Denis Noble
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Denis Noble (born 16 November 1936) is a British
physiologist Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a subdiscipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out chemical and ...
and
biologist A biologist is a scientist who conducts research in biology. Biologists are interested in studying life on Earth, whether it is an individual Cell (biology), cell, a multicellular organism, or a Community (ecology), community of Biological inter ...
who held the Burdon Sanderson Chair of
Cardiovascular Physiology Cardiovascular physiology is the study of the cardiovascular system, specifically addressing the physiology of the heart ("cardio") and blood vessels ("vascular"). These subjects are sometimes addressed separately, under the names cardiac physiolog ...
at the
University of Oxford The University of Oxford is a collegiate university, collegiate research university in Oxford, England. There is evidence of teaching as early as 1096, making it the oldest university in the English-speaking world and the List of oldest un ...
from 1984 to 2004 and was appointed professor emeritus and co-director of computational physiology. He is one of the pioneers of
systems biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological system ...
and developed the first viable model of the working
heart The heart is a muscular Organ (biology), organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrie ...
in 1960.Biography
, Denis Noble homepage.
In 2014, Noble established The Third Way of Evolution (TWE) project with James A. Shapiro which rejects
natural selection Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
as the primary cause of
evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...
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 Emanuel School is a private, co-educational day school in Battersea, south-west London. The school was founded in 1594 by Anne Sackville, Lady Dacre and Queen Elizabeth I and today occupies a 12-acre (4.9 ha) site close to Clapham Junction ...
and
University College London University College London (Trade name, branded as UCL) is a Public university, public research university in London, England. It is a Member institutions of the University of London, member institution of the Federal university, federal Uni ...
(UCL). In 1958 he began his investigations into the mechanisms of heartbeat. This led to two seminal papers in ''
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
'' 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 A Doctor of Philosophy (PhD, DPhil; or ) is a terminal degree that usually denotes the highest level of academic achievement in a given discipline and is awarded following a course of graduate study and original research. The name of the deg ...
working under the supervision of Otto Hutter at UCL.


Research

Noble's research focuses on using
computer models Computer simulation is the running of a mathematical model on a computer, the model being designed to represent the behaviour of, or the outcome of, a real-world or physical system. The reliability of some mathematical models can be determin ...
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 ''The Economist'' is a British newspaper published weekly in printed magazine format and daily on Electronic publishing, digital platforms. It publishes stories on topics that include economics, business, geopolitics, technology and culture. M ...
25-Oct-2007 discussing Noble's work
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 The physiome of an individual's or species' physiological state is the description of its functional behavior. The physiome describes the physiological dynamics of the normal intact organism and is built upon information and structure (genome, prot ...
Project, an international project to use computer simulations to create the quantitative physiological models necessary to interpret the
genome A genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding genes, other functional regions of the genome such as ...
, and he was elected president of the IUPS at its world congress in
Kyoto Kyoto ( or ; Japanese language, Japanese: , ''Kyōto'' ), officially , is the capital city of Kyoto Prefecture in the Kansai region of Japan's largest and most populous island of Honshu. , the city had a population of 1.46 million, making it t ...
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


