Denis Noble

This article is about the British biologist. For the British baritone, see Dennis Noble.
Denis Noble
Born (1936-11-16) 16 November 1936[1]
Residence UK
Nationality British
Fields
Institutions University of Oxford
Alma mater University College London (BSc, MA, PhD)
Thesis Ion conductance of cardiac muscle (1961)
Doctoral advisor Otto Hutter
Notable awards
Spouse Susan Jennifer Barfield[1]
Children one son, one daughter[1]

Website

Denis Noble CBE FRS FRCP FMedSci (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

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

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]

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[15]

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[16]

Reductionism

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".[17]

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."[18]

Evolution

Noble has called for an extended evolutionary synthesis, and more controversially a replacement for the modern synthesis.[19][20]

He has argued that from research in epigenetics, acquired characteristics can be inherited and in contrast to the modern synthesis, genetic change is "far from random" and not always gradual. He has also claimed that the central dogma of molecular biology has been broken and a new synthesis will integrate research from physiology with evolutionary biology.[21][22][23]

Evolutionary biologist Jerry Coyne has disputed Noble's views about evolution moving beyond the modern synthesis, stating that all his claims are wrong. According to Coyne "he fails to show a convincing case of long-term evolution induced by an environmental modification of the genetic material... However famous Noble may be in physiology, he’s a blundering tyro when it comes to evolutionary biology."[24] Noble has replied to Coyne on the Answers pages of his Music of Life website.

Principles of Systems Biology

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

Noble has proposed Ten Principles of Systems Biology:[25][26]

  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

Publications

Noble has published over 450 articles in academic journals,[2][14] including Nature,[9][10][30][31][32][33] Science,[34][35] PNAS,[36] Journal of Physiology,[37][38][39][40][41] Progress in Biophysics & Molecular Biology;[42] Many articles in national press. He is the author or editor of 11 books, including:

Awards and honours

His major invited lectures include the Darwin Lecture for the British Association in 1966,[43] 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 Science 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 1998, he also became a founding Fellow of the Academy of Medical Sciences.[44] In 1998 he was awarded a CBE.[45]

He has honorary doctorates from the University of Sheffield (2004),[46] the Université de Bordeaux (2005) and the University of Warwick (2008).[47]

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), Medal of Merit (2008)[48] and the British Heart Foundation Gold Medal (1985).

He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique (1993),[49] and received the Pavlov Medal of the Russian Academy of Sciences (2004).

Personal life

He plays classical guitar and sings Occitan troubadour and folk songs (OxfordTrobadors). In addition to English, he has lectured in French on YouTube, Italian on YouTube, Occitan, Japanese and Korean.[50]

