Editing Human genetic enhancement (section)

== Other uses ==
Other hypothetical gene therapies could include changes to physical appearance, metabolism, mental faculties such as memory and intelligence, and well-being (by increasing resistance to [[Depression (mood)|depression]] or relieving [[chronic pain]], for example).<ref name="Reversal of depressed behaviors in">{{cite journal | vauthors = Alexander B, Warner-Schmidt J, Eriksson T, Tamminga C, Arango-Lievano M, Ghose S, Vernov M, Stavarache M, Musatov S, Flajolet M, Svenningsson P, Greengard P, Kaplitt MG | display-authors = 6 | title = Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens | journal = Science Translational Medicine | volume = 2 | issue = 54 | pages = 54ra76 | date = October 2010 | pmid = 20962330 | pmc = 3026098 | doi = 10.1126/scitranslmed.3001079 }}</ref><ref>{{Cite news| vauthors = Doctrow B |date=March 30, 2021|title=Gene therapy for chronic pain relief|work=National Institutes of Health|url=https://www.nih.gov/news-events/nih-research-matters/gene-therapy-chronic-pain-relief|access-date=February 23, 2022|archive-url=https://web.archive.org/web/20211121040656/https://www.nih.gov/news-events/nih-research-matters/gene-therapy-chronic-pain-relief|archive-date=November 21, 2021}}</ref><!--Copy/pasted this from Gene therapy article, subsection Human genetic engineering, needs refs-->

=== Physical appearance ===
{{See also|Morphological freedom}}
The exploration of challenges in understanding the effects of gene alterations on phenotypes, particularly within natural genetic diversity, is highlighted. Emphasis is placed on the potential of systems biology and advancements in [[Genotype|genotyping]]/[[Phenotype|phenotyping]] technologies for studying complex traits. Despite progress, persistent difficulties in predicting the influence of gene alterations on phenotypic changes are acknowledged, emphasizing the ongoing need for research in this area.<ref>{{cite journal | vauthors = Benfey PN, Mitchell-Olds T | title = From genotype to phenotype: systems biology meets natural variation | journal = Science | volume = 320 | issue = 5875 | pages = 495–7 | date = April 2008 | pmid = 18436781 | pmc = 2727942 | doi = 10.1126/science.1153716 | bibcode = 2008Sci...320..495B }}</ref>

Some congenital disorders (such as [[:Category:Congenital disorders of musculoskeletal system|those affecting the muscoskeletal system]]) may affect physical appearance, and in some cases may also cause physical discomfort. Modifying the genes causing these congenital diseases (on those diagnosed to have mutations of the gene known to cause these diseases) may prevent this.

''- Phenotypic Impacts of CRISPR-Cas9 Editing in Mice Targeting the Tyr Gene:''

In a comprehensive [[CRISPR]]-[[Cas9]] study on gene editing, the Tyr gene in mice was targeted, seeking to instigate genetic alterations. The analysis found no off-target effects across 42 subjects, observing modifications exclusively at the intended Tyr locus. Though specifics were not explicitly discussed, these alterations may potentially influence non-defined aspects, such as coat color, emphasizing the broader potential of gene editing in inducing diverse phenotype changes.<ref>{{cite journal | vauthors = Parikh BA, Beckman DL, Patel SJ, White JM, Yokoyama WM | title = Detailed phenotypic and molecular analyses of genetically modified mice generated by CRISPR-Cas9-mediated editing | journal = PLOS ONE | volume = 10 | issue = 1 | pages = e0116484 | date = 2015-01-14 | pmid = 25587897 | pmc = 4294663 | doi = 10.1371/journal.pone.0116484 | bibcode = 2015PLoSO..1016484P | doi-access = free }}</ref>

Also changes in the myostatin gene<ref name="Haisma">{{cite journal | vauthors = Gavish B, Gratton E, Hardy CJ | title = Adiabatic compressibility of globular proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 80 | issue = 3 | pages = 750–4 | date = February 1983 | pmid = 6572366 | pmc = 393457 | doi = 10.1073/pnas.80.3.750 | doi-access = free | bibcode = 1983PNAS...80..750G }}</ref> may alter appearance.

