeing little of him over subsequent years.

The teenage Rose developed a fascination with the brain and a brief interest in a medical career during summers spent working in the psychiatric ward of a local Spokane hospital. But when he enrolled in Washington State College, he found no courses in neurobiology and, as he later wrote in an autobiographical essay for the Nobel committee, shifted his focus to the science of “less obscure matters.”

After a short stint in the U.S. Navy, Rose finished his undergraduate and graduate work at the University of Chicago. His doctoral thesis was an attempt to measure the effect of vitamin B12 on the DNA content of rat tissue. “This project was doomed to failure when the genomic nature of DNA was revealed, and I found that the DNA content per cell of liver was independent of diet,” Rose wrote.

He plucked a new thesis project from his freshman biochemistry notes: a study of whether all of cytidine including its ribose was used in the biosynthesis of deoxycytidine. Rose admitted that working on the enzymology of ribonucleotide reduction would have been a reasonable next step after such a study but found he wasn’t interested in such a “heroic” problem so soon after graduation. Instead, he chose to dig deeper into the principles of enzymology.

After postdoctoral training at Western Reserve University and New York University, Rose became a biochemistry instructor at Yale University, where he met his wife, Ph.D. student Zelda Budenstein. The two moved together to Fox Chase, where Zelda had a lab studying the metabolism of red blood cells and Rose worked to further understanding of enzyme mechanism.

Zelda’s widowed mother lived with the couple and helped care for their growing family of four. In the late 1980s, Zelda left science to devote herself to peace and justice causes, and the family stayed in Philadelphia until Rose’s retirement.

Rose’s early retirement years were spent in Laguna Woods in Southern California. During a videotaped interview with Nobelprize.org, Rose advised fellow scientists not to retire, saying, “I’m very embarrassed when people ask me what are my hobbies. I don’t have any hobbies. I mean it’s just enough to keep up with the things I’m trying to solve.”

According to the Los Angeles Times, Rose worked on a bench in the lab of his friend Ralph Bradshaw at nearby UC Irvine. The school named him a distinguished researcher-in-residence in the Department of Physiology and Biophysics.

Bradshaw told ABC News that in Rose’s later years, as he continued to dissect enzymes and publish, the Nobelist could be counted on to help students and researchers with experiments, still possessed of an intelligence that was “in the stratosphere compared with the rest of us in the field.”

Lauren Dockett Lauren Dockett is the managing editor of ASBMB Today.