‘Extreme’ Organisms and the Problem of Generalization: Interpreting the Krogh Principle

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights

‘Extreme’ organisms and the problem of generalization: interpreting the Krogh principle

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that "for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied". Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms "Krogh organisms". We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as "negative models" in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights.Sara Green, Michael R. Dietrich, Sabina Leonelli, Rachel A. Anken

‘Extreme’ Organisms and the Problem of Generalization: Interpreting the Krogh Principle

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights

‘Extreme’ Organisms and the Problem of Generalization: Interpreting the Krogh Principle

Many biologists appeal to the so-called Krogh principle when justifying their choice of experimental organisms. The principle states that “for a large number of problems there will be some animal of choice, or a few such animals, on which it can be most conveniently studied”. Despite its popularity, the principle is often critiqued for implying unwarranted generalizations from optimal models. We argue that the Krogh principle should be interpreted in relation to the historical and scientific contexts in which it has been developed and used. We interpret the Krogh Principle as a heuristic, i.e., as a recommendation to approach biological problems through organisms where a specific trait or physiological mechanism is expected to be most distinctively displayed or most experimentally accessible. We designate these organisms “Krogh organisms.” We clarify the differences between uses of model organisms and non-standard Krogh organisms. Among these is the use of Krogh organisms as “negative models” in biomedical research, where organisms are chosen for their dissimilarity to human physiology. Importantly, the representational scope of Krogh organisms and the generalizability of their characteristics are not fixed or assumed but explored through experimental studies. Research on Krogh organisms is steeped in the comparative method characteristic of zoology and comparative physiology, in which studies of biological variation produce insights into general physiological constraints. Accordingly, we conclude that the Krogh principle exemplifies the advantages of studying biological variation as a strategy to produce generalizable insights

Planaria: an animal model that integrates development, regeneration and pharmacology

Although planarians are established model organisms in developmental biology and regeneration studies, in the last forty years or so, they have caught the attention of pharmacologists, especially to study the pharmacology of drugs of abuse. This review covers the following topics: some fundamentals of the history of animal models and planarians in biomedical research; an abbreviated story of systematic pharmacology research using planarians as a model organism; an example of how planarians are contributing to the search for compounds against acute cocaine toxicity; an analysis of the number of papers on planarians and pharmacological topics from 1900- 2016; some perspectives on pharmacology in developmental and regeneration studies, arguing in favor of the planarian model as a leading subject for this interdisciplinary area of research, and finally some concluding thoughts

Faraway, so close. The comparative method and the potential of non-model animals in mitochondrial research

Inference from model organisms has been the engine for many discoveries in life science, but indiscriminate generalization leads to oversimplifications and misconceptions. Model organisms and inductive reasoning are irreplaceable: there is no other way to tackle the complexity of living systems. At the same time, it is not advisable to infer general patterns from a restricted number of species, which are very far from being representative of the diversity of life. Not all models are equal. Some organisms are suitable to find similarities across species, other highly specialized organisms can be used to focus on differences. In this opinion piece, we discuss the dominance of the mechanistic/reductionist approach in life sciences and make a case for an enhanced application of the comparative approach to study processes in all their various forms across different organisms. We also enlist some rising animal models in mitochondrial research, to exemplify how non-model organisms can be chosen in a comparative framework. These taxa often do not possess implemented tools and dedicated methods/resources. However, because of specific features, they have the potential to address still unanswered biological questions. Finally, we discuss future perspectives and caveats of the comparative method in the age of ‘big data’

How to Choose Your Research Organism

Despite August Krogh’s famous admonition that a ‘convenient’ organism exists for every biological problem, we argue that appeals to ‘convenience’ are not sufficient to capture reasoning about organism choice. Instead, we offer a detailed analysis based on empirical data and philosophical arguments for a working set of twenty criteria that interact with each other in the highly contextualized judgements that biologists make about organism choice. We propose to think of these decisions as a form of ‘differential analysis’ where researchers weigh multiple criteria for organismal choice against each other, and often utilize multidimensional refinement processes to finalize their choices. The specific details of any one case make it difficult to draw generalizations or to abstract away from specific research situations. However, this analysis of criteria for organismal choice and how these are related in practice allows us to reflect more generally on what makes a particular organism useful or ‘good.

Sex Bias in Neuroscience and Biomedical Research

Female mammals have long been neglected in biomedical research. The NIH mandated enrollment of women in human clinical trials in 1993, but no similar initiatives exist to foster research on female animals. We reviewed sex bias in research on mammals in 10 biological fields for 2009 and their historical precedents. Male bias was evident in 8 disciplines and most prominent in neuroscience, with single-sex studies of male animals outnumbering those of females 5.5 to 1. In the past half-century, male bias in non-human studies has increased while declining in human studies. Studies of both sexes frequently fail to analyze results by sex. Underrepresentation of females in animal models of disease is also commonplace, and our understanding of female biology is compromised by these deficiencies. The majority of articles in several journals are conducted on rats and mice to the exclusion of other useful animal models. The belief that non-human female mammals are intrinsically more variable than males and too troublesome for routine inclusion in research protocols is without foundation. We recommend that when only one sex is studied, this should be indicated in article titles, and that funding agencies favor proposals that investigate both sexes and analyze data by sex