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Nobel Jews
Portrait of Irwin Rose
Photo: Photograph by Avi Blizovsky, cropped from: image:Nobel2004chemistrylaurets.JPG · CC BY-SA 3.0 via Wikimedia Commons

Nobel Prize in Chemistry · 2004

Irwin Rose

A Brooklyn-born enzyme chemist whose lab hosted the discovery of how cells tag unwanted proteins for destruction.

The Nobel citation: “for the discovery of ubiquitin-mediated protein degradation”
Born
July 16, 1926, Brooklyn, NY, USA
Died
June 3, 2015, Deerfield, MA, USA
Affiliation at the time
University of California, USA

Chemistry prize

2004

Shared with 2 other laureates.

Age that year

78years

Born in 1926.

Headline credited impact

60,000–95,000people benefited

Patients treated with proteasome-inhibitor drugs, mostly for multiple myeloma (2003-2025). How it was built

Sources cited

29

Fact-checked September 24, 2026.

  • On the day his Nobel Prize was announced, he carried two test tubes in his shirt pocket and that night tested them on a UC Irvine mass spectrometer.
  • After retiring, he kept a spectrophotometer in his kitchen so he could run small experiments at home.
  • He spent about 20 years on the side trying to learn why cells burn energy to break down their own proteins.
  • A Fox Chase colleague said all the seminal ubiquitin work was done in his lab, yet he never tried to take credit for it.
  • The mystery tag was matched to ubiquitin after a postdoc in the lab next door was asked if he knew of any two proteins joined by a chemical bond.

The breakthrough

Helping uncover the cell's 'kiss of death' tag for unwanted proteins

Your cells are always building proteins, and they must also destroy them: worn-out ones, faulty ones, and ones whose job is done. Since the 1950s scientists had known that this destruction inside cells oddly uses energy, but no one knew why. Rose had been working on that puzzle on the side since 1955. In 1977 Avram Hershko of Israel's Technion began spending sabbaticals and summers in Rose's lab at the Fox Chase Cancer Center in Philadelphia, and Hershko's student Aaron Ciechanover soon joined him. Working with extracts of young red blood cells, the team reported in 1980 that a small protein gets fastened by a strong chemical bond onto proteins due for destruction, often many copies at once. Think of it as a 'shred me' sticker: a protein covered in these stickers is fed into the cell's shredder, the proteasome. Two postdocs in Rose's lab, with a postdoc from the lab next door, showed that the sticker was ubiquitin, a protein that was already known but had no known job. Rose's specialty was working out how enzymes act step by step. With Arthur Haas he showed how the first enzyme in the chain, called E1, spends energy to switch ubiquitin on. He also found and studied an enzyme that frees ubiquitin again so it can be reused. That answered the old puzzle: the energy pays for the tagging.[2],[4],[5],[12],[13],[14],[15]

“So that's my recommendation, do not retire. Do not retire fellas.”
Irwin Rose, Joint interview with his co-laureates in Stockholm, 9 December 2004, after describing the lab he kept in his kitchen following his retirement.[6]

What it meant for humanity

The discovery changed how biologists see the cell. Destroying proteins turned out to be a precise control system, not simple garbage disposal. The Nobel Prize's official explainer listed cell division, DNA repair, quality control of new proteins and parts of the immune defence among the processes it governs. Up to 30% of newly made proteins are destroyed this way because they fail the cell's quality checks. When the system goes wrong, people get sick. A virus linked to cervical cancer hijacks it to destroy p53, a protein that normally guards against cancer. In cystic fibrosis, the most common faulty version of a chloride channel is destroyed before it can reach the cell surface. Once researchers understood the machine, they could aim drugs at it. Bortezomib (Velcade), which blocks the proteasome, was approved in the United States in 2003 for multiple myeloma, a blood cancer. It became part of the preferred treatment and had been given to more than 550,000 patients by 2014. We estimate that 1.2 to 1.9 million patients received it through 2025. It usually extends life rather than curing the disease. Rose's own role was that of host, careful critic and expert on how enzymes work. Several key experiments, including the 1979 finding that the tag is fastened onto proteins bound for destruction, were done in his Fox Chase lab, and two of his postdocs, Keith Wilkinson and Arthur Haas, helped show that the mystery tag was ubiquitin. At UC Irvine, colleagues remembered him sitting with struggling students and young researchers to work out why an experiment had failed.

