Editing Model organism (section)

==Limitations==
Many animal models serving as test subjects in biomedical research, such as rats and mice, may be selectively [[sedentary lifestyle|sedentary]], [[obese]] and [[glucose intolerance|glucose intolerant]]. This may confound their use to model human metabolic processes and diseases as these can be affected by dietary energy intake and [[exercise]].<ref>{{cite journal |vauthors=Martin B, Ji S, Maudsley S, Mattson MP | year=2010 | title="Control" laboratory rodents are metabolically morbid: Why it matters | journal=Proceedings of the National Academy of Sciences | volume=107 | pages=6127–6133 | doi=10.1073/pnas.0912955107 | pmid=20194732 | issue=14 | pmc=2852022| bibcode=2010PNAS..107.6127M | doi-access=free }}</ref> Similarly, there are differences between the immune systems of model organisms and humans that lead to significantly altered responses to stimuli,<ref>{{cite journal |last1=Mestas |first1=Javier |last2=Hughes |first2=Christopher C. W. |title=Of Mice and Not Men: Differences between Mouse and Human Immunology |journal=The Journal of Immunology |date=March 2004 |volume=172 |issue=5 |pages=2731–2738 |doi=10.4049/jimmunol.172.5.2731 |pmid=14978070 |doi-access=free }}</ref><ref>{{cite journal |last1=Seok |first1=Junhee |last2=Warren |first2=H. Shaw |last3=Cuenca |first3=Alex G. |last4=Mindrinos |first4=Michael N. |last5=Baker |first5=Henry V. |last6=Xu |first6=Weihong |last7=Richards |first7=Daniel R. |last8=McDonald-Smith |first8=Grace P. |last9=Gao |first9=Hong |last10=Hennessy |first10=Laura |last11=Finnerty |first11=Celeste C. |last12=López |first12=Cecilia M. |last13=Honari |first13=Shari |last14=Moore |first14=Ernest E. |last15=Minei |first15=Joseph P. |last16=Cuschieri |first16=Joseph |last17=Bankey |first17=Paul E. |last18=Johnson |first18=Jeffrey L. |last19=Sperry |first19=Jason |last20=Nathens |first20=Avery B. |last21=Billiar |first21=Timothy R. |last22=West |first22=Michael A. |last23=Jeschke |first23=Marc G. |last24=Klein |first24=Matthew B. |last25=Gamelli |first25=Richard L. |last26=Gibran |first26=Nicole S. |last27=Brownstein |first27=Bernard H. |last28=Miller-Graziano |first28=Carol |last29=Calvano |first29=Steve E. |last30=Mason |first30=Philip H. |last31=Cobb |first31=J. Perren |last32=Rahme |first32=Laurence G. |last33=Lowry |first33=Stephen F. |last34=Maier |first34=Ronald V. |last35=Moldawer |first35=Lyle L. |last36=Herndon |first36=David N. |last37=Davis |first37=Ronald W. |last38=Xiao |first38=Wenzhong |last39=Tompkins |first39=Ronald G. |last40=Abouhamze |first40=Amer |last41=Balis |first41=Ulysses G. J. |last42=Camp |first42=David G. |last43=De |first43=Asit K. |last44=Harbrecht |first44=Brian G. |last45=Hayden |first45=Douglas L. |last46=Kaushal |first46=Amit |last47=O'Keefe |first47=Grant E. |last48=Kotz |first48=Kenneth T. |last49=Qian |first49=Weijun |last50=Schoenfeld |first50=David A. |last51=Shapiro |first51=Michael B. |last52=Silver |first52=Geoffrey M. |last53=Smith |first53=Richard D. |last54=Storey |first54=John D. |last55=Tibshirani |first55=Robert |last56=Toner |first56=Mehmet |last57=Wilhelmy |first57=Julie |last58=Wispelwey |first58=Bram |last59=Wong |first59=Wing H |title=Genomic responses in mouse models poorly mimic human inflammatory diseases |journal=Proceedings of the National Academy of Sciences of the United States of America |date=2013-02-26 |volume=110 |issue=9 |pages=3507–3512 |doi=10.1073/pnas.1222878110 |pmid=23401516 |pmc=3587220 |bibcode=2013PNAS..110.3507S |doi-access=free }}</ref><ref name="Jubb-Young-Hume">{{cite journal |last1=Jubb |first1=Alasdair W |last2=Young |first2=Robert S |last3=Hume |first3=David A |last4=Bickmore |first4=Wendy A |title=Enhancer turnover is associated with a divergent transcriptional response to glucocorticoid in mouse and human macrophages |journal=Journal of Immunology |date=15 January 2016 |volume=196 |issue=2 |pages=813–822 |doi=10.4049/jimmunol.1502009 |pmid=26663721 |pmc=4707550 }}</ref> although the underlying principles of genome function may be the same.<ref name="Jubb-Young-Hume" /> The impoverished environments inside standard laboratory cages deny research animals of the mental and physical challenges are necessary for healthy emotional development.<ref>{{Citation|last=Lahvis|first=Garet|title=The inescapable problem of lab animal restraint|date=5 December 2019 |url=https://www.ted.com/talks/garet_lahvis_the_inescapable_problem_of_lab_animal_restraint|language=en|access-date=2020-10-26}}</ref> Without day-to-day variety, risks and rewards, and complex environments, some have argued that animal models are irrelevant models of human experience.<ref>{{cite journal |last1=Lahvis |first1=Garet P |title=Unbridle biomedical research from the laboratory cage |journal=eLife |year=2017 |volume=6 |pages=e27438 |doi=10.7554/eLife.27438 |pmid=28661398 |pmc=5503508 |doi-access=free }}</ref>

