Biography:Denis Noble

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Denis Noble

CBE FRS FMedSci MAE
Born (1936-11-16) 16 November 1936 (age 89)[1]
NationalityBritish
EducationEmanuel School
Alma materUniversity College London (BSc, MA, PhD)
Spouse(s)
Susan Jennifer Barfield (m. 1965)
[1] Died 2015
Children2[1]
Awards
Scientific career
Fields
InstitutionsBalliol College, University of Oxford
ThesisIon conductance of cardiac muscle (1961)
Doctoral advisorOtto Hutter
Website

Denis Noble CBE FRS FMedSci MAE[3] (born 16 November 1936) is a British physiologist and 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 model of the working heart in 1960.[4][5][6][7][8]

In 2014, Noble established The Third Way of Evolution (TWE) project with James A. Shapiro which rejects natural selection as the primary cause of evolution and predicts that the entire framework of the modern synthesis of evolution will be replaced,[9] though these claims have not gained support from mainstream evolutionary biology, and TWE has been described as a "fringe movement".[9]

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[10][11] giving the first experimentally-based mathematical simulation of the electrical rhythm of the heart,[12] extensively developed with Richard Tsien in 1975,[13] and with Dario DiFrancesco in 1985.[14] All three articles form the foundations of modern electrophysiology of the heart. The 1985 article was included in 2015 in the Royal Society's 350-year celebration of the publication of Philosophical Transactions.[15]

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 involving the various ion channels. In 1961 he obtained his PhD working under the supervision of Otto Hutter at UCL.[16][17]

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.[18][19]

As secretary-general of the International Union of Physiological Sciences 1993–2001, he played a major role, together with Peter Hunter, 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.[20]

Noble is also a philosopher of biology, with many publications in journals and books of philosophy.[21][22][23]

His books The Music of Life, Dance to the Tune of Life and Understanding Living Systems challenge the foundations of current biological sciences, question the central dogma, its unidirectional view of information flow, and its imposition of a bottom-up methodology for research in the life sciences[24]

Reductionism

He contrasts Richard 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".[25]

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."[26]

The Third Way of Evolution

Noble has rejected natural selection as the primary mechanism of evolution, contrary to the longstanding consensus of evolutionary biologists, and called for an extended evolutionary synthesis, and a replacement for the modern synthesis known as The Third Way of Evolution (TWE).[9][27][28]

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 as an "embodiment of the Weismann Barrier",[29] and a new synthesis will integrate research from physiology with evolutionary biology.[30][31][32][33][34]

Noble and James A. Shapiro established The Third Way of Evolution (TWE) project in 2014. The TWE which is also known as the "Integrated Synthesis" shares many similarities with the extended evolutionary synthesis but is more radical in its claims.[9] The TWE consists of a group of researchers who provide a "Third Way" alternative to creationism and the modern synthesis. The TWE predicts that the modern synthesis will be replaced with an entirely new evolutionary framework. Similar to the extended evolutionary synthesis (EES), advocates cite examples of developmental bias, genetic assimilation, niche construction, non-genetic inheritance, phenotypic plasticity and other evolutionary processes.[9] Shapiro's natural genetic engineering, a process described to account for novelty created in biological evolution is also important for the TWE.[33][34][35] The difference between the extended synthesis and the TWE is that the latter calls for an entire replacement of the modern synthesis rather than an extension.[9]

In 2023, evolutionary biologist Erik Svensson commented that "to date, there are few leading evolutionary biologists who have openly embraced the TWE" and it is unlikely that an entire replacement of the modern synthesis will occur as there has been little visibility of such a forthcoming paradigm shift during the past decade, and described TWE as a "fringe movement outside mainstream evolutionary biology" that is ideologically adjacent to Lamarckism. Svensson described Noble's claims as based on "biased and historically misleading characterizations" of the modern evolutionary synthesis, conflating it with both the earlier "Neo-Darwinism", as well as later developments such as the selfish gene hypothesis. Svensson also criticised Noble's claim that genetic mutations were directed and purposeful, contrary to the mainstream consensus that mutations are entirely random. Noble had in Svensson's view, failed to present a viable alternative to natural selection, with Svensson stating it was "unclear if [Noble's proposed mechanism for evolution] is even a scientific one".[9]

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:[36][37]

