Editing Genetics (section)

== History ==
{{Main|History of genetics}}

The observation that living things inherit [[Phenotypic trait|traits]] from their parents has been used since prehistoric times to improve crop plants and animals through [[selective breeding]].<ref name="Publishing2009">{{cite book |title=Science: The Definitive Visual Guide |url=https://books.google.com/books?id=sFiJFuzRVFQC&pg=PA362 |year=2009 |publisher=Penguin |isbn=978-0-7566-6490-9 |page=362}}</ref><ref name="Poczai and Santiago-Blay 2022a">{{cite journal | vauthors = Poczai P, Santiago-Blay JA | title = Themes of Biological Inheritance in Early Nineteenth Century Sheep Breeding as Revealed by J. M. Ehrenfels | journal = Genes | volume = 13 | issue = 8 | page = 1311 | date = July 2022 | pmid = 35893050 | pmc = 9332421 | doi = 10.3390/genes13081311 | doi-access = free }}</ref> The modern science of genetics, seeking to understand this process, began with the work of the [[Augustinians|Augustinian]] friar [[Gregor Mendel]] in the mid-19th century.<ref name=Weiling>{{cite journal | vauthors = Weiling F | title = Historical study: Johann Gregor Mendel 1822-1884 | journal = American Journal of Medical Genetics | volume = 40 | issue = 1 | pages = 1–25; discussion 26 | date = July 1991 | pmid = 1887835 | doi = 10.1002/ajmg.1320400103 }}</ref>
[[File:Festetics Imre-Oelenhainz.jpg|thumb|Portrait of [[Imre Festetics]], the first [[geneticist]] and [[Ethology|ethologist]]. His concepts of [[Selection (biology)|selection]] and [[evolution]] were later formulated in [[Natural selection|Charles Darwin's theory of evolution]].]]
Prior to Mendel, [[Imre Festetics]], a [[Hungary|Hungarian]] noble, who lived in Kőszeg before Mendel, was the first who used the word "genetic" in hereditarian context, and is considered the first geneticist. He described several rules of biological inheritance in his work ''The genetic laws of nature'' (Die genetischen Gesetze der Natur, 1819).<ref name="Poczai and Santiago-Blay 2021" /> His second law is the same as that which Mendel published.<ref name="Poczai and Szabó 2019">{{cite journal | vauthors = Szabó AT, Poczai P | title = The emergence of genetics from Festetics' sheep through Mendel's peas to Bateson's chickens | journal = Journal of Genetics | volume = 98 | issue = 2 | page = 63 | date = June 2019 | pmid = 31204695 | doi = 10.1007/s12041-019-1108-z | hdl-access = free | s2cid = 174803150 | hdl = 10138/324962 }}</ref> In his third law, he developed the basic principles of mutation (he can be considered a forerunner of [[Hugo de Vries]]).<ref>{{cite journal | vauthors = Poczai P, Bell N, Hyvönen J | title = Imre Festetics and the Sheep Breeders' Society of Moravia: Mendel's Forgotten "Research Network" | journal = PLOS Biology | volume = 12 | issue = 1 | pages = e1001772 | date = January 2014 | pmid = 24465180 | pmc = 3897355 | doi = 10.1371/journal.pbio.1001772 | df = dmy-all | doi-access = free }}</ref> Festetics argued that changes observed in the generation of farm animals, plants, and humans are the result of scientific laws.<ref name="Poczai 2022">{{cite book | vauthors = Poczai P  |title=Heredity Before Mendel: Festetics and the Question of Sheep's Wool in Central Europe |date=2022 |publisher=CRC Press |location=Boca Raton, Florida |isbn=978-1-032-02743-2 |page=113 |edition= |url=https://books.google.com/books?id=QJRwEAAAQBAJ&dq=info:maQOFGaQPfYJ:scholar.google.com&pg=PT6 |access-date=30 August 2022}}</ref> Festetics empirically deduced that organisms inherit their characteristics, not acquire them. He recognized recessive traits and inherent variation by postulating that traits of past generations could reappear later, and organisms could produce progeny with different attributes.<ref name="Poczai et al. 2022">{{cite journal | vauthors = Poczai P, Santiago-Blay JA, Sekerák J, Bariska I, Szabó AT | title = Mimush Sheep and the Spectre of Inbreeding: Historical Background for Festetics's Organic and Genetic Laws Four Decades Before Mendel's Experiments in Peas | journal = Journal of the History of Biology | volume = 55 | issue = 3 | pages = 495–536 | date = October 2022 | pmid = 35670984 | pmc = 9668798 | doi = 10.1007/s10739-022-09678-5 | s2cid = 249433049 }}</ref> These observations represent an important prelude to Mendel's theory of particulate inheritance insofar as it features a transition of heredity from its status as myth to that of a scientific discipline, by providing a fundamental theoretical basis for genetics in the twentieth century.<ref name="Poczai and Santiago-Blay 2021">{{cite journal | vauthors = Poczai P, Santiago-Blay JA | title = Principles and biological concepts of heredity before Mendel | journal = Biology Direct | volume = 16 | issue = 1 | pages = 19 | date = October 2021 | pmid = 34674746 | pmc = 8532317 | doi = 10.1186/s13062-021-00308-4 | doi-access = free }} [[File:CC-BY icon.svg|50px]] Text was copied from this source, which is available under a [https://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International License] {{Webarchive|url=https://web.archive.org/web/20171016050101/https://creativecommons.org/licenses/by/4.0/ |date=16 October 2017 }}.</ref><ref name="Poczai and Santiago-Blay 2022b">{{cite journal | vauthors = Poczai P, Santiago-Blay JA | title = Chip Off the Old Block: Generation, Development, and Ancestral Concepts of Heredity | journal = Frontiers in Genetics | volume = 13 | pages = 814436 | date = 2022 | pmid = 35356423 | pmc = 8959437 | doi = 10.3389/fgene.2022.814436 | doi-access = free }}</ref>

