Editing Genetically modified organism (section)

== Bacteria ==
{{Main|Genetically modified bacteria}}
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'''Right:''' Bacteria transformed with pGLO visualized under ultraviolet light
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[[Bacteria]] were the first organisms to be genetically modified in the laboratory, due to the relative ease of modifying their chromosomes.<ref name="Melo">{{cite journal | vauthors = Melo EO, Canavessi AM, Franco MM, Rumpf R | title = Animal transgenesis: state of the art and applications | journal = Journal of Applied Genetics | volume = 48 | issue = 1 | pages = 47–61 | date = March 2007 | pmid = 17272861 | doi = 10.1007/BF03194657 | s2cid = 24578435 | url = http://ainfo.cnptia.embrapa.br/digital/bitstream/item/156019/1/art3A10.10072FBF03194657.pdf }}</ref> This ease made them important tools for the creation of other GMOs. Genes and other genetic information from a wide range of organisms can be added to a [[plasmid]] and inserted into bacteria for storage and modification. Bacteria are cheap, easy to grow, [[Clone (cell biology)|clonal]], multiply quickly and can be stored at −80&nbsp;°C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria, providing an unlimited supply for research.<ref>{{cite web|url=https://www.learner.org/courses/biology/textbook/gmo/gmo_2.html|title=Rediscovering Biology – Online Textbook: Unit 13 Genetically Modified Organisms|website=www.learner.org|access-date=18 August 2017|archive-date=3 December 2019|archive-url=https://web.archive.org/web/20191203123559/http://www.learner.org/courses/biology/textbook/gmo/gmo_2.html|url-status=dead}}</ref> A large number of custom plasmids make manipulating DNA extracted from bacteria relatively easy.<ref>{{cite journal | vauthors = Fan M, Tsai J, Chen B, Fan K, LaBaer J | title = A central repository for published plasmids | journal = Science | volume = 307 | issue = 5717 | pages = 1877 | date = March 2005 | pmid = 15790830 | doi = 10.1126/science.307.5717.1877a | s2cid = 27404861 }}</ref>

Their ease of use has made them great tools for scientists looking to study gene function and [[evolution]].  The simplest [[model organism]]s come from bacteria, with most of our early understanding of [[molecular biology]] coming from studying ''[[Escherichia coli]]''.<ref>{{cite journal | vauthors = Cooper GM |date=2000|title=Cells As Experimental Models|url=https://www.ncbi.nlm.nih.gov/books/NBK9917/|journal=The Cell: A Molecular Approach |edition=2nd}}</ref> Scientists can easily manipulate and combine genes within the bacteria to create novel or disrupted proteins and observe the effect this has on various molecular systems. Researchers have combined the genes from bacteria and [[archaea]], leading to insights on how these two diverged in the past.<ref>{{cite journal | vauthors = Patel P | title = Microbe Mystery | journal = [[Scientific American]] | volume = 319 | issue = 1 | pages = 18 | date = June 2018 | pmid = 29924081 | doi = 10.1038/scientificamerican0718-18a | bibcode = 2018SciAm.319a..18P | s2cid = 49310760 }}</ref> In the field of [[synthetic biology]], they have been used to test various synthetic approaches, from synthesizing genomes to creating novel [[nucleotides]].<ref>{{cite journal | vauthors = Arpino JA, Hancock EJ, Anderson J, Barahona M, Stan GB, Papachristodoulou A, Polizzi K | title = Tuning the dials of Synthetic Biology | journal = Microbiology | volume = 159 | issue = Pt 7 | pages = 1236–53 | date = July 2013 | pmid = 23704788 | pmc = 3749727 | doi = 10.1099/mic.0.067975-0 | doi-access = free }}</ref><ref name="NYT-20140507">{{cite news|url=https://www.nytimes.com/2014/05/08/business/researchers-report-breakthrough-in-creating-artificial-genetic-code.html |archive-url=https://ghostarchive.org/archive/20220102/https://www.nytimes.com/2014/05/08/business/researchers-report-breakthrough-in-creating-artificial-genetic-code.html |archive-date=2 January 2022 |url-access=limited |url-status=live|title=Researchers Report Breakthrough in Creating Artificial Genetic Code| vauthors = Pollack A |date=7 May 2014|work=The New York Times|access-date=7 May 2014}}{{cbignore}}</ref><ref name="NATJ-20140507">{{cite journal | vauthors = Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR, Romesberg FE | title = A semi-synthetic organism with an expanded genetic alphabet | journal = Nature | volume = 509 | issue = 7500 | pages = 385–8 | date = May 2014 | pmid = 24805238 | pmc = 4058825 | doi = 10.1038/nature13314 | bibcode = 2014Natur.509..385M }}</ref>

