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Oliver Smithies

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Oliver Smithies
Smithies with theAmerican Institute of Chemists Gold Medal(2009)
Born(1925-06-23)23 June 1925
Halifax,West Yorkshire, England
Died10 January 2017(2017-01-10)(aged 91)
Chapel Hill,North Carolina, US
NationalityBritish, American
Alma materUniversity of Oxford(BA, DPhil)
Known for
SpouseNobuyo Maeda[3]
Awards
Scientific career
Fields
Institutions
ThesisPhysico-chemical properties of solutions of proteins(1951)
Doctoral advisorAlexander G. Ogston[2]

Oliver Smithies(23 June 1925 – 10 January 2017) was a British-Americangeneticistandphysical biochemist.He is known for introducingstarchas a medium forgel electrophoresisin 1955,[4]and for the discovery, simultaneously withMario CapecchiandMartin Evans,of the technique ofhomologous recombinationof transgenicDNAwith genomic DNA, a much more reliable method of altering animal genomes than previously used, and the technique behindgene targetingandknockout mice.[5][6][7]He received theNobel Prize in Physiology or Medicinein 2007 for his genetics work.[8][9]

Early life and education[edit]

Smithies was born inHalifax,West Yorkshire,England, to William Smithies and his wife Doris, née Sykes. His father sold life insurance policies and his mother taught English atHalifax Technical College.He had a twin brother and a younger sister. He attended a primary school in the nearby village ofCopleyand then went toHeath Grammar Schoolin Halifax.[10]He said that his love of science came from an early fascination with radios andtelescopes.[11]

He attendedBalliol College, Oxfordon aBrackenbury Scholarship,initially readingmedicine.He studiedanatomyandphysiology,winning a prize in anatomy, and graduated with afirst-classBachelor of Artsdegree in animal physiology, includingbiochemistry,in 1946. Inspired by tutorials fromAlexander G. Ogstonon applyingphysical chemistryto biological systems, Smithies then switched away from medicine to earn a second bachelor's degree in chemistry.[10][11][12]He published his first research paper, co-written with Ogston, in 1948.[10]In 1951, he received aMaster of Artsdegree and aDoctor of Philosophyin biochemistry under Ogston's supervision; his thesis was entitled "Physico-chemical properties of solutions of proteins".[13][2]

Career[edit]

Oliver Smithies (second on the left)

Smithies was awarded aCommonwealth Fundfellowship to take up a post-doctoral position in the United States, in the laboratory of J. W. Williams at theUniversity of Wisconsin–Madison's Department of Chemistry.[10]A problem with acquiring a U.S. visa, due to a condition of the Commonwealth Fund fellowship, then forced him to leave the U.S. From 1953 to 1960, he worked as an associate research faculty member, underinsulinresearcher David A. Scott, in theConnaught Medical Research Laboratoryat theUniversity of Torontoin Canada.[10][11]He learnedmedical geneticsfrom Norma Ford Walker at theHospital for Sick Childrenin Toronto.[14]

In 1960, Smithies returned to the University of Wisconsin–Madison, where he worked in the Department of Genetics until 1988 as, successively, assistant, associate and Leon J. Cole and Hilldale Professor of Genetics and Medical Genetics.[11]Subsequently, he was the Excellence Professor of Pathology and Laboratory Medicine at theUniversity of North Carolina at Chapel Hill.[15]He continued to work in his lab there daily into his eighties.[6][16]He co-authored a total of more than 350 research papers and reviews, dating from 1948 to 2016.[17]

Research[edit]

Smithies developed the technique ofgel electrophoresisusing astarchmatrix, as a sideline of (unproductive) research into an insulin precursor molecule, at the University of Toronto.[10][18]This improved the ability to resolve proteins by electrophoresis.[6]He was assisted technically in his later electrophoresis work by Otto Hiller. He used starch electrophoresis to reveal differences between normal humanplasma proteins,and in collaboration with Norma Ford Walker, showed that the variation was inherited, which stimulated his interest ingenetics.[10]

While at the University of Wisconsin in the 1980s, Smithies developedgene targetingin mice, a method of replacing single mouse genes usinghomologous recombination.Mario Capecchialso developed the technique independently.[15][18]This research is the basis of methods used worldwide to investigate the role of particular genes in a wide range of human diseases includingcancer,cystic fibrosisanddiabetes.[19]In 2002, Smithies worked with his wife,Nobuyo Maeda,studyinghigh blood pressureusing genetically altered mice.[15]

