Human genetic enhancement

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.

Ethics

Genetic engineering is a topic of moral debate among bioethicists. Genetic testing, genetic engineering, and stem cell research are often discussed together due to the interrelated moral arguments surrounding these topics. The distinction between repairing genes and enhancing genes is a central idea in many moral debates surrounding genetic enhancement because some argue that repairing genes is morally permissible, but that genetic enhancement is not due to its potential to lead to social injustice through discriminatory eugenics initiatives.[4]

Moral questions related to genetic testing are often related to duty to warn family members if an inherited disorder is discovered, how physicians should navigate patient autonomy and confidentiality with regard to genetic testing, the ethics of genetic discrimination, and the moral permissibility of using genetic testing to avoid causing seriously disabled persons to exist, such as through selective abortion.[4]

Ethical issues related to gene therapy and human genetic enhancement concern the medical risks and benefits of the therapy, the duty to use the procedures to prevent suffering, reproductive freedom in genetic choices, and the morality of practicing positive genetics, which includes attempts to improve normal functions.[4]

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 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, ...).[5]

In November 2018, Lulu and Nana were created.[6] 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.[7] 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.[8]

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).[9][10]

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[11] may alter appearance.

Behavior
Further information: Behavioural genetics and Genetics of aggression

Behavior may also be modified by genetic intervention.[12] Some people may be aggressive, selfish, and may not be able to function well in society. 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[13])

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.[14]

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.[15] 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.[16]

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).[17] 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.[18]

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.[19]

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.[20][21]

Military

In 2022, the People's Liberation Army Academy of Military Sciences reported that a team of military scientists inserted a gene from the tardigrade into human embryonic stem cells in an experiment with the stated possibility of enhancing soldiers' resistance to acute radiation syndrome to survive nuclear fallout.[22]

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.[23][24]

See also

References
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  2. "1990 The Declaration of Inuyama". 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. Vaughn, Lewis (2023). Bioethics: Principles, Issues, and Cases (5th ed.). Oxford University Press. p. 500. ISBN 978-0-19-760902-6.
  5. 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.
  6. 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.
  7. "WADA Gene Doping". WADA. Archived from the original on 21 November 2009. Retrieved 27 September 2013.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
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  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. Neyfakh L (May 13, 2012). "In search of the money gene". The Boston Globe.
  21. Entine J (14 October 2012). "Genoeconomics: Is Our Financial Future In Our Chromosomes?". Science 2.0.
  22. Chen, Stephen (March 29, 2023). "Chinese team behind extreme animal gene experiment says it may lead to super soldiers who survive nuclear fallout". South China Morning Post. Archived from the original on March 29, 2023. Retrieved March 30, 2023.
  23. "George Church told us why he's listing "superhuman" gene hacks". Futurism. Retrieved 25 July 2021.
  24. "Protective alleles". arep.med.harvard.edu. Retrieved 25 July 2021.
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