Bacteria have been used in the production of food for a long time, and specific strains have been developed and selected for that work on an [[Industry (manufacturing)|industrial]] scale. They can be used to produce [[enzyme]]s, [[amino acid]]s, [[flavoring]]s, and other compounds used in food production. With the advent of genetic engineering, new genetic changes can easily be introduced into these bacteria. Most food-producing bacteria are [[lactic acid bacteria]], and this is where the majority of research into genetically engineering food-producing bacteria has gone. The bacteria can be modified to operate more efficiently, reduce toxic byproduct production, increase output, create improved compounds, and remove unnecessary [[Biological pathway|pathways]].<ref name=":2">{{cite book|chapter=Genetically Modified Microorganisms|vauthors=Kärenlampi SO, von Wright AJ|title=Encyclopedia of Food and Health |date=1 January 2016|publisher=Encyclopedia of Food and Health|isbn=978-0-12-384953-3|pages=211–216|doi=10.1016/B978-0-12-384947-2.00356-1}}</ref> Food products from genetically modified bacteria include [[alpha-amylase]], which converts starch to simple sugars, [[chymosin]], which clots milk protein for cheese making, and [[pectinesterase]], which improves fruit juice clarity.<ref>Panesar, Pamit et al. (2010) ''Enzymes in Food Processing: Fundamentals and Potential Applications'', Chapter 10, I K International Publishing House, {{ISBN|978-93-80026-33-6}}</ref> The majority are produced in the US and even though regulations are in place to allow production in Europe, as of 2015 no food products derived from bacteria are currently available there.<ref>{{Cite book|title=Genetic Modification and Food Quality: A Down to Earth Analysis| vauthors = Blair R, Regenstein JM |date=3 August 2015|publisher=John Wiley & Sons|isbn=978-1-118-75641-6|pages=20–24}}</ref>