Awards and honors[edit]

Smithies won the 2001Albert Lasker Award for Basic Medical Research,jointly withMartin Evans(Cardiff University) andMario Capecchi(University of Utah), for their work on homologous recombination.[20]He received theWolf Prize in Medicine,with Capecchi andRalph L. Brinster,in 2002/3.[21]He won the 2007Nobel Prize in Physiology or Medicine,jointly with Capecchi and Evans, "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells."[8]

His other awards include twoGairdner Foundation International Awards(1990 and 1993),[22][23]theNorth Carolina Awardfor Science (1993),[24]theAlfred P. Sloan, Jr. Prizefrom the General Motors Foundation, jointly with Capecchi (1994),[25]the Ciba Award from the American Heart Foundation (1996),[18]theBristol Myers SquibbAward (1997),[26]theAssociation of American Medical Colleges' Award for Distinguished Research, jointly with Capecchi (1998),[18]the International Okamoto Award from the Japan Vascular Disease Research Foundation (2000),[27]theO. Max GardnerAward, the highest award for faculty in theUniversity of North Carolinasystem (2002),[18]theMassry Prizeof the Meira and Shaul G. Massry Foundation (2002), shared with Capecchi,[15]theMarch of Dimes Prize in Developmental Biology,jointly with Capecchi (2005),[28]and theAmerican Institute of Chemists Gold Medal(2009).[29]

Smithies was elected to theUnited States National Academy of Sciences(1971),[18]theAmerican Academy of Arts and Sciences(1978),[18]theAmerican Association for the Advancement of Science(1986),[18]theInstitute of Medicine(2003),[26]and as a foreign member of theRoyal Society[30](ForMemRS; 1998).[1]He received honorary degrees from theUniversity of Chicago(1991),[31]theUniversity of São Paulo(2008)[32]and theUniversity of Oxford(2011).[33]

Ablue plaqueto him was erected by theHalifax Civic Trust.[34]

Personal life[edit]

Smithies married Lois Kitze, a virologist at the University of Wisconsin, in the 1950s; they separated in 1978.[10][12]His second wife,Nobuyo Maeda,is a pathology professor at the University of North Carolina.[12]Smithies was a naturalized American citizen,[35]and, despite beingcolor-blind,was a licensed private airplane pilot who enjoyed gliding.[11][12]He described himself as an atheist.[13]

Smithies died on 10 January 2017 at the age of 91.[36]

References[edit]

