Denis Noble
Denis Noble 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.
Education
Noble was educated at Emanuel School and University College London. In 1958 he began his investigations into the mechanisms of heartbeat. This led to two seminal papers in Nature in 1960 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.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.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.
Noble is also a philosopher of biology, and his books The Music of Life and Dance to the Tune of Life 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
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 with an alternative view: "Now they 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".
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."
Evolution
Noble has called for an extended evolutionary synthesis, and more controversially a replacement for the modern synthesis.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", and a new synthesis will integrate research from physiology with evolutionary biology.
Principles of Systems Biology
Noble has proposed Ten Principles of Systems Biology:- Biological functionality is multi-level
- Transmission of information is not one way
- DNA is not the sole transmitter of inheritance
- The theory of biological relativity: there is no privileged level of causality
- Gene ontology will fail without higher-level insight
- There is no genetic program
- There are no programs at any other level
- There are no programs in the brain
- The self is not an object
- 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]
- 1963–1984 – Fellow and tutor, Balliol College, Oxford. University Lecturer in Physiology
- From 1967 – Editor of Progress in Biophysics and Molecular Biology
- 1969–1970 – Visiting professor and visiting scientist of the Canadian MRC
- 1971–1989 – Head 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
- From 2009 – Co-founder and editor of Voices from Oxford
- 2011–2017 – Editor in chief of Interface Focus
- From 2014 – Member and co-founder of The Third Way Of Evolution
Publications
- ', sole author;
- ' OUP, 1975. With J.J.B.Jack & R.W.Tsien
- ', Academic Press 1987, with T Powell
- ', Unwin Hyman 1989, with Alan Montefiore, and author
- ', OUP, 1989, with T.J.A. Allen and H. Reuter, and author
- ', Springer, 1993, 2013, with Y.E. Earm
- ', co-editor with CAR Boyd, and author;
- ' co-editor with J-D Vincent;
- ' OUP, 2006, sole author
- ' CUP, 2016, sole author
- Academic Press, 2019, co-editor, and author
Awards and honours
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 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. In 1998 he was awarded a CBE.
He has honorary doctorates from the University of Sheffield, the Université de Bordeaux and the University of Warwick.
He is an Honorary Foreign Member of the :fr:Académie royale de médecine de Belgique|Académie Royale de Médecine de Belgique, of the Istituto Lombardo Accademia di Scienze e Lettere, and received the Pavlov Medal of the Russian Academy of Sciences.