Theoretical biology/Addendum

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This addendum is a continuation of the article Theoretical biology.

Biologists' comments on the province of theoretical biology

Professor Richard Gordon, President of the Canadian Society for Theoretical Biology, writes:

The theoretical biologist delves deeply into all the data available, comes up with unexpected relationships, tries to quantify them using all the tools of reason (math, logic, computers, etc.), and makes specific predictions about the outcome of future experiments and observations. Sometimes a critical experiment would never have been done without the inspiration of your theory in the first place.[1]

Biophysicist and mathematical biologist Marc Mangel,[2] in his 2006 book The Theoretical Biologist’s Toolbox,[3] elaborates on Professor Gordon's brief description of theoretical biology:

Theoretical biology begins with the natural world, which we want to understand. By thinking about observations of the world, we begin to conceive an idea about how it works. This is theory, and may already lead to predictions, which can then flow back into our observations ot the world. The idea about how the world works can also be formalized using mathematical models that describe appropriate variables and processes. The analysis of such models then provides another level of predictions which we can take back to the world (from which new observations may flow). In some cases, analysis may be insufficient and we choose to implement our models using computers through programming (software engineering). These programs then provide another level of prediction, which can also flow back to the models or to the natural world. [3]

In describing their research program, the Biospheric Theory and Modeling group[4] of the Max-Planck-Institut für Biogeochemie[5] highlight many of the main approaches and advantages of theoretical biology:

Our research aims to identify the general organizing principles of the biosphere in order to better understand and predict its interactions with biogeochemical cycles and the climate system….Our view of biospheric theory….is that the development of theory goes hand in hand with observations, which serve as a reality check for the theory, as well as inspiration for more precise research questions. The precise research questions in return can be used to streamline the experiments and measurement campaigns to allow new insights. As the theory develops, models become helpful for understanding the implications of the theory and for rejecting unrealistic assumptions or formulating new research questions. Conceptual models are particularly helpful for determining similarities or incompatibilities between different theories. Emergence-based models are useful for linking small-scale processes with large-scale effects, while Optimality-based models are useful for making reproducible predictions directly at the scale of interest.... Theoretical concepts help us to formulate hypotheses how the biosphere should function and respond to change. We work on several concepts, such as optimality, multiple steady states, and pattern formation.[4]

In summary, observational checks of theory, inspiring more precise questions, leading to better experiments, with modeling to test assumptions, leading to new questions and revised theories: a systems biology approach. Most biologists will recognize themselves as theoretical biologists on some level and at some times.

In their 2003 book on the organization of organismal form, Gerd B. Müller and Stuart A. Newman[6] stress the breadth of the field and its applicability beyond mathematical biology:

heoretical biology is firmly rooted in the experimental biology movement of early twentieth-century Vienna. Paul Weiss and Ludwig von Bertalanffy were among the first to use the term theoretical biology in a modern scientific context. In their understanding the subject was not limited to mathematical formalization, as is often the case today, but extended to the general theoretical foundations of biology. Their synthetic endeavors aimed at connecting the laws underlying the organization, metabolism, development, and evolution of organisms….A successful integrative theoretical biology must encompass not only genetic, developmental, and evolutionary components, the major connective concepts in modem biology, but also relevant aspects of computational biology, semiotics, and cognition, and should have continuities with a modern philosophy of the sciences of natural systems.[6]

Geneticist and Nobel laureate, Sydney Brenner, discusses his views of theoretical biology in the 21st century, emphasizing the need for a theoretic framework based on living systems as “information processing machines”:[7]

