Primum Non Nocere: Should Gene Therapy Be Used to Prevent Potentially Fatal Disease but Enable Potentially Destructive Behavior?
Primum Non Nocere: Should Gene Therapy Be Used to Prevent Potentially Fatal Disease but Enable Potentially Destructive Behavior?
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Primum Non Nocere：基因治疗是否应该用于预防潜在的致命疾病，但会引发潜在的破坏性行为？
DOI：
10.1089/hum.2021.039
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发表时间：
2021
影响因子：
4.2
通讯作者：
Crystal,RonaldG
中科院分区：
文献类型：
--
作者：
deMelo-Martin,Inmaculada;Crystal,RonaldG
乙醛脱氢酶 2 (ALDH2) 缺乏症是最常见的遗传性酶缺乏症之一，影响 35% 至 40% 的东亚人和 8% 的世界人口。它会导致众所周知的亚洲酒精脸红综合症，其特征是饮酒时面部潮红、心悸、心动过速、恶心和其他不愉快的感觉。它还与多种严重疾病的风险显着增加有关，包括食道癌和骨质疏松症。我们最近对小鼠模型的研究表明，一次性施用表达人类 ALDH2 编码序列 (AAVrh.10hALDH2) 的腺相关病毒 (AAV) 基因转移载体将纠正缺陷状态并预防酒精引起的食道和骨骼异常。如果在人类身上取得成功，这种策略将减少与风险增加相关的疾病，如食道癌和骨质疏松症，同时还能预防亚洲酒精脸红综合症。因此，这种治疗引起了伦理问题：虽然它有可能预防致命的疾病，但它也可能使受影响的个人饮酒而不会患上亚洲酒精脸红综合症，因此有可能导致个人破坏性行为。在这里，我们探讨了反对开发 ALDH2 缺乏症基因疗法的伦理争论，我们发现这些争论是有缺陷的。我们认为，开发此类治疗方法在伦理上是适当的，并且应该成为针对这种情况提供的解决方案的重要组成部分。
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.
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影响因子：
11.2
作者：
A. Berchuck;R. Whitaker;G. Olt;J. Soper;D. Clarke‐Pearson;A. Kamel;A. Kamel;R. Bast;B. Kerns;R. Kinney;R. Dodge;P. Marks;S. McKenzie;S. Yin
通讯作者：
A. Berchuck;R. Whitaker;G. Olt;J. Soper;D. Clarke‐Pearson;A. Kamel;A. Kamel;R. Bast;B. Kerns;R. Kinney;R. Dodge;P. Marks;S. McKenzie;S. Yin
风险评估中的人类高变序列：癌症患者中罕见的 Ha-ras 等位基因。
影响因子：
10.4
作者：
Krontiris,TG;DiMartino,NA;Mitcheson,HD;Lonergan,JA;Begg,C;Parkinson,DR
通讯作者：
Parkinson,DR
Ha-ras-1 限制性片段长度多态性与结肠腺癌的易感性。
影响因子：
8.8
作者：
Luca Ceccherini;V. D. Re;Alessandra Viel;G. Molaro;L. Zilli;C. Clemente;M. Boiocchi
通讯作者：
M. Boiocchi
颅内肿瘤患者中罕见的 Ha-ras 和 c-mos 等位基因
影响因子：
9.9
作者：
U. Diedrich;Ottmar Eckermann;J. Schmidtke
通讯作者：
J. Schmidtke
罕见的 HRAS 等位基因和人类乳腺癌的易感性。
影响因子：
4.4
作者：
Hall,JM;Huey,B;Morrow,J;Newman,B;Lee,M;Jones,E;Carter,C;Buehring,GC;King,MC
通讯作者：
King,MC