Pierre Grabar
Born(1898-09-10)September 10, 1898
DiedJanuary 26, 1986(1986-01-26) (aged 87)
Alma materÉcole des Hautes Études Industrielles, University of Strasbourg, Sorbonne
Known forImmunoelectrophoresis
Scientific career
FieldsImmunology, Biochemistry
InstitutionsUniversity of Strasbourg, Institut Pasteur, l'Institut de recherches sur le cancer (CNRS)

Pierre Grabar (September 10, 1898, Kiev - January 26, 1986, Paris) was a French biochemist and immunologist, born in Russia.[1] He was the founding president of the Société Française d'Immunologie.[2][3] He studied antigen-antibody reactions and developed a "carrier" theory of antibody function.[4][5] His award-winning development of Immunoelectrophoresis made it possible to identify specific bodily proteins, opening new avenues in medical research.[6]

An important figure for a generation of immunologists and biochemists, he helped to rebuild the field of French and European immunology after World War II though his teaching and research.[4][7] He welcomed many international students to his laboratory, which has been described as "extraordinarily vibrant and active" and "one of the best in the world".[8]

In 1963 Grabar received a Canada Gairdner International Award and in 1968 the Prix Jaffé. In 1958 he received the Emil von Behring Prize and in 1977 the Robert Koch Medal. In 1962 he became a member of the German National Academy of Sciences Leopoldina. He was an officer in the French Legion of Honor.

Childhood and studies

Pierre Grabar was born in Kiev, Russia, on September 10, 1898. His father was Nicolas (Nikolay S.) Grabar (1852-1924), a lawyer and State Counsellor at the Court of Cassation of St Petersburg. His mother was Baroness Elisabeth de Prittwitz (1866-1924), an artist.[9] His older brother André Grabar became a prominent professor of ancient Christian and Byzantine archaeology and art.[10]

Pierre Grabar completed high school in Kiev in 1916.[1] During the Russian Revolution of 1917, Grabar's family fled the country to France. During the Russian Civil War Grabar was an officer in the White Army.[11]

In 1921, Grabar went to France.[11] He entered the École des Hautes Études Industrielles in Lille, France and obtained a chemical engineering degree in 1924.[1] Pierre Grabar became a naturalized citizen of France as of August 8, 1929.[12]

Grabar received a doctorate from the University of Strasbourg in 1930, after working on uremia and salt deficiency (see below).[1][2] He also earned a Doctor of Sciences degree from the Sorbonne in 1942, for his work on ultrafiltration and its applications.[1]

Career

After working briefly in industry Grabar became chief (chef de laboratoire) of a clinical laboratory at the University of Strasbourg from 1926‑1930.[13] There he began doing medical research on kidney function with professor Leon Blum. Grabar received his doctorate in 1930, having worked on uremia and salt deficiency and published "Azotemie par manque de sel" (Uremia due to salt deficiency).[1][2]

From 1930‑1936,[13] Grabar became assistant to Maurice Nicloux in the department of clinical medicine at the University of Strasbourg. Grabar then developed a technique of fractionation of proteins through nitrocellulose ultrafilters of defined porosity, making it possible to specify the dimensions of proteins, toxins and viruses. This work was confirmed later by electron microscopy.[14][15][16][17]

In 1937-1938 Grabar was a Rockefeller Foundation Fellow at Columbia University in New York, USA.[18] There he met the founder of quantitative immunology, Michael Heidelberger and found his vocation for the relatively new science of immunology.[2]

Returning to Paris in 1938, Grabar joined the Institut Pasteur as head of the laboratory (Chef de Laboratoire) from 1938-1946. He served as head of microbial chemistry (Chef de Service de Chimie microbienne) from 1946-1960.[13]

During the 1950s, a time when translations of abstracts and papers often were not available, Pierre Grabar contributed to the Annual Review of Microbiology by writing reviews of recent Russian research.[19] In 1954, Grabar was president of the Société française de biochimie et de biologie moléculaire (SFBBM, originally named the Société de Chimie Biologique).[20] In 1966, Pierre Grabar founded the Société Française d'Immunologie (SFI), serving as its first president from 1966-1969.[21][22][2]