[[File:Blending Inheritance.svg|thumb|[[Blending inheritance]] leads to the averaging out of every characteristic, which as the engineer [[Fleeming Jenkin]] pointed out, makes [[evolution]] by [[natural selection]] impossible.]]

Other theories of inheritance preceded Mendel's work. A popular theory during the 19th century, and implied by [[Charles Darwin]]'s 1859 ''[[On the Origin of Species]]'', was [[blending inheritance]]: the idea that individuals inherit a smooth blend of traits from their parents.<ref name="Hamilton2011">{{cite book | vauthors = Hamilton H |title=Population Genetics |url=https://books.google.com/books?id=ng85sd1UR7EC&pg=PT26 |year=2011 |publisher=Georgetown University |isbn=978-1-4443-6245-9 |page=26}}</ref> Mendel's work provided examples where traits were definitely not blended after hybridization, showing that traits are produced by combinations of distinct genes rather than a continuous blend. Blending of traits in the progeny is now explained by the action of multiple genes with [[Quantitative genetics|quantitative effects]]. Another theory that had some support at that time was the [[inheritance of acquired characteristics]]: the belief that individuals inherit traits strengthened by their parents. This theory (commonly associated with [[Jean-Baptiste Lamarck]]) is now known to be wrong—the experiences of individuals do not affect the genes they pass to their children.<ref>Lamarck, J-B (2008). In [[Encyclopædia Britannica]]. Retrieved from [http://www.search.eb.com/eb/article-273180 Encyclopædia Britannica Online] {{Webarchive|url=https://web.archive.org/web/20200414173437/http://www.search.eb.com/eb/article-273180 |date=14 April 2020 }} on 16 March 2008.</ref> Other theories included Darwin's [[pangenesis]] (which had both acquired and inherited aspects) and [[Francis Galton]]'s reformulation of pangenesis as both particulate and inherited.<ref>[[Peter J. Bowler]], ''The Mendelian Revolution: The Emergency of Hereditarian Concepts in Modern Science and Society'' (Baltimore: Johns Hopkins University Press, 1989): chapters 2 & 3.</ref>

=== Mendelian genetics ===
[[File:Sexlinked inheritance white.jpg|thumb|Morgan's observation of [[Sex linkage|sex-linked inheritance]] of a mutation causing white eyes in ''[[Drosophila]]'' led him to the hypothesis that genes are located upon chromosomes.]]