  • Up to 30% of newly made proteins in a cell fail its quality control and are destroyed through the ubiquitin system the three laureates described.[5]
  • Bortezomib, a drug that blocks the proteasome, became part of the preferred treatment for multiple myeloma and had been given to more than 550,000 patients worldwide by 2014.[18],[19]
  • The system explains how a virus linked to cervical cancer switches off p53, a key anti-cancer protein, by tricking the cell into tagging it for destruction.[5]
  • Three postdocs at Fox Chase, two of them from the Rose-Hershko lab, showed in 1980 that the tag protein was ubiquitin.[4],[13]

Impact in numbers

Rose's main gift was understanding. The work done in his lab showed that cells destroy proteins on purpose and with precision, a control system now known to shape cell division, DNA repair, immunity and the quality control of new proteins. Most of that value cannot honestly be counted. The clearest countable result is proteasome-blocking drugs for multiple myeloma, which we estimate were given to 1.2 to 1.9 million patients from 2003 through 2025. We count patients treated, not lives saved, because myeloma is still incurable and the drugs usually buy time. We credit Rose with 5% of that outcome, the same as each co-laureate, because others characterized the proteasome and companies and clinicians invented and tested the drugs. We also count a harm: severe nerve damage in a minority of bortezomib patients, often temporary. Rose also helped train scientists who shaped the field, which cannot be measured.

HealthFundamental science

Each number is the laureate’s credited share of a real-world outcome, cumulative to 2025. The whole outcome, the share of credit, and the reasoning are shown so you can check the arithmetic. Outcomes shared with other laureates are counted once on the impact page.

  • Medium confidenceRippleModeledHealth

    Patients treated with proteasome-inhibitor drugs, mostly for multiple myeloma (2003-2025)

    60,000–95,000

    people benefited, credited share

    That is 5% of 1.2–1.9 million people benefited since 2003.

    How this number was built

    Bortezomib got US approval in 2003 (Kane). It had been given to >400,000 patients by 2012 (Goldberg) and >550,000 by Oct 2014 (Takeda). For Nov 2014-2025 (~11 yr) we assume 60,000-120,000 new patients a year, about 30-60% of the ~196,000 new myeloma cases a year worldwide (GLOBOCAN 2024). Low: 550k + 11 x 60k = 1.21M; high: 550k + 11 x 120k = 1.87M; rounded 1.2M-1.9M, the same range as Hershko's profile. Carfilzomib users are not added, since most had bortezomib first. 'Benefited' means treated; not all respond and few are cured. Share 0.05: the proteasome was characterized by others, and the drug was invented and proven by company scientists and clinicians. The three 2004 laureates get 0.05 each, 0.15 together.[18],[19],[20],[25]

    Sources: Journal of Cell Biology (via PubMed Central); Takeda Pharmaceutical Company; International Agency for Research on Cancer, Global Cancer Observatory; The Oncologist (via PubMed)

  • HarmLow confidenceRippleModeledHealth

    Patients with severe (grade 3+) nerve damage from bortezomib (2003-2025)

    3,150–8,000

    people harmed, credited share

    That is 5% of 63,000–160,000 people harmed since 2003.

    How this number was built

    Shared outcome; same range for Hershko, Ciechanover and Rose. Base: the 1.2M-1.9M bortezomib patients of the benefit claim; over 400,000 had been treated by 2012 (Goldberg), mostly by vein twice weekly. Grade 3+ neuropathy on that schedule: 9% in the phase 3 APEX trial with a dose-modification guideline (Richardson 2009), 13% in phase 2 trials without one (Richardson 2006), 16% by vein in Moreau 2011 and 15.6% pooled over four randomised trials (Liu 2019), so 9-16%. Later patients mostly get it under the skin: 3.4% pooled (Liu 2019); Hu 2017's risk ratio of 0.4 x 16% = 6.4%, near Moreau's 6%, so 3.4-6.4%. Low: 400k x 9% + 0.8M x 3.4% = 63,000; high: 400k x 16% + 1.5M x 6.4% = 160,000. Most severe cases (64-71%) improved or resolved after dose cuts or stopping, so these are serious episodes, not all permanent. Share 0.05 each, matching the benefit claim: about 3,150-8,000 credited.[18],[21],[22],[27],[28],[29]

    Sources: Journal of Cell Biology (via PubMed Central); Journal of Clinical Oncology (via PubMed); Lancet Oncology (via PubMed); Zhongguo Shi Yan Xue Ye Xue Za Zhi (PubMed record); International Journal of Clinical Pharmacology and Therapeutics (PubMed record); British Journal of Haematology (PubMed record)

The double edge

We found no harmful use of the discovery and no misconduct by Rose. The harms lie in the side effects of drugs built on it. Bortezomib often damages nerves in the hands and feet. In early trials about 13% of patients had severe cases, though most severe cases improved after the dose was cut or stopped. In a 2011 trial, injecting it under the skin instead of into a vein cut severe cases from 16% to 6%. In trials of carfilzomib, a later proteasome blocker, heart and blood-vessel problems were reported in 18% of patients, and serious ones in 8%. The prize also drew debate about credit. Alexander Varshavsky, who shared the 2000 Lasker Award for the ubiquitin system with Hershko and Ciechanover, was left out of the Nobel, while Rose, who had not shared the Lasker, was included. In November 2004, 29 scientists signed a letter in Science titled 'Varshavsky's contributions'. They included Keith Wilkinson and Cecile Pickart, who had both worked with Rose.