From 1960 to 1968 Grabar was director of l'Institut de recherches sur le cancer (Cancer Research Institute) of the Centre National de la Recherche Scientifique (CNRS) in Villejuif, France where he carried out research on proteins and cancer.[13]

In 1969, Grabar returned to the Pasteur Institute, where he was named honorary chief (chef de service honoraire).[13]

Immuno-electrophoretic analysis

In 1948, Grabar began to expand on the work of the physico-chemist Arne Tiselius, who won a Nobel Prize in chemistry for his work on the electrophoresis of macromolecules. Pierre Grabar spent several years simplifying Tiselius' methodology, modifying his method by introducing antibodies.[23]

In 1953 Grabar developed immunoelectrophoresis, combining electrophoresis and immunochemical analysis to create an "immuno-electrophoretic method".[24] He used a gel medium, designed by Jacques Oudin, also at the Institut Pasteur, and developed the immunoelectrophoretic analysis method with the help of American student Curtis A. Williams, Jr.[24][25][26][27]

Firstly, electrophoresis of the substance to be studied is carried out in a 1.5-2% agar gel ... Then the precipitating immune serum is diffused perpendicularly to the electrophoretic migration axis. Each constituent of the mixture studied gives an independent specific precipitation band, which can be distinguished owing to its immunological specificity and defined by its relative electrophoretic mobility.[24][28]

They published a brief introductory report in 1953 and a longer exposition in 1955, both in Biochimica et Biophysica Acta.[24] Simple and inexpensive, immunoelectrophoresis quickly became a widely-used method of analysis in clinical biology with application in a broad range of areas. As of 1980, the 1955 paper was considered a "Citation classic" with over 680 citations.[29]

The paper describes a simple method which in a single operation enables the definition of complex mixtures of antigens or haptens by three independent criteria: the chemical or biochemical properties of the antigens (using various dyes or enzyme substrates), their electrophoretic mobility, and their antigenic specificity.[29]

Grabar and Williams discussed applications of the technique to the study of serum proteins in three further papers in the Journal of Immunology. These focused on immunological studies of human serum fractions; antiserum types and the distribution of their constituent antibodies; and human γ-globulin.[24]

Immunological phenomena

Grabar's research on immunological phenomena led him to have unorthodox views on the role of molecules. Grabar suggested that immune mechanisms could be viewed in terms of transporter functions, part of a normal system for handling metabolic and catabolic substances. This hypothesis was disputed by many of his contemporaries who viewed them as defensive mechanisms. Pierre Grabar fiercely defended his position for many years, confirming his theory through experiments. This idea has since become accepted.[30][31][32][33][34][35]

