Roger Y. Tsien

Roger Y. Tsien 錢永健

Born	February 1, 1952 (1952-02-01) (age 60) New York City, United States
Residence	San Diego
Citizenship	United States
Nationality	American
Fields	Biochemistry
Institutions	UC San Diego UC Berkeley
Alma mater	Harvard University University of Cambridge
Known for	GFP Calcium imaging
Notable awards	Nobel Prize in Chemistry (2008) E. B. Wilson Medal (2008) Rosenstiel Award (2006) Wolf Prize in Medicine (2004) Keio Medical Science Prize (2004) Dr A.H. Heineken Prize (2002) Artois-Baillet Latour Health Prize (1995) Gairdner Foundation International Award (1995)

Personal life

Tsien and his family are descendants of the royal family of the Kingdom of Wuyue. According to historic records, Tsien is the 34th-generational grandson of the King Qian Liu (Tsien Liu).^[4]

Tsien had a number of accomplished engineers in his extended family, including his father Hsue-Chu Tsien who was a mechanical engineer and his mother's brothers who were engineering professors at MIT. Both of Tsien's parents came from Zhejiang Province, China. The famous rocket scientist Tsien Hsue-shen, regarded as the co-founding father of JPL of Caltech and later the director of the Chinese ballistic-missile and space programs, is a cousin of Tsien's father.^[5] Tsien's brother Richard Tsien is also a renowned scientist at Stanford. Tsien, who calls his own work molecular engineering, once said, "I'm doomed by heredity to do this kind of work."^[6]

Tsien was born in New York, in 1952.^[7] He grew up in Livingston, New Jersey^[7] and attended Livingston High School there.^[8]

Tsien suffered from asthma as a child, and as a result, he was often indoors. He spent hours conducting chemistry experiments in his basement laboratory. When he was 16, he won first prize in the nationwide Westinghouse talent search with a project investigating how metals bind to thiocyanate.^[7]

He attended Harvard University on a National Merit Scholarship, where he was elected to Phi Beta Kappa as a junior.^[9] He graduated summa cum laude with a Bachelor of Science in chemistry and physics in 1972. According to his freshman-year roommate, economist and Iowa politician Herman Quirmbach, “It’s probably not an exaggeration to say he’s the smartest person I ever met... [a]nd I have met a lot of brilliant people.”^[10]

After completing his bachelor's degree, he joined the Physiological Laboratory at the University of Cambridge in Cambridge, England with the aid of a Marshall Scholarship.^[11] He received his PhD in physiology from Churchill College, University of Cambridge in 1977, with the doctoral dissertation The Design and Use of Organic Chemical Tools in Cellular Physiology (1976) supervised by Prof. Jeremy Sanders.^[11]

Tsien was a Research Fellow at Gonville and Caius College, University of Cambridge from 1977 to 1981.^[11] He was appointed to the faculty at the University of California, Berkeley, from 1982 to 1989. Since 1989 he has been working at the University of California, San Diego, as Professor of Pharmacology and Professor of Chemistry and Biochemistry,^[2] and an investigator of the Howard Hughes Medical Institute.^[12]^[13]

Research

Tsien is renowned for revolutionizing the fields of cell biology and neurobiology by allowing scientists to peer inside living cells and watch the behavior of molecules in real time.

In 2004, Tsien was awarded the Wolf Prize in Medicine "for his seminal contribution to the design and biological application of novel fluorescent and photolabile molecules to analyze and perturb cell signal transduction."^[14]

In 2008, Tsien shared the Nobel Prize in Chemistry with Osamu Shimomura and Martin Chalfie for "the green fluorescent protein: discovery, expression and development."^[3] ^[15]

Development of GFPs and other fluorescent proteins

The multicolored fluorescent proteins developed in Tsien's lab are used by scientists to track where and when certain genes are expressed in cells or in whole organisms. Typically, the gene coding for a protein of interest is fused with the gene for a fluorescent protein, which causes the protein of interest to glow inside the cell and allows microscopists to track its location in real time. This is such a popular technique that it has added a new dimension to the fields of molecular biology, cell biology, and biochemistry.^[16]

Since the discovery of the wild type GFP, numerous different mutants of GFP have been engineered and tested.^[17] The first significant leap forward was a single point mutation (S65T) reported by Tsien in 1995 in Nature.^[18] This mutation dramatically improved the fluorescent (both intensity and photostability) and spectral characteristics of GFP. A shift of the major excitation peak to 488 nm with the emission peak staying at 509 nm thus can be clearly observed, which matched very well the spectral characteristics of commonly available FITC facilities. All these then largely amplified the practicality of using GFP by scientists in their research. Tsien mainly contributed to much of our understanding of how GFP works and for developing new techniques and mutants of GFP.

