Denis Noble

Denis Noble 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.
In 2014, Noble established The Third Way of Evolution 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. 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, extensively developed with Richard Tsien in 1975, and with Dario DiFrancesco in 1985. 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.
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.

Career positions

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
1967–2024 – Editor-in Chief 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-in-chief of Voices from Oxford
2011–2017 – Editor in chief of Interface Focus
From 2014 – Member and co-founder of The Third Way of Evolution
From 2021 – Co-Founder 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.
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 is also a philosopher of biology, with many publications in journals and books of philosophy.
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
In 2023 the 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 stated in the introduction 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. 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 Richard 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."

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.
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.
Noble and James A. Shapiro established The Third Way of Evolution 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, advocates cite examples of developmental bias, genetic assimilation, niche construction, non-genetic inheritance, phenotypic plasticity and other evolutionary processes. Shapiro's natural genetic engineering, a process described 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 is even a scientific one".

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
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 author and/or editor of many books, including:

from Google Books.
from Google Books.
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from Google Books.