Denis Noble Explained

Denis Noble
Birth Date:	1936 11, df=yes
Nationality:	British
Doctoral Advisor:	Otto Hutter
Education:	Emanuel School
Alma Mater:	University College London (BSc, MA, PhD)
Thesis Title:	Ion conductance of cardiac muscle
Thesis Url:	https://copac.jisc.ac.uk/id/50502493?style=html
Thesis Year:	1961
Work Institution:	Balliol College, University of Oxford
Spouse:	Died 2015
Children:	2

Denis Noble ^[1] (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 mathematical model of the working heart in 1960.^{[2] [3] [4]} Noble established The Third Way of Evolution (TWE) project with James A. Shapiro which predicts that the entire framework of the modern synthesis will be replaced.

Education

Noble was educated at Emanuel School and University College London (UCL).^[2] In 1958 he began his investigations into the mechanisms of heartbeat. This led to two seminal papers in Nature in 1960 giving the first experimentally-based mathematical simulation of the electrical rhythm of the heart,^[5] extensively developed with Richard Tsien in 1975,^[6] and with Dario DiFrancesco in 1985.^[7] 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.^[8]

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.^{[9] [10]}

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.^[11]

As secretary-general of the International Union of Physiological Sciences 1993–2001, he played a major role, together with Sir 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.^[12]

Noble is also a philosopher of biology, with many publications in journals and books of philosophy.^{[13] [14] [15]}

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^[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". His 2016 book Dance to the Tune of Life sets these ideas out in a broad sweep from the general principle of relativity applied to biology, through to the role of purpose in evolution and to the relativity of epistemology.

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]

The Third Way of Evolution

Noble has called for an extended evolutionary synthesis, and more controversially a replacement for the modern synthesis known as The Third Way of Evolution (TWE).^{[19] [20] [21]}

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",^[22] and a new synthesis will integrate research from physiology with evolutionary biology.^{[23] [24] [25] [26] [27]}

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 extreme in its claims.^[19] 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.^[19] Shapiro's natural genetic engineering, a process described to account for novelty created in biological evolution is also important for the TWE.^{[26] [27] [28]} 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.^[19]

In 2022, the HowTheLightGetsIn Festival at Hay-on-Wye featured Noble and Richard Dawkins in a "conversation" on evolution.^[29] In 2024 he was featured in Forbes with a video and associated article. He has now (2024) published more than 50 articles and books on evolutionary biology.

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.^[19]

Principles of Systems Biology

Noble has proposed Ten Principles of Systems Biology:^{[30] [31]}

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)^[32]
• 1963–1984 – Fellow and tutor, Balliol College, Oxford. University Lecturer in Physiology
• 1967–2024 – Editor-in Chief of Progress in Biophysics and Molecular Biology^[33]
• 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^[34]
• From 2009 – Co-founder and editor-in-chief of Voices from Oxford^[35]
• 2011–2017 – Editor in chief of Interface Focus^{[36] [37] [38]}
• From 2014 – Member and co-founder of The Third Way of Evolution^[39]
• From 2021 – Co-Founder Oxford Longevity Project^[40]

Publications

Noble has published over 700 articles in academic journals, including Nature,^{[41] [42] [43] [44] [45] [46]} Science,^{[47] [48]} PNAS,^[49] Journal of Physiology,^{[50] [51] [52] [53] [54]} Progress in Biophysics & Molecular Biology;^[55] Many articles in national press. He is the author or editor of many books, including:

• The Initiation of the Heartbeat (OUP, 1975, 1979 and Japanese translation), sole author;
• Electric Current Flow in Excitable Cells OUP, 1975. With J.J.B.Jack & R.W.Tsien
• Electrophysiology of Single Cardiac Cells, Academic Press 1987, with T Powell
• Goals, No Goals and Own Goals, Unwin Hyman 1989, with Alan Montefiore, and author
• Sodium-Calcium Exchange, OUP, 1989, with T.J.A. Allen and H. Reuter, and author
• Ionic Channels and the Effect of Taurine on the Heart, Springer, 1993, 2013, with Y.E. Earm
• The Logic of Life (OUP 1993), co-editor with CAR Boyd, and author;
• The Ethics of Life (UNESCO 1997) co-editor with J-D Vincent;
• The Music of Life, Biology beyond the genome OUP, 2006 (9 translations), sole author
• Dance to the Tune of Life. Biological Relativity CUP, 2016, sole author
• Exosomes: A Clinical Compendium Academic Press, 2019, co-editor, and author
• The Language of Symmetry Chapman & Hall, 2023, co-editor, and author
• Understanding Living Systems Cambridge University Press, 2023, co-author with Raymond Noble
• Evolution "On Purpose": Teleonomy in Living Systems. MIT Press, 2023, co-Editor, and author

