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Human genetic enhancement

March 03, 2023

Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification. This could be done in order to cure diseases (gene therapy), prevent the possibility of getting a particular disease[1] (similarly to vaccines), to improve athlete performance in sporting events (gene doping), or to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. These genetic enhancements may or may not be done in such a way that the change is heritable (which has raised concerns within the scientific community).[2]

An illustration of viral vector-mediated gene transfer using an adenovirus as the vector.

Gene therapy

Further information: Gene therapy

Genetic modification in order to cure genetic diseases is referred to as gene therapy. Many such gene therapies are available, made it through all phases of clinical research and are approved by the FDA. Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.[3] As of 2017, Spark Therapeutics' Luxturna (RPE65 mutation-induced blindness) and Novartis' Kymriah (Chimeric antigen receptor T cell therapy) are the FDA's first approved gene therapies to enter the market. Since that time, drugs such as Novartis' Zolgensma and Alnylam's Patisiran have also received FDA approval, in addition to other companies' gene therapy drugs. Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters.

Disease prevention

Main article: Preventive healthcare
Further information: DNA immunization
See also: Immunocompromisation

Some people are immunocompromised and their bodies are hence much less capable of fending off and defeating diseases (i.e. influenza, ...). In some cases this is due to genetic flaws[clarification needed] or even genetic diseases such as SCID. Some gene therapies have already been developed or are being developed to correct these genetic flaws/diseases, hereby making these people less susceptible to catching additional diseases (i.e. influenza, ...).[4]

In November 2018, Lulu and Nana were created.[5] By using clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9, a gene editing technique, they disabled a gene called CCR5 in the embryos, aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus.

Gene doping

Main article: Gene doping

Athletes might adopt gene therapy technologies to improve their performance.[6] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[7]

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 or relieving chronic pain, for example).[8][9]

Physical appearance

See also: Morphological freedom

Some congenital disorders (such as 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.

Also changes in the mystatin gene[10] may alter appearance.

Behavior

Further information: Behavioural genetics and Genetics of aggression

Behavior may also be modified by genetic intervention.[11] Some people may be aggressive, selfish, and may not be able to function well in society.[clarification needed] 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[12])

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.[13]

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.[14] 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.[15]

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).[16] 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.[17]

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.[18]

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.[19][20]

Databases about potential modifications

George Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep, cognition-related changes that protect against Alzheimer's disease, disease resistances, higher lean muscle mass and enhanced learning abilities along with some of the associated studies and potential negative effects.[21][22]

