Denis Noble

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This article is about the British biologist. For the British baritone, see Dennis Noble.
Denis Noble
Denis Noble.jpg
Born (1936-11-16) 16 November 1936 (age 77)[1]
Residence UK
Nationality British
Fields
Institutions University of Oxford
Alma mater University College London (BSc, MA, PhD)
Thesis Ion conductance of cardiac muscle (1962)
Doctoral advisor Otto Hutter
Notable awards
Spouse Susan Jennifer Barfield[1]
Children one son, one daughter[1]
Website

Denis Noble CBE FRS FRCP (born 16 November 1936) is a British biologist who held the Burdon Sanderson Chair of Cardiovascular Physiology at the University of Oxford from 1984 to 2004 and was appointed Professor Emeritus and co-Director of Computational Physiology. He is one of the pioneers of Systems Biology and developed the first viable mathematical model of the working heart in 1960.[4][5][6][7][8]

Education[edit]

Noble was educated at Emanuel School and University College London (UCL).[1][4] In 1958 he began his investigations into the mechanisms of heartbeat. This led to two seminal papers in Nature in 1960[9][10] giving the first proper simulation of the heart. From this work it became clear that there was not a single oscillator which controlled heartbeat, but rather this was an emergent property of the feedback loops in the various channels. In 1961 he obtained his PhD working under the supervision of Otto Hutter at UCL.[11][12]

Research[edit]

Noble's research focuses on using computer models of biological organs and organ systems to interpret function from the molecular level to the whole organism. Together with international collaborators, his team has used supercomputers to create the first virtual organ, the virtual heart.[13][14][15]

As Secretary-General of the International Union of Physiological Sciences 1993-2001, he played a major role in launching the Physiome Project, an international project to use computer simulations to create the quantitative physiological models necessary to interpret the genome, and he was elected President of the IUPS at its world congress in Kyoto in 2009[16]

Noble is also a philosopher of biology, and his book The Music of Life challenges the foundations of current biological sciences, questions the central dogma, its unidirectional view of information flow, and its imposition of a bottom-up methodology for research in the life sciences[17]

Reductionism[edit]

His 2006 book The Music of Life examines some of the basic aspects of systems biology, and is critical of the ideas of genetic determinism and genetic reductionism. He points out that there are many examples of feedback loops and "downward causation" in biology, and that it is not reasonable to privilege one level of understanding over all others. He also explains that genes in fact work in groups and systems, so that the genome is more like a set of organ pipes than a "blueprint for life".

He contrasts Dawkins's famous statement in The Selfish Gene ("Now they [genes] swarm ... safe inside gigantic lumbering robots ... they created us, body and mind; and their preservation is the ultimate rationale for our existence") with an alternative view: "Now they [genes] are trapped in huge colonies, locked inside highly intelligent beings, moulded by the outside world, communicating with it by complex processes, through which, blindly, as if by magic, function emerges. They are in you and me; we are the system that allows their code to be read; and their preservation is totally dependent on the joy we experience in reproducing ourselves. We are the ultimate rationale for their existence". He then suggests that there is no empirical difference between these statements, and says that they differ in "metaphor" and "sociological or polemical viewpoint".[18]

He argues that "the paradigms for genetic causality in biological systems are seriously confused" and that "The metaphors that served us well during the molecular biological phase of recent decades have limited or even misleading impacts in the multilevel world of systems biology. New paradigms are needed if we are to succeed in unravelling multifactorial genetic causation at higher levels of physiological function and so to explain the phenomena that genetics was originally about."[19]

Principles of Systems Biology[edit]

Denis Noble at a meeting on Systems Biology at Chicheley Hall, August 2013

Noble has proposed Ten Principles of Systems Biology:[20][21]

  1. Biological functionality is multi-level
  2. Transmission of information is not one way
  3. DNA is not the sole transmitter of inheritance
  4. The theory of biological relativity: there is no privileged level of causality
  5. Gene ontology will fail without higher-level insight
  6. There is no genetic program
  7. There are no programs at any other level
  8. There are no programs in the brain
  9. The self is not an object
  10. There are many more to be discovered; a genuine ‘theory of biology’ does not yet exist

Career[edit]