{{main|Mendelian inheritance}}

Modern genetics started with Mendel's studies of the nature of inheritance in plants. In his paper "''Versuche über Pflanzenhybriden''" ("[[Experiments on Plant Hybridization]]"), presented in 1865 to the ''Naturforschender Verein'' (Society for Research in Nature) in [[Brno]], Mendel traced the inheritance patterns of certain traits in pea plants and described them mathematically. Although this pattern of inheritance could only be observed for a few traits, Mendel's work suggested that heredity was particulate, not acquired, and that the inheritance patterns of many traits could be explained through simple rules and ratios.<ref name="mendel">{{cite web |title=Mendel's Paper in English |url=http://www.mendelweb.org/Mendel.html | vauthors = Blumberg RB |url-status=live |archive-url=https://web.archive.org/web/20160113051202/http://www.mendelweb.org/Mendel.html |archive-date=13 January 2016}}</ref>

The importance of Mendel's work did not gain wide understanding until 1900, after his death, when [[Hugo de Vries]] and other scientists rediscovered his research. [[William Bateson]], a proponent of Mendel's work, coined the word ''genetics'' in 1905.<ref>genetics, ''n.'', [[Oxford English Dictionary]], 3rd ed.</ref><ref>{{cite web |url=http://www.jic.ac.uk/corporate/about/bateson.htm |title=Letter from William Bateson to Alan Sedgwick in 1905 |publisher=The John Innes Centre |access-date=15 March 2008 |vauthors=Bateson W |url-status=dead |archive-url=https://web.archive.org/web/20071013020831/http://www.jic.ac.uk/corporate/about/bateson.htm |archive-date=13 October 2007}} The letter was to an Adam Sedgwick, a zoologist and "Reader in Animal Morphology" at [[Trinity College, Cambridge]]</ref> The adjective ''genetic'', derived from the Greek word ''genesis''—γένεσις, "origin", predates the noun and was first used in a biological sense in 1860.<ref>genetic, ''adj.'', Oxford English Dictionary, 3rd ed.</ref> Bateson both acted as a mentor and was aided significantly by the work of other scientists from Newnham College at Cambridge, specifically the work of [[Edith Rebecca Saunders|Becky Saunders]], [[Nora Darwin Barlow]], and [[Muriel Wheldale Onslow]].<ref>{{cite journal | vauthors = Richmond ML | title = Opportunities for women in early genetics | journal = Nature Reviews. Genetics | volume = 8 | issue = 11 | pages = 897–902 | date = November 2007 | pmid = 17893692 | doi = 10.1038/nrg2200 | url = http://www.nature.com/reviews/genetics | url-status = live | s2cid = 21992183 | df = dmy-all | archive-url = https://web.archive.org/web/20080516070928/http://www.nature.com/reviews/genetics/ | archive-date = 16 May 2008 | url-access = subscription }}</ref> Bateson popularized the usage of the word ''genetics'' to describe the study of inheritance in his inaugural address to the Third International Conference on Plant Hybridization in [[London]] in 1906.<ref name="bateson_genetics">{{cite conference |vauthors=Bateson W |title=The Progress of Genetic Research |editor=Wilks, W |book-title=Report of the Third 1906 International Conference on Genetics: Hybridization (the cross-breeding of genera or species), the cross-breeding of varieties, and general plant breeding|publisher=Royal Horticultural Society |location=London |year=1907}} :Initially titled the "International Conference on Hybridisation and Plant Breeding", the title was changed as a result of Bateson's speech. See: {{Cite book|vauthors=Cock AG, Forsdyke DR |year=2008|title=Treasure your exceptions: the science and life of William Bateson|url=https://archive.org/details/treasureyourexce00cock |url-access=limited |publisher=Springer|isbn=978-0-387-75687-5|page=[https://archive.org/details/treasureyourexce00cock/page/n265 248]}}</ref>