Former trainees include Atsushi Miyawaki and Alice Y. Ting.

Timelines of GFP-development involved by Tsien^[15]:

1994: Tsien showed the mechanism that GFP chromophore is formed in a chemical reaction which requires oxygen but without help from the other proteins.
1994–1998: Tsien and collaborators made various GFP mutants by genetic modification and structural tweaking. Newly created variants of GFP can shine more brightly and show different colours, such as yellow, cyan, and blue.
2000–2002: Tsien produced stable variants of DsRED, which can glow in shades of red, pink, and orange. Remarkably, since then complicated marcromolecular networks of living organisms can be labelled or marked by using "all the colours of the rainbow".

Other detailed highlights involved by Tsien^[19]:

2002: The critical structural difference between GFP and DsRed was revealed. One extra double-bond in the chromophore of DsRed extends its conjugation thus causes the red-shift.
2002: Monomeric DsRed (mRFP) was first developed.
2004: New "fruit" FPs were generated (by in vitro and in vivo directed evolutions).

In 2009, a new kind of IFP was developed by Tsien's group, and further reported and described by Science. The new IFPs are developed from bacterial phytochromes instead of from multicellular organism like jellyfish. Under normal conditions, bacterial phytochromes absorb light for signaling instead of fluorescence, but they can be turned fluorescent after deleting some of the signaling parts by genetic means such as site-directed mutagenesis. In order to fluorescence, tetrapyrrole is also required, however, it's abundant in living bodies.^[20]

Calcium imaging

Tsien is a key pioneer of calcium imaging and well known for developing various dyes which change color in the presence of particular ions such as calcium. One such dye, Fura-2, is widely used to track the movement of calcium within cells. Indo-1, another popular calcium indicator, was also developed by Tsien's group in 1985.

Aequorin is also a useful tool to indicate calcium level inside cells; however, it has some limitations, primarily is that its prosthetic group coelenterazine is consumed irreversibly when emits light, thus requires continuous addition of coelenterazine into the media. To overcome such issues, Tsien's group also developed the calmodulin-based sensor, named Cameleon.^[21]

FlAsH-EDT2

FlAsH-EDT2 is a biochemical method for specific covalent labeling inside live cells. It's a method based on recombinant protein molecules, and was developed by Tsien and his colleagues in 1998.^[22]

"FLASH-EDT2": Fluorescein arsenical helix binder, bis-EDT adduct,
"EDT": 1,2-ethanedithiol.

Fluorescence-assisted cancer surgery

According to experimental (in mouse) results from Tsien's group, cancer surgery can be guided and assisted by fluorescent peptides. The peptides are used as probes, and are harmless to living tissues and organs. Their lifetime in the body is only 4 or 5 days. The human testing is hoped to be ready within two or three years.^[23]

Industrial and educational activities

Tsien is also a notable biochemical inventor and holds or co-holds about 100 patents till 2010. In 1996, Tsien co-founded the Aurora Biosciences Corporation, which started its public commerce in 1997. In 2001, Aurora was acquired by the Vertex Pharmaceuticals. Similarly, Tsien was also a scientific co-founder of Senomyx in 1999.^[7]

Dr. Tsien also helps promote science education to promising young scientists through the first-ever San Diego Science Festival Lunch with a Laureate Program.^[24]

Awards and honors

Roger Y. Tsien has received numerous honors and awards in his life, including:

National 1st Prize, Westinghouse Science Talent Search (1968)
National Merit Scholarship, USA (1968)
Detur Prize, Harvard College (1969)
Marshall Scholarship, British government (1972)
Comyns Berkeley Research Fellowship, Gonville and Caius College, Cambridge (1977)
Gedge Prize, University of Cambridge (1978)
Searle Scholar, Searle Scholar program (1983)
Lamport Prize, New York Academy of Sciences (1986)
Javits Neuroscience Investigator Award, National Institute of Neurological Disorders and Stroke (1989)
Young Scientist Award, Passano Foundation (1991)
W. Alden Spencer Award in Neurobiology, Columbia University (1991)
Artois-Baillet-Latour Health Prize, Belgium (1995)
Gairdner Foundation International Award, Canada (1995)
Basic Research Prize, American Heart Association (1995)
Elected to the United States Institute of Medicine (1995)
Doctorate honoris causa, Katholieke Universiteit Leuven, Belgium (1995)
Faculty Research Lecturer, UC San Diego (1997)
Elected to the American Academy of Arts and Sciences (1998)
Elected to the United States National Academy of Sciences (1998)
Award for Innovation in High Throughput Screening, Society for Biomolecular Screening (1998)
Pearse Prize, Royal Microscopical Society (2000)
ACS Award for Creative Invention, American Chemical Society (2002)
Christian B. Anfinsen Award, Protein Society (2002)
Heineken Prize for Biochemistry and Biophysics, Royal Netherlands Academy of Arts and Sciences (2002)
Max Delbrück Medal, Max Delbrück Centrum für Molekulare Medizin, Berlin (2002)^[25]
Wolf Prize in Medicine, Israel (2004)
Keio Medical Science Prize, Japan (2004)
UCSD Chancellor's Associates Award for Excellence in Science & Engineering Research, UC San Diego (2004)
Perl Prize in Neuroscience, University of North Carolina (2004)
Associate Member, European Molecular Biology Organization (2005)
J.Allyn Taylor International Prize in Medicine, Robarts Research Institute, Canada (2005)
ABRF Award, Association of Biomolecular Resource Facilities (2006)
Lewis S. Rosenstiel Award for Distinguished Work in the Basic Medical Sciences, Brandeis University (2006)^[26]
Foreign Fellow of the Royal Society, UK (2006)^[27]
BioPharma Leadership Award, the 6th Annual San Diego BioPharma Conference, San Diego (2007)
US Department of Defense (DoD) Breast Cancer Innovator Award
Nobel Prize in Chemistry, Sweden (2008)^[3]
E.B. Wilson Medal, American Society for Cell Biology (2008)
Honorary Fellow of the Royal Society of Chemistry (HonFRSC), UK (2008)^[28]
Honorary Academician, Academia Sinica (2008)^[29]
February 18, 2009, Roger Tsien Day, in the City of San Diego, California, USA
Distinguished Science and Technology Award, The 2009 Asian American Engineers of the Year (AAEoY) Award (April 2009)^[30]
Lifetime Innovation Award, UC San Diego (May 20, 2009)^[31]
AHA Distinguished Scientists, American Heart Association (2009)
Molecular Imaging Achievement Award, Society of Molecular Imaging (2009)
Doctor of Science honoris causa, The University of Hong Kong (2009)^[32]
Doctor of Science honoris causa, Chinese University of Hong Kong (2009)^[33]
General President Gold Medal, the 97th Indian Science Congress, India (January 3, 2010)^[34]
Spiers Memorial Award, Royal Society of Chemistry, UK (2010)^[35]

Named lectureship

Bowditch Lectureship, American Physiological Society (1992)
Hans L. Falk Memorial Lectureship, National Institute of Environmental Health Sciences (1993)
Quastel Lectureship, Hebrew University of Jerusalem (1994)
President's Lectureship, American Thoracic Society (1994)
Roger Eckert Memorial Lecture, Göttingen Neurobiology Conference of the German Neuroscience Society (1995)
Melvin Calvin Lectureship, UC Berkeley (1999)
Herbert Sober Lectureship, American Society for Biochemistry and Molecular Biology (2000)
Keith Porter Lectureship, American Society for Cell Biology (2003)
Konrad Bloch Lectureship, Harvard University (2003)
Grass Foundation Lectureship, Society for Neuroscience (2004)
The 1st Academia Sinica Lecturer (the highest honor of the academy), Dec 2009^[36]^[37]
The 2010 National Lecturer of the Biophysical Society (the highest honor of the society)^[38]
The 2011 UCL Prize Lecture in Clinical Science (University College, London)^[39]