  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

  • 1961–1963 – Assistant lecturer in Physiology, University College London
  • 1961–1963 – Vice-warden of Connaught Hall (University of London)[38]
  • 1963–1984 – Fellow and tutor, Balliol College, Oxford. University Lecturer in Physiology
  • 1967–2024 – Editor-in Chief of Progress in Biophysics and Molecular Biology[39]
  • 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
  • 1986 – co-founder of Save British Science, now the Campaign for Science and Engineering
  • 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, 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[40]
  • From 2009 – Co-founder and editor-in-chief of Voices from Oxford[41]
  • 2011–2017 – Editor in chief of Interface Focus[42][43][44]
  • From 2014 – Member and co-founder of The Third Way of Evolution[45]
  • From 2021 – Co-Founder Oxford Longevity Project[46]

Publications

Noble has published over 700 articles in academic journals,[2][19] including Nature,[10][11][47][48][49][50] Science,[51][52] PNAS,[53] Journal of Physiology,[54][55][56][57][58] Progress in Biophysics & Molecular Biology,[59] and many articles in the national press. He is the (co-)author and/or editor of many books, including:

Awards and honours

His major invited lectures include the Darwin Lecture for the British Association in 1966,[60] 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. Many further invited lectures during his election as Secretary-General (1993-2001) and President (2009-2017) of IUPS.

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

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 Physiological Society of Japan in 1998. In 1989 he was elected a Member of the Academia Europaea. In 1998, he also became a founding Fellow of the Academy of Medical Sciences.[61] In 1998 he was awarded a CBE.[62] In 2021 he was elected a Fellow of the IUPS Academy. In 2022 he was elected a Fellow of The Linnean Society (FLS)

He has honorary doctorates from the University of Sheffield (2004),[63] the Université de Bordeaux (2005) and the University of Warwick (2008).[64]

He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique (1993),[65] of the Istituto Lombardo Accademia di Scienze e Lettere, and received the Pavlov Medal of the Russian Academy of Sciences (2004). In 2022 he was elected Foreign Member of the Russian Academy of Sciences and was also awarded the Lomonosov Gold Medal.[66]

Personal life

Noble was born in London in 1936 to working-class tailors, George and Ethel Noble.[67]

He plays classical guitar and sings Occitan troubadour and folk songs (Oxford Trobadors[68]). In addition to English, he has lectured in French, Italian, Performance with Nadau & Peiraguda Occitan,[69][70] Japanese and Korean.[71]

In 2011, Alison MacLeod's story, "The Heart of Denis Noble", featuring a fictionalised version of Denis Noble recovering from a heart attack, was shortlisted for the BBC National Short Story Award.[72]