See also

References

  1. ^ Veit W (2018). "Procreative Beneficence and Genetic Enhancement – KRITERION". Journal of Philosophy. 32 (1): 75–92. doi:10.13140/RG.2.2.11026.89289.
  2. ^ . 5 August 2001. Archived from the original on 5 August 2001.{{cite web}}: CS1 maint: bot: original URL status unknown (link)
  3. ^ "Gene Therapy Clinical Trials Worldwide Database". The Journal of Gene Medicine. Wiley. June 2016.s
  4. ^ Garcia-Perez L, van Eggermond M, van Roon L, Vloemans SA, Cordes M, Schambach A, et al. (June 2020). "Successful Preclinical Development of Gene Therapy for Recombinase-Activating Gene-1-Deficient SCID". Molecular Therapy. Methods & Clinical Development. 17: 666–682. doi:10.1016/j.omtm.2020.03.016. PMC 7163047. PMID 32322605. S2CID 216061532.
  5. ^ Ma H, Marti-Gutierrez N, Park SW, Wu J, Lee Y, Suzuki K, et al. (August 2017). "Correction of a pathogenic gene mutation in human embryos". Nature. 548 (7668): 413–419. Bibcode:2017Natur.548..413M. doi:10.1038/nature23305. PMID 28783728. S2CID 205258702.
  6. ^ . WADA. Archived from the original on 21 November 2009. Retrieved 27 September 2013.
  7. ^ Kayser B, Mauron A, Miah A (March 2007). "Current anti-doping policy: a critical appraisal". BMC Medical Ethics. 8 (1): 2. doi:10.1186/1472-6939-8-2. PMC 1851967. PMID 17394662.
  8. ^ Alexander B, Warner-Schmidt J, Eriksson T, Tamminga C, Arango-Lievano M, Arango-Llievano M, et al. (October 2010). "Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens". Science Translational Medicine. 2 (54): 54ra76. doi:10.1126/scitranslmed.3001079. PMC 3026098. PMID 20962330.
  9. ^ Doctrow B (March 30, 2021). . National Institutes of Health. Archived from the original on November 21, 2021. Retrieved February 23, 2022.
  10. ^ Gavish B, Gratton E, Hardy CJ (February 1983). "Adiabatic compressibility of globular proteins". Proceedings of the National Academy of Sciences of the United States of America. 80 (3): 750–754. Bibcode:1983PNAS...80..750G. doi:10.1073/pnas.80.3.750. PMC 393457. PMID 6572366.
  11. ^ Lupton ML (1994). "Behaviour modification by genetic intervention--the law's response". Medicine and Law. 13 (5–6): 417–431. PMID 7845173.
  12. ^ Thompson GJ, Hurd PL, Crespi BJ (23 December 2013). "Genes underlying altruism". Biology Letters. 9 (6): 20130395. doi:10.1098/rsbl.2013.0395. PMC 3871336. PMID 24132092.
  13. ^ Thome J, Hässler F, Zachariou V (September 2011). "Gene therapy for psychiatric disorders". The World Journal of Biological Psychiatry. 12 Suppl 1 (sup1): 16–18. doi:10.3109/15622975.2011.601927. PMC 3394098. PMID 21905989.
  14. ^ Ocaranza P, Quintanilla ME, Tampier L, Karahanian E, Sapag A, Israel Y (January 2008). "Gene therapy reduces ethanol intake in an animal model of alcohol dependence". Alcoholism: Clinical and Experimental Research. 32 (1): 52–57. doi:10.1111/j.1530-0277.2007.00553.x. hdl:10533/139024. PMID 18070247.
  15. ^ Alexander B, Warner-Schmidt J, Eriksson T, Tamminga C, Arango-Lievano M, Arango-Llievano M, et al. (October 2010). "Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens". Science Translational Medicine. 2 (54): 54ra76. doi:10.1126/scitranslmed.3001079. PMC 3026098. PMID 20962330.
  16. ^ Caccamo A, Majumder S, Richardson A, Strong R, Oddo S (April 2010). "Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments". The Journal of Biological Chemistry. 285 (17): 13107–13120. doi:10.1074/jbc.M110.100420. PMC 2857107. PMID 20178983.
  17. ^ Spencer B, Marr RA, Rockenstein E, Crews L, Adame A, Potkar R, et al. (November 2008). "Long-term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice". BMC Neuroscience. 9: 109. doi:10.1186/1471-2202-9-109. PMC 2596170. PMID 19014502.
  18. ^ Carty NC, Nash K, Lee D, Mercer M, Gottschall PE, Meyers C, et al. (September 2008). "Adeno-associated viral (AAV) serotype 5 vector mediated gene delivery of endothelin-converting enzyme reduces Abeta deposits in APP + PS1 transgenic mice". Molecular Therapy. 16 (9): 1580–1586. doi:10.1038/mt.2008.148. PMC 2706523. PMID 18665160. ProQuest 1792610385.
  19. ^ Neyfakh L (May 13, 2012). "In search of the money gene". The Boston Globe.
  20. ^ Entine J (14 October 2012). "Genoeconomics: Is Our Financial Future In Our Chromosomes?". Science 2.0.
  21. ^ "George Church told us why he's listing "superhuman" gene hacks". Futurism. Retrieved 25 July 2021.
  22. ^ "Protective alleles". arep.med.harvard.edu. Retrieved 25 July 2021.

