Theoretical biology

Theoretical biology applies reason toward the goal of explaining the biological world, and aspects of it, through ideas and theories. It thereby distinguishes itself from observational and experimental biology, though without the latter disciplines of biology, theoretical biologists would have no information with which to produce theories, or evaluate them.

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.

In describing their research program, the Biospheric Theory and Modeling group of the Max-Planck-Institut für Biogeochemie 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|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.

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 describing the aims of the Dutch journal of theoretical biology, Acta Biotheoretica, Thomas A. C. Reydon and Lia Hemerik 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.

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The 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. 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.

  —Journal's 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:

• Thermodynamics of natural selection I: Energy flow and the limits on organization
• Biofilms in the large bowel suggest an apparent function of the human vermiform appendix
• Modeling the segmentation clock as a network of coupled oscillations in the Notch, Wnt and FGF 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

  —Journal's 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:

• 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.

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". 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.

In the Table of Contents of the committee's report, they center their report around these questions:

• 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)
• How Do Cells Really Work? (81-89)
• What Are the Engineering Principles of Life? (90-109)
• What Is the Information That Defines and Sustains Life? (110-129)
• 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 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.

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.