Irwin A. Rose, the Brooklyn-born biochemist who shared a 2004 Nobel Prize for explaining how living cells recycle and dispose of unneeded molecules, a discovery that opened the way for new medical therapies, died June 2 in Deerfield, Mass., at the home of a son. He was 88.
His son Robert Rose confirmed the death but did not cite a cause.
In the cellular process discovered by Dr. Rose and two Israeli scientists, a molecule called ubiquitin marks unwanted molecules for destruction by latching onto them in what has been described as a molecular “kiss of death.”
Ubiquitin, as its name suggests, comes from the same root as ubiquitous, in recognition of its virtual omnipresence within cells.
The delineation of the role of ubiquitin was carried out in the early 1980s at the Fox Chase Cancer Center in Philadelphia by Dr. Rose and the two Israelis who were there on sabbaticals, Aaron Ciechanover and Avram Hershko.
In the Bible, Ecclesiastes speaks of a time to build up and a time to break down. To a great degree, modern biology has been the story of DNA and its role in building up the proteins required for life.
Dr. Rose and colleagues focused their efforts on the other part of the cycle of life: how molecules are broken down. In this, they were recognized in their discipline as boldly swimming against the current.
Yet the work seized the scientific imagination, and the dramatic nature of the processes identified could be recognized in the vivid language of the news release issued in 2004 by the Nobel committee.
It was in the news release that the clutching of the doomed proteins by the ubiquitin was described as a biochemical “kiss of death.”
In another seeming departure from the often staid language of the scientific world, the release went on to say that after being targeted, the unwanted proteins were sent into what were in effect cellular “waste disposers.”
These structures, contained within individual cells, are known as proteasomes and, in them, undesired protein molecules are chopped into bits.
Not an indiscriminate sweeping out of the cell interior, the destruction process mediated by ubiquitin is highly specific and selective.
After embracing the particular protein molecule that is fated for destruction, ubiquitin journeys with it through the cell to the proteasomes. A process of shape recognition prompts proteasome ingestion of the unwanted molecule. Before this occurs, according to scientists’ understanding, the ubiquitin detaches, taking its leave of the soon-to-be consumed protein, to return to the job for which it was created.
In itself, the mere elucidation of so subtle and sophisticated a molecular process might seem a milestone of research.
To the Nobel Prize winners’ colleagues, it was even more, offering new approaches to the understanding of such basic processes of life as DNA repair, cell division and the operation of the body’s immune system.
Specialists in the field have said that a cell’s inability to eliminate unwanted proteins may lead to illness, including types of cancer. Specialists in the field have said that understanding the process by which cells destroy proteins may aid in developing treatments for cystic fibrosis, forms of cancer and other ailments.
At the time the Nobel Prize was awarded, Harvard cell biologist Alfred L. Goldberg lauded it as a “particularly insightful” choice. Dr. Rose and the two Israelis, he wrote, were scientists “whose seminal work has altered modern biology.”
Since the inception of the Nobel Prize, Americans have won almost half . Many American winners have immigrated from other countries, but Dr. Rose’s first school was P.S. 134 in Brooklyn and all his succeeding work was done in this country.
Irwin Allan Rose, who was often called Ernie, was born July 16, 1926, and lived in Brooklyn until the age of 13, when it was decided that dry climate might benefit a younger brother with rheumatic fever. His mother took her two sons to Spokane, Wash., where they had relatives.
Dr. Rose’s father stayed in New York to look after his flooring business — an arrangement, the future Nobel laureate later wrote, “that I never understood and felt conflicted about. Father’s visits were few and far between.” His mother did secretarial work in the Navy Supply Depot in Spokane during World War II.
In summers, Dr. Rose worked at a local hospital, which ignited his interest in “solving medical problems.” After Navy service as a radio technician during the war, he went to the University of Chicago on the GI Bill and received a bachelor’s degree in 1948 and a doctorate in biochemistry in 1952.
Within a few years, he joined the faculty of the Yale University School of Medicine, where he met his future wife, Zelda Budenstein, a graduate student who became a research scientist.
In a Nobel Prize biographical sketch, Dr. Rose acknowledged the contributions of his mother-in-law to his wife’s career and his own. Her help with the Roses’ four children helped make time for the couple to pursue their careers in science.
In addition to his wife, of Deerfield, survivors include twin sons Frederic Rose of Deerfield and Robert Rose of Raleigh, N.C.; another son, Howard Rose of San Francisco; a brother; and five grandchildren. A daughter, Sarah Rose, died in 2005.
Dr. Rose, who became a member of the National Academy of Sciences, left Yale for Fox Chase in 1963 and remained there until his retirement in 1995. He moved to Laguna Woods, Calif., but was restless without a laboratory and, through a friend, continued to conduct research at the nearby University of California at Irvine. He was at Irvine when the Nobel Prize was announced.
Colleagues described him as modest, unpretentious and devoted to his work. On the day the Nobel Prize was announced, the California university said, “he tucked two test tubes in his shirt pocket and that night quietly slipped into” a campus building housing a powerful mass spectrometer to analyze the contents.