March 03, 2023
human, genetic, enhancement, human, genetic, engineering, refers, human, enhancement, means, genetic, modification, this, could, done, order, cure, diseases, gene, therapy, prevent, possibility, getting, particular, disease, similarly, vaccines, improve, athle. Human genetic enhancement or human genetic engineering refers to human enhancement by means of a genetic modification This could be done in order to cure diseases gene therapy prevent the possibility of getting a particular disease 1 similarly to vaccines to improve athlete performance in sporting events gene doping or to change physical appearance metabolism and even improve physical capabilities and mental faculties such as memory and intelligence These genetic enhancements may or may not be done in such a way that the change is heritable which has raised concerns within the scientific community 2 An illustration of viral vector mediated gene transfer using an adenovirus as the vector Contents 1 Gene therapy 2 Disease prevention 3 Gene doping 4 Other uses 4 1 Physical appearance 4 2 Behavior 5 Databases about potential modifications 6 See also 7 ReferencesGene therapy EditFurther information Gene therapy Genetic modification in order to cure genetic diseases is referred to as gene therapy Many such gene therapies are available made it through all phases of clinical research and are approved by the FDA Between 1989 and December 2018 over 2 900 clinical trials were conducted with more than half of them in phase I 3 As of 2017 update Spark Therapeutics Luxturna RPE65 mutation induced blindness and Novartis Kymriah Chimeric antigen receptor T cell therapy are the FDA s first approved gene therapies to enter the market Since that time drugs such as Novartis Zolgensma and Alnylam s Patisiran have also received FDA approval in addition to other companies gene therapy drugs Most of these approaches utilize adeno associated viruses AAVs and lentiviruses for performing gene insertions in vivo and ex vivo respectively ASO siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non viral delivery systems and utilize alternative mechanisms for trafficking to liver cells by way of GalNAc transporters Disease prevention EditMain article Preventive healthcare Further information DNA immunization See also Immunocompromisation Some people are immunocompromised and their bodies are hence much less capable of fending off and defeating diseases i e influenza In some cases this is due to genetic flaws clarification needed or even genetic diseases such as SCID Some gene therapies have already been developed or are being developed to correct these genetic flaws diseases hereby making these people less susceptible to catching additional diseases i e influenza 4 In November 2018 Lulu and Nana were created 5 By using clustered regularly interspaced short palindromic repeat CRISPR Cas9 a gene editing technique they disabled a gene called CCR5 in the embryos aiming to close the protein doorway that allows HIV to enter a cell and make the subjects immune to the HIV virus Gene doping EditMain article Gene doping Athletes might adopt gene therapy technologies to improve their performance 6 Gene doping is not known to occur but multiple gene therapies may have such effects Kayser et al argue that gene doping could level the playing field if all athletes receive equal access Critics claim that any therapeutic intervention for non therapeutic enhancement purposes compromises the ethical foundations of medicine and sports 7 Other uses EditOther 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 or relieving chronic pain for example 8 9 Physical appearance Edit See also Morphological freedom Some congenital disorders such as 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 Also changes in the mystatin gene 10 may alter appearance Behavior Edit Further information Behavioural genetics and Genetics of aggression Behavior may also be modified by genetic intervention 11 Some people may be aggressive selfish and may not be able to function well in society clarification needed 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 12 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 13 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 14 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 15 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 16 The same authors were also able to show in this study that accumulation of amyloid b Ab interfered with CREB activity which is physiologically involved in memory formation In another study it was shown that Ab 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 17 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 Ab deposits in a transgenic mouse model of Alzeimer s dementia 18 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 update the results have been inconclusive Some minor correlations have been identified 19 20 Databases about potential modifications EditGeorge Church has compiled a list of potential genetic