Mice differ from humans in several immune properties: mice are more resistant to some [[toxins]] than humans; have a lower total [[neutrophil]] fraction in the [[blood]], a lower [[neutrophil]] [[enzymatic]] capacity, lower activity of the [[complement system]], and a different set of [[pentraxins]] involved in the [[inflammatory process]]; and lack genes for important components of the immune system, such as [[Interleukin 8|IL-8]], [[IL-37]], [[TLR10]], [[ICAM3|ICAM-3]], etc.<ref name="Mouse Models of Sepsis and Septic S"/> Laboratory mice reared in [[specific-pathogen-free]] (SPF) conditions usually have a rather immature immune system with a deficit of [[memory T cells]]. These mice may have limited diversity of the [[microbiota]], which directly affects the immune system and the development of pathological conditions. Moreover, persistent virus infections (for example, [[Herpesviridae|herpesviruses]]) are activated in humans, but not in [[specific-pathogen-free|SPF]] mice, with [[Sepsis|septic]] complications and may change the resistance to bacterial [[coinfections]]. "Dirty" mice are possibly better suitable for mimicking human pathologies. In addition, inbred mouse strains are used in the overwhelming majority of studies, while the [[human population]] is heterogeneous, pointing to the importance of studies in interstrain hybrid, [[outbred]], and nonlinear mice.<ref name="Mouse Models of Sepsis and Septic S"/>

=== Unintended bias ===
Some studies suggests that inadequate published data in animal testing may result in irreproducible research, with missing details about how experiments are done omitted from published papers or differences in testing that may introduce bias. Examples of hidden bias include a 2014 study from [[McGill University]] in [[Montreal|Montreal, Canada]] which suggests that mice handled by men rather than women showed higher stress levels.<ref>{{cite news|url=https://www.economist.com/news/christmas-specials/21712058-evolution-scientific-mainstay-worlds-favourite-lab-animal-has-been-found|title=The world's favourite lab animal has been found wanting, but there are new twists in the mouse's tale|newspaper=The Economist|access-date=2017-01-10}}</ref><ref>{{cite journal |last1=Katsnelson |first1=Alla |title=Male researchers stress out rodents |journal=Nature |date=2014-04-28 |pages=nature.2014.15106 |doi=10.1038/nature.2014.15106 |doi-access=free }}</ref><ref>{{Cite news|url=https://www.science.org/content/article/male-scent-may-compromise-biomedical-research|title=Male Scent May Compromise Biomedical Research|date=2014-04-28|newspaper=Science {{!}} AAAS|access-date=2017-01-10}}</ref> Another study in 2016 suggested that gut [[Microbiota|microbiomes]] in mice may have an impact upon scientific research.<ref>{{Cite news|url=https://www.science.org/content/article/mouse-microbes-may-make-scientific-studies-harder-replicate|title=Mouse microbes may make scientific studies harder to replicate|date=2016-08-15|newspaper=Science {{!}} AAAS|access-date=2017-01-10}}</ref>

===Alternatives===
Ethical concerns, as well as the cost, maintenance and relative inefficiency of animal research has encouraged development of alternative methods for the study of disease. Cell culture, or ''in vitro'' studies, provide an alternative that preserves the physiology of the living cell, but does not require the sacrifice of an animal for mechanistic studies. Human, inducible [[pluripotent]] stem cells can{{fact|date=December 2023}} also elucidate new mechanisms for understanding cancer and cell regeneration. Imaging studies (such as MRI or PET scans) enable non-invasive study of human subjects. Recent advances in genetics and genomics can identify disease-associated genes, which can be targeted for therapies.

Many biomedical researchers argue that there is no substitute for a living organism when studying complex interactions in disease pathology or treatments.<ref>{{cite journal | title=FDA: Why are animals used for testing medical products? | journal=FDA| url=https://www.fda.gov/AboutFDA/Transparency/Basics/ucm194932.htm| date=2019-06-18}}</ref><ref>{{cite web | title=Society Of Toxicology: Advancing valid alternatives | url=http://www.toxicology.org/ms/air4.asp| archive-url=https://web.archive.org/web/20130105120605/http://www.toxicology.org/ms/air4.asp| url-status=dead| archive-date=2013-01-05}}</ref>