References

  1. ↑ 1.0 1.1 1.2 1.3 Anon (2014). ",". Who's Who (online Oxford University Press ed.). A & C Black, an imprint of Bloomsbury Publishing plc. doi:10.1093/ww/9780199540884.013.U29605. https://www.ukwhoswho.com/view/article/oupww/whoswho/U29605.  (subscription or UK public library membership required)
  2. ↑ 2.0 2.1 Denis Noble publications indexed by Google Scholar
  3. ↑ 3.0 3.1 "EC/1979/28: Noble, Denis". London: The Royal Society. Archived from the original on 30 May 2014. https://archive.today/20140530133026/https://collections.royalsociety.org/DServe.exe?dsqIni=Dserve.ini&dsqApp=Archive&dsqDb=Catalog&dsqCmd=show.tcl&dsqSearch=(RefNo=='EC/1979/28'). 
  4. ↑ 4.0 4.1 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 (8): 1235–1243. 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–H1589. doi:10.1152/ajpheart.00794.2003. PMID 14656705. 
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 Svensson, Erik I. (2023). "The Structure of Evolutionary Theory: Beyond Neo-Darwinism, Neo-Lamarckism and Biased Historical Narratives About the Modern Synthesis". Evolutionary Biology: Contemporary and Historical Reflections Upon Core Theory. Evolutionary Biology – New Perspectives on Its Development. 6. pp. 173–217. doi:10.1007/978-3-031-22028-9_11. ISBN 978-3-031-22027-2. https://ecoevorxiv.org/repository/view/4002/. 
  10. ↑ 10.0 10.1 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. Bibcode: 1960Natur.188..495N. 
  11. ↑ 11.0 11.1 Hutter, Otto F.; Noble, Denis (1960). "Rectifying properties of heart muscle". Nature 188 (4749): 495. doi:10.1038/188495a0. PMID 13717088. Bibcode: 1960Natur.188..495H. 
  12. ↑ Noble, Denis (1962). "A modification of the Hodgkin—Huxley equations applicable to Purkinje fibre action and pacemaker potentials". The Journal of Physiology 160 (2): 317–352. doi:10.1113/jphysiol.1962.sp006849. PMID 14480151. 
  13. ↑ McAllister, Eric; Noble, Denis; Tsien, Richard (2022). "Reconstruction of the electrical activity of cardiac Purkinje fibres.". Journal of Physiology 251 (1): 1–59. doi:10.1113/jphysiol.1975.sp011080. PMID 1185607. 
  14. ↑ DiFrancesco, Dario; Noble, Denis (2022). "A model of cardiac electrical activity incorporating ionic pumps and concentration changes". Philosophical Transactions of the Royal Society B 307 (1133): 353–398. doi:10.1098/rstb.1985.0001. PMID 2578676. 
  15. ↑ Partridge, Linda (2015). "Celebrating 350 years of Philosophical Transactions: life sciences papers". Philosophical Transactions of the Royal Society B 370 (1666). doi:10.1098/rstb.2014.0380. PMID 25750243. 
  16. ↑ Noble, Denis (1962). Ion conductance of cardiac muscle (PhD thesis). University College London.
  17. ↑ Dennis Noble (2006). The Music of Life, ISBN 0-19-929573-5
  18. ↑ All systems go article in The Economist 25-Oct-2007 discussing Noble's work
  19. ↑ 19.0 19.1 Denis Noble's publications indexed by the Scopus bibliographic database. (Subscription content?)
  20. ↑ "Auckland Bioengineering Institute - The University of Auckland". https://www.auckland.ac.nz/en/abi.html. 
  21. ↑ Noble, Denis (1967). "Charles Taylor on Teleological Explanation". Analysis 27 (3): 96–103. doi:10.2307/3326802. 
  22. ↑ Noble, Denis (1993). "The logic of life: the public perception of science and its threat to the values of society". Science and Public Policy. doi:10.1093/spp/20.3.187. 
  23. ↑ Noble, Raymond; Noble, Denis (2022). "Can reasons and values influence action: how might intentional agency work physiologically?". Journal for General Philosophy of Science 52 (2): 277–295. doi:10.1007/s10838-020-09525-3. 
  24. ↑ Werner, E. (2007). "SYSTEMS BIOLOGY: How Central is the Genome?". Science 317 (5839): 753–754. doi:10.1126/science.1141807. 
  25. ↑ The Music of Life, pp. 12-14
  26. ↑ Noble, D. (Sep 2008). "Genes and causation". Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences 366 (1878): 3001–3015. doi:10.1098/rsta.2008.0086. ISSN 1364-503X. PMID 18559318. Bibcode: 2008RSPTA.366.3001N. 
  27. ↑ "The theory of evolution has evolved". The Physiological Society.
  28. ↑ "Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble" (in en). 2014-05-10. https://www.huffingtonpost.com/suzan-mazur/replace-the-modern-sythes_b_5284211.html. 
  29. ↑ Noble, Denis (2018). "Central Dogma or Central Debate?". Physiology 33 (4): 246–249. doi:10.1152/physiol.00017.2018. ISSN 1548-9213. PMID 29873598. 
  30. ↑ 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. 
  31. ↑ "Physiology and the revolution in Evolutionary Biology" . Voices from Oxford.
