This was published 8 years ago
Nobel prize for chemistry with proteins
Irwin Rose shared the 2004 Nobel Prize in Chemistry with two collaborators for unravelling the mystery of how cells identify old and damaged proteins and transform them into pieces for new proteins.
Irwin Rose shared the 2004 Nobel Prize in Chemistry with two collaborators for unravelling 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.
He 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.
Obituaries dinkus.
"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 Rose spent most of his career. "There were not very many people working on it," Chernoff added. "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, Rose collaborated with Avram Hershko of the Technion-Israel Institute of Technology in Haifa, Israel, and Aaron Ciechanover, a graduate student of Hershko's. Rose later shared 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 jnr, 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," Knudson wrote in a memo dated October 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, Knudson recalled Rose's coming to him to request money to finance the extended stay for Hershko and Ciechanover - nearly $50,000.
"I knew in a million years, Ernie wouldn't come to me if it wasn't important," 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, 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 pile-up 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 his wife, Ella (nee 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, 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, Washington, 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, Rose wrote, that "I came to see myself following some career that involved solving medical problems."
After high school he attended Washington State College, but his studies were interrupted by naval service in World War II. He completed his bachelor's degree at the University of Chicago in 1948 and obtained a doctorate in biochemistry there in 1952.
He went on to become a faculty member of the Yale School of Medicine's biochemistry department, from 1954 to 1963, when he moved to Fox Chase. There, while studying a variety of enzymes, he continued to ponder, almost as a sidelight, the question of protein disposal.
"The smartest thing was sticking with this problem," Chernoff said.
Rose met Hershko at a scientific conference.
He was a member of the National Academy of Sciences.
After he retired from Fox Chase, Rose and his wife moved to Laguna Woods, California, not far from the University of California, Irvine, where an old friend, Ralph Bradshaw, now retired, worked as a physiology and biophysicist professor. Bradshaw recalled in an interview the morning Rose showed up at his office without warning. "No call," Bradshaw said. "No message. All of a sudden, Ernie was in my office."
Rose was looking for laboratory space to conduct some research, and Bradshaw let him use some of his. The university soon appointed Rose to a research position.
James S Nowick, an Irvine chemistry professor who also collaborated with Rose, remembered the October day in 2004 that he learned that Rose had received a Nobel Prize. Hours later, Nowick was able to get through by telephone to offer congratulations.
"By then, he was just fed up with the phone ringing," Nowick said. "He was so happy to talk with me. By the end of the day, he was back in the laboratory at UCI chemistry department, doing experiments."
Irwin Rose is survived by his wife, Zelda, children Howard, Frederic and Robert and five grandchildren. A daughter, Sarah, died in 2005.
Kenneth Chang, New York Times