=== Behavior ===
{{Further|Behavioural genetics|Genetics of aggression}}

Significant [[Quantitative genetics|quantitative genetic]] discoveries were made in the 1970s and 1980s, going beyond estimating heritability. However, issues such as [[The Bell Curve]] resurfaced, and by the 1990s, scientists recognized the importance of [[genetics]] for behavioral traits such as [[intelligence]]. The [[American Psychological Association]]'s Centennial Conference in 1992 chose [[Behavioural genetics|behavioral genetics]] as a theme for the past, present, and future of [[psychology]]. [[Molecular genetics]] synthesized, resulting in the [[DNA]] revolution and behavioral [[genomics]], as [[Quantitative genetics|quantitative genetic]] discoveries slowed. Individual behavioral differences can now be predicted early thanks to the [[Behavioural sciences|behavioral sciences']] DNA revolution. The first law of behavioral genetics was established in 1978 after a review of thirty twin studies revealed that the average heritability estimate for intelligence was 46%.<ref>{{cite journal | vauthors = Plomin R | title = Celebrating a Century of Research in Behavioral Genetics | journal = Behavior Genetics | volume = 53 | issue = 2 | pages = 75–84 | date = March 2023 | pmid = 36662387 | pmc = 9922236 | doi = 10.1007/s10519-023-10132-3 }}</ref> [[Behavior]] may also be modified by genetic intervention.<ref>{{cite journal | vauthors = Lupton ML | title = Behaviour modification by genetic intervention--the law's response | journal = Medicine and Law | volume = 13 | issue = 5–6 | pages = 417–431 | date = 1994 | pmid = 7845173 }}</ref>  Some people may be aggressive, selfish, and may not be able to function well in society. Mutations in GLI3 and other patterning genes have been linked to HH etiology, according to genetic research. Approximately 50%-80% of children with HH have acute wrath and violence, and the majority of patients have externalizing problems. Epilepsy may be preceded by behavioral instability and intellectual incapacity.<ref>{{cite journal | vauthors = Cohen NT, Cross JH, Arzimanoglou A, Berkovic SF, Kerrigan JF, Miller IP, Webster E, Soeby L, Cukiert A, Hesdorffer DK, Kroner BL, Saper CB, Schulze-Bonhage A, Gaillard WD | display-authors = 6 | title = Hypothalamic Hamartomas: Evolving Understanding and Management | journal = Neurology | volume = 97 | issue = 18 | pages = 864–873 | date = November 2021 | pmid = 34607926 | pmc = 8610628 | doi = 10.1212/WNL.0000000000012773 }}</ref> There is currently research ongoing on genes that are or may be (in part) responsible for selfishness (e.g. [[ruthlessness gene]]), aggression (e.g. [[warrior gene]]), altruism (e.g. [[OXTR]], [[CD38]], [[COMT]], [[DRD4]], [[DRD5]], [[IGF2]], [[GABRB2]]<ref>{{cite journal | vauthors = Thompson GJ, Hurd PL, Crespi BJ | title = Genes underlying altruism | journal = Biology Letters | volume = 9 | issue = 6 | pages = 20130395 | date = 23 December 2013 | pmid = 24132092 | pmc = 3871336 | doi = 10.1098/rsbl.2013.0395 }}</ref>)

There has been a great anticipation of [[Genetic engineering|gene editing]] technology to modify genes and regulate our [[biology]] since the invention of recombinant DNA technology. These expectations, however, have mostly gone unmet. Evaluation of the appropriate uses of germline interventions in reproductive medicine should not be based on concerns about enhancement or eugenics, despite the fact that gene editing research has advanced significantly toward clinical application.<ref>{{cite journal | vauthors = Cwik B | title = Moving Beyond 'Therapy' and 'Enhancement' in the Ethics of Gene Editing | journal = Cambridge Quarterly of Healthcare Ethics | volume = 28 | issue = 4 | pages = 695–707 | date = October 2019 | pmid = 31526421 | pmc = 6751566 | doi = 10.1017/S0963180119000641 }}</ref>