  • 1961—1963 Assistant Lecturer in Physiology, University College London
  • 1961—1963 Vice-Warden of Connaught Hall (University of London)
  • 1963—1984 Fellow and Tutor, Balliol College, Oxford. University Lecturer in Physiology
  • 1969—1970 Visiting Professor and Visiting Scientist of the Canadian MRC
  • 1971—1989 Head (Praefectus) of the Balliol College Graduate Centre at Holywell Manor
  • 1975—1985 Leader of MRC Programme Grant team
  • 1983—1985 Vice-Master of Balliol College
  • 1984—2004 Burdon Sanderson Professor of Cardiovascular Physiology, Oxford University
  • 1984—2004 Professorial Fellow, Balliol College
  • From 2004 Emeritus Professor of Cardiovascular Physiology, Oxford University
  • From 2004 Emeritus Fellow of Balliol College, Oxford
  • From 2004 Director of Computational Physiology, Co-Director of e-science centre, Oxford
  • 2003-2007 Adjunct Professor Xi’an Jiaotong University, Shaanxi province, China
  • From 2005 Visiting Professor, Osaka University, Japan
  • 2009-2017 President, International Union of Physiological Sciences (IUPS)
  • From 2011 Editor in Chief - Interface Focus[22][23][24]

Publications[edit]

Noble has published over 450 articles in academic journals,[15][2] including Nature,[25][26][27][28][9][10] Science,[29][30] PNAS,[31] Journal of Physiology,[32][33][34][35][36] Progress in Biophysics & Molecular Biology;[37] Many articles in national press. He is the author or editor of 11 books, including:

Awards and honours[edit]

His major invited lectures include the Darwin Lecture for the British Association in 1966, the Nahum Lecture at Yale in 1977 and the Ueda lecture at Tokyo University in 1985 and 1990. He was President of the Medical Section of the British Association 1991-92.

In 1979 he was elected a Fellow of the Royal Society. His nomination for the Royal Society reads:

Distinguished for the discovery of slowly activated potassium currents in the heart and a quantitative analysis of their role in controlling repolarization and pacemaker activity; the discovery of the ionic mechanisms by which adrenaline increases heart rate. He has shown that therapeutic levels of cardiac glycosides may increase, rather than decrease, potassium gradients in the heart, and has published an analytical treatment of membrane excitation theory and cable theory that provides a modern basis for the concepts of safety factor, liminal length, excitation time constants and the phenomenon of repetitive firing.[3]

He was elected an Honorary Member of the Royal College of Physicians in 1988 and an Honorary Fellow in 1994, an Honorary Member of the American Physiological Society in 1996 and of the Japanese Physiological Society in 1998. In 1999 he was awarded a CBE.

He has honorary doctorates from the University of Sheffield (2004), the Université de Bordeaux (2005) and the University of Warwick (2008).

He was awarded the Pierre Rijlant Prize (1991), Baly Medal Royal College of Physicians (1993), Pavlov Medal Russian Academy of Sciences (2004), Mackenzie Prize (2005)[citation needed], Medal of Merit (2008) [40] and the British Heart Foundation Gold Medal (1985).[citation needed]

He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique (1993), and received the Pavlov Medal of the Russian Academy of Sciences (2004).

Personal life[edit]

He plays classical guitar and sings Occitan troubadour and folk songs (OxfordTrobadors). In addition to English, he has lectured in French, Italian, Occitan, Japanese and Korean.[41]

References[edit]

