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非人灵长类动物脑疾病模型构建中的伦理问题。

Ethical issues when modelling brain disorders innon-human primates.

机构信息

Division of Medical Ethics, New York University School of Medicine, New York, USA.

出版信息

J Med Ethics. 2018 May;44(5):323-327. doi: 10.1136/medethics-2016-104088. Epub 2017 Aug 11.

Abstract

Non-human animal models of human diseases advance our knowledge of the genetic underpinnings of disease and lead to the development of novel therapies for humans. While mice are the most common model organisms, their usefulness is limited. Larger animals may provide more accurate and valuable disease models, but it has, until recently, been challenging to create large animal disease models. Genome editors, such as Clustered Randomised Interspersed Palindromic Repeat (CRISPR), meet some of these challenges and bring routine genome engineering of larger animals and non-human primates (NHPs) well within reach. There is growing interest in creating NHP models of brain disorders such as autism, depression and Alzheimer's, which are very difficult to model or study in other organisms, including humans. New treatments are desperately needed for this set of disorders. This paper is novel in asking: Insofar as NHPs are being considered for use as model organisms for brain disorders, can this be done ethically? The paper concludes that it cannot. Notwithstanding ongoing debate about NHPs' moral status, (1) animal welfare concerns, (2) the availability of alternative methods of studying brain disorders and (3) unmet expectations of benefit justify a stop on the creation of NHP model organisms to study brain disorders. The lure of using new genetic technologies combined with the promise of novel therapeutics presents a formidable challenge to those who call for slow, careful, and only necessary research involving NHPs. But researchers should not create macaques with social deficits or capuchin monkeys with memory deficits just because they can.

摘要

非人类动物疾病模型促进了我们对疾病遗传基础的认识,并为人类开发新的治疗方法。虽然小鼠是最常见的模式生物,但它们的用途有限。更大的动物可能提供更准确和有价值的疾病模型,但直到最近,创建大型动物疾病模型一直具有挑战性。基因组编辑技术,如成簇规律间隔短回文重复序列(CRISPR),满足了这些挑战中的一些,并使大型动物和非人类灵长类动物(NHP)的常规基因组工程成为可能。人们越来越感兴趣地创建 NHP 模型来模拟自闭症、抑郁症和阿尔茨海默病等脑部疾病,这些疾病在其他生物体中(包括人类)非常难以建模或研究。对于这一组疾病,迫切需要新的治疗方法。本文的新颖之处在于提出了这样一个问题:既然 NHP 被认为是脑部疾病的模型生物,那么从伦理角度考虑,这种做法是否可行?本文的结论是不行。尽管关于 NHP 的道德地位仍存在争议,(1)动物福利问题,(2)研究脑部疾病的替代方法的可用性,以及(3)对获益的期望未得到满足,这些都证明停止创建 NHP 模型生物来研究脑部疾病是合理的。使用新的遗传技术的诱惑以及新型治疗方法的前景,对那些呼吁进行缓慢、谨慎且只涉及 NHP 的必要研究的人构成了巨大挑战。但是,研究人员不应该仅仅因为他们能够做到,就制造出具有社交缺陷的猕猴或具有记忆缺陷的卷尾猴。

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