Awards and honours

His major invited lectures include the Darwin Lecture for the British Association in 1966,^[56] 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.^[57] In 1998 he was awarded a CBE.^[58] 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),^[59] the Université de Bordeaux (2005) and the University of Warwick (2008).^[60]

He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique (1993),^[61] 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.^[62]

Personal life

Noble was born in London in 1936 to working-class tailors, George and Ethel Noble.Web site: George Noble. The family lost its home in London when a high explosive bomb, probably intended for Clapham Junction, destroyed several houses in nearby Lavender Sweep.Web site: Lavender Sweep High Explosive bomb. As a teenager, he was trained as a magician by a stage performer, Tommy Dee, who may have been a model for the famous TV magician, Tommy Cooper.He plays classical guitar and sings Occitan troubadour and folk songs (Oxford Trobadors^[63]). In addition to English, he has lectured in,, Performance with Nadau & Peiraguda Occitan,^{[64] [65]} Japanese and Korean.^[66]

Notes and References

1. Web site: EC/1979/28: Noble, Denis . The Royal Society . 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')

   . London . dead. 30 May 2014 .
2. http://noble.physiol.ox.ac.uk/People/DNoble/ Biography
3. 10.1113/expphysiol.2012.071134. Physiology is rocking the foundations of evolutionary biology. Experimental Physiology. 1235–1243. 2013. Noble . D.. 23585325. 98. 8. 19689192. free.
4. 10.1152/ajpheart.00794.2003. 14656705. A model for human ventricular tissue. AJP: Heart and Circulatory Physiology. 286. 4. H1573–H1589. 2003. Ten Tusscher . K. H. W. J..
5. 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 . 10.1113/jphysiol.1962.sp006849. 14480151 . 1359535 .
6. McAllister . Eric . Noble . Denis . Tsien . Richard . 2022 . Reconstruction of the electrical activity of cardiac Purkinje fibres. . Journal of Physiology. 251 . 1 . 1–59 . 10.1113/jphysiol.1975.sp011080. 1185607 . 1348375 .
7. 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 . 10.1098/rstb.1985.0001. 2578676 .
8. Partridge . Linda . 2015 . Celebrating 350 years of Philosophical Transactions: life sciences papers. Philosophical Transactions of the Royal Society B . 370 . 1666 . 10.1098/rstb.2014.0380. 25750243 . 4360128 .
9. PhD . Denis. Noble . Ion conductance of cardiac muscle . University College London . 1962 . Denis Noble.
10. Dennis Noble (2006). The Music of Life,
11. http://www.economist.com/science/displayStory.cfm?story_id=10018596&fsrc=nwlptwfree All systems go
12. Web site: Auckland Bioengineering Institute - The University of Auckland. www.Auckland.ac.nz. 15 April 2019.
13. Noble . Denis . 1967 . Charles Taylor on Teleological Explanation . Analysis . 27 . 3 . 96–103 . 10.2307/3326802 . 3326802 .
14. Noble . Denis . 1993 . The logic of life: the public perception of science and its threat to the values of society . Science and Public Policy . 10.1093/spp/20.3.187 .
15. 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 . 10.1007/s10838-020-09525-3. 228947493 . free .
16. 10.1126/science.1141807. SYSTEMS BIOLOGY: How Central is the Genome?. Science. 317. 5839. 753–754. 2007. Werner . E.. 82065292.
17. The Music of Life, pp. 12-14
18. Noble . D.. Genes and causation. Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences. 366. 1878. 3001–3015. Sep 2008 . 1364-503X. 18559318 . 10.1098/rsta.2008.0086. 2008RSPTA.366.3001N . 17592966.
19. Svensson, E.I. (2023). The Structure of Evolutionary Theory: Beyond Neo-Darwinism, Neo-Lamarckism and Biased Historical Narratives About the Modern Synthesis. In: Dickins, T.E., Dickins, B.J. (eds) Evolutionary Biology: Contemporary and Historical Reflections Upon Core Theory. Springer. pp. 173–217.
