Denis Noble

Denis Noble
Born	(1936-11-16) 16 November 1936[1]
Residence	UK
Nationality	British
Fields	Systems biology Physiology[2] Computational biology
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	FRS (1979)[3] FMedSci (1998) CBE (1998)
Spouse	Susan Jennifer Barfield[1]
Children	one son, one daughter[1]
Website www.dpag.ox.ac.uk/team/group-leaders/denis-noble

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

• 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^[27][28][29]

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:

• The Initiation of the Heartbeat (OUP, 1975, 1979 and Japanese translation), sole author;
• Electrophysiology of Single Cardiac Cells, Academic Press 1987
• Goals, No Goals and Own Goals, Unwin Hyman 1989
• Sodium-Calcium Exchange, OUP, 1989
• Ionic Channels and the Effect of Taurine on the Heart, Springer, 1993, 2013
• 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;

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:

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