Gorelick Root
School of Life Sciences, Arizona State University, Tempe, AZ 85287-4501, USA.
Med Hypotheses. 2004;62(2):299-303. doi: 10.1016/S0306-9877(03)00329-3.
Darwinian medicine is the treatment of disease based on evolution. The underlying assumption of Darwinian medicine is that traits are coded by genes, which are often assumed to be sequences of DNA nucleotides. The quantitative genetic ramification of this perspective is that traits, including disease susceptibility, are either caused by genes or by the environment, with genotype-by-environment interactions usually considered statistical artefacts. I emphasize also examining those epigenetic signals that can be altered by environmental perturbations and then transmitted to subsequent generations. Although seldom studied, environmentally-alterable meiotically-heritable epigenetic signals exist and provide a mechanism underlying genotype-by-environment interactions. Environment of a parent can affect its descendants by heritably altering epigenetic signals. Neo-Lamarckian medicine is the application of these evolutionary epigenetic notions to diseases and could have enormous public health and environmental policy implications. If industrial contaminants adversely affect organisms by meiotically-heritably altering their epigenetic signals, then cleaning up these contaminants will not remedy the problem. Once contaminants have adversely altered an individual's epigenetic signals, this harm will be transmitted to future generations even if they are not exposed to the contaminant. Exposure to environmental shocks such as free radicals or other carcinogens can alter cytosine methylation patterns on regulatory genes. This can cause cancer by up-regulating genes for cell division or by down-regulating tumour suppressor genes. Environmentally-alterable meiotically-heritable epigenetic signals could also underlie other diseases, such as diabetes, Prader-Willi syndrome, and many complex diseases. If environmentally-altered meiotically-heritable epigenetic effects are widespread - which is an important open empirical question - they have the potential to alter paradigmatic views of evolutionary medicine and the putative dichotomy of nature versus nurture. Neo-Lamarckian medicine would thereby shift emphasis from cure to prevention of diseases.
达尔文医学是基于进化原理对疾病进行的治疗。达尔文医学的基本假设是,性状由基因编码,而基因通常被认为是DNA核苷酸序列。从这一观点衍生出的数量遗传学观点是,包括疾病易感性在内的性状要么由基因引起,要么由环境引起,基因与环境的相互作用通常被视为统计假象。我还强调要研究那些可被环境扰动改变并随后传递给后代的表观遗传信号。尽管很少被研究,但确实存在可被环境改变的减数分裂可遗传表观遗传信号,它们为基因与环境相互作用提供了一种机制。亲本的环境可通过遗传改变表观遗传信号来影响其后代。新拉马克医学是将这些进化表观遗传学概念应用于疾病研究,可能会对公共卫生和环境政策产生巨大影响。如果工业污染物通过减数分裂可遗传地改变生物体的表观遗传信号而对其产生不利影响,那么清理这些污染物并不能解决问题。一旦污染物对个体的表观遗传信号产生了不利改变,即使后代没有接触到该污染物,这种危害也会传递给他们。暴露于自由基或其他致癌物等环境冲击下,可改变调控基因上的胞嘧啶甲基化模式。这可通过上调细胞分裂相关基因或下调肿瘤抑制基因而导致癌症。可被环境改变的减数分裂可遗传表观遗传信号也可能是其他疾病的基础,如糖尿病、普拉德-威利综合征和许多复杂疾病。如果环境改变引起的减数分裂可遗传表观遗传效应很普遍——这是一个重要的开放性实证问题——那么它们有可能改变进化医学的范式观点以及自然与 nurture 之间假定的二分法。新拉马克医学将因此把重点从疾病治疗转向疾病预防。 (注:原文中“nurture”可能有误,推测可能是“nature”,但按照要求未作修改。)