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 Reductionism is any of several related philosophical ideas regarding the associations between phenomena which can be described in terms of simpler or more fundamental phenomena. It is also described as an intellectual and philosophical positi ...
. He points out that there are many examples of
feedback loop Feedback occurs when outputs of a system are routed back as inputs as part of a chain of cause and effect that forms a circuit or loop. The system can then be said to ''feed back'' into itself. The notion of cause-and-effect has to be handle ...
s and "
downward causation In philosophy, downward causation is a causal relationship from higher levels of a system to lower-level parts of that system: for example, mental events acting to cause physical events. The term was originally coined in 1974 by the philosopher and ...
" in biology, and that it is not reasonable to privilege one level of understanding over all others. He also explains that
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s 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 Richard Dawkins (born 26 March 1941) is a British evolutionary biology, evolutionary biologist, zoologist, science communicator and author. He is an Oxford fellow, emeritus fellow of New College, Oxford, and was Simonyi Professor for the Publ ...
's famous statement in ''
The Selfish Gene ''The Selfish Gene'' is a 1976 book on evolution by ethologist Richard Dawkins that promotes the gene-centred view of evolution, as opposed to views focused on the organism and the group. The book builds upon the thesis of George C. Willia ...
'' ("Now they enesswarm ... 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 enesare 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 Natural selection is the differential survival and reproduction of individuals due to differences in phenotype. It is a key mechanism of evolution, the change in the Heredity, heritable traits characteristic of a population over generation ...
as the primariy mechanism of evolution, contrary to the longstanding consensus of evolutionary biologists, and called for an
extended evolutionary synthesis The Extended Evolutionary Synthesis (EES) consists of a set of theoretical concepts argued to be more comprehensive than the earlier modern synthesis of evolutionary biology that took place between 1918 and 1942. The extended evolutionary synthe ...
, and a replacement for the
modern synthesis Modern synthesis or modern evolutionary synthesis refers to several perspectives on evolutionary biology, namely: * Modern synthesis (20th century), the term coined by Julian Huxley in 1942 to denote the synthesis between Mendelian genetics and s ...
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 The gradual ( or ) is a certain chant or hymn in liturgical Christian worship. It is practiced in the Catholic Mass, Lutheran Divine Service, Anglican service and other traditions. It gets its name from the Latin (meaning "step") because i ...
. He has also claimed that the
central dogma of molecular biology The central dogma of molecular biology deals with the flow of genetic information within a biological system. It is often stated as "DNA makes RNA, and RNA makes protein", although this is not its original meaning. It was first stated by Francis Cr ...
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 (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 Creationism is the faith, religious belief that nature, and aspects such as the universe, Earth, life, and humans, originated with supernatural acts of Creation myth, divine creation, and is often Pseudoscience, pseudoscientific.#Gunn 2004, Gun ...
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 Genetic assimilation is a process described by Conrad H. Waddington by which a phenotype originally produced in response to an environmental condition, such as exposure to a teratogen, later becomes genetically encoded via artificial selection ...
,
niche construction Niche construction is the ecological process by which an organism alters its own (or another species') local environment. These alterations can be a physical change to the organism’s environment, or it can encompass the active movement of an or ...
, non-genetic inheritance,
phenotypic plasticity Phenotypic plasticity refers to some of the changes in an organism's behavior, morphology and physiology in response to a unique environment. Fundamental to the way in which organisms cope with environmental variation, phenotypic plasticity encompa ...
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 A paradigm shift is a fundamental change in the basic concepts and experimental practices of a scientific discipline. It is a concept in the philosophy of science that was introduced and brought into the common lexicon by the American physicist a ...
during the past decade, and described TWE as a " fringe movement outside mainstream evolutionary biology" that is ideologically adjacent to
Lamarckism Lamarckism, also known as Lamarckian inheritance or neo-Lamarckism, is the notion that an organism can pass on to its offspring physical characteristics that the parent organism acquired through use or disuse during its lifetime. It is also calle ...
. 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 Neo-Darwinism is generally used to describe any integration of Charles Darwin's theory of evolution by natural selection with Gregor Mendel's theory of genetics. It mostly refers to evolutionary theory from either 1895 (for the combinations of D ...
", as well as later developments such as the selfish gene hypothesis. Svensson also criticised Noble's claim that
genetic mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...
were directed and purposeful, contrary to the mainstream consensus that mutations are entirely
random In common usage, randomness is the apparent or actual lack of definite pattern or predictability in information. A random sequence of events, symbols or steps often has no order and does not follow an intelligible pattern or combination. ...
. Noble had in Svensson's view, failed to present a viable alternative to natural selection, with Svensson stating it was "unclear if oble's proposed mechanism for evolutionis even a scientific one".


Principles of Systems Biology

Noble has proposed Ten Principles of
Systems Biology Systems biology is the computational modeling, computational and mathematical analysis and modeling of complex biological systems. It is a biology-based interdisciplinary field of study that focuses on complex interactions within biological system ...
: # 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 The Gene Ontology (GO) is a major bioinformatics initiative to unify the representation of gene and gene product attributes across all species. More specifically, the project aims to: 1) maintain and develop its controlled vocabulary of gene and ...
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 (University of London) * 1963–1984 – Fellow and tutor, Balliol College, Oxford. University Lecturer in Physiology * 1967–2024 – Editor-in Chief of ''
Progress in Biophysics and Molecular Biology ''Progress in Biophysics and Molecular Biology'' is a peer-reviewed scientific journal publishing review articles in the fields of biophysics and molecular biology. It was established in 1950 as ''Progress in Biophysics and Biophysical Chemistry'' ...
'' * 1969–1970 – Visiting professor and visiting scientist of the Canadian MRC * 1971–1989 – Head (praefectus) of the Balliol College Graduate Centre at
Holywell Manor Holywell Manor is a historic building in central Oxford, England, in the parish of Holywell, Oxford, Holywell. It currently houses some of Balliol College, Oxford, Balliol College's postgraduate student population. It is on the corner of Mano ...
* 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 The Campaign for Science and Engineering (CaSE) is a non-profit organisation that is the UK's leading independent advocate for science and engineering. It focuses on arguing for more research funding, promoting a high-tech and knowledge-based e ...
* 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 The , abbreviated as UOsaka or , is a List of national universities in Japan, national research university in Osaka, Japan. The university traces its roots back to Edo period, Edo-era institutions Tekijuku (1838) and Kaitokudō, Kaitokudo (1724), ...
, 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 ''Interface Focus'' is the Royal Society's cross-disciplinary themed publication promoting research at the interface between the physical and life sciences. It is the sister journal to '' Journal of the Royal Society Interface'' with the main dif ...
'' * From 2014 – Member and co-founder of The Third Way of Evolution * From 2021 – Co-Founder Oxford Longevity Project


