Denis Noble (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.Biography , Denis Noble homepage. Since 2025, he is a Distinguished Chair Professor at Daegu-Gyeongbuk Institute of Science and Technology (DGIST).
Historical reviews of cardiac electrophysiology identify Noble’s 1962 model as the first to use the Hodgkin–Huxley equations to investigate the long plateau of the cardiac action potential. His subsequent work helped establish computational cardiac electrophysiology as a field.
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, though these claims have not gained support from mainstream evolutionary biology, and TWE has been described as a "fringe movement".
Education Noble was educated at Emanuel School and University College London (UCL). 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. In 1961 he obtained his PhD working under the supervision of Otto Hutter at UCL.Dennis Noble (2006). The Music of Life,
This work was subsequently developed extensively with Richard Tsien in 1975, and with Dario DiFrancesco in 1985, forming 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.
The 1962 model was developed after Noble and Otto Hutter identified two potassium conductances in cardiac Purkinje fibres. By modifying the Hodgkin–Huxley formulation used for nerve axons, Noble was able to reproduce the longer cardiac action potential and spontaneous pacemaker behaviour.
The McAllister–Noble–Tsien model of 1975 extended this approach by incorporating a larger range of experimentally characterized membrane currents. In 1985, the DiFrancesco–Noble model became the first cardiac model to represent changes in intracellular and extracellular ion concentrations during the action potential, including calcium uptake and release by the sarcoplasmic reticulum.
Later reviews have treated these models as an important lineage in the development of cardiac-cell electrophysiology. Several of the models have subsequently been reconstructed in CellML, allowing their equations and numerical behaviour to be examined and reproduced using modern software.
Career He began his career as an assistant lecturer in physiology at University College London, also serving as vice-warden at the University of London. In 1963, he joined Balliol College, Oxford as a fellow and tutor, later becoming head of its graduate centre and vice-master.
From 1984 to 2004, he was Burdon Sanderson Professor of Cardiovascular Physiology at the University of Oxford and a professorial fellow at Balliol College. He subsequently became emeritus professor and continued as director of computational physiology. He also held appointments at Xi'an Jiaotong University and Osaka University.
Alongside his academic work, he led major research programmes, co-founded Save British Science, and served as editor-in-chief of Progress in Biophysics and Molecular Biology. He later became president of the International Union of Physiological Sciences and held editorial roles at Interface Focus and the Oxford Longevity Project.
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.All systems go article in The Economist 25-Oct-2007 discussing Noble's work
This programme connected ion-channel and cellular models with anatomically based tissue and whole-organ models. Published accounts describe the virtual-heart work as a framework for investigating arrhythmias, the cardiac effects of drugs and the operation of devices such as defibrillators; these uses should not be interpreted as evidence that all such models had entered routine clinical practice.
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.
Noble and bioengineer James Bassingthwaighte initiated the IUPS Physiome Project, and an IUPS Physiome Committee was established at the organization’s 1997 congress in Saint Petersburg to coordinate its development. The project sought to connect quantitative descriptions across molecular, cellular, tissue, organ and whole-body scales. In its cardiac component, multiscale models were developed to relate ion-channel activity and mutations to tissue electrophysiology, whole-heart arrhythmias and electrocardiographic patterns. The project also encouraged open model-description standards and repositories, including CellML and FieldML.
Noble is also a philosopher of biology, with many publications in journals and books of philosophy. In a review of The Music of Life, a book discussing systems biology, a colleague has stated that "by challenging the foundations of current biological sciences, he questions the central dogma, its unidirectional view of information flow, and its imposition of a bottom-up methodology for research in the life sciences."
The introduction to the 2023 book Evolution "On Purpose": Teleonomy in Living Systems, co-edited by Noble along with Addy Pross, Peter Corning, Stuart Kauffman, James A. Shapiro and Richard I. Vane-Wright, concludes with the claim that "Teleonomy in living systems is not, after all, only "apparent". It is a fundamental fact of life."
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.The Music of Life, pp. 12-14
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."
Noble calls his multilevel account “biological relativity”. It holds that no organizational level—such as the gene, cell, organ or organism—automatically has privileged causal status, and that biological explanation may require interactions operating in both upward and downward directions between levels. The proposal has received both qualified support and criticism. Reviewing Dance to the Tune of Life, Sepehr Ehsani described Noble’s historical analysis and case for multilevel interaction as informative, but questioned whether biological relativity could generate sufficiently testable hypotheses and whether its rejection of privileged levels adequately accounted for monogenic disease and biological hierarchy.
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 has called for an extended evolutionary synthesis, known as The Third Way of Evolution (TWE), as a replacement for the modern synthesis."The theory of evolution has evolved". The Physiological Society.
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."Physiology and the revolution in Evolutionary Biology" . Voices from Oxford.
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. 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 of TWE cite examples of developmental bias, genetic assimilation, niche construction, non-genetic inheritance, phenotypic plasticity and other evolutionary processes. The concept of natural genetic engineering, a process which Shapiro proposed to account for novelty created in biological evolution, is also important for the TWE. 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.
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".
Publications Noble has published over 700 articles in academic journals, including Nature, Science, PNAS, Journal of Physiology, Progress in Biophysics & Molecular Biology, and many articles in the national press. He is the (co-)author and/or editor of many books, including:
Historical reviews continue to use the Noble models as reference points in the development of mechanistic cardiac modelling, from early representations of Purkinje-fibre activity to models incorporating ion pumps, calcium handling and changing ionic concentrations.
[ Partial preview] from Google Books.
[ Partial preview] from Google Books.
[ Partial preview] from Google Books.
[ Partial preview] from Google Books.
Awards and honours His major invited lectures include the Darwin Lecture for the British Association in 1966, 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.