  • Moderate

    Nerve damage from bortezomib

    In early trials of twice-weekly intravenous bortezomib, 35% of patients developed new nerve damage and about 13% had severe (grade 3) cases. Of patients with severe cases or who stopped because of it, 71% improved or returned to baseline. A 2011 trial found severe cases fell from 16% to 6% when the drug was injected under the skin.[21],[22]

  • Moderate

    Heart problems with carfilzomib

    A 2018 review of 24 trials with 2,594 myeloma patients found heart and blood-vessel problems reported in 18.1% of patients given carfilzomib, and serious ones (grade 3 or higher) in 8.2%. In the three randomized trials, the risk was roughly double that of patients not given the drug.[26]

  • Minor

    Debate over who was left out of the prize

    The 2000 Lasker Award for the ubiquitin system went to Hershko, Ciechanover and Alexander Varshavsky, and credited Rose with advice and with hosting the work. The 2004 Nobel went to Hershko, Ciechanover and Rose. In November 2004, 29 researchers, including two who had worked with Rose, signed a Science letter on Varshavsky's contributions.[3],[16],[17]

Against the odds

Rose grew up in a secular Jewish family with roots in Hungary on his mother's side and in the Odessa region on his father's. We found no record that he faced antisemitic barriers himself, and he never described any. His hardships were more ordinary. In 1939, when he was 13, his brother's rheumatic fever sent his mother and the boys to Spokane, Washington, for its dry climate. His father stayed behind in Brooklyn to run his flooring business and rarely visited, an arrangement Rose said he never understood. In Spokane he felt out of place and unpopular, and spent much of his time in the public library. No one in his family had done research, and he had no one to ask for advice. The Great Depression had pushed one uncle out of a hoped-for law career and into a government job. The wider climate was less welcoming than today. From the 1920s, elite American universities limited how many Jewish students they admitted. Yale kept an unwritten quota of about 10% for Jewish students from 1923 until the early 1960s, overlapping the years Rose taught at Yale's medical school, from the mid-1950s to 1963. We found nothing showing that it affected him.

  • 1939

    Other

    At 13 he moved with his mother and brother from Brooklyn to Spokane because of his brother's rheumatic fever, while his father stayed behind and rarely visited. He later recalled adapting poorly and being unpopular at school.[2],[6]

  • —

    Quota

    Elite US universities limited Jewish admissions from the 1920s. Yale kept an unwritten 10% quota for Jewish students from 1923 until the early 1960s, the period when Rose taught at its medical school. We found no evidence it affected him personally.[23],[24]

Jewish background

Both parents JewishIdentified as Jewish, secular

Rose was born in Brooklyn to Jewish parents. His mother, Ella Greenwald, was American-born; her siblings were born in Hungary. His father, Harry Royze, came from a family from the Odessa region. In his Nobel autobiography Rose described both families as secular Jews, and the children as even more so. He and his younger brother went to Hebrew school for a time to please their grandfather. We found no record that he practiced Judaism as an adult.[2],[7]

Key dates

  1. July 16, 1926

    Born in Brooklyn, New York, to Ella (Greenwald) and Harry Royze.[1],[2]

  2. 1939

    Moves with his mother and brother to Spokane, Washington. He later studies at Washington State College, serves briefly in the US Navy, then goes to the University of Chicago.[2],[7]

  3. 1952

    Earns his PhD at the University of Chicago, then does postdoctoral work at Western Reserve University and with Severo Ochoa at New York University.[2],[3]

  4. 1955

    Joins Yale's medical school as an instructor in biochemistry and learns from Melvin Simpson that protein breakdown in cells seems to need energy.[2],[4]

  5. 1963

    Moves to the Institute for Cancer Research at the Fox Chase Cancer Center in Philadelphia.[2],[4]

  6. 1977

    Avram Hershko begins working in Rose's lab during sabbaticals and summers, later joined by Aaron Ciechanover.[2],[4],[5],[8]

  7. 1980

    Hershko, Ciechanover, Rose and colleagues report that proteins due for destruction are tagged with many copies of a small protein, soon identified as ubiquitin.[5],[12],[13]

  8. 1982

    With Arthur Haas, works out how the enzyme E1 uses energy to activate ubiquitin.[4],[14]

  9. 1997

    Retires from Fox Chase, moves to Laguna Woods, California, and keeps doing research at UC Irvine.[2],[10]

  10. October 6, 2004

    Awarded a share of the Nobel Prize in Chemistry with Aaron Ciechanover and Avram Hershko for the discovery of ubiquitin-mediated protein degradation.[3],[10],[11]