  1. ^ a b c d "NOBLE, Prof. Denis". Who's Who 2014, A & C Black, an imprint of Bloomsbury Publishing plc, 2014; online edn, Oxford University Press. (subscription required)
  2. ^ a b List of publications from Google Scholar
  3. ^ a b "EC/1979/28: Noble, Denis". London: The Royal Society. Archived from the original on 2014-05-30. 
  4. ^ a b Biography, Denis Noble homepage.
  5. ^ Music of Life lecture in Maribor 2012 on YouTube
  6. ^ Lecture on Evolution IUPS Opening plenary 2013 on YouTube
  7. ^ Noble, D. (2013). "Physiology is rocking the foundations of evolutionary biology". Experimental Physiology: no. doi:10.1113/expphysiol.2012.071134. 
  8. ^ Ten Tusscher, K. H. W. J. (2003). "A model for human ventricular tissue". AJP: Heart and Circulatory Physiology 286 (4): H1573. doi:10.1152/ajpheart.00794.2003. 
  9. ^ a b Noble, Denis (1960). "Cardiac action and pacemaker potentials based on the Hodgkin-Huxley equations". Nature 188 (4749): 495–7. doi:10.1038/188495b0. PMID 13729365. 
  10. ^ a b Hutter, Otto F.; Noble, Denis (1960). "Rectifying properties of heart muscle". Nature 188: 495. PMID 13717088. 
  11. ^ Noble, Denis (1962). Ion conductance of cardiac muscle (PhD thesis). University College London. (subscription required)
  12. ^ Dennis Noble (2006). The Music of Life, ISBN 0-19-929573-5
  13. ^ All systems go article in The Economist 25-Oct-2007 discussing Noble's work
  14. ^ Denis Noble CV at Music of Life site
  15. ^ a b Denis Noble from the Scopus bibliographic database
  16. ^ Denis Noble Elected President of IUPS
  17. ^ Werner, E. (2007). "SYSTEMS BIOLOGY: How Central is the Genome?". Science 317 (5839): 753. doi:10.1126/science.1141807. 
  18. ^ The Music of Life, pp. 12-14
  19. ^ Noble, D. (Sep 2008). "Genes and causation" (Free full text). Philosophical transactions. Series A, Mathematical, physical, and engineering sciences 366 (1878): 3001–3015. Bibcode:2008RSPTA.366.3001N. doi:10.1098/rsta.2008.0086. ISSN 1364-503X. PMID 18559318. 
  20. ^ Noble, D (2008). "Claude Bernard, the first systems biologist, and the future of physiology". Experimental Physiology 93 (1): 16–26. doi:10.1113/expphysiol.2007.038695. PMID 17951329. 
  21. ^ Video Lecture on the 10 principles
  22. ^ Noble, D. (2011). "A theory of biological relativity: No privileged level of causation". Interface Focus 2 (1): 55–64. doi:10.1098/rsfs.2011.0067. PMC 3262309. PMID 23386960. 
  23. ^ Noble, D (2011). "Differential and integral views of genetics in computational systems biology". Interface Focus 1 (1): 7–15. doi:10.1098/rsfs.2010.0444. PMC 3262251. PMID 22419970. 
  24. ^ Noble, D (2011). "Editorial". Interface Focus 1 (1): 1–2. doi:10.1098/rsfs.2010.0385. PMC 3262238. PMID 22419969. 
  25. ^ Blakemore, C; Dawkins, R; Noble, D; Yudkin, M (2003). "Is a scientific boycott ever justified?". Nature 421 (6921): 314. doi:10.1038/421314b. PMID 12540875. 
  26. ^ Egan, T. M.; Noble, D; Noble, S. J.; Powell, T; Twist, V. W. (1987). "An isoprenaline activated sodium-dependent inward current in ventricular myocytes". Nature 328 (6131): 634–7. doi:10.1038/328634a0. PMID 2441262. 
  27. ^ Cohen, I; Giles, W; Noble, D (1976). "Cellular basis for the T wave of the electrocardiogram". Nature 262 (5570): 657–61. PMID 958437. 
  28. ^ Hall, A. E.; Noble, D (1963). "Transient Responses of Purkinje Fibres to Non-Uniform Currents". Nature 199: 1294–5. PMID 14074602. 
  29. ^ Noble, D (2002). "Modeling the heart--from genes to cells to the whole organ". Science 295 (5560): 1678–82. doi:10.1126/science.1069881. PMID 11872832. 
  30. ^ Hauswirth, O; Noble, D; Tsien, R. W. (1968). "Adrenaline: Mechanism of action on the pacemaker potential in cardiac Purkinje fibers". Science 162 (3856): 916–7. PMID 4386717. 
  31. ^ Noble, D (2002). "Unraveling the genetics and mechanisms of cardiac arrhythmia". Proceedings of the National Academy of Sciences 99 (9): 5755–6. doi:10.1073/pnas.102171699. PMC 122846. PMID 11983875. 
  32. ^ Noble, D (1962). "A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials". The Journal of physiology 160: 317–52. PMC 1359535. PMID 14480151. 
  33. ^ McAllister, R. E.; Noble, D; Tsien, R. W. (1975). "Reconstruction of the electrical activity of cardiac Purkinje fibres". The Journal of physiology 251 (1): 1–59. PMC 1348375. PMID 1185607. 
  34. ^ Noble, D; Tsien, R. W. (1969). "Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres". The Journal of physiology 200 (1): 205–31. PMC 1350425. PMID 5761944. 
  35. ^ Noble, D; Tsien, R. W. (1968). "The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres". The Journal of physiology 195 (1): 185–214. PMC 1557911. PMID 5639799. 
  36. ^ Noble, D (1984). "The surprising heart: A review of recent progress in cardiac electrophysiology". The Journal of physiology 353: 1–50. PMC 1193291. PMID 6090637. 
  37. ^ Noble, D. (2013). "Systems biology and reproduction". Progress in Biophysics and Molecular Biology 113 (3): 355. doi:10.1016/j.pbiomolbio.2013.11.004. PMID 24314295. 
  38. ^ Music of Life Website
  39. ^ Selected Papers of Denis Noble CBE FRS, The: A Journey in Physiology Towards Enlightenment Website
  40. ^ EU-ISHR
  41. ^ Biovision Conference Programme