  1. ^ab"Fellows of the Royal Society".London:Royal Society.Archived fromthe originalon 16 March 2015.
  2. ^abSmithies, Oliver (1951).Physico-chemical properties of solutions of proteins.jisc.ac.uk(DPhil thesis). University of Oxford.EThOSuk.bl.ethos.672736.
  3. ^"The Nobel Prize in Physiology or Medicine 2007".
  4. ^Smithies, Oliver (December 1955)."Zone electrophoresis in starch gels: group variations in the serum proteins of normal human adults".The Biochemical Journal.61(4): 629–641.doi:10.1042/bj0610629.ISSN0264-6021.PMC1215845.PMID13276348.
  5. ^Smithies, Oliver (2001). "Forty years with homologous recombination".Nature Medicine.7(10): 1083–1086.doi:10.1038/nm1001-1083.ISSN1078-8956.PMID11590419.S2CID26845944.
  6. ^abcWilliams, R. (2011)."Oliver Smithies: Born Inventor".Circulation Research.108(6): 650–652.doi:10.1161/RES.0b013e318216f105.ISSN0009-7330.PMID21415407.
  7. ^Gitschier, Jane (2015)."The Whole of a Scientific Career: An Interview with Oliver Smithies".PLOS Genetics.11(5): e1005224.doi:10.1371/journal.pgen.1005224.ISSN1553-7404.PMC4447374.PMID26020970.Open access icon
  8. ^ab"The Nobel Prize in Physiology or Medicine 2007".The Nobel Foundation.Retrieved8 October2007.
  9. ^Skipper, Magda(2005)."An Interview With Oliver Smithies".Nature Reviews Genetics.6(5): 350.doi:10.1038/nrg1627.ISSN1471-0056.PMID15880879.S2CID33591979.
  10. ^abcdefgh"Oliver Smithies - Biographical".Nobelprize.org.Nobel Media. 2014.Retrieved13 January2017.
  11. ^abcdeAltman, Lawrence K. (9 October 2007)."3 Win Nobel in Medicine for Gene Technology".The New York Times.Retrieved10 October2007.
  12. ^abcdKolata, Gina (17 October 1995)."Scientist at Work: Oliver Smithies; Sprinting Along for Five Decades".The New York Times.Retrieved10 October2007.
  13. ^ab"Oliver Smithies Interview: Session 1"(PDF).UCLA Oral History of Human Genetics.27 October 2005. Archived fromthe original(PDF)on 13 January 2017.Retrieved13 January2017.But that tells you about my religious affiliation, which is not very strong, and I must say I'm not even an agnostic. I'm just an atheist in real life.
  14. ^Oliver Smithies; Tom Coffman (2015). "A Conversation with Oliver Smithies".Annual Review of Physiology.77:1–11.doi:10.1146/annurev-physiol-021014-071806.PMID25668016.S2CID43393155.
  15. ^abcd"Smithies wins top award from Massry Foundation".University of North Carolina at Chapel Hill News Service.Retrieved10 October2007.
  16. ^Mark Derewicz (1 January 2008)."Life at the Bench".Endeavors.Retrieved13 January2017.
  17. ^"Bibliography".Dr. Oliver Smithies Research Archive.University of North Carolina.Retrieved13 January2017.
  18. ^abcdefgh"Oliver Smithies, Carolina's first Nobel laureate, passes away at 91 – The University of North Carolina at Chapel Hill".The University of North Carolina at Chapel Hill.11 January 2017.
  19. ^Oliver Smithies: Biography,Royal Society,retrieved13 January2017
  20. ^"2001 Albert Lasker Award for Basic Medical Research".Lasker Foundation. Archived fromthe originalon 30 September 2007.Retrieved1 October2007.
  21. ^Gurdon, Sir John (March 2012).Wolf Prize in Medicine 1978–2008.World Scientific.doi:10.1142/7565.ISBN978-981-4291-73-6.
  22. ^"Oliver Smithies MA, PhD: Recipient of the Canada Gairdner International Award, 1990".Gairdner Foundation.Retrieved13 January2017.
  23. ^"Oliver Smithies MA, PhD: Recipient of the Canada Gairdner International Award, 1993".Gairdner Foundation.Archived fromthe originalon 16 January 2017.Retrieved13 January2017.
  24. ^North Carolina Award for Science, 1993Archived15 August 2008 at theWayback Machine:NC Awardswebsite. Retrieved on 23 January 2008.
  25. ^"Previous Prize Winners: Alfred P. Sloan, Jr. Prize (1990 - 2002)".General Motors. Archived fromthe originalon 19 November 2005.Retrieved13 January2017.
  26. ^ab"Institute of Medicine elects Oliver Smithies".University of North Carolina at Chapel Hill News Service.Retrieved10 October2007.
  27. ^"Oliver Smithies wins major award from Japanese research foundation".University of North Carolina at Chapel Hill News Service.Retrieved10 October2007.
  28. ^"March of Dimes Awards $250,000 Prize to Pioneers in Genetic Research".March of Dimes.Retrieved14 November2014.
  29. ^"Gold Medal Award Winners".American Institute of Chemists.Retrieved18 January2015.
  30. ^Ballou, Byron (2024)."Oliver Smithies. 23 June 1925 — 10 January 2017".Biographical Memoirs of Fellows of the Royal Society.76.
  31. ^"Commencements; First Lady Urges Tolerance at Northeastern Graduation".The New York Times.16 June 1991.Retrieved10 October2007.
  32. ^"Oliver Smithies receives theDoctor Honoris Causa".University of São Paulo.Retrieved13 January2017.
  33. ^"Honorary degrees awarded at Encaenia".University of Oxford. Archived fromthe originalon 2 May 2013.Retrieved16 May2013.
  34. ^"List of Blue Plaques".Halifax Civic Trust. Archived fromthe originalon 30 April 2019.Retrieved30 April2019.
  35. ^"The y-chromosome is the biggest threat to humanity".The Local. 10 December 2007.Retrieved23 January2008.
  36. ^Gellene, Denise (11 January 2017)."Oliver Smithies, Tinkerer Who Transformed Genetics and Won a Nobel, Dies at 91".The New York Times.Retrieved12 January2017.

External links[edit]

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