  32. ↑ Noble, D; Jablonka, E; Joyner, MJ; Müller, GB; Omholt, SW (2014). "Evolution evolves: physiology returns to centre stage". The Journal of Physiology 592 (11): 2237–44. doi:10.1113/jphysiol.2014.273151. PMID 24882808. 
  33. ↑ 33.0 33.1 Noble, Denis (2021). "The Illusions of the Modern Synthesis". Experimental Physiology 107 (9): 1015–1028. doi:10.1113/EP090133. PMID 35871280. 
  34. ↑ 34.0 34.1 Noble, Denis (2022). "Modern Physiology vindicates Darwin's Dream". Experimental Physiology 107 (9): 1015–1028. doi:10.1113/EP090133. PMID 35871280. 
  35. ↑ Shapiro J, Noble D (2021). "What prevents mainstream evolutionists teaching the whole truth about how genomes evolve?". Prog Biophys Mol Biol 165: 140–152. doi:10.1016/j.pbiomolbio.2021.04.004. PMID 33933502. 
  36. ↑ 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. 
  37. ↑ "Principle of Systems Biology illustrated using the Virtual Heart". http://videolectures.net/eccs07_noble_psb/. 
  38. ↑ "Archived copy". http://www.connaught-hall.org.uk/. 
  39. ↑ "Progress in Biophysics & Molecular Biology". https://www.journals.elsevier.com/progress-in-biophysics-and-molecular-biology/. 
  40. ↑ IUPS
  41. ↑ "Voices From Oxford". http://www.voicesfromoxford.org/. 
  42. ↑ 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. PMID 23386960. 
  43. ↑ 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. PMID 22419970. 
  44. ↑ Noble, D (2011). "Editorial". Interface Focus 1 (1): 1–2. doi:10.1098/rsfs.2010.0385. PMID 22419969. 
  45. ↑ "Home - The Third Way of Evolution". https://www.thethirdwayofevolution.com/. 
  46. ↑ "Oxford Longevity Project". https://oxfordlongevityproject.org/. 
  47. ↑ 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. 
  48. ↑ 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. Bibcode: 1987Natur.328..634E. 
  49. ↑ Cohen, I; Giles, W; Noble, D (1976). "Cellular basis for the T wave of the electrocardiogram". Nature 262 (5570): 657–61. doi:10.1038/262657a0. PMID 958437. Bibcode: 1976Natur.262..657C. 
  50. ↑ Hall, A. E.; Noble, D (1963). "Transient Responses of Purkinje Fibres to Non-Uniform Currents". Nature 199 (4900): 1294–5. doi:10.1038/1991294a0. PMID 14074602. Bibcode: 1963Natur.199.1294H. 
  51. ↑ 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. Bibcode: 2002Sci...295.1678N. 
  52. ↑ 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. doi:10.1126/science.162.3856.916. PMID 4386717. Bibcode: 1968Sci...162..916H. 
  53. ↑ 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. PMID 11983875. Bibcode: 2002PNAS...99.5755N. 
  54. ↑ Noble, D (1962). "A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials". The Journal of Physiology 160 (2): 317–52. doi:10.1113/jphysiol.1962.sp006849. PMID 14480151. 
  55. ↑ 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. PMID 1185607. 
  56. ↑ 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. PMID 5761944. 
  57. ↑ 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. PMID 5639799. 
  58. ↑ 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. PMID 6090637. 
  59. ↑ 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. 
  60. ↑ Noble, D (1966). "The Initiation of the Heart Beat. (Darwin Lecture, British Association)". The Advancement of Science 23: 412–418. 
  61. ↑ "Professor Denis Noble | the Academy of Medical Sciences". http://www.acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/professor-denis-noble/. 
  62. ↑ "Queen's Birthday honours 1998". 1998-06-12. https://www.independent.co.uk/arts-entertainment/queens-birthday-honours-1998-1164586.html. 
  63. ↑ "Archived copy". http://calendar.dept.shef.ac.uk/calendar/21_hon_grad.pdf. 
  64. ↑ "Our honorary graduates". http://www2.warwick.ac.uk/alumni/ouralumni/hongrads/allhongrads/. 
  65. ↑ "Archived copy". http://www.armb.be/index.php?eID=tx_nawsecuredl&u=0&g=0&hash=9b3bbce437184c4e213127eb735def496c70980b&file=fileadmin%2Fsites%2Farmb%2Fupload%2Farmb_super_editor%2Farmb_editor%2Fpdf%2FBulletin_de_l_Academie%2F2012%2Ftableau_Acad_1.pdf. 
  66. ↑ Lomonosov Gold Medal 2022 (in Russian)
  67. ↑ "George Noble". https://channillo.com/series/who-am-i-who-are-you-/752-4855. 
  68. ↑ "Oxford Trobadors". http://www.oxfordtrobadors.com/. 
  69. ↑ "Oxford Trobadors". http://www.oxfordtrobadors.com/StoryOc.html. 
  70. ↑ "Dordogne-Périgord, le Département". https://www.facebook.com/watch/?v=4922906717795243. 
  71. ↑ "Biovision Conference Programme". http://www.biovision.org/speaker-info.html/26-denis-noble. 
  72. ↑ "BBC National Short Story Award". https://www.bbc.co.uk/programmes/articles/2YnlfzMWv242HnQJLTcPLgR/the-2016-award. 



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