  11. June 2, 2015

    Dies in his sleep in Deerfield, Massachusetts, aged 88.[2],[9]

Sources

  1. 1.Irwin Rose - Facts · NobelPrize.org (Nobel Prize Outreach)
  2. 2.Irwin Rose - Biographical (from Les Prix Nobel 2004) · NobelPrize.org, 2005
  3. 3.The Nobel Prize in Chemistry 2004 - Press release · NobelPrize.org (Royal Swedish Academy of Sciences), 2004
  4. 4.Ubiquitin at Fox Chase (Nobel Lecture, 8 December 2004) · NobelPrize.org, 2004
  5. 5.The Nobel Prize in Chemistry 2004 - Popular information · NobelPrize.org (Royal Swedish Academy of Sciences), 2004
  6. 6.Irwin Rose - Interview (with Aaron Ciechanover and Avram Hershko, 9 December 2004) · NobelPrize.org, 2004
  7. 7.Early work on the ubiquitin proteasome system, an interview with Irwin Rose · Cell Death & Differentiation 12:1162-1166, 2005
  8. 8.Irwin Allan Rose (1926-2015) (obituary by Keith Wilkinson and Avram Hershko) · Nature 523:532, 2015
  9. 9.Nobel laureate Irwin Rose dead at 88 · UC Irvine News, 2015
  10. 10.Nobel calling: The prize is welcome, but Irwin Rose finds his work equally rewarding · UC Irvine News, 2005
  11. 11.The day Irwin Rose won the Nobel Prize (James S. Nowick) · UC Irvine News, 2015
  12. 12.Proposed role of ATP in protein breakdown: conjugation of protein with multiple chains of the polypeptide of ATP-dependent proteolysis (Hershko A, Ciechanover A, Heller H, Haas AL, Rose IA) · Proceedings of the National Academy of Sciences (via PubMed), 1980
  13. 13.Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes (Wilkinson KD, Urban MK, Haas AL) · Journal of Biological Chemistry (via PubMed), 1980
  14. 14.Ubiquitin-activating enzyme. Mechanism and role in protein-ubiquitin conjugation (Haas AL, Warms JV, Hershko A, Rose IA) · Journal of Biological Chemistry (via PubMed), 1982
  15. 15.Ubiquitin carboxyl-terminal hydrolase acts on ubiquitin carboxyl-terminal amides (Pickart CM, Rose IA) · Journal of Biological Chemistry (via PubMed), 1985
  16. 16.Ubiquitin system for regulated protein degradation - 2000 Albert Lasker Basic Medical Research Award · Lasker Foundation, 2000
  17. 17.Varshavsky's contributions (letter; Baumeister W et al., 29 authors) · Science (via PubMed), 2004
  18. 18.Development of proteasome inhibitors as research tools and cancer drugs (Goldberg AL) · Journal of Cell Biology (via PubMed Central), 2012
  19. 19.FDA Approves VELCADE (bortezomib) for Injection for Previously Untreated Patients with Mantle Cell Lymphoma · Takeda Pharmaceutical Company, 2014
  20. 20.Multiple myeloma fact sheet (GLOBOCAN 2024) · International Agency for Research on Cancer, Global Cancer Observatory
  21. 21.Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib (Richardson PG et al.) · Journal of Clinical Oncology (via PubMed), 2006
  22. 22.Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma (Moreau P et al.) · Lancet Oncology (via PubMed), 2011
  23. 23.How the Ivy League's Jewish quotas shaped higher education (interview with Mark Oppenheimer) · Inside Higher Ed, 2022
  24. 24.Joining the Club: A History of Jews and Yale, by Dan A. Oren (review by Gideon Rose) · Commentary
  25. 25.Velcade: U.S. FDA approval for the treatment of multiple myeloma progressing on prior therapy (Kane RC, Bross PF, Farrell AT, Pazdur R) · The Oncologist (via PubMed), 2003
  26. 26.Carfilzomib-Associated Cardiovascular Adverse Events: A Systematic Review and Meta-analysis (Waxman AJ et al.) · JAMA Oncology (via PubMed), 2018
  27. 27.[Incidence and risk of peripheral neuropathy caused by intravenous and subcutaneous injection of bortezomib] (Liu ZQ et al., meta-analysis of 4 RCTs; Chinese with English abstract) · Zhongguo Shi Yan Xue Ye Xue Za Zhi (PubMed record), 2019
  28. 28.Efficacy and safety of subcutaneous versus intravenous bortezomib in multiple myeloma: a meta-analysis (Hu B et al.) · International Journal of Clinical Pharmacology and Therapeutics (PubMed record), 2017
  29. 29.Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline (Richardson PG et al.) · British Journal of Haematology (PubMed record), 2009

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