References

  1. 1 2 3 4 "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. 1 2 Denis Noble's publications indexed by Google Scholar
  3. 1 2 "EC/1979/28: Noble, Denis". London: The Royal Society. Archived from the original on 2014-05-30.
  4. 1 2 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. 98: no. doi:10.1113/expphysiol.2012.071134. PMID 23585325.
  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. 1 2 Noble, Denis (1960). "Cardiac action and pacemaker potentials based on the Hodgkin-Huxley equations". Nature. 188 (4749): 495–7. Bibcode:1960Natur.188..495N. doi:10.1038/188495b0. PMID 13729365.
  10. 1 2 Hutter, Otto F.; Noble, Denis (1960). "Rectifying properties of heart muscle". Nature. 188: 495. Bibcode:1960Natur.188..495H. doi:10.1038/188495a0. 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. 1 2 Denis Noble's publications indexed by the Scopus bibliographic database, a service provided by Elsevier. (subscription required)
  15. ↑ Denis Noble Elected President of IUPS
  16. ↑ Werner, E. (2007). "SYSTEMS BIOLOGY: How Central is the Genome?". Science. 317 (5839): 753–754. doi:10.1126/science.1141807.
  17. ↑ The Music of Life, pp. 12-14
  18. ↑ 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.
  19. ↑ "The theory of evolution has evolved". The Physiological Society.
  20. ↑ "Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble". Huffington Post.
  21. ↑ Noble, Denis (2013). "Physiology is rocking the foundations of evolutionary biology". Experimental Physiology. 98 (8): 1235–1243. doi:10.1113/expphysiol.2012.071134. PMID 23585325.
  22. ↑ "Physiology and the revolution in Evolutionary Biology". Voices from Oxford.
  23. ↑ "Evolution evolves: physiology returns to centre stage". Journal of Experimental Biology. 592: 2237–44. 2014. doi:10.1113/jphysiol.2014.273151. PMC 4048083Freely accessible. PMID 24882808.
  24. ↑ Coyne, Jerry (August 25, 2013). "Famous physiologist embarrasses himself by claiming that the modern theory of evolution is in tatters". Why Evolution Is True (Blog). Retrieved 2015-12-06.
  25. ↑ 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.
  26. ↑ Video Lecture on the 10 principles
  27. ↑ 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 3262309Freely accessible. PMID 23386960.
  28. ↑ 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 3262251Freely accessible. PMID 22419970.
  29. ↑ Noble, D (2011). "Editorial". Interface Focus. 1 (1): 1–2. doi:10.1098/rsfs.2010.0385. PMC 3262238Freely accessible. PMID 22419969.
  30. ↑ 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.
  31. ↑ 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.
  32. ↑ Cohen, I; Giles, W; Noble, D (1976). "Cellular basis for the T wave of the electrocardiogram". Nature. 262 (5570): 657–61. Bibcode:1976Natur.262..657C. doi:10.1038/262657a0. PMID 958437.
  33. ↑ Hall, A. E.; Noble, D (1963). "Transient Responses of Purkinje Fibres to Non-Uniform Currents". Nature. 199: 1294–5. Bibcode:1963Natur.199.1294H. doi:10.1038/1991294a0. PMID 14074602.
  34. ↑ Noble, D (2002). "Modeling the heart--from genes to cells to the whole organ". Science. 295 (5560): 1678–82. Bibcode:2002Sci...295.1678N. doi:10.1126/science.1069881. PMID 11872832.
  35. ↑ 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. Bibcode:1968Sci...162..916H. doi:10.1126/science.162.3856.916. PMID 4386717.
  36. ↑ Noble, D (2002). "Unraveling the genetics and mechanisms of cardiac arrhythmia". Proceedings of the National Academy of Sciences. 99 (9): 5755–6. Bibcode:2002PNAS...99.5755N. doi:10.1073/pnas.102171699. PMC 122846Freely accessible. PMID 11983875.
  37. ↑ 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. doi:10.1113/jphysiol.1962.sp006849. PMC 1359535Freely accessible. PMID 14480151.
  38. ↑ 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. doi:10.1113/jphysiol.1975.sp011080. PMC 1348375Freely accessible. PMID 1185607.
  39. ↑ 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. doi:10.1113/jphysiol.1969.sp008689. PMC 1350425Freely accessible. PMID 5761944.
  40. ↑ 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. doi:10.1113/jphysiol.1968.sp008454. PMC 1557911Freely accessible. PMID 5639799.
  41. ↑ Noble, D (1984). "The surprising heart: A review of recent progress in cardiac electrophysiology". The Journal of Physiology. 353: 1–50. doi:10.1113/jphysiol.1984.sp015320. PMC 1193291Freely accessible. PMID 6090637.
  42. ↑ 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.
  43. ↑ Noble, D. (1966). "The Initiation of the Heart Beat. (Darwin Lecture, British Association)." The Advancement of Science 23: 412-418.
  44. ↑ http://www.acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/professor-denis-noble/
  45. ↑ http://www.independent.co.uk/arts-entertainment/queens-birthday-honours-1998-1164586.html
  46. ↑ http://calendar.dept.shef.ac.uk/calendar/21_hon_grad.pdf
  47. ↑ http://www2.warwick.ac.uk/alumni/ouralumni/hongrads/allhongrads/
  48. ↑ EU-ISHR
  49. ↑ http://www.armb.be/index.php?eID=tx_nawsecuredl&u=0&g=0&hash=9b3bbce437184c4e213127eb735def496c70980b&file=fileadmin/sites/armb/upload/armb_super_editor/armb_editor/pdf/Bulletin_de_l_Academie/2012/tableau_Acad_1.pdf
  50. ↑ Biovision Conference Programme
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