References

^ "钱永健研水母发光盼助治癌 (Tsien hopes jellyfish fluorescence research can help cancer therapy)" (in (Chinese)). Lianhe Zaobao. October 3, 2008. http://www.zaobao.com/special/newspapers/2008/10/hongkong081003b.shtml. Retrieved October 4, 2008. .
^ ^a ^b "Roger Tsien at UCSD Department of Chemistry & Biochemistry" (Official web page). UCSD. 2008. http://www-chem.ucsd.edu/research/profile.cfm?cid=C01821. Retrieved November 4, 2008.
^ ^a ^b ^c "2008 Nobel Prize in Chemistry Laureates" (Official web page). The Nobel Foundation. October 8, 2008. http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/index.html. Retrieved October 8, 2008.
^ "诺贝尔化学奖得主钱永健系吴越国王34世孙 (Nobel Chemistry Prize winner Roger Tsien is the 34th-generational grandson of the King of Wuyue)" (in (Chinese)) (Web page). Sina.com. October 9, 2008. http://news.sina.com.cn/c/2008-10-09/001116418702.shtml. Retrieved October 9, 2008.
^ Ruth Williams; Horsfall, MJ; Van Helten, JB; Glickman, BW; Mohn, GR (2007 October 8). "People & Ideas – Roger Tsien: Bringing color to cell biology". J Cell Biol 179 (1): 6–8. doi:10.1083/jcb.1791pi. PMC 2064723. PMID 17923526. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2064723.
^ Steele, D. (2004) Cells aglow. HHMI Bulletin, Summer 2004, 22–26
^ ^a ^b ^c ^d Nicole Kresge, Robert D. Simoni, and Robert L. Hill. "The Chemistry of Fluorescent Indicators: the Work of Roger Y. Tsien", Journal of Biological Chemistry, September 15, 2006. Accessed September 18, 2007. "At age 16, Tsien won first prize in the nationwide Westinghouse talent search with a project investigating how metals bind to thiocyanate."
^ Swayze, Bill. "Jersey teens call science a winner: Two finalists say just being in Westinghouse talent competition is prize enough", The Star-Ledger, March 11, 1997. Accessed September 18, 2007. "Only one New Jersey teenager has ever captured top honors in the history of the competition. That was Roger Tsien in 1968. The then-16-year-old Livingston High School math-science whiz explored the way subatomic particles act as bridges between two dissimilar metal atoms in various complex molecules."
^ "Phi Beta Kappa" (Web page). The Harvard Crimson. Saturday, April 24, 1971. http://www.thecrimson.com/article/1971/4/24/phi-beta-kappa-pthe-alpha-chapter/. Retrieved October 9, 2008.
^ June Q. Wu, CRIMSON STAFF WRITER (Thursday, October 9, 2008). "Harvard Alumni Win Nobel Prize – Three chemists share award for green fluorescent jellyfish protein" (Web page). The Harvard Crimson. http://www.thecrimson.com/article/2008/10/9/harvard-alumni-win-nobel-prize-in/. Retrieved October 9, 2008.
^ ^a ^b ^c "Cambridge graduate wins Nobel Prize for Chemistry" (Web page). The University of Cambridge. October 8, 2008. http://www.admin.cam.ac.uk/news/dp/2008100801. Retrieved October 8, 2008.
^ "HHMI Scientist Abstract: Roger Y. Tsien, PhD" (Web page). HHMI. August 20, 2007. http://www.hhmi.org/research/investigators/tsien.html. Retrieved October 8, 2008.
^ "HHMI Scientist Bio: Roger Y. Tsien, PhD" (Web page). HHMI. http://www.hhmi.org/research/investigators/tsien_bio.html. Retrieved October 8, 2008.
^ "The Wolf Foundation Prize in Medicine" (Web page). The Wolf Foundation. 2004. http://www.wolffund.org.il/cat.asp?id=24&cat_title=MEDICINE. Retrieved October 8, 2008.
^ ^a ^b "The green fluorescent protein: discovery, expression and development" (PDF). The Royal Swedish Academy of Sciences, Information Department. October 8, 2008. http://nobelprize.org/nobel_prizes/chemistry/laureates/2008/chemadv08.pdf. Retrieved October 8, 2008.
^ Nobel lecture
^ Shaner N, Steinbach P, Tsien R (2005). "A guide to choosing fluorescent proteins" (PDF). Nat Methods 2 (12): 905–9. doi:10.1038/nmeth819. PMID 16299475. http://tsienlab.ucsd.edu/Publications/Shaner%202005%20Nature%20Methods%20-%20Choosing%20fluorescent%20proteins.pdf.
^ Heim R, Cubitt A, Tsien R (1995). "Improved green fluorescence" (PDF). Nature 373 (6516): 663–4. doi:10.1038/373663b0. PMID 7854443. http://tsienlab.ucsd.edu/Publications/Heim%201995%20Nature%20-%20Improved%20GFP.PDF.
^ "Green Fluorescent Protein: Timeline" (Web page). Conncoll.edu. 18-Nov-09. http://www.conncoll.edu/ccacad/zimmer/GFP-ww/timeline.html. Retrieved December 22, 2009.