The databases of [genome] sequence information are now growing at an immense rate and the number and productivity of biological researchers has also vastly increased. There seems to be no limit to the amount of information that we can accumulate, and today, at the end of the millennium, we face the question of what is to be done with all of this information….Writing in the last months of this millennium, it is clear that the prime intellectual task of the future lies in constructing an appropriate theoretical framework for biology….Unfortunately, theoretical biology has a bad name because of its past. Physicists were concerned with questions such as whether biological systems are compatible with the second law of thermodynamics and whether they could be explained by quantum mechanics….There have also been attempts to seek general mathematical theories of de¬velopment and of the brain: the application of catastrophe theory is but one example. Even though alternatives have been suggested, such as computational biology, biological systems theory and integrative biology, I have decided to forget and forgive the past and call it theoretical biology….But none of [physics and chemistry] captures the novel feature of biological systems: that, in addition to flows of matter and energy, there is also the flow of information. Biological systems are information-processing machines and this must be an essential part of any theory we may construct….I believe that this is what we should be trying to do in the next century. It will require theoretical biology.[italics added][7]

Descriptions of theoretical biology by academic journals focusing on the subject

   —Journal of Theoretical Biology

The diversity of biological disciplines represented in the Journal of Theoretical Biology indicates the diversity of biologists engaged in theoretical biology.[8] The editors of the journal emphasize the role of theory in giving insight to biological processes:

The Journal of Theoretical Biology is the leading forum for theoretical papers that give insight into biological processes. It covers a very wide range of topics and is of interest to biologists in many areas of research. Many of the papers make use of mathematics, and an effort is made to make the papers intelligible to biologists as a whole. Experimental material bearing on theory is acceptable…. Research Areas Include: Cell Biology and Development; Developmental Biology; Ecology; Evolution; Immunology; Infectious Diseases; Mathematical Modeling, Statistics, and Data Bases; Medical Sciences and Plant Pathology; Microbiology; Molecular Biology and Biochemistry; Physiology.[8]

    • Ten most downloaded articles in agricultural and biological sciences, April-June 2008

A listing of the ten most downloaded articles from the journal (in agricultural and biological sciences, April-June 2008) give an indication of the kinds of theoretical and conceptual approaches and topics that interest theoretical biologists:[9]

  • From the Abstract: This is the first of three papers analyzing the representation of information in the biosphere, and the energetic constraints limiting the imposition or maintenance of that information. Biological information is inherently a chemical property, but is equally an aspect of control flow and a result of processes equivalent to computation. The current paper develops the constraints on a theory of biological information capable of incorporating these three characterizations and their quantitative consequences….The main result of the paper is that the limits on the minimal energetic cost of information flow will be tractable and universal whereas the assembly of more literal process models into a system-level description often is not.
  • From the Abstract: The function of the human appendix has long been a matter of debate, with the structure often considered to be a vestige of evolutionary development despite evidence to the contrary based on comparative primate anatomy. Based (a) on a recently acquired understanding of immune-mediated biofilm formation by commensal bacteria in the mammalian gut, (b) on biofilm distribution in the large bowel, (c) the association of lymphoid tissue with the appendix, (d) the potential for biofilms to protect and support colonization by commensal [living together, with some benefitting, none detrimenting] bacteria, and (e) on the architecture of the human bowel, we propose that the human appendix is well suited as a “safe house” for commensal bacteria, providing support for bacterial growth and potentially facilitating re-inoculation of the colon in the event that the contents of the intestinal tract are purged following exposure to a pathogen.
  • Modeling the segmentation clock as a network of coupled oscillations in the Notch, Wnt and FGF signaling pathways
  • From the Abstract: The formation of somites [body segments containing the same internal structures] in the course of vertebrate segmentation is governed by an oscillator known as the segmentation clock, which is characterized by a period ranging from 30 min to a few hours depending on the organism. This oscillator permits the synchronized activation of segmentation genes in successive cohorts of cells in the presomitic mesoderm in response to a periodic signal emitted by the segmentation clock, thereby defining the future segments….A complex oscillating network of [three] signaling genes underlies the mouse segmentation clock….By means of computational modeling, we investigate the conditions in which sustained oscillations occur in these three signaling pathways. The model provides a framework for analyzing the dynamics of the segmentation clock in terms of a network of oscillating modules involving the….signaling pathways.
  • Thermodynamics of natural selection II: Chemical Carnot cycles
  • A protein interaction network associated with asthma
  • Self-organization at the origin of life
  • The timing of TNF and IFN-γ signaling affects macrophage activation strategies during Mycobacterium tuberculosis infection
  • Thermodynamics of natural selection III: Landauer's principle in computation and chemistry
  • Prevention of avian influenza epidemic: What policy should we choose?
  • Evolutionary stability on graphs