Selected publications

Awards and honors

References

  1. 1 2 3 4 5 6 Grabar, Pierre (February 1982). "An old biologist remembers ..." Electrophoresis. 3 (1): 1–8. doi:10.1002/elps.1150030102. S2CID 96847411. Retrieved 23 July 2021.
  2. 1 2 3 4 5 Seligmann, M (July 1, 1986). "Obituary: Pierre Grabar 1898-1986". The Journal of Immunology. 137 (1): 391. doi:10.4049/jimmunol.137.1.391. S2CID 83306971. Retrieved 22 July 2021.
  3. Courtois, J. E. (1986). "Eulogy for Pierre Grabar (1898-1986)". Bull Acad Natl Med (in French). 170 (5): 635–639. PMID 3536026.
  4. 1 2 Cruse, Julius M.; Lewis, Robert E. (April 20, 2009). Illustrated Dictionary of Immunology. CRC Press. p. 300. ISBN 9780849379888. Retrieved 23 July 2021.
  5. Poletaev, Alexander (19 July 2014). "The Natural Autoimmunity: Self-Recognition, Self-Interaction, and Self-Maintenance". J Autoimmun Res. 1 (1): 1001–. Retrieved 23 July 2021.
  6. 1 2 "Pierre Grabar DSC". Canada Gairdner International Award. Retrieved 22 July 2021.
  7. Cinader, B. (May 10, 2014). "Introduction". In Cinader, B.; Miller, Richard G. (eds.). Progress in Immunology VI: Sixth International Congress of Immunology. Elsevier. p. 3. ISBN 9781483276106. Retrieved 23 July 2021.
  8. Szentivanyi, Andor; Friedman, Herman (October 25, 1993). The Immunologic Revolution: Facts and Witnesses. CRC Press. pp. 26–27. ISBN 9780849347221. Retrieved 24 July 2021.
  9. "Pierre Grabar". Geneanet. Retrieved 23 July 2021.
  10. Казански, Никола Р. "André Nikolaevitch Grabar". SESDiva. Retrieved 23 July 2021.
  11. 1 2 Heifets, Leonid (February 5, 2013). The Second Coming of the White Plague. Tate Publishing. pp. 53–56. ISBN 9781621478751. Retrieved 23 July 2021.
  12. Le Goff, rmelle. "Introduction au guide de recherches sur les relations franco-russesdans les fonds des Archives national" (PDF). Archives nationales (France)Carte de Russie (1734), avec cartouche représentant Saint-. Retrieved 23 July 2021.
  13. 1 2 3 4 5 "Fonds Pierre Grabar (1898‑1986)". Répertoire de fonds pour l'histoire et la philosophie des sciences et des techniques. Retrieved 23 July 2021.
  14. Jacobs, Stanley (September 25, 2009). "Ultrafilter membranes in biochemistry". In Glick, David (ed.). Methods of Biochemical Analysis. Vol. 119. John Wiley & Sons. p. 310. ISBN 9780470110843. Retrieved 23 July 2021.
  15. Carr, Charles W. (September 12, 2013). "3. Membranes for Dialysis". In Berl, Walter G. (ed.). Physical Methods in Chemical Analysis: Volume IV. Vol. 4. Elsevier. p. 20. ISBN 9781483274416. Retrieved 23 July 2021.
  16. Van Gilse, Henriette A. (April 1955). "Adsorption as a Major Phenomenon in the Concentration of Gonadotrophins by Ultrafiltration". Nature. 175 (4459): 686–687. Bibcode:1955Natur.175..686V. doi:10.1038/175686a0. PMID 14370196. S2CID 4211523. Retrieved 23 July 2021.
  17. Grabar, P. (1 January 1938). "The Influence of Collodion Membrane Structure on the Ultrafiltration of Proteins". Cold Spring Harbor Symposia on Quantitative Biology. 6: 252–261. doi:10.1101/SQB.1938.006.01.025. Retrieved 23 July 2021.
  18. Heidelberger, Michael (June 1979). "A "Pure" Organic Chemists Downward Path: Chapter 2-The Years at P. and S." Annual Review of Biochemistry. 48 (1): 1–22. doi:10.1146/annurev.bi.48.070179.000245. PMID 382981.
  19. "Preface". Annual Review of Microbiology. 9 (1): annurev.mi.9.073106.100001. October 1955. doi:10.1146/annurev.mi.9.073106.100001.
  20. 1 2 "Société de Chimie Biologique, Celebration de Cinquantenaire, Paris, 6-9 Avril 1964" (PDF). Société française de biochimie et de biologie moléculaire. Retrieved 23 July 2021.
  21. Monteiro, Renato; Tabiasco, Julie; Magerus, Aude; Gautreau-Rolland, Laetitia; Yssel, Hans (June 2020). "French Immunology: from Louis Pasteur to present, always driving forward". European Journal of Immunology. 50 (6): 763–767. doi:10.1002/eji.202070065. PMID 32501561.