After the rediscovery of Mendel's work, scientists tried to determine which molecules in the cell were responsible for inheritance. In 1900, Nettie Stevens began studying the mealworm.<ref name="net">{{cite web |title=Nettie Stevens: A Discoverer of Sex Chromosomes |url=https://www.nature.com/scitable/topicpage/nettie-stevens-a-discoverer-of-sex-chromosomes-6580266/ |website=Scitable |publisher=Nature Education |access-date=8 June 2020}}</ref> Over the next 11 years, she discovered that females only had the X chromosome and males had both X and Y chromosomes.<ref name="net" /> She was able to conclude that sex is a chromosomal factor and is determined by the male.<ref name="net" /> In 1911, [[Thomas Hunt Morgan]] argued that genes are on [[chromosome]]s, based on observations of a sex-linked [[White (mutation)|white eye]] mutation in [[Drosophila melanogaster|fruit flies]].<ref>{{cite journal |doi=10.1093/icb/23.4.855 |title=Thomas Hunt Morgan – The Geneticist |year=1983 | vauthors = Moore JA |journal=Integrative and Comparative Biology |volume=23 |pages=855–865 |issue=4|doi-access= }}</ref> In 1913, his student [[Alfred Sturtevant]] used the phenomenon of [[genetic linkage]] to show that genes are arranged linearly on the chromosome.<ref>{{cite journal |vauthors=Sturtevant AH |year=1913 |title=The linear arrangement of six sex-linked factors in Drosophila, as shown by their mode of association |journal=Journal of Experimental Biology |volume=14 |issue=1 |pages=43–59 |url=http://www.esp.org/foundations/genetics/classical/holdings/s/ahs-13.pdf |doi=10.1002/jez.1400140104 |bibcode=1913JEZ....14...43S |url-status=live |archive-url=https://web.archive.org/web/20080227183131/http://www.esp.org/foundations/genetics/classical/holdings/s/ahs-13.pdf |archive-date=27 February 2008 |citeseerx=10.1.1.37.9595 |s2cid=82583173}}</ref>

=== Molecular genetics ===
{{Main|Molecular genetics}}
[[File:DNA Overview2.png|thumb|upright=0.6|[[DNA]], the molecular basis for [[Heredity|biological inheritance]]. Each strand of DNA is a chain of [[nucleotide]]s, matching each other in the center to form what look like rungs on a twisted ladder.]]