    • Ten most downloaded articles in biochemistry, genetics, and molecular biology, April-June 2008

The corresponding top ten downloads in the areas of biochemistry, genetics and molecular biology:[10]

  • The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
  • Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
  • Direct Reprogramming of Terminally Differentiated Mature B Lymphocytes to Pluripotency
  • Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors
  • SnapShot: Hematopoiesis
  • Nuclear Receptor-Enhanced Transcription Requires Motor- and LSD1-Dependent Gene Networking in Interchromatin Granules
  • The Hallmarks of Cancer
  • TGF-β Primes Breast Tumors for Lung Metastasis Seeding through Angiopoietin-like 4
  • Acetylation Is Indispensable for p53 Activation
  • An Extended Transcriptional Network for Pluripotency of Embryonic Stem Cells

It appears from the titles alone that currently theoretical biology covers a widely diverse types of subject matter, not all qualifying as mathematical or philosophical biology.

   —Acta Biotheoretica

In describing the aims of the Dutch journal of theoretical biology, Acta Biotheoretica, Thomas A. C. Reydon and Lia Hemerik[11] illustrate the Dutch perspective on theoretical biology:

In this understanding, theoretical biology is seen as encompassing the entire spectrum of theoretical investigation of the living world, ranging from philosophy of biology to mathematical biology. Consequently, the process of biological theory formation in the journal is allowed to range from purely verbal argumentation to the mathematical analysis of biological theory.[11]

One can appreciate to some extent the broad range of topic categories published by theoretical biologists in Acta Biotheoretica from the Table of Contents shown in the cited reference to the Current Themes book by Reydon and Hemerik.[11]. As theoretical biology transcends national boundaries, those topic categories qualify as representative of the field.

The National Academies' National Research Council report on theoretical biology

A committee of the National Research Council of the National Academies reported in 2008 on "The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research"[12]. In the summary of their report they discuss the nature of theoretical biology:

The committee was charged with examining the role of concepts and theories in biology, including how that role might differ across various subdisciplines. One facet of that examination was to consider the role of the concepts and theories in driving scientific advances and to make recommendations about the best way to encourage creative, dynamic, and innovative research in biology....The committee concluded that a more explicit focus on theory and a concerted attempt to look for cross-cutting issues would likely help stimulate future advances in biology. To illustrate this point, the committee chose seven questions to examine in detail. The list of questions is not comprehensive but rather illustrative. The questions, as shown below, were chosen to show that a focus on theory could play a role in helping to address many different types of interesting and important questions at many different levels.[12]

   —The Committee's central questions in theoretical biology

In the Table of Contents of the committee's report,[12] they center their report around these questions, the excerpts added giving further information on the work of theoretical biologists:

  • Are There Still New Life Forms to Be Discovered? The Diversity of Life - Why It Exists and Why It's Important (38-66)
  • What Role Does Life Play in the Metabolism of Planet Earth? (67-80)
  • Excerpt: A recent flurry of theoretical explorations attempts to explain not only the seeming universal dependence of aerobic respiration on body mass and temperature but also the putative ubiquity of the value of ¾ in the exponent of the power function that relates metabolic rate with body size. The theories have led to the conjecture that the value of this power is the consequence of the structure of the systems that distribute oxygen and nutrients in organisms[13]. The theory has been extended to terrestrial vascular plants and has led to the remarkable prediction that both photosynthetic rate and respiration should also scale with plant mass to the ¾ power. This theoretical research has been accompanied by attempts to include these relationships in scaling exercises that predict ecosystem-level properties such as the metabolic balance of the oceans and the productivity and decomposition rates in terrestrial ecosystems[14] These calculations suggest that first-order estimates about the magnitude of these processes can be made from knowledge about the size distribution of the organisms that structure these ecosystems and from the temperature at which they operate. [italics added]
  • How Do Cells Really Work? (81-89)
  • What Are the Engineering Principles of Life? (90-109)
  • Excerpt: Across many fields of biology, from the organization of the cell, to the development of multicellular organisms, to the function of the brain, to the group behavior of insects and birds, to the response of ecosystems to environmental change, complex coordinated phenomena are seen to arise out of interaction of a myriad of components. The engineering principles that make possible a space shuttle can be encapsulated in an engineering textbook. Is it possible that there are similarly fundamental principles governing the organization of dynamic interacting systems that hold across all scales of biology? The key to understanding such organizational principles will involve developing a theoretical basis for how biological entities generate aggregates of higher complexity: that is, the constructive principles of biological organizations. Advances in understanding of these biological systems is an especially promising area of research in biology that could have immediate consequences for the understanding of organisms and further applications to complex, human-engineered systems. [italics added]
  • What Is the Information That Defines and Sustains Life? (110-129)
  • Excerpt: The refinement and application of theories of information to biology present a deep challenge and an opportunity for furthering our understanding of life. Existing theories of information borrowed from other fields can be difficult to apply to biology, a field in which context is so important, but the conceptual gain may be well worth the challenge….Biological systems differ from nonliving systems in several ways, but the most profound differences might lie in their information content. It can be useful for this purpose to think of biological systems as evolved transducers of information, since organisms accumulate, process, store, and share information of different types and on different time scales. An organism needs information about its internal condition to manage its internal functions….The transition from the inanimate to animate might well be thought of as the acquisition of the singular ability to increase the storage and transmission of information, in quantity and quality. The possibility of this increase of information, well beyond what is ever seen in inanimate matter, is fundamental to the process called evolution….An attempt to characterize living systems by citing just two essential properties would probably include, first, that they are thermodynamically far from equilibrium, and second, that they store, accumulate, and transmit large amounts of information.
  • What Determines How Organisms Behave in Their Worlds? (130-144)
  • How Much Can We Tell About the Past - and Predict About the Future - by Studying Life on Earth Today? (145-156)

Achieving answers to those kinds of questions would seem to require interdisciplinary collaboration among many different biological and non-biological scientific disciples, which brings a diversity of concepts, hypotheses, and theories.

   —The Committee's conclusions

The NRC committee emphasized the integral role of theory in biology, in chapter so titled, and selected for the chapter's epigraph a quote from Leonardo da Vinci: He who loves practice without theory is like the sailor who boards ship without a rudder and compass and never knows where he may cast. The first chapter, broken to bullet sentences, serves to summarize their conclusion:

  • This chapter:
  • describes several different ideas about scientific theories,
  • emphasizes the diversity of theoretical activities throughout biology, and
  • discusses ways in which theory is integral to each specific kind of scientific activity, including
  • experimentation,
  • observation,
  • exploration,
  • description, and
  • technology development as well as
  • hypothesis testing.
  • Biologists use a theoretical and conceptual framework to inform the entire scientific process, and they frequently advance theory even when their work is not explicitly recognized as theoretical.
  • Explicit recognition of the many entry points of theory into the scientific enterprise may provide greater opportunity for developing
  • new concepts, principles, theories, and perspectives in biology that would
  • not only enhance current scientific practices
  • but also facilitate the exploration of cross-cutting questions that are difficult to address by traditional means.[12]

   —The Committee's recommendations

The committee makes a specific recommendation:

Theory, as an important but under appreciated component of biology, should be given a measure of attention commensurate with that given other components of biological research (such as observation and experiment). Theoretical approaches to biological problems should be explicitly recognized as an important and integral component of funding agencies’ research portfolios. Increased attention to the theoretical and conceptual components of basic biology research has the potential to leverage the results of basic biology research and should be considered as a balance to programs that focus on mission-oriented research.[12]