^ Xiaokun Shu, Antoine Royant, Michael Z. Lin, Todd A. Aguilera, Varda Lev-Ram, Paul A. Steinbach, Roger Y. Tsien (2009). "Mammalian Expression of Infrared Fluorescent Proteins Engineered from a Bacterial Phytochrome". Science 324 (5928): 804–07. doi:10.1126/science.1168683. PMC 2763207. PMID 19423828. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2763207.
^ Miyawaki A, Llopis J, Heim R, McCaffery JM, Adams JA, Ikurak M, Tsien RY (1997). "Fluorescent indicators for Ca²⁺ based on green fluorescent proteins and calmodulin.". Nature 388 (6645): 882–7. doi:10.1038/42264. PMID 9278050.
^ B. Albert Griffin, Stephen R. Adams, Roger Y. Tsien (1998). "Specific Covalent Labeling of Recombinant Protein Molecules Inside Live Cells". Science 281 (5374): 269–72. doi:10.1126/science.281.5374.269. PMID 9657724.
^ "PNAS: Fluorescence + MR imaging probe can guide cancer surgery" (php). PNAS. Last Updated ( Thursday, March 4, 2010 ). http://www.healthimaging.com/index.php?option=com_articles&view=portal&id=publication:10:article:21021:pnas-fluorescence-mr-imaging-probe-can-guide-cancer-surgery&division=hiit. Retrieved March 11, 2010.
^ San Diego Science Festival Lunch with a Laureate
^ Barbara Bachtler (November 21, 2002). "Prof. Roger Tsien Honoured with Max Delbrueck Medal" (Web page). Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch. http://www.mdc-berlin.de/en/news/2002/20021121-prof__roger_tsien_honoured_with_max_delbru/index.html. Retrieved October 8, 2008.
^ "Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Science Past Winners". Rosenstiel Basic Medical Sciences Research Center. 2006. http://www.rose.brandeis.edu/Center/rose_past.html. Retrieved December 31, 2009.
^ "New Foreign members & Honorary Fellow 2006" (Web page). The Royal Society. 2006. http://royalsociety.org/page.asp?tip=1&id=4710. Retrieved September 27, 2008.
^ "Who are our Honorary Fellows?" (asp). The Royal Society of Chemistry. http://www.rsc.org/Membership/AboutRscMembership/HonFRSC/index.asp. Retrieved December 27, 2009.
^ "New Nobel laureate to be named honorary academician". The China Post. Taiwan (ROC). Updated Thursday, October 16, 2008 9:55 am TWN, CNA. http://www.chinapost.com.tw/taiwan/int%27l--community/2008/10/16/178879/New-Nobel.htm. Retrieved December 27, 2009.
^ Roger S. Dong (Volume XXIV, No. 4 – April 2009). "2009 AAEOY Awards" (pdf). National Engineers Week Foundation. http://www.eweek.org/site/pdfs/2009_AAEOY_Highlights.pdf. Retrieved December 27, 2009.
^ "Salute to Innovation" (shtml). UC San Diego Technology Transfer Office (TTO). May 20, 2009. http://invent.ucsd.edu/info/salute_may09.shtml. Retrieved May 20, 2009.
^ "HKU to award Honorary Degree to Nobel Laureate Professor Roger Yonchien Tsien". The University of Hong Kong. Oct 29, 2009. http://www.hku.hk/press/news_detail_6047.html. Retrieved October 29, 2009.
^ "The Chinese University of Hong Kong Holds 67th Congregation for Conferment of Degrees". The Chinese University of Hong Kong. December 10, 2009. http://www.cuhk.edu.hk/cpr/pressrelease/091210e.htm. Retrieved December 10, 2009.
^ "PM Dr. Manmohan Singh gives away awards to prominent scientists" (asp). India Education Dairy.com. Sunday, January 3, 2010. http://www.indiaeducationdiary.in/Showlatest.asp?newsid=2341. Retrieved January 4, 2010.
^ "RSC Spiers Memorial Award 2010 winner – Roger Tsien, UCSD, USA" (asp). The Royal Society of Chemistry. 2009. http://www.rsc.org/ScienceAndTechnology/Awards/SpiersMemorialAward/2010Winner.asp. Retrieved December 22, 2009.
^ "本院邀請諾貝爾化學獎得主錢永健教授12月蒞臨「中央研究院講座」演講" (in (Chinese)). Academia Sinica. December 11, 2009. http://newsletter.sinica.edu.tw/news/read_news.php?nid=4288. Retrieved December 27, 2009.
^ "Academia Sinica to welcome lectures by 2008 Nobel laureate". eTaiwan News (Central News Agency). December 11, 2009<!- – 12:00 am -->. http://www.etaiwannews.com/etn/news_content.php?id=1129640&lang=eng_news&cate_img=logo_taiwan&cate_rss=TAIWAN_eng. Retrieved December 27, 2009.
^ "The 2010 National Lecture will be given by Roger Tsien, UCSD" (aspx). The Biophysical Society. 2009. http://www.biophysics.org/Program/ScientificSessions/NationalLecture/tabid/791/Default.aspx. Retrieved September 10, 2009.
^ http://blogs.ucl.ac.uk/events/2011/10/26/prize-lecture-in-clinical-science-roger-tsien/