Publications

Noble has published over 700 articles in academic journals, including
Nature Nature is an inherent character or constitution, particularly of the Ecosphere (planetary), ecosphere or the universe as a whole. In this general sense nature refers to the Scientific law, laws, elements and phenomenon, phenomena of the physic ...
,
Science Science is a systematic discipline that builds and organises knowledge in the form of testable hypotheses and predictions about the universe. Modern science is typically divided into twoor threemajor branches: the natural sciences, which stu ...
,
PNAS ''Proceedings of the National Academy of Sciences of the United States of America'' (often abbreviated ''PNAS'' or ''PNAS USA'') is a peer-reviewed multidisciplinary scientific journal. It is the official journal of the National Academy of S ...
,
Journal of Physiology ''The Journal of Physiology'' is a semi-monthly peer-reviewed scientific journal that was established in 1878 and is published by Wiley-Blackwell on behalf of The Physiological Society. It covers research on all aspects of physiology, with an emp ...
, Progress in Biophysics & Molecular Biology, and many articles in the national press. He is the (co-)author and/or editor of many books, including: * * * * * * * * *
Partial preview Partial may refer to: Mathematics *Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial ...
from
Google Books Google Books (previously known as Google Book Search, Google Print, and by its code-name Project Ocean) is a service from Google that searches the full text of books and magazines that Google has scanned, converted to text using optical charac ...
. * *
Partial preview Partial may refer to: Mathematics *Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial ...
from Google Books. *
Partial preview Partial may refer to: Mathematics *Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial ...
from Google Books. * *
Partial preview Partial may refer to: Mathematics *Partial derivative, derivative with respect to one of several variables of a function, with the other variables held constant ** ∂, a symbol that can denote a partial derivative, sometimes pronounced "partial ...
from Google Books.