modifications based on scientific studies for possibly advantageous traits such as less need for sleep cognition related changes that protect against Alzheimer s disease disease resistances higher lean muscle mass and enhanced learning abilities along with some of the associated studies and potential negative effects 21 22 See also EditBiohappiness Crossbreeding Directed evolution transhumanism Designer baby Epigenetics Genetic screening allows detecting personal genetic weaknesses to be addressed Genetic factors of addiction Procreative beneficence New eugenics Life extensionReferences Edit Veit W 2018 Procreative Beneficence and Genetic Enhancement KRITERION Journal of Philosophy 32 1 75 92 doi 10 13140 RG 2 2 11026 89289 1990 The Declaration of Inuyama 5 August 2001 Archived from the original on 5 August 2001 a href Template Cite web html title Template Cite web cite web a CS1 maint bot original URL status unknown link Gene Therapy Clinical Trials Worldwide Database The Journal of Gene Medicine Wiley June 2016 s Garcia Perez L van Eggermond M van Roon L Vloemans SA Cordes M Schambach A et al June 2020 Successful Preclinical Development of Gene Therapy for Recombinase Activating Gene 1 Deficient SCID Molecular Therapy Methods amp Clinical Development 17 666 682 doi 10 1016 j omtm 2020 03 016 PMC 7163047 PMID 32322605 S2CID 216061532 Ma H Marti Gutierrez N Park SW Wu J Lee Y Suzuki K et al August 2017 Correction of a pathogenic gene mutation in human embryos Nature 548 7668 413 419 Bibcode 2017Natur 548 413M doi 10 1038 nature23305 PMID 28783728 S2CID 205258702 WADA Gene Doping WADA Archived from the original on 21 November 2009 Retrieved 27 September 2013 Kayser B Mauron A Miah A March 2007 Current anti doping policy a critical appraisal BMC Medical Ethics 8 1 2 doi 10 1186 1472 6939 8 2 PMC 1851967 PMID 17394662 Alexander B Warner Schmidt J Eriksson T Tamminga C Arango Lievano M Arango Llievano M et al October 2010 Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens Science Translational Medicine 2 54 54ra76 doi 10 1126 scitranslmed 3001079 PMC 3026098 PMID 20962330 Doctrow B March 30 2021 Gene therapy for chronic pain relief National Institutes of Health Archived from the original on November 21 2021 Retrieved February 23 2022 Gavish B Gratton E Hardy CJ February 1983 Adiabatic compressibility of globular proteins Proceedings of the National Academy of Sciences of the United States of America 80 3 750 754 Bibcode 1983PNAS 80 750G doi 10 1073 pnas 80 3 750 PMC 393457 PMID 6572366 Lupton ML 1994 Behaviour modification by genetic intervention the law s response Medicine and Law 13 5 6 417 431 PMID 7845173 Thompson GJ Hurd PL Crespi BJ 23 December 2013 Genes underlying altruism Biology Letters 9 6 20130395 doi 10 1098 rsbl 2013 0395 PMC 3871336 PMID 24132092 Thome J Hassler F Zachariou V September 2011 Gene therapy for psychiatric disorders The World Journal of Biological Psychiatry 12 Suppl 1 sup1 16 18 doi 10 3109 15622975 2011 601927 PMC 3394098 PMID 21905989 Ocaranza P Quintanilla ME Tampier L Karahanian E Sapag A Israel Y January 2008 Gene therapy reduces ethanol intake in an animal model of alcohol dependence Alcoholism Clinical and Experimental Research 32 1 52 57 doi 10 1111 j 1530 0277 2007 00553 x hdl 10533 139024 PMID 18070247 Alexander B Warner Schmidt J Eriksson T Tamminga C Arango Lievano M Arango Llievano M et al October 2010 Reversal of depressed behaviors in mice by p11 gene therapy in the nucleus accumbens Science Translational Medicine 2 54 54ra76 doi 10 1126 scitranslmed 3001079 PMC 3026098 PMID 20962330 Caccamo A Majumder S Richardson A Strong R Oddo S April 2010 Molecular interplay between mammalian target of rapamycin mTOR amyloid beta and Tau effects on cognitive impairments The Journal of Biological Chemistry 285 17 13107 13120 doi 10 1074 jbc M110 100420 PMC 2857107 PMID 20178983 Spencer B Marr RA Rockenstein E Crews L Adame A Potkar R et al November 2008 Long term neprilysin gene transfer is associated with reduced levels of intracellular Abeta and behavioral improvement in APP transgenic mice BMC Neuroscience 9 109 doi 10 1186 1471 2202 9 109 PMC 2596170 PMID 19014502 Carty NC Nash K Lee D Mercer M Gottschall PE Meyers C et al September 2008 Adeno associated viral AAV serotype 5 vector mediated gene delivery of endothelin converting enzyme reduces Abeta deposits in APP PS1 transgenic mice Molecular Therapy 16 9 1580 1586 doi 10 1038 mt 2008 148 PMC 2706523 PMID 18665160 ProQuest 1792610385 Neyfakh L May 13 2012 In search of the money gene The Boston Globe Entine J 14 October 2012 Genoeconomics Is Our Financial Future In Our Chromosomes Science 2 0 George Church told us why he s listing superhuman gene hacks Futurism Retrieved 25 July 2021 Protective alleles arep med harvard edu Retrieved 25 July 2021 Retrieved from https en wikipedia org w index php title Human genetic enhancement amp oldid 1109261899, wikipedia, wiki, book, books, library,

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