{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T21:15:30Z","timestamp":1777670130331,"version":"3.51.4"},"reference-count":59,"publisher":"SAGE Publications","issue":"11-12","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:p>Aldehyde dehydrogenase 2 (ALDH2) deficiency constitutes one of the most common hereditary enzyme deficiencies, affecting 35% to 40% of East Asians and 8% of the world population. It causes the well-known Asian Alcohol Flush Syndrome, characterized by facial flushing, palpitation, tachycardia, nausea, and other unpleasant feelings when alcohol is consumed. It is also associated with a marked increase in the risk of a variety of serious disorders, including esophageal cancer and osteoporosis. Our recent studies with murine models have demonstrated that a one-time administration of an adeno-associated virus (AAV) gene transfer vector expressing the human ALDH2 coding sequence (AAVrh.10hALDH2) will correct the deficiency state and prevent alcohol-induced abnormalities of the esophagus and bone. If successful in humans, such strategy would reduce the increased risk-associated disorders such as esophageal cancer and osteoporosis, but also prevent the Asian Alcohol Flush Syndrome. This treatment thus raises ethical concerns: although it would potentially prevent fatal disease, it could also allow affected individuals to drink alcohol without suffering the Asian Alcohol Flush Syndrome and, hence, potentially enable personal destructive behavior. Here we explore the ethical arguments against the development of a gene therapy for ALDH2 deficiency and we find them wanting. We contend that development of such treatments is ethically appropriate and should be part and parcel of the solutions offered against the condition.<\/jats:p>","DOI":"10.1089\/hum.2021.039","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T04:45:36Z","timestamp":1616474736000},"page":"529-534","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["<i>Primum Non Nocere:<\/i>\n                    Should Gene Therapy Be Used to Prevent Potentially Fatal Disease but Enable Potentially Destructive Behavior?"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8656-8497","authenticated-orcid":false,"given":"Inmaculada","family":"de Melo-Martin","sequence":"first","affiliation":[{"name":"Division of Medical Ethics, Department of Medicine, New York, New York, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6177-6839","authenticated-orcid":false,"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Department of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2021,6,16]]},"reference":[{"key":"e_1_3_4_2_2","unstructured":"National Center for Chronic Disease P Health Promotion Office on Smoking and Health. Reports of the surgeon general. In: The Health Consequences of Smoking\u201450 Years of Progress: a Report of the Surgeon General. Atlanta GA: Centers for Disease Control and Prevention (US) 2014."},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000000298"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi9521093"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01091.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1177\/108155899604400205","article-title":"Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues","volume":"44","author":"Stewart MJ","year":"1996","unstructured":"Stewart MJ, , Malek K, , Crabb DW. Distribution of messenger RNAs for aldehyde dehydrogenase 1, aldehyde dehydrogenase 2, and aldehyde dehydrogenase 5 in human tissues. J Investig Med, 1996; 44:42\u201346.","journal-title":"J Investig Med"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1432-1327.1998.2510549.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01710-5"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2797(00)00221-0"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M607959200"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2008.12.021"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq192"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12215"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010814-124915"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1510757112"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1000050"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2013"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/FPC.0b013e3282609e67"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2019.08.004"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2019.268"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-011-1116-4"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1037\/0033-2909.132.4.607"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1037\/a0035486"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1996.tb01080.x"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1037\/0893-164X.15.4.306"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.2009.00903.x"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.111.005538"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1908137116"},{"key":"e_1_3_4_29_2","unstructured":"World Health Organization. Global Status Report on Alcohol and Health. Geneva Switzerland 2018:xiii +376."},{"key":"e_1_3_4_30_2","unstructured":"National Institute on Drug Abuse. Principles of drug abuse treatment for criminal justice populations: A research-based guide. Bethesda MD: NIDA 2014."},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2008.02500.x"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2015.05.031"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v38.1.03"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-28720-6_198"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12130"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1177\/009145090903600106"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v38.1.05"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/dar.12820"},{"key":"e_1_3_4_39_2","first-page":"22","article-title":"ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review","volume":"30","author":"Eng MY","year":"2007","unstructured":"Eng MY, , Luczak SE, , Wall TL. ALDH2, ADH1B, and ADH1C genotypes in Asians: a literature review. Alcohol Res Health, 2007; 30:22\u201327.","journal-title":"Alcohol Res Health"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/ags017"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-00503-2"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1349-7006.2008.00807.x"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-06-0435"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1997.12.7.998"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1999.tb04126.x"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1634"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-004-1734-y"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-007-0543-5"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-006-0077-2"},{"key":"e_1_3_4_50_2","first-page":"283","article-title":"What is equality? 2. Equality of Resources","volume":"10","author":"Dworkin R.","year":"1981","unstructured":"Dworkin R. What is equality? 2. Equality of Resources. Philos Public Affairs, 1981; 10:283\u2013345.","journal-title":"Philos Public Affairs"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1086\/293126"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1086\/233272"},{"key":"e_1_3_4_53_2","doi-asserted-by":"crossref","unstructured":"Daniels N. Just Health: Meeting Health Needs Fairly. Cambridge New York: Cambridge University Press 2008.","DOI":"10.1017\/CBO9780511809514"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61228-8"},{"key":"e_1_3_4_55_2","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.19.241737"},{"key":"e_1_3_4_56_2","first-page":"E44","article-title":"GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study (vol 392, pg 1015, 2016)","volume":"393","author":"Lorkowski S.","year":"2019","unstructured":"Lorkowski S. GBD 2016 Alcohol Collaborators. Alcohol use and burden for 195 countries and territories, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study (vol 392, pg 1015, 2016). Lancet, 2019; 393:E44\u2013E44.","journal-title":"Lancet"},{"key":"e_1_3_4_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30373-X"},{"key":"e_1_3_4_58_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11126-018-9589-0"},{"key":"e_1_3_4_59_2","first-page":"631","article-title":"Opioid overdose prevention programs providing naloxone to laypersons\u2014United States, 2014","volume":"64","author":"Wheeler E","year":"2015","unstructured":"Wheeler E, , Jones TS, , Gilbert MK, et al. Opioid overdose prevention programs providing naloxone to laypersons\u2014United States, 2014. MMWR Morb Mortal Wkly Rep, 2015; 64:631\u2013635.","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"e_1_3_4_60_2","unstructured":"United Nations Office on Drugs and Crime\/World Health Organization (UNODC\/WHO). Opioid Overdose: Preventing and Reducing Opioid Overdose Mortality. Vienna: United Nations 2013."}],"container-title":["Human Gene Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/hum.2021.039","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2021.039","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/hum.2021.039","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:55:39Z","timestamp":1777449339000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/hum.2021.039"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":59,"journal-issue":{"issue":"11-12","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1089\/hum.2021.039"],"URL":"https:\/\/doi.org\/10.1089\/hum.2021.039","relation":{},"ISSN":["1043-0342","1557-7422"],"issn-type":[{"value":"1043-0342","type":"print"},{"value":"1557-7422","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]}}}