Awards and honours

His major invited lectures include the Darwin Lecture for the
British Association The British Science Association (BSA) is a charity and learned society founded in 1831 to aid in the promotion and development of science. Until 2009 it was known as the British Association for the Advancement of Science (BA). The current Chief ...
in 1966, the Nahum Lecture at
Yale Yale University is a private Ivy League research university in New Haven, Connecticut, United States. Founded in 1701, Yale is the third-oldest institution of higher education in the United States, and one of the nine colonial colleges ch ...
in 1977 and the Ueda lecture at
Tokyo University The University of Tokyo (, abbreviated as in Japanese and UTokyo in English) is a public research university in Bunkyō, Tokyo, Japan. Founded in 1877 as the nation's first modern university by the merger of several pre-westernisation era ins ...
in 1985 and 1990. He was President of the Medical Section of the
British Science Association The British Science Association (BSA) is a charity and learned society founded in 1831 to aid in the promotion and development of science. Until 2009 it was known as the British Association for the Advancement of Science (BA). The current Chief ...
1991–92. Many further invited lectures during his election as Secretary-General (1993-2001) and President (2009-2017) of IUPS. In 1979 he was elected a Fellow of the
Royal Society The Royal Society, formally The Royal Society of London for Improving Natural Knowledge, is a learned society and the United Kingdom's national academy of sciences. The society fulfils a number of roles: promoting science and its benefits, re ...
. His nomination for the Royal Society reads: He was elected an Honorary Member of the
Royal College of Physicians The Royal College of Physicians of London, commonly referred to simply as the Royal College of Physicians (RCP), is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of ph ...
in 1988 and an Honorary Fellow in 1994, an Honorary Member of the
American Physiological Society The American Physiological Society is a non-profit professional society for physiologists. It has nearly 10,000 members, most of whom hold doctoral degrees in medicine, physiology, or other health professions. Its mission is to support research ...
in 1996 and of the Physiological Society of Japan in 1998. In 1989 he was elected a Member of the
Academia Europaea The Academia Europaea is a pan-European Academy of humanities, letters, law, and sciences. The Academia was founded in 1988 as a functioning Europe-wide Academy that encompasses all fields of scholarly inquiry. It acts as co-ordinator of Europe ...
. In 1998, he also became a founding Fellow of the
Academy of Medical Sciences The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society. Its ...
. In 1998 he was awarded a
CBE The Most Excellent Order of the British Empire is a British order of chivalry, rewarding valuable service in a wide range of useful activities. It comprises five classes of awards across both civil and military divisions, the most senior two o ...
. In 2021 he was elected a Fellow of the IUPS Academy. In 2022 he was elected a Fellow of The
Linnean Society The Linnean Society of London is a learned society dedicated to the study and dissemination of information concerning natural history, evolution, and taxonomy. It possesses several important biological specimen, manuscript and literature collec ...
(FLS) He has honorary doctorates from the
University of Sheffield The University of Sheffield (informally Sheffield University or TUOS) is a public university, public research university in Sheffield, South Yorkshire, England. Its history traces back to the foundation of Sheffield Medical School in 1828, Fir ...
(2004), the
Université de Bordeaux The University of Bordeaux (, ) is a public research university based in Nouvelle-Aquitaine in southwestern France. It has several campuses in the cities and towns of Bordeaux, Dax, Gradignan, Périgueux, Pessac, and Talence. There are also ...
(2005) and the
University of Warwick The University of Warwick ( ; abbreviated as ''Warw.'' in post-nominal letters) is a public research university on the outskirts of Coventry between the West Midlands and Warwickshire, England. The university was founded in 1965 as part of ...
(2008). He is an Honorary Foreign Member of the Académie Royale de Médecine de Belgique (1993), of the Istituto Lombardo Accademia di Scienze e Lettere, and received the Pavlov Medal of the
Russian Academy of Sciences The Russian Academy of Sciences (RAS; ''Rossíyskaya akadémiya naúk'') consists of the national academy of Russia; a network of scientific research institutes from across the Russian Federation; and additional scientific and social units such ...
(2004). In 2022 he was elected Foreign Member of the
Russian Academy of Sciences The Russian Academy of Sciences (RAS; ''Rossíyskaya akadémiya naúk'') consists of the national academy of Russia; a network of scientific research institutes from across the Russian Federation; and additional scientific and social units such ...
and was also awarded the
Lomonosov Gold Medal The Lomonosov Gold Medal ( ''Bol'shaya zolotaya medal' imeni M. V. Lomonosova''), named after Russian scientist and polymath Mikhail Lomonosov, is awarded each year since 1959 for outstanding achievements in the natural sciences and the humaniti ...
.


Personal life

Noble was born in London in 1936 to working-class tailors, George and Ethel Noble. He plays classical guitar and sings
Occitan Occitan may refer to: * Something of, from, or related to the Occitania territory in parts of France, Italy, Monaco and Spain. * Something of, from, or related to the Occitania administrative region of France. * Occitan language, spoken in parts o ...
troubadour and folk songs (Oxford Trobadors). In addition to English, he has lectured in French, Italian, Performance with Nadau & Peiraguda Occitan, Japanese and Korean.


In popular culture

In 2011, Alison MacLeod's story, "The Heart of Denis Noble", featuring a fictionalised version of Denis Noble recovering from a heart attack, was shortlisted for the
BBC National Short Story Award The BBC National Short Story Award (known as the National Short Story Award in 2006 and 2007) has been described as "one of the most prestigious wardsfor a single short story" and the richest prize in the world for a single short story. It is an ...
.


External links

* Lecture in * Lecture in


References


External links

{{DEFAULTSORT:Noble, Denis 1936 births Living people 20th-century British biologists Extended evolutionary synthesis Systems biologists British bioinformaticians English agnostics Fellows of Balliol College, Oxford Fellows of the Royal Society Fellows of the Academy of Medical Sciences (United Kingdom) Academic staff of Osaka University People educated at Emanuel School Cardiac electrophysiologists 21st-century British biologists Philosophers of biology Commanders_of_the_Order_of_the_British_Empire