Irwin A. Rose, who shared the 2004 Nobel Prize in Chemistry with two collaborators for unraveling the mystery of how cells identify old and damaged proteins and transform them into pieces for new proteins — discoveries that led to the development of a new class of drugs to fight cancer — died on Tuesday in Deerfield, Mass. He was 88.
His son Howard said Dr. Rose died at the home of another son, Frederic, with whom he had been living.
Dr. Rose became fascinated with the problem of protein disposal in the 1950s, when few biochemists shared his enthusiasm. Scientific inquiry was focused then on how things were created — how cells read the blueprints encoded in DNA and use the information to manufacture proteins.
“He was interested in the opposite: How are proteins destroyed?” said Dr. Jonathan Chernoff, the scientific director of the Fox Chase Cancer Center in Philadelphia,
where Dr. Rose spent most of his career. “There were not very many people working on it,” Dr. Chernoff added in an interview on Tuesday. “I don’t think they particularly considered it an interesting question. But he thought it was an interesting question. And he was right.”
In 1975, other scientists discovered a small protein that was present in numerous tissues and organisms — so many places that it was named ubiquitin. But they had no idea what the protein did.
To pursue the answer, starting in the late 1970s, Dr. Rose collaborated with Avram Hershko of the Technion institute of technology in Israel and Aaron Ciechanover, a graduate student of Dr. Hershko’s. Dr. Rose would later share the Nobel Prize with them.
In 1979, their work took them to Fox Chase’s Institute for Cancer Research, where its director at the time, Dr. Alfred G. Knudson Jr., proposed that they extend their stay to a year.
“It seems that the entire problem of how the breakdown of cellular protein is regulated is accessible,” Dr. Knudson wrote in a memo dated Oct. 18, 1979. “This will surely have great implications for developmental process, for normal physiology, and for cell death and cancer. The implications are enormous.”
In an interview, Dr. Knudson recalled Dr. Rose’s coming to him to request money to finance the extended stay for Dr. Hershko and Mr. Ciechanover — nearly $50,000.
“I knew in a million years, Ernie wouldn’t come to me if it wasn’t important,” Dr. Knudson said. “He’s a person that didn’t talk fast. He felt like anything he talked about, he really thought about. He was a thinker.”
The experiments showed that ubiquitin serves as an inventory control tag — or, as some called it, a “kiss of death” — that is attached to a protein that had outlived its usefulness. The tagged protein is then taken to one of many barrel-shaped chambers called proteasomes, where it is sliced into bits to be recycled into new proteins.
An understanding of this process helped researchers understand diseases, like cystic fibrosis, Parkinson’s and many types of cancer, that occur when the process goes awry.
The team’s research led directly to the development of the drug Velcade, Dr. Chernoff said. Velcade, approved by the Food and Drug Administration in 2003, is used to treat multiple myeloma, a blood cancer, by disrupting the protein disposal system. The pileup of protein produced by growing cancer cells then kills them.
Irwin Allan Rose was born on July 16, 1926, in Brooklyn, a son of Harry Royze, who operated a flooring business, and the former Ella Greenwald. For a time, young Irwin attended Hebrew school.
When he was 13, his family was advised to move to “a high and dry climate” for the benefit of his brother, who had rheumatic fever, Dr. Rose wrote in an autobiographical essay for the Nobel committee. With his father remaining behind to tend to his business, the rest of the family moved to Spokane, Wash., where his mother’s sister took them in. His mother worked at a Navy supply depot, and the children went to public schools.
It was while working summers at a local hospital, Dr. Rose wrote, that “I came to see myself following some career that involved solving medical problems.”