[[Cystic Fibrosis (CF)|Cystic fibrosis (CF)]] is a [[hereditary disease]] caused by mutations in the [[Cystic fibrosis transmembrane conductance regulator|Cystic fibrosis transmembrane conductance regulator (CFTR)]] gene. While 90% of CF patients can be treated, current treatments are not curative and do not address the entire spectrum of CFTR mutations. Therefore, a comprehensive, long-term therapy is needed to treat all [[Cystic fibrosis|CF]] patients once and for all. [[CRISPR/Cas]] [[Genetic engineering|gene editing]] technologies are being developed as a viable platform for genetic treatment.<ref>{{cite journal | vauthors = Wang G | title = Genome Editing for Cystic Fibrosis | journal = Cells | volume = 12 | issue = 12 | page = 1555 | date = June 2023 | pmid = 37371025 | pmc = 10297084 | doi = 10.3390/cells12121555 | doi-access = free }}</ref> However, the difficulties of delivering enough [[CFTR (gene)|CFTR gene]] and sustaining expression in the lungs has hampered gene therapy's efficacy. Recent technical breakthroughs, including as [[Viral vector|viral]] and non-viral vector transport, alternative [[nucleic acid]] technologies, and new technologies like [[mRNA]] and [[CRISPR gene editing]], have taken use of our understanding of [[Cystic fibrosis|CF]] biology and airway epithelium.<ref>{{cite journal | vauthors = Allen L, Allen L, Carr SB, Davies G, Downey D, Egan M, Forton JT, Gray R, Haworth C, Horsley A, Smyth AR, Southern KW, Davies JC | display-authors = 6 | title = Future therapies for cystic fibrosis | journal = Nature Communications | volume = 14 | issue = 1 | pages = 693 | date = February 2023 | pmid = 36755044 | pmc = 9907205 | doi = 10.1038/s41467-023-36244-2 | bibcode = 2023NatCo..14..693A }}</ref>

Human [[gene transfer]] has held the promise of a lasting remedy to hereditary illnesses such as [[Cystic Fibrosis (CF)|cystic fibrosis (CF)]] since its conception and use. The emergence of sophisticated technologies that allow for site-specific alteration with programmable nucleases has greatly revitalized the area of [[gene therapy]].<ref>{{cite journal | vauthors = Maule G, Arosio D, Cereseto A | title = Gene Therapy for Cystic Fibrosis: Progress and Challenges of Genome Editing | journal = International Journal of Molecular Sciences | volume = 21 | issue = 11 | page = 3903 | date = May 2020 | pmid = 32486152 | pmc = 7313467 | doi = 10.3390/ijms21113903 | doi-access = free }}</ref> There is some research going on on the [[hypothetical]] treatment of psychiatric disorders by means of gene therapy. It is assumed that, with gene-transfer techniques, it is possible (in experimental settings using animal models) to alter CNS gene expression and thereby the intrinsic generation of molecules involved in neural plasticity and neural regeneration, and thereby modifying ultimately behaviour.<ref>{{cite journal | vauthors = Thome J, Hässler F, Zachariou V | title = Gene therapy for psychiatric disorders | journal = The World Journal of Biological Psychiatry | volume = 12 | issue = Suppl 1 | pages = 16–18 | date = September 2011 | pmid = 21905989 | pmc = 3394098 | doi = 10.3109/15622975.2011.601927 }}</ref>

In recent years, it was possible to modify ethanol intake in animal models. Specifically, this was done by targeting the expression of the aldehyde dehydrogenase gene (ALDH2), lead to a significantly altered alcohol-drinking behaviour.<ref>{{cite journal | vauthors = Ocaranza P, Quintanilla ME, Tampier L, Karahanian E, Sapag A, Israel Y | title = Gene therapy reduces ethanol intake in an animal model of alcohol dependence | journal = Alcoholism: Clinical and Experimental Research | volume = 32 | issue = 1 | pages = 52–57 | date = January 2008 | pmid = 18070247 | doi = 10.1111/j.1530-0277.2007.00553.x | hdl-access = free | hdl = 10533/139024 }}</ref> Reduction of p11, a serotonin receptor binding protein, in the nucleus accumbens led to depression-like behaviour in rodents, while restoration of the p11 gene expression in this anatomical area reversed this behaviour.<ref name="Reversal of depressed behaviors in"/>

Recently, it was also shown that the gene transfer of CBP (CREB (c-AMP response element binding protein) binding protein) improves cognitive deficits in an animal model of Alzheimer's dementia via increasing the expression of BDNF (brain-derived neurotrophic factor).<ref>{{cite journal | vauthors = Caccamo A, Majumder S, Richardson A, Strong R, Oddo S | title = Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments | journal = The Journal of Biological Chemistry | volume = 285 | issue = 17 | pages = 13107–20 | date = April 2010 | pmid = 20178983 | pmc = 2857107 | doi = 10.1074/jbc.M110.100420 | doi-access = free }}</ref> The same authors were also able to show in this study that accumulation of amyloid-β (Aβ) interfered with CREB activity which is physiologically involved in memory formation.