20. http://www.physoc.org/press-release/2014/theory-evolution-has-evolved "The theory of evolution has evolved"
21. https://www.huffingtonpost.com/suzan-mazur/replace-the-modern-sythes_b_5284211.html "Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble"
22. Noble. Denis. Central Dogma or Central Debate?. Physiology. 33. 4. 2018. 246–249. 1548-9213. 10.1152/physiol.00017.2018. 29873598. free.
23. Noble . Denis . 2013 . Physiology is rocking the foundations of evolutionary biology . Experimental Physiology . 98 . 8. 1235–1243 . 10.1113/expphysiol.2012.071134 . 23585325. 19689192 . free .
24. http://www.voicesfromoxford.org/video/physiology-and-the-revolution-in-evolutionary-biology/184 "Physiology and the revolution in Evolutionary Biology"
25. 4048083 . The Journal of Physiology . 24882808 . 10.1113/jphysiol.2014.273151 . 592 . 11 . Evolution evolves: physiology returns to centre stage . 2014 . 2237–44 . Noble . D . Jablonka . E . Joyner . MJ . Müller . GB . Omholt . SW.
26. Noble . Denis . 2021 . The Illusions of the Modern Synthesis . Experimental Physiology. 107 . 9 . 1015–1028 . 10.1113/EP090133 . 35871280 . 9543272 . 251019199 .
27. Noble . Denis . 2022 . Modern Physiology vindicates Darwin's Dream . Experimental Physiology . 107 . 9 . 1015–1028 . 10.1113/EP090133 . 35871280 . 9543272 . 251019199 .
28. Shapiro J, Noble D. 2021. What prevents mainstream evolutionists teaching the whole truth about how genomes evolve?. Prog Biophys Mol Biol. 165. 140–152. 10.1016/j.pbiomolbio.2021.04.004. 33933502.
29. https://iai.tv/video/the-gene-machine "The Gene Machine"
30. 17951329. 2008. Noble. D. Claude Bernard, the first systems biologist, and the future of physiology. Experimental Physiology. 93. 1. 16–26. 10.1113/expphysiol.2007.038695. 3080457.
31. Web site: Principle of Systems Biology illustrated using the Virtual Heart. videolectures.net. 15 April 2019.
32. Web site: Archived copy . 7 December 2013 . https://web.archive.org/web/20180730025304/http://www.connaught-hall.org.uk/ . 30 July 2018 . dead .
33. Web site: Progress in Biophysics & Molecular Biology. 15 April 2019. www.journals.elsevier.com.
34. http://www.IUPS.org IUPS
35. Web site: Voices From Oxford. Voices From Oxford. 15 April 2019.
36. 10.1098/rsfs.2011.0067. 23386960. A theory of biological relativity: No privileged level of causation. Interface Focus. 2. 1. 55–64. 2011. Noble . D.. 3262309.
37. 22419970. 2011. Noble. D. Differential and integral views of genetics in computational systems biology. Interface Focus. 1. 1. 7–15. 10.1098/rsfs.2010.0444. 3262251.
38. 22419969. 2011. Noble. D. Editorial. Interface Focus. 1. 1. 1–2. 10.1098/rsfs.2010.0385. 3262238.
39. Web site: Home - The Third Way of Evolution. www.thethirdwayofevolution.com. 15 April 2019.
40. Web site: Oxford Longevity Project. www.oxfordlongevityproject.org. 8 October 2022.
41. 13729365. 1960. Noble. Denis. Denis Noble. Cardiac action and pacemaker potentials based on the Hodgkin-Huxley equations. Nature. 188. 495–7. 10.1038/188495b0 . 4749. 1960Natur.188..495N . 4147174.
42. 13717088. 1960. Hutter. Otto F.. Rectifying properties of heart muscle. Nature. 188. 4749. 495. Noble. Denis. Denis Noble. 10.1038/188495a0. 1960Natur.188..495H . 4273708. free.
43. 12540875. 2003. Blakemore. C. Is a scientific boycott ever justified?. Nature. 421. 6921. 314. Dawkins. R. Noble. D. Yudkin. M. 10.1038/421314b. 47249920. free.
44. 2441262. 1987. Egan. T. M.. An isoprenaline activated sodium-dependent inward current in ventricular myocytes. Nature. 328. 6131. 634–7. Noble. D. Noble. S. J.. Powell. T. Twist. V. W.. 10.1038/328634a0. 1987Natur.328..634E. 4324641.