  22. Hosmalin, Anne; Sautès-Fridman, Catherine; Fougereau, Michel; Yssel, Hans; Fischer, Alain (July 2016). "50 th Anniversary of the French Society for Immunology (SFI): FORUM". European Journal of Immunology. 46 (7): 1545–1547. doi:10.1002/eji.201670073.
  23. Bettolo, G. B. Marini (1971). "Arne Tiselius (1902-1971)" (PDF). Commentarii. Pontifical Academy of Sciences. II (38): 6–7. Retrieved 23 July 2021.
  24. 1 2 3 4 5 Howard Hsueh-Hao Chiang (2009). "The Laboratory Technology of Discrete Molecular Separation: The Historical Development of Gel Electrophoresis and the Material Epistemology of Biomolecular Science, 1945-1970". Journal of the History of Biology. 42 (3): 495–527. doi:10.1007/s10739-008-9169-5. JSTOR 40271561. PMID 20027785. S2CID 17359037. Retrieved 24 July 2021.
  25. Moulin, Anne-Marie (2003). "Death and Resurrection of Immunology at the Pasteur Institute, 1917-1941". In Cazenave, Pierre-André (ed.). Immunology - Pasteur's Heritage. New Age International. p. 64. ISBN 9788122403206. Retrieved 23 July 2021.
  26. Klein, J. (1984). Immunology: The Science of Self-Nonself Discrimination. John Wiley & Sons, Incorporated. p. 162.
  27. Arquembourg, Pierre C. (1975). Immunoelectrophoresis: Theory, Methods, Identifications, Interpretation. S. Karger. pp. 6, 12.
  28. Grabar, Pierre; Williams, Curtis A. (January 1955). "Méthode immuno-électrophorétique d'analyse de mélanges de substances antigéniques". Biochimica et Biophysica Acta. 17 (1): 67–74. doi:10.1016/0006-3002(55)90320-6. PMID 13239629.
  29. 1 2 "This Week's Citation Classic Grabar P, Williams C A, Jr. & Courcon J. Méthode immuno-électrophorétique d'analyse de mélanges de substances antigéniques. (Method for immuno-electrophoretic analysis of mixtures of antigenic substances.) Biochim. Biophys. Acta 17:67-74,1955. [Service de Chimie Microbienne, Institut Pasteur, Paris, France.]" (PDF). January 7, 1980. {{cite journal}}: Cite journal requires |journal= (help)
  30. Poletaev, A; Boura, P (October 2011). "The immune system, natural autoantibodies and general homeostasis in health and disease". Hippokratia. 15 (4): 295–8. PMC 3876841. PMID 24391407.
  31. Pashnina, Irina A.; Krivolapova, Irina M.; Fedotkina, Tamara V.; Ryabkova, Varvara A.; Chereshneva, Margarita V.; Churilov, Leonid P.; Chereshnev, Valeriy A. (25 February 2021). "Antinuclear Autoantibodies in Health: Autoimmunity Is Not a Synonym of Autoimmune Disease". Antibodies. 10 (1): 9. doi:10.3390/antib10010009. PMC 8006153. PMID 33668697.
  32. Avalle, Bérangère; Padiolleau-Lefevre, Séverine; Friboulet, Alain (28 November 2019). "Structural and Functional Mise en Abyme". Frontiers in Molecular Biosciences. 6: 131. doi:10.3389/fmolb.2019.00131. PMC 6892749. PMID 31850365.
  33. Grabar, Pierre (June 1974). "" Self " and " Not-Self " in Immunology". The Lancet. 303 (7870): 1320–1322. doi:10.1016/S0140-6736(74)90685-0. PMID 4134299. Retrieved 23 July 2021.
  34. Grabar, Pierre (September 1975). "The "globulines-transporteurs" theory and auto-sensitization". Medical Hypotheses. 1 (5): 172–175. doi:10.1016/0306-9877(75)90045-6. PMID 765700. Retrieved 23 July 2021.
  35. Grabar, Pierre (December 1983). "Autoantibodies and the physiological role of immunoglobulins". Immunology Today. 4 (12): 337–340. doi:10.1016/0167-5699(83)90169-X. PMID 25290932. Retrieved 23 July 2021.
  36. "Distinguished Scientific Awards". American Association of Immunologists. Retrieved 23 July 2021.
  37. "Pierre Grabar". Leopoldina Nationale Akademie der Wissenschaften. Retrieved 22 July 2021.
  38. "LE PRIX JAFFÉ (50 000 F) A M. PIERRE GRABAR". Le Monde. 4 July 1968. Retrieved 23 July 2021.
  39. "Académie nationale de médecine - PARIS". Comité des travaux historiques et scientifiques. Retrieved 23 July 2021.
  40. "Robert-Koch-Medaille in Gold". Robert-Koch Stiftung. Retrieved 23 July 2021.
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