Animal Models in Drug Development

Greek, Ray

doi:10.5772/53893

Cited by 14 publications

(9 citation statements)

References 139 publications

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“…However, the success of animal studies in predicting the human physiological response in terms of both efficacy and toxicity is sometimes poor, and this practice has been increasingly questioned 5,7,8 . Moreover, animal models are also hampered by their poor ability to isolate cell-based mechanisms of action and pathways 9 .…”

Section: Introductionmentioning

confidence: 99%

Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofin-vitroliver technologies

et al. 2015

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The liver performs many key functions, the most prominent of which is serving as the metabolic hub of the body. For this reason, the liver is the focal point of many investigations aimed at understanding an organism’s toxicological response to endogenous and exogenous challenges. Because so many drug failures have involved direct liver toxicity or other organ toxicity from liver generated metabolites, the pharmaceutical industry has constantly sought superior, predictive in-vitro models that can more quickly and efficiently identify problematic drug candidates before they incur major development costs, and certainly before they are released to the public. In this broad review, we present a survey and critical comparison of in-vitro liver technologies along a broad spectrum, but focus on the current renewed push to develop “organs-on-a-chip”. One prominent set of conclusions from this review is that while a large body of recent work has steered the field towards an ever more comprehensive understanding of what is needed, the field remains in great need of several key advances, including establishment of standard characterization methods, enhanced technologies that mimic the in-vivo cellular environment, and better computational approaches to bridge the gap between the in-vitro and in-vivo results.

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Section: Introductionmentioning

confidence: 99%

Microengineered cell and tissue systems for drug screening and toxicology applications: Evolution ofin-vitroliver technologies

et al. 2015

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“…The predictive value of animal modeling falls far below 99%; for example, 3% in the above teratogenicity example. For more on this point, see Greek (2013aGreek ( , b, 2014b, Greek and Greek (2010), and Values this low mean animal modeling per se has, for all practical purposes, no predictive value for human response to drugs and disease. Some researchers argue that any predictive value greater than zero means animal models have some predictive value.…”

Section: Empirical Evidence: the Failure Of The Animal Model In Termsmentioning

confidence: 99%

The Scientific Problems with Using Non-Human Animals to Predict Human Response to Drugs and Disease

Greek¹,

Kramer²

2019

Animal Experimentation: Working Towards a Paradigm Change

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IntroductionEvery year, and in countries around the world, significant time and resources are devoted to the noble cause of developing drugs to treat and cure human disease. With rare exception, drug interventions cannot reach commercialization without safety and efficacy having first been demonstrated in animal models. The intention of regulations, which require the use of animal models in such contexts, is to ensure that only safe and effective drugs end up being used by patients. Similarly, it is standard practice for researchers to employ animal models in their attempts to understand the way diseases present and progress in humans. Unfortunately, there exist serious theoretical and empirical concerns regarding the standard practice of using non-human animals to model human response to perturbations, such as drugs and disease. These concerns are important because conducting disease research and drug development in a manner that is not supported by science will have suboptimal implications for the humans who rely on that research, which encompass the entire population. Based on complexity science, modern evolutionary biology, and empirical evidence, we demonstrate that animal models have failed as predictors of human response. That is, animal models do not and cannot have acceptably high predictive value for human response to drugs and disease. By this we mean that animal modeling, as a methodology, is for all practical purposes not predictive of human response to drugs and disease; and hence it should be abandoned in favor of human-based research and testing, such as personalized medicine, a new field that takes into account the unique genetic make-up of each individual patient.

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“…Shanks and I [5][6][7][8][9][10] further developed the foundations concerning the problem of using one evolved complex system to model another, and I [11][12][13][14][15][16][17][18][19][20][21] continue to publish on the topic. My position is summarized in Trans-Species Modeling Theory (TSMT), which states: ''While trans-species extrapolation is possible when perturbations concern lower levels of organization or when studying morphology and function on the gross level, one evolved complex system will not be of predictive value for another when the perturbation affects higher levels of organization'' [19].…”

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confidence: 99%