Two Models of Models in Biomedical Research

LaFollette, Hugh; Shanks, Niall

doi:10.2307/2220412

Cited by 98 publications

(38 citation statements)

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“…Animal models have been widely ever since and it has been suggested by the American Medical Association that many medical advances in the 20 th century involved the use of animal models in some way (as cited in Lafollete and Shanks [1]). Bernard reasoned that humans and animals were similar enough that results from animal experimentation could be extended by analogy to humans [2].…”

Section: Introductionmentioning

confidence: 99%

“…This perspective requires that the model and target have common, causally connected properties and that no differences between the model and target invalidate the use of the model [1]. Since the days of Bernard, it has become clear that significant differences among species often make it inappropriate to extend results by analogy from one species to another, leading some to conclude that animal models are generally not suitable for testing hypotheses about the causal mechanisms underlying human physiological and disease processes [1]. This does not diminish the value of models as tools for discovery.…”

Section: Introductionmentioning

confidence: 99%

“…In this context, the use of models leads to the development of new hypotheses to be tested in target species [3]. This distinction between what have been referred to as causal analog models (CAMs) and hypothetical analog models (HAMs) is important as it explains much of the controversy surrounding the use of models [1]. Often, models used to generating insight about how a system may work in another species (HAMs) are not useful as CAMs because functional similarities do not always imply causal similarities.…”

Section: Introductionmentioning

confidence: 99%

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Virtues and limitations of the preimplantation mouse embryo as a model system

Taft

2008

Theriogenology

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The mouse is the most widely used model of preimplantation embryo development, but is it a good model? Its small size, prolificacy and ease of handling make the mouse a relatively low cost, readily available and attractive alternative when embryos from other species are difficult or expensive to obtain. However, the real power of the mouse as a model lies in mouse genetics. The development of inbred mouse strains facilitated gene discovery as well as our understanding of gene function and regulation while the development of tools to introduce precise genetic modifications uniquely positioned the mouse as a powerful model system for uncovering gene function. However, all models have limitations; the small size of the mouse limits tissue availability and manipulations that can be performed and differences in physiology among species may make it inappropriate to extrapolate from the mouse to other species. Thus, rather than extrapolating directly from the mouse to other species, it may be more useful to use the mouse as a model system for developing and refining hypotheses to be tested directly in species of interest. In this brief review, the value of the preimplantation mouse embryo as a model is considered, both as a model for other species and as a model for the mouse, as understanding the virtues and limitations of the mouse as a model system is essential to its appropriate use.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Virtues and limitations of the preimplantation mouse embryo as a model system

Taft

2008

Theriogenology

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“…This turns on the question of whether the extrapolation from animal models to humans is reliable. Some have argued that there are always salient differences in the relevant mechanisms, such that no conclusion about humans can be established in this way (LaFollette and Shanks 1995;Howick et al 2013). It may be that the established carcinogenicity of benzo [a]pyrene to experimental animals, together with evidence of relevant mechanistic similarities in the animal models and humans, is still not sufficient to establish the carcinogenicity of benzo[a]pyrene to humans.…”

Section: Mechanisms and Extrapolationmentioning

confidence: 99%

Extrapolation and the Russo–Williamson thesis

Wilde

Parkkinen

2017

Synthese

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A particular tradition in medicine claims that a variety of evidence is helpful in determining whether an observed correlation is causal. In line with this tradition, it has been claimed that establishing a causal claim in medicine requires both probabilistic and mechanistic evidence. This claim has been put forward by Federica Russo and Jon Williamson. As a result, it is sometimes called the Russo-Williamson thesis. In support of this thesis, Russo and Williamson appeal to the practice of the International Agency for Research on Cancer (IARC). However, this practice presents some problematic cases for the Russo-Williamson thesis. One response to such cases is to argue in favour of reforming these practices. In this paper, we propose an alternative response according to which such cases are in fact consistent with the Russo-Williamson thesis. This response requires maintaining that there is a role for mechanism-based extrapolation in the practice of the IARC. However, the response works only if this mechanism-based extrapolation is reliable, and some have argued against the reliability of mechanism-based extrapolation. Against this, we provide some reasons for believing that reliable mechanism-based extrapolation is going on in the practice of the IARC. The reasons are provided by appealing to the role of robustness analysis.

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“…For the purpose of this discussion, I will divide animal models into their use as modalities that have predictive value for human response to drugs and disease (Table 1) and nonpredictive uses as typified by categories 3-9 in Table 1. The use of animal models as predictive modalities for human response to drugs and disease is an example of using animals as causal analogical models or CAMs [78][79][80]. CAMs assume that reductionism can discover all the relevant facts concerning a living system.…”

Section: Evolved Complex Adaptive Systemsmentioning

confidence: 99%

A Discussion of the Role of Complex Evolved Systems in the Development of Invasive Cardiovascular Interventions as Illustrated by the Blalock- Taussig Shunt and Intra-Arterial Stents

Greek¹

2014

Biol Syst Open Access

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Scientific disciplines normally thought of as outside the sphere of medical science have experienced advances over the past twenty years that currently have profound implications for medical care and medical research. Evolutionary and developmental biology, complexity and chaos science, along with the Human Genome Project and spinoff projects, have dramatically altered our understanding of how the human body functions and what can be expected from research methods like animal modeling. In this article, I summarize these advances and examine one historical medical development, the Blalock-Taussig shunt, in order to ascertain whether historically accepted representations of this development are consistent with current knowledge. I also examine an ongoing technology-intra-arterial stent development-to compare human data to the known animal data and place this comparison in the context of the aforementioned advances.

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Two Models of Models in Biomedical Research

Cited by 98 publications

References 0 publications

Virtues and limitations of the preimplantation mouse embryo as a model system

Virtues and limitations of the preimplantation mouse embryo as a model system

Extrapolation and the Russo–Williamson thesis

A Discussion of the Role of Complex Evolved Systems in the Development of Invasive Cardiovascular Interventions as Illustrated by the Blalock- Taussig Shunt and Intra-Arterial Stents

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