Although genes were known to exist on chromosomes, chromosomes are composed of both [[protein]] and DNA, and scientists did not know which of the two is responsible for inheritance. [[Griffith's experiment|In 1928]], [[Frederick Griffith]] discovered the phenomenon of [[Transformation (genetics)|transformation]]: dead bacteria could transfer [[genetic material]] to "transform" other still-living bacteria. Sixteen years later, in 1944, the [[Avery–MacLeod–McCarty experiment]] identified DNA as the molecule responsible for transformation.<ref name=Avery_et_al>{{cite journal | vauthors = Avery OT, Macleod CM, McCarty M | title = STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES : INDUCTION OF TRANSFORMATION BY A DESOXYRIBONUCLEIC ACID FRACTION ISOLATED FROM PNEUMOCOCCUS TYPE III | journal = The Journal of Experimental Medicine | volume = 79 | issue = 2 | pages = 137–158 | date = February 1944 | pmid = 19871359 | pmc = 2135445 | doi = 10.1084/jem.79.2.137 }} Reprint: {{cite journal | vauthors = Avery OT, MacLeod CM, McCarty M | title = Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Inductions of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III | journal = The Journal of Experimental Medicine | volume = 149 | issue = 2 | pages = 297–326 | date = February 1979 | pmid = 33226 | pmc = 2184805 | doi = 10.1084/jem.149.2.297 }}</ref> The role of the nucleus as the repository of genetic information in eukaryotes had been established by [[Joachim Hämmerling|Hämmerling]] in 1943 in his work on the single celled alga ''[[Acetabularia]]''.<ref>{{cite book |title=Cell and Molecular Biology | vauthors = Khanna P |publisher=I.K. International Pvt Ltd |date=2008 |page=221 |isbn=978-81-89866-59-4 }}</ref> The [[Hershey–Chase experiment]] in 1952 confirmed that DNA (rather than protein) is the genetic material of the viruses that infect bacteria, providing further evidence that DNA is the molecule responsible for inheritance.<ref>{{cite journal | vauthors = Hershey AD, Chase M | title = Independent functions of viral protein and nucleic acid in growth of bacteriophage | journal = The Journal of General Physiology | volume = 36 | issue = 1 | pages = 39–56 | date = May 1952 | pmid = 12981234 | pmc = 2147348 | doi = 10.1085/jgp.36.1.39 }}</ref>

[[James Watson]] and [[Francis Crick]] determined the structure of DNA in 1953, using the [[X-ray crystallography]] work of [[Rosalind Franklin]] and [[Maurice Wilkins]] that indicated DNA has a [[Helix|helical]] structure (i.e., shaped like a corkscrew).<ref>{{cite book |title=The Eighth Day of Creation: Makers of the Revolution in Biology | vauthors = Judson H |author-link=Horace Freeland Judson |year=1979 |publisher=Cold Spring Harbor Laboratory Press |isbn=978-0-87969-477-7 |pages=51–169}}</ref><ref name=watsoncrick_1953a>{{cite journal | vauthors = Watson JD, Crick FH | title = Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid | journal = Nature | volume = 171 | issue = 4356 | pages = 737–738 | date = April 1953 | pmid = 13054692 | doi = 10.1038/171737a0 | url = http://www.nature.com/nature/dna50/watsoncrick.pdf | url-status = live | s2cid = 4253007 | df = dmy-all | bibcode = 1953Natur.171..737W | archive-url = https://web.archive.org/web/20070204110320/http://www.nature.com/nature/dna50/watsoncrick.pdf | archive-date = 4 February 2007 }}</ref> Their double-helix model had two strands of DNA with the nucleotides pointing inward, each matching a complementary nucleotide on the other strand to form what look like rungs on a twisted ladder.<ref name=watsoncrick_1953b>{{cite journal | vauthors = Watson JD, Crick FH | title = Genetical implications of the structure of deoxyribonucleic acid | journal = Nature | volume = 171 | issue = 4361 | pages = 964–967 | date = May 1953 | pmid = 13063483 | doi = 10.1038/171964b0 | url = http://www.nature.com/nature/dna50/watsoncrick2.pdf | url-status = live | s2cid = 4256010 | df = dmy-all | bibcode = 1953Natur.171..964W | archive-url = https://web.archive.org/web/20030621051153/http://www.nature.com/nature/dna50/watsoncrick2.pdf | archive-date = 21 June 2003 }}</ref> This structure showed that genetic information exists in the sequence of nucleotides on each strand of DNA. The structure also suggested a simple method for [[DNA replication|replication]]: if the strands are separated, new partner strands can be reconstructed for each based on the sequence of the old strand. This property is what gives DNA its semi-conservative nature where one strand of new DNA is from an original parent strand.<ref>{{cite journal | vauthors = Stratmann SA, van Oijen AM | title = DNA replication at the single-molecule level | journal = Chemical Society Reviews | volume = 43 | issue = 4 | pages = 1201–1220 | date = February 2014 | pmid = 24395040 | doi = 10.1039/c3cs60391a | url = https://pure.rug.nl/ws/files/14412201/2014ChemSocRevStratmann.pdf | url-status = live | s2cid = 205856075 | archive-url = https://web.archive.org/web/20170706055534/https://pure.rug.nl/ws/files/14412201/2014ChemSocRevStratmann.pdf | archive-date = 2017-07-06 }}</ref>