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Wolf Prize in Medicine Laureates

George Snell / Jean Dausset / Jon J. van Rood (1978) Roger Sperry / Arvid Carlsson / Oleh Hornykiewicz (1979) César Milstein / Leo Sachs / James L. Gowans (1980) Barbara McClintock / Stanley Norman Cohen (1981) Jean-Pierre Changeux / Solomon H. Snyder / James W. Black (1982) Donald F. Steiner (1984/5) Osamu Hayaishi (1986) Pedro Cuatrecasas / Meir Wilchek (1987) Henri G. Hers / Elizabeth F. Neufeld (1988) John Gurdon / Edward B. Lewis (1989) Maclyn McCarty (1990) Seymour Benzer (1991) Judah Folkman (1992) Michael Berridge / Yasutomi Nishizuka (1994/5) Stanley B. Prusiner (1995/6) Mary F. Lyon (1996/7) Michael Sela / Ruth Arnon (1998) Eric Kandel (1999) Avram Hershko / Alexander Varshavsky (2001) Ralph L. Brinster / Mario Capecchi / Oliver Smithies (2002/3) Robert Weinberg / Roger Y. Tsien (2004) Alexander Levitzki / Anthony R. Hunter / Anthony Pawson (2005) Howard Cedar / Aharon Razin (2008)

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Nobel Laureates in Chemistry (2001–2025)

William Knowles / Ryoji Noyori / K. Barry Sharpless (2001) John B. Fenn / Koichi Tanaka / Kurt Wüthrich (2002) Peter Agre / Roderick MacKinnon (2003) Aaron Ciechanover / Avram Hershko / Irwin Rose (2004) Robert H. Grubbs / Richard R. Schrock / Yves Chauvin (2005) Roger D. Kornberg (2006) Gerhard Ertl (2007) Osamu Shimomura / Martin Chalfie / Roger Y. Tsien (2008) Venkatraman Ramakrishnan / Thomas A. Steitz / Ada E. Yonath (2009) Richard F. Heck / Akira Suzuki / Ei-ichi Negishi (2010) Dan Shechtman (2011)

Complete list (1901–1925) (1926–1950) (1951–1975) (1976–2000) (2001–2025)