Nuances in the Development of Vertebrate Models

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Vertebrate models are, intuitively, uniquely suited to human diseases research as their physiology most closely approximates that of humans. Nevertheless, the same considerations that elevated mice as the foremost model organism in biomedical research over less evolutionarily distant organisms (such as the great apes) may also factor into the relative usefulness of invertebrate and vertebrate models.

Trade-offs such as longer generation times, higher costs of maintenance, and greater ethical concerns may skew choices in favour of more convenient invertebrate models such as the common fruit fly Drosophila melanogaster and the simple nematode Caenorhabditis elegans (Wilson-Sanders, 2011). Consequently, compared to vertebrates, invertebrate models generally yield results in a shorter timeframe, and the feasibility of housing and experimenting on them in large numbers allows significantly more replicates, contributing to greater statistical power and confidence in results.

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The choice of a model organisms is not solely informed by their inherent benefits and/or disadvantages. As disease research builds on existing information and resources generated by the broader scientific community, the availability of knowledge (including publications and databases) and tools (such as antibodies and a variety of strains) relevant to each organism within the field of interest should also be taken into consideration (Rine, 2014).

Additionally, within specific fields, there are organisms that are often preferred for reasons including ease of manipulation and wealth of field-specific resources. For example, many early key discoveries in the field of genetics were made using D. melanogaster due in part to the relative ease of manipulating its genome (as compared to those of higher eukaryotes), resulting in an early expansion of its utility and establishing it as a classic model in genetics research (Bellen & Yamamoto, 2015).

Given that research into understanding and treating human diseases occurs in stages, and that these stages may differ significantly in achievable goals, it is common that a variety of organisms are used as research progresses from deconvoluting mechanisms to treatment development. Screening, such as of genes with mutagenesis and drugs in drug discovery, is impractical with costly vertebrate models (Wilson-Sanders, 2011). Additionally, research into the molecular mechanisms of highly conserved processes (such as apoptosis) still yield results relevant to humans when studied in evolutionarily distant organisms like C. elegans (Arvanitis, Li, Lee, & Mylonakis, 2013).

Nevertheless, due to physiological (as well as cellular) dissimilarities, treatments for diseases in tissues that do not exist in invertebrates (such as bone) can only be tested in more closely related species. Not to mention, authorities such as the Food and Drug Administration and the European Medicines Agency typically require preclinical safety testing in at least two mammalian species before human trials authorisation (Atanasov et al., 2015). While invertebrates may suffice for preliminary research, vertebrate (specifically mammalian) models must eventually be used if a treatment is intended to enter clinical trials.

The final decision on a model organism depends on a combination of the factors described above, and each study should give priority to appropriate factors based on its unique circumstances.

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