Encyclopedia summaries of theoretical biology

The Encyclopedia Britannica has no entry for theoretical biology, but NationMaster Encyclopedia[15], emphasizing that the theoretical biologist’s product is a model or theory, whether reached through the use of mathematical or computational tools, or through other means, and listing many of the biological areas of study in which theoretical biologists contribute:

The ultimate goal of the theoretical biologist is to explain the biological world using mainly mathematical and computational tools, though not necessarily. Though it is ultimately based on observations and experimental results, the theoretical biologist's product is a model or theory, and it is this that chiefly distinguishes the theoretical biologist from other biologists….Theoretical biology is an Interdisciplinary work is that which integrates concepts across different disciplines. New disciplines have arisen as a result of such syntheses…Many separate areas of biology fall under the concept of theoretical biology, according to the way they are studied. Some of these areas include:[15]

-animal behavior –biorhythms –cell biology –complexity of biological system –ecology –enzyme kinetics –evolutionary biology –genetics –immunology –membrane transport –microbiology –molecular structure –morphogenesis –physiological mechanisms –systems biology –origin of life –neurobiology -computational neuroscience[15]

References and notes cited in text

Many citations to articles listed here include links to full-text — in font-color blue. Accessing full-text may require personal or institutional subscription to the source. Nevertheless, many do offer free full-text, and if not, usually offer text or links that show the abstracts of the articles. Links to books variously may open to full-text, or to the publishers' description of the book with or without downloadable selected chapters, reviews, and table of contents. Books with links to Google Books often offer extensive previews of the books' text.