Genetically modified bacteria are used to produce large amounts of proteins for industrial use. The bacteria are generally grown to a large volume before the gene encoding the protein is activated. The bacteria are then harvested and the desired protein purified from them.<ref name=":3">{{cite book |title=Genetically Modified Organisms the Mystery Unraveled| vauthors = Jumba M |publisher=Eloquent Books|year=2009|isbn=978-1-60911-081-9|location=Durham|pages=51–54 }}</ref> The high cost of extraction and purification has meant that only high value products have been produced at an industrial scale.<ref name=":4">{{cite journal | vauthors = Zhou Y, Lu Z, Wang X, Selvaraj JN, Zhang G | title = Genetic engineering modification and fermentation optimization for extracellular production of recombinant proteins using Escherichia coli | journal = Applied Microbiology and Biotechnology | volume = 102 | issue = 4 | pages = 1545–1556 | date = February 2018 | pmid = 29270732 | doi = 10.1007/s00253-017-8700-z | s2cid = 253769838 }}</ref> The majority of these products are human proteins for use in medicine.<ref name="Leader2008">{{cite journal | vauthors = Leader B, Baca QJ, Golan DE | title = Protein therapeutics: a summary and pharmacological classification | journal = Nature Reviews. Drug Discovery | volume = 7 | issue = 1 | pages = 21–39 | date = January 2008 | pmid = 18097458 | doi = 10.1038/nrd2399 | series = A guide to drug discovery | s2cid = 3358528 }}</ref> Many of these proteins are impossible or difficult to obtain via natural methods and they are less likely to be contaminated with pathogens, making them safer.<ref name=":3" /> The first medicinal use of GM bacteria was to produce the protein [[insulin]] to treat [[diabetes]].<ref name="Walsh2005">{{cite journal | vauthors = Walsh G | title = Therapeutic insulins and their large-scale manufacture | journal = Applied Microbiology and Biotechnology | volume = 67 | issue = 2 | pages = 151–9 | date = April 2005 | pmid = 15580495 | doi = 10.1007/s00253-004-1809-x | s2cid = 5986035 }}</ref> Other medicines produced include [[coagulation|clotting factors]] to treat [[hemophilia]],<ref name="Pipe2008">{{cite journal | vauthors = Pipe SW | title = Recombinant clotting factors | journal = Thrombosis and Haemostasis | volume = 99 | issue = 5 | pages = 840–50 | date = May 2008 | pmid = 18449413 | doi = 10.1160/TH07-10-0593 | s2cid = 2701961 }}</ref> [[human growth hormone]] to treat various forms of [[dwarfism]],<ref name="Bryant2007">{{cite journal | vauthors = Bryant J, Baxter L, Cave CB, Milne R | title = Recombinant growth hormone for idiopathic short stature in children and adolescents | journal = The Cochrane Database of Systematic Reviews | issue = 3 | pages = CD004440 | date = July 2007 | pmid = 17636758 | doi = 10.1002/14651858.CD004440.pub2 | veditors = Bryant J | url = https://researchonline.lshtm.ac.uk/id/eprint/1236226/1/Bryant_et_al-2007-The_Cochrane_library.pdf }}</ref><ref>{{cite journal | vauthors = Baxter L, Bryant J, Cave CB, Milne R | title = Recombinant growth hormone for children and adolescents with Turner syndrome | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003887 | date = January 2007 | pmid = 17253498 | doi = 10.1002/14651858.CD003887.pub2 | veditors = Bryant J | url = https://researchonline.lshtm.ac.uk/id/eprint/1236240/1/Baxter_et_al-2007-The_Cochrane_library.pdf }}</ref> [[interferon]] to treat some cancers, [[erythropoietin]] for anemic patients, and [[tissue plasminogen activator]] which dissolves blood clots.<ref name=":3" /> Outside of medicine they have been used to produce [[biofuel]]s.<ref>Summers, Rebecca (24 April 2013). [https://www.newscientist.com/article/dn23431-bacteria-churn-out-first-ever-petrollike-biofuel.html "Bacteria churn out first ever petrol-like biofuel"]. ''New Scientist'', Retrieved 27 April 2013</ref> There is interest in developing an extracellular expression system within the bacteria to reduce costs and make the production of more products economical.<ref name=":4" />

With a greater understanding of the role that the [[Human microbiota|microbiome]] plays in human health, there is a potential to treat diseases by genetically altering the bacteria to, themselves, be therapeutic agents. Ideas include altering gut bacteria so they destroy harmful bacteria, or using bacteria to replace or increase deficient [[enzymes]] or proteins. One research focus is to modify ''[[Lactobacillus]]'', bacteria that naturally provide some protection against [[HIV]], with genes that will further enhance this protection. If the bacteria do not form [[Bacterial colony|colonies]] inside the patient, the person must repeatedly ingest the modified bacteria in order to get the required doses. Enabling the bacteria to form a colony could provide a more long-term solution, but could also raise safety concerns as interactions between bacteria and the human body are less well understood than with traditional drugs. There are concerns that [[horizontal gene transfer]] to other bacteria could have unknown effects. As of 2018 there are clinical trials underway testing the [[efficacy]] and safety of these treatments.<ref>{{cite journal | vauthors = Reardon S | title = Genetically modified bacteria enlisted in fight against disease | journal = Nature | volume = 558 | issue = 7711 | pages = 497–498 | date = June 2018 | pmid = 29946090 | doi = 10.1038/d41586-018-05476-4 | bibcode = 2018Natur.558..497R | doi-access = free }}</ref>

