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===Invertebrates=== {{Main|Animal testing on invertebrates}} {{See also|Pain in invertebrates}} [[File:Drosophila melanogaster - front (aka).jpg|thumb|[[Drosophila melanogaster|Fruit flies]] are an invertebrate commonly used in animal testing.]] Although many more invertebrates than vertebrates are used in animal testing, these studies are largely unregulated by law. The most frequently used invertebrate species are ''[[Drosophila melanogaster]]'', a fruit fly, and ''[[Caenorhabditis elegans]]'', a [[nematode]] worm. In the case of ''C. elegans'', the worm's body is completely transparent and the precise lineage of all the organism's cells is known,<ref>{{cite journal |vauthors=Antoshechkin I, Sternberg PW | title = The versatile worm: genetic and genomic resources for Caenorhabditis elegans research | journal = Nature Reviews Genetics | volume = 8 | issue = 7 | pages = 518β32 | year = 2007 | pmid = 17549065 | doi = 10.1038/nrg2105 | s2cid = 12923468 }}</ref> while studies in the fly ''D. melanogaster'' can use an amazing array of genetic tools.<ref>{{cite journal |vauthors=Matthews KA, Kaufman TC, Gelbart WM | title = Research resources for Drosophila: the expanding universe | journal = Nature Reviews Genetics | volume = 6 | issue = 3 | pages = 179β93 | year = 2005 | pmid = 15738962 | doi = 10.1038/nrg1554 | s2cid = 31002250 }}</ref> These invertebrates offer some advantages over vertebrates in animal testing, including their short life cycle and the ease with which large numbers may be housed and studied. However, the lack of an adaptive [[immune system]] and their simple organs prevent worms from being used in several aspects of medical research such as vaccine development.<ref name=Schulenburg>{{cite journal |vauthors=Schulenburg H, Kurz CL, Ewbank JJ | title = Evolution of the innate immune system: the worm perspective | journal = Immunological Reviews | volume = 198 | pages = 36β58 | year = 2004 | pmid = 15199953 | doi = 10.1111/j.0105-2896.2004.0125.x | s2cid = 21541043 }}</ref> Similarly, the fruit fly [[immune system]] differs greatly from that of humans,<ref>{{cite journal |vauthors=Leclerc V, Reichhart JM | title = The immune response of Drosophila melanogaster | journal = Immunological Reviews | volume = 198 | pages = 59β71 | year = 2004 | pmid = 15199954 | doi = 10.1111/j.0105-2896.2004.0130.x | s2cid = 7395057 }}</ref> and diseases in insects can be different from diseases in vertebrates;<ref>{{cite journal |vauthors=Mylonakis E, Aballay A | title = Worms and flies as genetically tractable animal models to study host-pathogen interactions | journal = Infection and Immunity | volume = 73 | issue = 7 | pages = 3833β41 | year = 2005 | pmid = 15972468 | pmc = 1168613 | doi = 10.1128/IAI.73.7.3833-3841.2005 }}</ref> however, fruit flies and [[waxworms]] can be useful in studies to identify novel virulence factors or pharmacologically active compounds.<ref name="ncbi.nlm.nih.gov">{{cite journal |vauthors=Kavanagh K, Reeves EP | title = Exploiting the potential of insects for in vivo pathogenicity testing of microbial pathogens | journal = FEMS Microbiology Reviews | volume = 28 | issue = 1 | pages = 101β12 | year = 2004 | pmid = 14975532 | doi = 10.1016/j.femsre.2003.09.002 | doi-access = free }}</ref><ref name="plosone.org">{{cite journal | vauthors = Antunes LC, Imperi F, Carattoli A, Visca P | title = Deciphering the Multifactorial Nature of Acinetobacter baumannii Pathogenicity | journal = PLOS ONE| volume = 6 | issue = 8 | pages = e22674 | year = 2011 | pmid = 21829642 | pmc = 3148234 | doi = 10.1371/journal.pone.0022674 | editor1-last = Adler | editor1-first = Ben |bibcode = 2011PLoSO...622674A | doi-access = free }}</ref><ref name="Aperis G 2011">{{cite journal |vauthors=Aperis G, Fuchs BB, Anderson CA, Warner JE, Calderwood SB, Mylonakis E | title = Galleria mellonella as a model host to study infection by the Francisella tularensis live vaccine strain | journal = Microbes and Infection / Institut Pasteur | volume = 9 | issue = 6 | pages = 729β34 | year = 2007 | pmid = 17400503 | pmc = 1974785 | doi = 10.1016/j.micinf.2007.02.016 }}</ref> Several invertebrate systems are considered acceptable alternatives to vertebrates in early-stage discovery screens.<ref>{{cite journal|vauthors=Waterfield NR, Sanchez-Contreras M, Eleftherianos I, Dowling A, Yang G, Wilkinson P, Parkhill J, Thomson N, Reynolds SE, Bode HB, Dorus S, Ffrench-Constant RH |doi=10.1073/pnas.0711114105|title=Rapid Virulence Annotation (RVA): Identification of virulence factors using a bacterial genome library and multiple invertebrate hosts|year=2008|journal=Proceedings of the National Academy of Sciences of the United States of America |volume=105|issue=41|pages=15967β72 |bibcode = 2008PNAS..10515967W |pmid=18838673 |pmc=2572985|doi-access=free}}</ref> Because of similarities between the innate immune system of insects and mammals, insects can replace mammals in some types of studies. ''Drosophila melanogaster'' and the ''[[Galleria mellonella]]'' waxworm have been particularly important for analysis of virulent traits of mammalian pathogens.<ref name="ncbi.nlm.nih.gov"/><ref name="plosone.org"/> Waxworms and other insects have also proven valuable for the identification of pharmaceutical compounds with favorable bioavailability.<ref name="Aperis G 2011"/> The decision to adopt such models generally involves accepting a lower degree of biological similarity with mammals for significant gains in experimental throughput.
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