Denis Noble

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.

In 1958 he began his investigations into the mechanisms of heartbeat.

He is one of the pioneers of systems biology and developed the first viable mathematical model of the working heart in 1960.

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.

Noble was educated at Emanuel School and University College London (UCL).

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.

In 1961 he obtained his PhD working under the supervision of Otto Hutter at UCL.

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.

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.

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.

He was President of the Medical Section of the British Science Association 1991–92.

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, 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

Many further invited lectures during his election as Secretary-General (1993-2001) and President (2009-2017) of IUPS.

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".

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.

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.

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 2022, the HowTheLightGetsIn Festival at Hay-on-Wye featured Noble and Richard Dawkins in a "conversation" on evolution.

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.

Noble has proposed Ten Principles of Systems Biology:

Noble has published over 700 articles in academic journals, including Nature, Science, PNAS, Journal of Physiology, Progress in Biophysics & Molecular Biology; Many articles in national press.

He is the author or editor of many books, including:

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".

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 has called for an extended evolutionary synthesis, and more controversially a replacement for the modern synthesis known as The Third Way of Evolution (TWE).

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.