In another study, it was shown that Aβ deposition and plaque formation can be reduced by sustained expression of the neprilysin (an endopeptidase) gene which also led to improvements on the behavioural (i.e. cognitive) level.<ref>{{cite journal | vauthors = Spencer B, Marr RA, Rockenstein E, Crews L, Adame A, Potkar R, Patrick C, Gage FH, Verma IM, Masliah E | display-authors = 6 | title = Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice | journal = BMC Neuroscience | volume = 9 | pages = 109 | date = November 2008 | pmid = 19014502 | pmc = 2596170 | doi = 10.1186/1471-2202-9-109 | doi-access = free }}</ref>

Similarly, the intracerebral gene transfer of ECE (endothelin-converting enzyme) via a virus vector stereotactically injected in the right anterior cortex and hippocampus, has also shown to reduce Aβ deposits in a transgenic mouse model of Alzeimer's dementia.<ref>{{cite journal | vauthors = Carty NC, Nash K, Lee D, Mercer M, Gottschall PE, Meyers C, Muzyczka N, Gordon MN, Morgan D | display-authors = 6 | title = Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice | journal = Molecular Therapy | volume = 16 | issue = 9 | pages = 1580–6 | date = September 2008 | pmid = 18665160 | pmc = 2706523 | doi = 10.1038/mt.2008.148 | id = {{ProQuest|1792610385}} }}</ref>

There is also research going on on [[genoeconomics]], a [[protoscience]] that is based on the idea that a person's [[financial]] behavior could be traced to their [[DNA]] and that [[genes]] are related to [[economic behavior]]. {{as of|2015}}, the results have been inconclusive. Some minor correlations have been identified.<ref>{{cite news| vauthors = Neyfakh L |title=In search of the money gene|url=http://www.boston.com/bostonglobe/ideas/articles/2012/05/13/webhed_are_we_born_to_be_poor_the_rise_of_genoeconomics/?page=full|work=The Boston Globe|date=May 13, 2012}}</ref><ref>{{cite news | vauthors = Entine J |title=Genoeconomics: Is Our Financial Future In Our Chromosomes? |url=https://www.science20.com/jon_entine_contrarian/genoeconomics_our_financial_future_our_chromosomes-95173 |work=Science 2.0 |date=14 October 2012 }}</ref>

Some studies show that our genes may affect some of our behaviors. For example, some genes may follow our state of stagnation, while others may be responsible for our bad habits. To give an example, the MAOA (Mono oxidase A) gene, the feature of this gene affects the release of hormones such as serotonin, epinephrine and dopamine and suppresses them. It prevents us from reacting in some situations and from stopping and making quick decisions in other situations, which can cause us to make wrong decisions in possible bad situations. As a result of some research, mood states such as aggression, feelings of compassion and irritability can be observed in people carrying this gene. Additionally, as a result of research conducted on people carrying the MAOA gene, this gene can be passed on genetically from parents, and mutations can also develop due to later epigenetic reasons. If we talk about epigenetic reasons, children of families growing up in bad environments begin to implement whatever they see from their parents. For this reason, those children begin to exhibit bad habits or behaviors such as irritability and aggression in the future.<ref name="pmid8211186">{{cite journal | vauthors = Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA | title = Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A | journal = Science | volume = 262 | issue = 5133 | pages = 578–580 | date = October 1993 | pmid = 8211186 | doi = 10.1126/science.8211186 | bibcode = 1993Sci...262..578B }}</ref>

=== Military ===
In December 2020, then-[[Director of National Intelligence]] [[John Ratcliffe (American politician)|John Ratcliffe]] said in an editorial for [[The Wall Street Journal]] that US intelligence shows China had conducted human testing on People's Liberation Army soldiers with the aim of creating "biologically enhanced" soldiers.<ref>{{Cite news |last=Ratcliffe |first=John |date=2020-12-03 |title=China Is National Security Threat No. 1 |url=https://www.wsj.com/articles/china-is-national-security-threat-no-1-11607019599 |access-date=2024-11-19 |work=The Wall Street Journal}}</ref><ref>{{Cite news |last=Gabbatt |first=Adam |date=2020-12-04 |title=China conducting biological tests to create super soldiers, US spy chief says |url=https://www.theguardian.com/world/2020/dec/04/china-super-soldiers-biologically-enhanced-john-ratcliffe |access-date=2024-11-19 |work=The Guardian |language=en-GB |issn=0261-3077}}</ref>