45. 958437. 1976. Cohen. I. Cellular basis for the T wave of the electrocardiogram. Nature. 262. 5570. 657–61. Giles. W. Noble. D . 10.1038/262657a0. 1976Natur.262..657C . 4174864.
46. 14074602. 1963. Hall. A. E.. Transient Responses of Purkinje Fibres to Non-Uniform Currents. Nature. 199. 4900. 1294–5. Noble. D . 10.1038/1991294a0. 1963Natur.199.1294H . 4217721.
47. 11872832. 2002. Noble. D. Modeling the heart--from genes to cells to the whole organ. Science. 295. 5560. 1678–82. 10.1126/science.1069881. 2002Sci...295.1678N . 6756983.
48. 4386717. 1968. Hauswirth. O. Adrenaline: Mechanism of action on the pacemaker potential in cardiac Purkinje fibers. Science. 162. 3856. 916–7. Noble. D. Tsien. R. W. . 10.1126/science.162.3856.916. 1968Sci...162..916H . 23508494.
49. 11983875. 2002. Noble. D. Unraveling the genetics and mechanisms of cardiac arrhythmia. Proceedings of the National Academy of Sciences. 99. 9. 5755–6. 10.1073/pnas.102171699. 122846. 2002PNAS...99.5755N . free.
50. 14480151. 1962. Noble. D. A modification of the Hodgkin--Huxley equations applicable to Purkinje fibre action and pace-maker potentials. The Journal of Physiology. 160. 2. 317–52. 1359535 . 10.1113/jphysiol.1962.sp006849.
51. 1185607. 1975. McAllister. R. E.. Reconstruction of the electrical activity of cardiac Purkinje fibres. The Journal of Physiology. 251. 1. 1–59. Noble. D. Tsien. R. W.. 1348375 . 10.1113/jphysiol.1975.sp011080.
52. 5761944. 1969. Noble. D. Outward membrane currents activated in the plateau range of potentials in cardiac Purkinje fibres. The Journal of Physiology. 200. 1. 205–31. Tsien. R. W.. 1350425 . 10.1113/jphysiol.1969.sp008689.
53. 5639799. 1968. Noble. D. The kinetics and rectifier properties of the slow potassium current in cardiac Purkinje fibres. The Journal of Physiology. 195. 1. 185–214. Tsien. R. W.. 1557911 . 10.1113/jphysiol.1968.sp008454.
54. 6090637. 1984. Noble. D. The surprising heart: A review of recent progress in cardiac electrophysiology. The Journal of Physiology. 353. 1–50. 1193291 . 10.1113/jphysiol.1984.sp015320.
55. 10.1016/j.pbiomolbio.2013.11.004. 24314295. Systems biology and reproduction. Progress in Biophysics and Molecular Biology. 113. 3. 355. 2013. Noble . D. .
56. Noble . D . 1966 . The Initiation of the Heart Beat. (Darwin Lecture, British Association) . The Advancement of Science . 23 . 412–418 .
57. Web site: Professor Denis Noble | the Academy of Medical Sciences . 1 May 2015 . 3 March 2016 . https://web.archive.org/web/20160303234151/http://www.acmedsci.ac.uk/fellows/fellows-directory/ordinary-fellows/professor-denis-noble/ . dead .
58. Web site: Queen's Birthday honours 1998. Independent.co.uk. 1998-06-12.
59. Web site: Archived copy . 1 May 2015 . 29 October 2013 . https://web.archive.org/web/20131029192732/http://calendar.dept.shef.ac.uk/calendar/21_hon_grad.pdf . dead .
60. Web site: Our honorary graduates . 1 May 2015 . 13 January 2016 . https://web.archive.org/web/20160113004209/https://www2.warwick.ac.uk/alumni/ouralumni/hongrads/allhongrads/ . dead .
61. Web site: Archived copy . 16 February 2022 . 21 July 2020 . https://web.archive.org/web/20200721185652/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 . dead .
62. https://www.ras.ru/news/shownews.aspx?id=8caa02a0-74b3-40c8-86a5-09200303a8b2 Lomonosov Gold Medal 2022 (in Russian)
63. Web site: Oxford Trobadors. www.oxfordtrobadors.com. 15 April 2019.
64. Web site: Oxford Trobadors. www.oxfordtrobadors.com. 15 April 2019.
65. Web site: Dordogne-Périgord, le Département . .
66. Web site: Biovision Conference Programme. biovision.org. 15 April 2019. https://web.archive.org/web/20110725080312/http://www.biovision.org/speaker-info.html/26-denis-noble. 25 July 2011. dead.