  1. Careers in Theoretical Biology.
  2. Marc Mangel's Biography
  3. 3.0 3.1 Mangel M. (2006) The Theoretical Biologist's Toolbox: Quantitative Methods for Ecology and Evolutionary Biology. Cambridge University Press. ISBN 0521830451, ISBN 9780521830454.
    • Book description: Mathematical modelling is widely used in ecology and evolutionary biology and it is a topic that many biologists find difficult to grasp. In this new textbook Marc Mangel provides a no-nonsense introduction to the skills needed to understand the principles of theoretical and mathematical biology. Fundamental theories and applications are introduced using numerous examples from current biological research, complete with illustrations to highlight key points. Exercises are also included throughout the text to show how theory can be applied and to test knowledge gained so far. Suitable for advanced undergraduate courses in theoretical and mathematical biology, this book forms an essential resource for anyone wanting to gain an understanding of theoretical ecology and evolution.
  4. 4.0 4.1 Biospheric Theory and Modeling
  5. Max-Planck-Institut für Biogeochemie
  6. 6.0 6.1 Müller GB, Newman SA (2003) Origination of Organismal Form: Beyond the Gene in Developmental and Evolutionary Biology. MIT Press. ISBN 0262134195, ISBN 9780262134194.
    • Book description: The field of evolutionary biology arose from the desire to understand the origin and diversity of biological forms. In recent years, however, evolutionary genetics, with its focus on the modification and inheritance of presumed genetic programs, has all but overwhelmed other aspects of evolutionary biology. This has led to the neglect of the study of the generative origins of biological form. Drawing on work from developmental biology, paleontology, developmental and population genetics, cancer research, physics, and theoretical biology, this book explores the multiple factors responsible for the origination of biological form. It examines the essential problems of morphological evolution--why, for example, the basic body plans of nearly all metazoans arose within a relatively short time span, why similar morphological design motifs appear in phylogenetically independent lineages, and how new structural elements are added to the body plan of a given phylogenetic lineage. It also examines discordances between genetic and phenotypic change, the physical determinants of morphogenesis, and the role of epigenetic processes in evolution. The book discusses these and other topics within the framework of evolutionary developmental biology, a new research agenda that concerns the interaction of development and evolution in the generation of biological form. By placing epigenetic processes, rather than gene sequence and gene expression changes, at the center of morphological origination, this book points the way to a more comprehensive theory of evolution.
  7. 7.0 7.1 Brenner S. (1999) Theoretical Biology in the Third Millennium. Philosophical Transactions: Biological Sciences 354:1963-1965. Millennium Issue (Dec. 29, 1999).
    • Abstract:> During the 20th century our understanding of genetics and the processes of gene expression have undergone revolutionary change. Improved technology has identified the components of the living cell, and knowledge of the genetic code allows us to visualize the pathway from genotype to phenotype. We can now sequence entire genes, and improved cloning techniques enable us to transfer genes between organisms, giving a better understanding of their function. Due to the improved power of analytical tools databases of sequence information are growing at an exponential rate. Soon complete sequences of genomes and the three-dimensional structure of all proteins may be known. The question we face in the new millennium is how to apply this data in a meaningful way. Since the genes carry the specification of an organism, and because they also record evolutionary changes, we need to design a theoretical framework that can take account of the flow of information through biological systems.
  8. 8.0 8.1 Journal of Theoretical Biology: About Us Cite error: Invalid <ref> tag; name "jtb" defined multiple times with different content
  9. Top 25 Hottest Articles, Agricultural and Biological Sciences, Journal of Theoretical Biology, April-June 2008.
  10. Top 25 Hottest Articles, Biochemistry, Genetics and Molecular Biology, Journal of Theoretical Biology, April-June 2008.
  11. 11.0 11.1 11.2 Reydon TAC, Hemerik L. (2005) Current Themes in Theoretical Biology: A Dutch Perspective. Springer. ISBN 1402029012, ISBN 9781402029011.
    • Table of contents:
    1. The History of Acta Biotheoretica and the Nature of Theoretical Biology; Thomas A.C. Reydon, Piet Dullemeijer and Lia Hemerik
    2. Images of the Genome: From Public Debates to Biology, and Back, and Forth; Cor van der Weele
    3. The Functional Perspective of Organismal Biology; Arno Wouters
    4. Infectious Biology: Curse or Blessing? Reflections on Biology in Other Disciplines, with a Case Study of Migraine; Wim J. van der Steen
    5. The Composite Species Concept: A Rigorous Basis for Cladistic Practice; D.J. Kornet and James W. McAllister
    6. The Wonderful Crucible of Life’s Creation: An Essay on Contingency versus Inevitability of Phylogenetic Development; R. Hengeveld
    7. The Symbiontic Nature of Metabolic Evolution; S.A.L.M. Kooijman and R. Hengeveld
    8. The Founder and Allee Effects in the Patch Occupancy Metapopulation Model; Rampal S. Etienne and Lia Hemerik
    9. Balancing Statistics and Ecology: Lumping Experimental Data for Model Selection; Nelly van der Hoeven, Lia Hemerik and Patrick A. Jansen
    10. Resilience and Persistence in the Context of Stochastic Population Models; Johan Grasman, Onno A. van Herwaarden and Thomas J. Hagenaars
    11. Evolution of Specialization and Ecological Character Displacement: Metabolic Plasticity Matters; Martijn Egas.
  12. 12.0 12.1 12.2 12.3 12.4 National Research Council of the National Academies, Division of Earth and Life Studies, Board on Life Sciences, Report of the Committee on Defining and Advancing the Conceptual Basis of Biological Sciences in the 21st Century. (2008) The Role of Theory in Advancing 21st-Century Biology: Catalyzing Transformative Research. The National Academies Press. Washington, D.C.
  13. West GB, Brown JH, Enquist BJ. (1997) A general model for the origin of allometric scaling laws in biology. Science 276:122-126.
  14. López-Urrutia A, San Martín AE, Harris RP, and Irigoien X. (2006) Scaling the metabolic balance of the oceans. Proceedings of the National Academy of Sciences USA 103:8739-8744.
  15. 15.0 15.1 15.2 Theoretical biology.