In 2022, the People's Liberation Army Academy of Military Sciences reported a notable experiment where military scientists inserted a [[gene]] from the [[tardigrade]] into human [[embryonic stem cell]]s. This experiment aimed to explore the potential enhancement of soldiers' resistance to acute [[radiation syndrome]], thereby increasing their ability to survive nuclear fallout. This development reflects the intersection of genetic engineering and [[military]] research, with a focus on bioenhancement for military personnel.
<ref>{{cite journal |vauthors=Karl JP, Margolis LM, Fallowfield JL, Child RB, Martin NM, McClung JP |title=Military nutrition research: Contemporary issues, state of the science and future directions |journal=Eur J Sport Sci |volume=22 |issue=1 |pages=87–98 |date=January 2022 |pmid=33980120 |doi=10.1080/17461391.2021.1930192 }}</ref>

[[Cas9|CRISPR/Cas9]] technologies have garnered attention for their potential applications in military contexts. Various projects are underway, including those focused on protecting soldiers from specific challenges. For instance, researchers are exploring the use of CRISPR/Cas9 to provide protection from [[frostbite]], reduce stress levels, alleviate [[sleep deprivation]], and enhance strength and endurance. The Defense Advanced Research Projects Agency ([[DARPA]]) is actively involved in researching and developing these technologies. One of their projects aims to engineer [[human cells]] to function as nutrient factories, potentially optimizing soldiers' performance and resilience in challenging environments.
<ref>{{cite journal |vauthors=Pang C, Chen ZD, Wei B, Xu WT, Xi HQ |title=Military training-related abdominal injuries and diseases: Common types, prevention and treatment |journal=Chin J Traumatol |volume=25 |issue=4 |pages=187–192 |date=July 2022 |pmid=35331607 |pmc=9252930 |doi=10.1016/j.cjtee.2022.03.002 }}</ref>

Additionally, military researchers are conducting animal trials to explore the prophylactic treatment for long-term protection against chemical weapons of mass destruction. This involves using non-pathogenic AAV8 vectors to deliver a candidate catalytic bioscavenger, PON1-IF11, into the [[bloodstream]] of [[mice]]. These initiatives underscore the broader exploration of [[Genetic engineering|genetic]] and molecular interventions to enhance military capabilities and protect personnel from various threats.<ref>{{cite journal |vauthors=Ogden HB, Rawcliffe AJ, Delves SK, Roberts A |title=Are young military personnel at a disproportional risk of heat illness? |journal=BMJ Mil Health |volume=169 |issue=6 |pages=559–564 |date=November 2023 |pmid=35241622 |pmc=10715519 |doi=10.1136/bmjmilitary-2021-002053 }}</ref>

In the realm of bioenhancement, concerns have been raised about the use of dietary supplements and other [[biomedical]] enhancements by military personnel. A significant portion of American special operations forces reportedly use dietary supplements to enhance performance, but the extent of the use of other bioenhancement methods, such as steroids, human growth hormone, and erythropoietin, remains unclear. The lack of completed safety and efficacy testing for these bioenhancements raises ethical and regulatory questions. This concern is not new, as issues surrounding the off-label use of products like [[pyridostigmine bromide]] and botulinum toxoid vaccine during the [[Gulf War]], as well as the DoD's Anthrax Vaccine Immunization Program in 1998, have prompted discussions about the need for thorough [[Food and Drug Administration|FDA approval]] for specific military applications.<ref>{{cite journal |vauthors=Hellwig LD, Krokosky A, Vargason A, Turner C |title=Genetic Counseling Considerations for Military Beneficiaries |journal=Mil Med |volume=187 |issue=Suppl 1 |pages=36–39 |date=December 2021 |pmid=34967403 |pmc=8717321 |doi=10.1093/milmed/usab007 }}</ref>

The intersection of [[genetic engineering]], [[Cas9|CRISPR/Cas9]] technologies, and military research introduces complex ethical considerations regarding the potential augmentation of human capabilities for military purposes. Striking a balance between scientific advancements, ethical standards, and regulatory oversight over classified projects remain crucial as these technologies continue to evolve.<ref>{{cite journal |vauthors=Merrigan JJ, Stone JD, Thompson AG, Hornsby WG, Hagen JA |title=Monitoring Neuromuscular Performance in Military Personnel |journal=Int J Environ Res Public Health |volume=17 |issue=23 |pages=9147 |date=December 2020 |pmid=33297554 |pmc=7730580 |doi=10.3390/ijerph17239147 |doi-access=free }}</ref>