For over a century, bacteria have been used in agriculture. Crops have been [[Inoculation|inoculated]] with [[Rhizobia]] (and more recently ''[[Azospirillum]]'') to increase their production or to allow them to be grown outside their original [[habitat]]. Application of ''[[Bacillus thuringiensis]]'' (Bt) and other bacteria can help protect crops from insect infestation and plant diseases. With advances in genetic engineering, these bacteria have been manipulated for increased efficiency and expanded host range. Markers have also been added to aid in tracing the spread of the bacteria. The bacteria that naturally colonize certain crops have also been modified, in some cases to express the Bt genes responsible for pest resistance. ''[[Pseudomonas]]'' strains of bacteria cause frost damage by [[Nucleation|nucleating]] water into [[ice crystals]] around themselves. This led to the development of [[ice-minus bacteria]], which have the ice-forming genes removed. When applied to crops they can compete with the non-modified bacteria and confer some frost resistance.<ref>{{cite journal | vauthors = Amarger N | title = Genetically modified bacteria in agriculture | journal = Biochimie | volume = 84 | issue = 11 | pages = 1061–72 | date = November 2002 | pmid = 12595134 | doi = 10.1016/s0300-9084(02)00035-4 }}</ref>

[[File:FPbeachTsien.jpg|thumb|This artwork is made with bacteria modified to express 8 different colors of [[green fluorescent protein|fluorescent proteins]].]]
Other uses for genetically modified bacteria include [[bioremediation]], where the bacteria are used to convert pollutants into a less toxic form. Genetic engineering can increase the levels of the enzymes used to degrade a toxin or to make the bacteria more stable under environmental conditions.<ref>{{cite journal | vauthors = Sharma B, Dangi AK, Shukla P | title = Contemporary enzyme based technologies for bioremediation: A review | journal = Journal of Environmental Management | volume = 210 | pages = 10–22 | date = March 2018 | pmid = 29329004 | doi = 10.1016/j.jenvman.2017.12.075 | bibcode = 2018JEnvM.210...10S }}</ref> [[BioArt|Bioart]] has also been created using genetically modified bacteria. In the 1980s artist [[Joe Davis (artist)|Jon Davis]] and geneticist [[Dana Boyd]] converted the Germanic symbol for femininity (ᛉ) into binary code and then into a DNA sequence, which was then expressed in ''[[Escherichia coli]]''.<ref name=":6">{{cite journal | vauthors = Yetisen AK, Davis J, Coskun AF, Church GM, Yun SH | title = Bioart | journal = Trends in Biotechnology | volume = 33 | issue = 12 | pages = 724–734 | date = December 2015 | pmid = 26617334 | doi = 10.1016/j.tibtech.2015.09.011 | s2cid = 259584956 | url = https://resolver.caltech.edu/CaltechAUTHORS:20151207-104216157 }}</ref> This was taken a step further in 2012, when a whole book was encoded onto DNA.<ref>{{cite journal | vauthors = Church GM, Gao Y, Kosuri S | title = Next-generation digital information storage in DNA | journal = Science | volume = 337 | issue = 6102 | pages = 1628 | date = September 2012 | pmid = 22903519 | doi = 10.1126/science.1226355 | bibcode = 2012Sci...337.1628C | doi-access = free }}</ref> Paintings have also been produced using bacteria transformed with fluorescent proteins.<ref name=":6" />