Although the structure of DNA showed how inheritance works, it was still not known how DNA influences the behavior of cells. In the following years, scientists tried to understand how DNA controls the process of [[Protein biosynthesis|protein production]].<ref name="Betz2010">{{cite book |vauthors = Frederick B |title=Managing Science: Methodology and Organization of Research |url=https://books.google.com/books?id=1ARRexcXgAgC&pg=PA76 |year=2010 |publisher=Springer |isbn=978-1-4419-7488-4 |page=76}}</ref> It was discovered that the cell uses DNA as a template to create matching [[messenger RNA]], molecules with [[nucleotide]]s very similar to DNA. The nucleotide sequence of a messenger RNA is used to create an [[amino acid]] sequence in protein; this translation between nucleotide sequences and amino acid sequences is known as the [[genetic code]].<ref name="Rice2009">{{cite book | vauthors = Rice SA |title=Encyclopedia of Evolution |url=https://books.google.com/books?id=YRcAVvmE6eMC&pg=PA134 |year=2009 |publisher=Infobase Publishing |isbn=978-1-4381-1005-9 |page=134}}</ref>

With the newfound molecular understanding of inheritance came an explosion of research.<ref name="Sarkar1998">{{cite book | vauthors = Sarkar S |title=Genetics and Reductionism |url=https://books.google.com/books?id=7lzpDHFw-40C&pg=PA140 |year=1998 |publisher=Cambridge University Press |isbn=978-0-521-63713-8 |page=140}}</ref> A notable theory arose from [[Tomoko Ohta]] in 1973 with her amendment to the [[neutral theory of molecular evolution]] through publishing the [[nearly neutral theory of molecular evolution]]. In this theory, Ohta stressed the importance of natural selection and the environment to the rate at which genetic [[evolution]] occurs.<ref>{{cite journal | vauthors = Ohta T | title = Slightly deleterious mutant substitutions in evolution | journal = Nature | volume = 246 | issue = 5428 | pages = 96–98 | date = November 1973 | pmid = 4585855 | doi = 10.1038/246096a0 | s2cid = 4226804 | bibcode = 1973Natur.246...96O }}</ref> One important development was chain-termination [[DNA sequencing]] in 1977 by [[Frederick Sanger]]. This technology allows scientists to read the nucleotide sequence of a DNA molecule.<ref name=sanger_et_al>{{cite journal | vauthors = Sanger F, Nicklen S, Coulson AR | title = DNA sequencing with chain-terminating inhibitors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 74 | issue = 12 | pages = 5463–5467 | date = December 1977 | pmid = 271968 | pmc = 431765 | doi = 10.1073/pnas.74.12.5463 | doi-access = free | bibcode = 1977PNAS...74.5463S }}</ref> In 1983, [[Kary Banks Mullis]] developed the [[polymerase chain reaction]], providing a quick way to isolate and amplify a specific section of DNA from a mixture.<ref name=saiki_et_al>{{cite journal | vauthors = Saiki RK, Scharf S, Faloona F, Mullis KB, Horn GT, Erlich HA, Arnheim N | title = Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia | journal = Science | volume = 230 | issue = 4732 | pages = 1350–1354 | date = December 1985 | pmid = 2999980 | doi = 10.1126/science.2999980 | bibcode = 1985Sci...230.1350S }}</ref> The efforts of the [[Human Genome Project]], Department of Energy, NIH, and parallel private efforts by [[Celera Genomics]] led to the sequencing of the [[human genome]] in 2003.<ref name=human_genome_project /><ref>{{Cite journal|title=The sequence of the human genome|journal=Science|volume=291}}</ref>